NCBI Conserved Domain Search

Catalytic kinase domain, second repeat, of Giant Serine/Threonine Kinase Striated muscle preferentially expressed protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Striated muscle preferentially expressed gene (SPEG) generates 4 different isoforms through alternative promoter use and splicing in a tissue-specific manner: SPEGalpha and SPEGbeta are expressed in cardiac and skeletal striated muscle; Aortic Preferentially Expressed Protein-1 (APEG-1) is expressed in vascular smooth muscle; and Brain preferentially expressed gene (BPEG) is found in the brain and aorta. SPEG proteins have mutliple immunoglobulin (Ig), 2 fibronectin type III (FN3), and two kinase domains. They are necessary for cardiac development and survival. The SPEG subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271013 [Multi-domain] Cd Length: 257 Bit Score: 480.47 E-value: 6.40e-155

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3296 PQKPYTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISEC 3375
Cdd:cd14111      1 PQKPYTFLDEKARGRFGVIRRCRENATGKNFPAKIVPYQAEEKQGVLQEYEILKSLHHERIMALHEAYITPRYLVLIAEF 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3376 CSGKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLKQFSPP 3455
Cdd:cd14111     81 CSGKELLHSLIDRFRYSEDDVVGYLVQILQGLEYLHGRRVLHLDIKPDNIMVTNLNAIKIVDFGSAQSFNPLSLRQLGRR 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3456 IGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLSKLYQNVSQSASLFIKKILCS 3535
Cdd:cd14111    161 TGTLEYMAPEMVKGEPVGPPADIWSIGVLTYIMLSGRSPFEDQDPQETEAKILVAKFDAFKLYPNVSQSASLFLKKVLSS 240

                          250
                   ....*....|....*..
gi 1207186029 3536 YPWARPTIKDCFTNSWL 3552
Cdd:cd14111    241 YPWSRPTTKDCFAHAWL 257

Catalytic kinase domain, first repeat, of Giant Serine/Threonine Kinase Striated muscle preferentially expressed protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Striated muscle preferentially expressed gene (SPEG) generates 4 different isoforms through alternative promoter use and splicing in a tissue-specific manner: SPEGalpha and SPEGbeta are expressed in cardiac and skeletal striated muscle; Aortic Preferentially Expressed Protein-1 (APEG-1) is expressed in vascular smooth muscle; and Brain preferentially expressed gene (BPEG) is found in the brain and aorta. SPEG proteins have mutliple immunoglobulin (Ig), 2 fibronectin type III (FN3), and two kinase domains. They are necessary for cardiac development and survival. The SPEG subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271010 [Multi-domain] Cd Length: 255 Bit Score: 468.61 E-value: 7.01e-151

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1659 TDYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITELC 1738
Cdd:cd14108      1 TDYYDIHKEIGRGAFSYLRRVKEKSSDLSFAAKFIPVRAKKKTSARRELALLAELDHKSIVRFHDAFEKRRVVIIVTELC 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1739 HEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSDQIRICDFGNAVKFMPDEAQYCKYG 1818
Cdd:cd14108     81 HEELLERITKRPTVCESEVRSYMRQLLEGIEYLHQNDVLHLDLKPENLLMADQKTDQVRICDFGNAQELTPNEPQYCKYG 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1819 TPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDLCHEAKGFVIKLLVAD 1898
Cdd:cd14108    161 TPEFVAPEIVNQSPVSKVTDIWPVGVIAYLCLTGISPFVGENDRTTLMNIRNYNVAFEESMFKDLCREAKGFIIKVLVSD 240

                          250
                   ....*....|....*
gi 1207186029 1899 RLRPDANECLRHPWF 1913
Cdd:cd14108    241 RLRPDAEETLEHPWF 255

Catalytic kinase domain of Myosin Light Chain Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This family is composed of MLCKs and related MLCK-like kinase domains from giant STKs such as titin, obscurin, SPEG, Unc-89, Trio, kalirin, and Twitchin. Also included in this family are Death-Associated Protein Kinases (DAPKs) and Death-associated protein kinase-Related Apoptosis-inducing protein Kinase (DRAKs). MLCK phosphorylates myosin regulatory light chain and controls the contraction of all muscle types. Titin, obscurin, Twitchin, and SPEG are muscle proteins involved in the contractile apparatus. The giant STKs are multidomain proteins containing immunoglobulin (Ig), fibronectin type III (FN3), SH3, RhoGEF, PH and kinase domains. Titin, obscurin, Twitchin, and SPEG contain many Ig domain repeats at the N-terminus, while Trio and Kalirin contain spectrin-like repeats. The MLCK-like family is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270908 [Multi-domain] Cd Length: 247 Bit Score: 352.34 E-value: 2.15e-110

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITELCH-EELLDRL 1746
Cdd:cd14006      1 LGRGRFGVVKRCIEKATGREFAAKFIPKRDKKKEAVLREISILNQLQHPRIIQLHEAYESPTELVLILELCSgGELLDRL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1747 TKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSDQIRICDFGNAVKFMPDEAQYCKYGTPEFVAPE 1826
Cdd:cd14006     81 AERGSLSEEEVRTYMRQLLEGLQYLHNHHILHLDLKPENILLADRPSPQIKIIDFGLARKLNPGEELKEIFGTPEFVAPE 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1827 IVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDLCHEAKGFVIKLLVAD-RLRPDAN 1905
Cdd:cd14006    161 IVNGEPVSLATDMWSIGVLTYVLLSGLSPFLGEDDQETLANISACRVDFSEEYFSSVSQEAKDFIRKLLVKEpRKRPTAQ 240


                   ....*..
gi 1207186029 1906 ECLRHPW 1912
Cdd:cd14006    241 EALQHPW 247

Catalytic kinase domain of Myosin Light Chain Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This family is composed of MLCKs and related MLCK-like kinase domains from giant STKs such as titin, obscurin, SPEG, Unc-89, Trio, kalirin, and Twitchin. Also included in this family are Death-Associated Protein Kinases (DAPKs) and Death-associated protein kinase-Related Apoptosis-inducing protein Kinase (DRAKs). MLCK phosphorylates myosin regulatory light chain and controls the contraction of all muscle types. Titin, obscurin, Twitchin, and SPEG are muscle proteins involved in the contractile apparatus. The giant STKs are multidomain proteins containing immunoglobulin (Ig), fibronectin type III (FN3), SH3, RhoGEF, PH and kinase domains. Titin, obscurin, Twitchin, and SPEG contain many Ig domain repeats at the N-terminus, while Trio and Kalirin contain spectrin-like repeats. The MLCK-like family is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270908 [Multi-domain] Cd Length: 247 Bit Score: 318.06 E-value: 1.75e-98

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3307 ARGRFGVIRECRENATGNLYMAKIVPYEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLHSLI 3386
Cdd:cd14006      2 GRGRFGVVKRCIEKATGREFAAKFIPKRDKKKEAVLREISILNQLQHPRIIQLHEAYESPTELVLILELCSGGELLDRLA 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3387 DRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVT--YMNVVKIIDFGSAQTFNPlfLKQFSPPIGTLDYMSP 3464
Cdd:cd14006     82 ERGSLSEEEVRTYMRQLLEGLQYLHNHHILHLDLKPENILLAdrPSPQIKIIDFGLARKLNP--GEELKEIFGTPEFVAP 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3465 EMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLSKLY-QNVSQSASLFIKKILCSYPWARPTI 3543
Cdd:cd14006    160 EIVNGEPVSLATDMWSIGVLTYVLLSGLSPFLGEDDQETLANISACRVDFSEEYfSSVSQEAKDFIRKLLVKEPRKRPTA 239


                   ....*...
gi 1207186029 3544 KDCFTNSW 3551
Cdd:cd14006    240 QEALQHPW 247

Catalytic kinase domain, first repeat, of the Giant Serine/Threonine Kinase Obscurin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Obscurin, approximately 800 kDa in size, is one of three giant proteins expressed in vetebrate striated muscle, together with titin and nebulin. It is a multidomain protein composed of tandem adhesion and signaling domains, including 49 immunoglobulin (Ig) and 2 fibronectin type III (FN3) domains at the N-terminus followed by a more complex region containing more Ig domains, a conserved SH3 domain near a RhoGEF and PH domains, non-modular regions, as well as IQ and phosphorylation motifs. The obscurin gene also encode two kinase domains, which are not expressed as part of the 800 kDa protein, but as a smaller, alternatively spliced product present mainly in the heart muscle, also called obscurin-MLCK. Obscurin is localized at the peripheries of Z-disks and M-lines, where it is able to communicate with the surrounding myoplasm. It interacts with diverse proteins including sAnk1, myosin, titin, and MyBP-C. It may act as a scaffold for the assembly of elements of the contractile apparatus. The obscurin subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271009 [Multi-domain] Cd Length: 257 Bit Score: 302.96 E-value: 4.31e-93

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1661 YYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITELCH- 1739
Cdd:cd14107      3 VYEVKEEIGRGTFGFVKRVTHKGNGECCAAKFIPLRSSTRARAFQERDILARLSHRRLTCLLDQFETRKTLILILELCSs 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1740 EELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSDQIRICDFGNAVKFMPDEAQYCKYGT 1819
Cdd:cd14107     83 EELLDRLFLKGVVTEAEVKLYIQQVLEGIGYLHGMNILHLDIKPDNILMVSPTREDIKICDFGFAQEITPSEHQFSKYGS 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1820 PEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDLCHEAKGFVIKLLVAD- 1898
Cdd:cd14107    163 PEFVAPEIVHQEPVSAATDIWALGVIAYLSLTCHSPFAGENDRATLLNVAEGVVSWDTPEITHLSEDAKDFIKRVLQPDp 242

                          250
                   ....*....|....*
gi 1207186029 1899 RLRPDANECLRHPWF 1913
Cdd:cd14107    243 EKRPSASECLSHEWF 257

Catalytic kinase domain, second repeat, of the Giant Serine/Threonine Kinase Obscurin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Obscurin, approximately 800 kDa in size, is one of three giant proteins expressed in vetebrate striated muscle, together with titin and nebulin. It is a multidomain protein composed of tandem adhesion and signaling domains, including 49 immunoglobulin (Ig) and 2 fibronectin type III (FN3) domains at the N-terminus followed by a more complex region containing more Ig domains, a conserved SH3 domain near a RhoGEF and PH domains, non-modular regions, as well as IQ and phosphorylation motifs. The obscurin gene also encode two kinase domains, which are not expressed as part of the 800 kDa protein, but as a smaller, alternatively spliced product present mainly in the heart muscle, also called obscurin-MLCK. Obscurin is localized at the peripheries of Z-disks and M-lines, where it is able to communicate with the surrounding myoplasm. It interacts with diverse proteins including sAnk1, myosin, titin, and MyBP-C. It may act as a scaffold for the assembly of elements of the contractile apparatus. The obscurin subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271012 [Multi-domain] Cd Length: 257 Bit Score: 279.11 E-value: 1.14e-84

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3298 KPYTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCS 3377
Cdd:cd14110      3 KTYAFQTEINRGRFSVVRQCEEKRSGQMLAAKIIPYKPEDKQLVLREYQVLRRLSHPRIAQLHSAYLSPRHLVLIEELCS 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3378 GKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPlflKQFSPPIG 3457
Cdd:cd14110     83 GPELLYNLAERNSYSEAEVTDYLWQILSAVDYLHSRRILHLDLRSENMIITEKNLLKIVDLGNAQPFNQ---GKVLMTDK 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3458 TLDY---MSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLSKLYQNVSQSASLFIKKILC 3534
Cdd:cd14110    160 KGDYvetMAPELLEGQGAGPQTDIWAIGVTAFIMLSADYPVSSDLNWERDRNIRKGKVQLSRCYAGLSGGAVNFLKSTLC 239

                          250
                   ....*....|....*...
gi 1207186029 3535 SYPWARPTIKDCFTNSWL 3552
Cdd:cd14110    240 AKPWGRPTASECLQNPWL 257

The catalytic domain of CAMK family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. CaMKII is a signaling molecule that translates upstream calcium and reactive oxygen species (ROS) signals into downstream responses that play important roles in synaptic function and cardiovascular physiology. CAMKIV is implicated in regulating several transcription factors like CREB, MEF2, and retinoid orphan receptors, as well as in T-cell development and signaling. The CAMK family also consists of other related kinases including the Phosphorylase kinase Gamma subunit (PhKG), the C-terminal kinase domains of Ribosomal S6 kinase (RSK) and Mitogen and stress-activated kinase (MSK), Doublecortin-like kinase (DCKL), and the MAPK-activated protein kinases MK2, MK3, and MK5, among others. The CAMK family is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270687 [Multi-domain] Cd Length: 258 Bit Score: 262.41 E-value: 6.47e-79

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFIS---ARAKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITELC 1738
Cdd:cd05117      2 YELGKVLGRGSFGVVRLAVHKKTGEEYAVKIIDkkkLKSEDEEMLRREIEILKRLDHPNIVKLYEVFEDDKNLYLVMELC 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1739 HE-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSD-QIRICDFGNAVKFMPDEAQYCK 1816
Cdd:cd05117     82 TGgELFDRIVKKGSFSEREAAKIMKQILSAVAYLHSQGIVHRDLKPENILLASKDPDsPIKIIDFGLAKIFEEGEKLKTV 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1817 YGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDLCHEAKGFVIKLLV 1896
Cdd:cd05117    162 CGTPYYVAPEVLKGKGYGKKCDIWSLGVILYILLCGYPPFYGETEQELFEKILKGKYSFDSPEWKNVSEEAKDLIKRLLV 241

                          250
                   ....*....|....*..
gi 1207186029 1897 AD-RLRPDANECLRHPW 1912
Cdd:cd05117    242 VDpKKRLTAAEALNHPW 258

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK phosphorylates myosin regulatory light chain and controls the contraction of all muscle types. In vertebrates, different MLCKs function in smooth (MLCK1), skeletal (MLCK2), and cardiac (MLCK3) muscles. A fourth protein, MLCK4, has also been identified through comprehensive genome analysis although it has not been biochemically characterized. The MLCK1 gene expresses three transcripts in a cell-specific manner: a short MLCK1 which contains three immunoglobulin (Ig)-like and one fibronectin type III (FN3) domains, PEVK and actin-binding regions, and a kinase domain near the C-terminus; a long MLCK1 containing six additional Ig-like domains at the N-terminus compared to the short MLCK1; and the C-terminal Ig module. MLCK2, MLCK3, and MLCK4 share a simpler domain architecture of a single kinase domain near the C-terminus and the absence of Ig-like or FN3 domains. The MLCK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271005 [Multi-domain] Cd Length: 250 Bit Score: 249.84 E-value: 1.12e-74

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYVKRVIQKAGKLEYAAKFISAR-AKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITELCH-EELLDR 1745
Cdd:cd14103      1 LGRGKFGTVYRCVEKATGKELAAKFIKCRkAKDREDVRNEIEIMNQLRHPRLLQLYDAFETPREMVLVMEYVAgGELFER 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1746 LTKKSTIL-ESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSDQIRICDFGNAVKFMPDEAQYCKYGTPEFVA 1824
Cdd:cd14103     81 VVDDDFELtERDCILFMRQICEGVQYMHKQGILHLDLKPENILCVSRTGNQIKIIDFGLARKYDPDKKLKVLFGTPEFVA 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1825 PEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDLCHEAKGFVIKLLVAD-RLRPD 1903
Cdd:cd14103    161 PEVVNYEPISYATDMWSVGVICYVLLSGLSPFMGDNDAETLANVTRAKWDFDDEAFDDISDEAKDFISKLLVKDpRKRMS 240


                   ....*....
gi 1207186029 1904 ANECLRHPW 1912
Cdd:cd14103    241 AAQCLQHPW 249

Serine/Threonine protein kinases, catalytic domain; Phosphotransferases. Serine or threonine-specific kinase subfamily.

Pssm-ID: 214567 [Multi-domain] Cd Length: 254 Bit Score: 243.98 E-value: 1.62e-72

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPESK--QTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCS 3377
Cdd:smart00220    1 YEILEKLGEGSFGKVYLARDKKTGKLVAIKVIKKKKIKKdrERILREIKILKKLKHPNIVRLYDVFEDEDKLYLVMEYCE 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  3378 GKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPlfLKQFSPPIG 3457
Cdd:smart00220   81 GGDLFDLLKKRGRLSEDEARFYLRQILSALEYLHSKGIVHRDLKPENILLDEDGHVKLADFGLARQLDP--GEKLTTFVG 158

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  3458 TLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPF-TENDPAETEARIQAAKFDLSKLYQNVSQSASLFIKKILCSY 3536
Cdd:smart00220  159 TPEYMAPEVLLGKGYGKAVDIWSLGVILYELLTGKPPFpGDDQLLELFKKIGKPKPPFPPPEWDISPEAKDLIRKLLVKD 238

                           250
                    ....*....|....*.
gi 1207186029  3537 PWARPTIKDCFTNSWL 3552
Cdd:smart00220  239 PEKRLTAEEALQHPFF 254

The catalytic domain of CAMK family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. CaMKII is a signaling molecule that translates upstream calcium and reactive oxygen species (ROS) signals into downstream responses that play important roles in synaptic function and cardiovascular physiology. CAMKIV is implicated in regulating several transcription factors like CREB, MEF2, and retinoid orphan receptors, as well as in T-cell development and signaling. The CAMK family also consists of other related kinases including the Phosphorylase kinase Gamma subunit (PhKG), the C-terminal kinase domains of Ribosomal S6 kinase (RSK) and Mitogen and stress-activated kinase (MSK), Doublecortin-like kinase (DCKL), and the MAPK-activated protein kinases MK2, MK3, and MK5, among others. The CAMK family is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270687 [Multi-domain] Cd Length: 258 Bit Score: 242.77 E-value: 4.19e-72

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIV---PYEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECC 3376
Cdd:cd05117      2 YELGKVLGRGSFGVVRLAVHKKTGEEYAVKIIdkkKLKSEDEEMLRREIEILKRLDHPNIVKLYEVFEDDKNLYLVMELC 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3377 SGKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMN---VVKIIDFGSAQTFNP-LFLKQf 3452
Cdd:cd05117     82 TGGELFDRIVKKGSFSEREAAKIMKQILSAVAYLHSQGIVHRDLKPENILLASKDpdsPIKIIDFGLAKIFEEgEKLKT- 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3453 spPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDL-SKLYQNVSQSASLFIKK 3531
Cdd:cd05117    161 --VCGTPYYVAPEVLKGKGYGKKCDIWSLGVILYILLCGYPPFYGETEQELFEKILKGKYSFdSPEWKNVSEEAKDLIKR 238

                          250       260
                   ....*....|....*....|
gi 1207186029 3532 ILCSYPWARPTIKDCFTNSW 3551
Cdd:cd05117    239 LLVVDPKKRLTAAEALNHPW 258

Serine/Threonine protein kinases, catalytic domain; Phosphotransferases. Serine or threonine-specific kinase subfamily.

Pssm-ID: 214567 [Multi-domain] Cd Length: 254 Bit Score: 238.20 E-value: 1.71e-70

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRK--ASALRELNILSHLDHERILYFHDAFEKKNAVIIITELC- 1738
Cdd:smart00220    1 YEILEKLGEGSFGKVYLARDKKTGKLVAIKVIKKKKIKKdrERILREIKILKKLKHPNIVRLYDVFEDEDKLYLVMEYCe 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  1739 HEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSsdQIRICDFGNAvKFMPDEAQYCKY- 1817
Cdd:smart00220   81 GGDLFDLLKKRGRLSEDEARFYLRQILSALEYLHSKGIVHRDLKPENILLDEDG--HVKLADFGLA-RQLDPGEKLTTFv 157

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  1818 GTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLN-IRNYNVAFEESMFtDLCHEAKGFVIKLLV 1896
Cdd:smart00220  158 GTPEYMAPEVLLGKGYGKAVDIWSLGVILYELLTGKPPFPGDDQLLELFKkIGKPKPPFPPPEW-DISPEAKDLIRKLLV 236

                           250
                    ....*....|....*...
gi 1207186029  1897 AD-RLRPDANECLRHPWF 1913
Cdd:smart00220  237 KDpEKRLTAEEALQHPFF 254

The catalytic domain of the Giant Serine/Threonine Kinases, Twitchin and Projectin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. Twitchin and Projectin are both associated with thick filaments. Twitchin is localized in the outer parts of A-bands and is involved in regulating muscle contraction. It interacts with the myofibrillar proteins myosin and actin in a phosphorylation-dependent manner, and may be involved in regulating the myosin cross-bridge cycle. The kinase activity of Twitchen is activated by Ca2+ and the Ca2+ binding protein S100A1. Projectin is associated with the end of thick filaments and is a component of flight muscle connecting filaments. The kinase domain of Projectin may play roles in autophosphorylation and transphosphorylation, which impact the formation of myosin filaments. The Twitchin-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271016 [Multi-domain] Cd Length: 259 Bit Score: 228.62 E-value: 4.62e-67

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1660 DYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFI-SARAKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITE-L 1737
Cdd:cd14114      2 DHYDILEELGTGAFGVVHRCTERATGNNFAAKFImTPHESDKETVRKEIQIMNQLHHPKLINLHDAFEDDNEMVLILEfL 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1738 CHEELLDRLTKKSTIL-ESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSDQIRICDFGNAVKFMPDEAQYCK 1816
Cdd:cd14114     82 SGGELFERIAAEHYKMsEAEVINYMRQVCEGLCHMHENNIVHLDIKPENIMCTTKRSNEVKLIDFGLATHLDPKESVKVT 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1817 YGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDLCHEAKGFVIKLLV 1896
Cdd:cd14114    162 TGTAEFAAPEIVEREPVGFYTDMWAVGVLSYVLLSGLSPFAGENDDETLRNVKSCDWNFDDSAFSGISEEAKDFIRKLLL 241

                          250
                   ....*....|....*...
gi 1207186029 1897 AD-RLRPDANECLRHPWF 1913
Cdd:cd14114    242 ADpNKRMTIHQALEHPWL 259

Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related Apoptosis-inducing protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DRAKs, also called STK17, were named based on their similarity (around 50% identity) to the kinase domain of DAPKs. They contain an N-terminal kinase domain and a C-terminal regulatory domain. Vertebrates contain two subfamily members, DRAK1 and DRAK2. Both DRAKs are localized to the nucleus, autophosphorylate themselves, and phosphorylate myosin light chain as a substrate. They may play a role in apoptotic signaling. The DRAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271008 [Multi-domain] Cd Length: 268 Bit Score: 226.46 E-value: 2.78e-66

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1654 KMRRLTDYYDV-HKEIGRGAFSYVKRVIQKAGKLEYAAKFIsaRAKRKASALR-----ELNILSH-LDHERILYFHDAFE 1726
Cdd:cd14106      1 STENINEVYTVeSTPLGRGKFAVVRKCIHKETGKEYAAKFL--RKRRRGQDCRneilhEIAVLELcKDCPRVVNLHEVYE 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1727 KKNAVIIITELCHE-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMA-DHSSDQIRICDFGNA 1804
Cdd:cd14106     79 TRSELILILELAAGgELQTLLDEEECLTEADVRRLMRQILEGVQYLHERNIVHLDLKPQNILLTsEFPLGDIKLCDFGIS 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1805 VKFMPDEAQYCKYGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDLC 1884
Cdd:cd14106    159 RVIGEGEEIREILGTPDYVAPEILSYEPISLATDMWSIGVLTYVLLTGHSPFGGDDKQETFLNISQCNLDFPEELFKDVS 238

                          250       260       270
                   ....*....|....*....|....*....|
gi 1207186029 1885 HEAKGFVIKLLVAD-RLRPDANECLRHPWF 1913
Cdd:cd14106    239 PLAIDFIKRLLVKDpEKRLTAKECLEHPWL 268

Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DAPKs mediate cell death and act as tumor suppressors. They are necessary to induce cell death and their overexpression leads to death-associated changes including membrane blebbing, cell rounding, and formation of autophagic vesicles. Vertebrates contain three subfamily members with different domain architecture, localization, and function. DAPK1 is the prototypical member of the subfamily and is also simply referred to as DAPK. DAPK2 is also called DAPK-related protein 1 (DRP-1), while DAPK3 has also been named DAP-like kinase (DLK) and zipper-interacting protein kinase (ZIPk). These proteins are ubiquitously expressed in adult tissues, are capable of cross talk with each other, and may act synergistically in regulating cell death. The DAPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271007 [Multi-domain] Cd Length: 269 Bit Score: 225.44 E-value: 7.05e-66

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1660 DYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARaKRKASAL--------RELNILSHLDHERILYFHDAFEKKNAV 1731
Cdd:cd14105      5 DFYDIGEELGSGQFAVVKKCREKSTGLEYAAKFIKKR-RSKASRRgvsredieREVSILRQVLHPNIITLHDVFENKTDV 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1732 IIITELCHE-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSD--QIRICDFGNAVKFM 1808
Cdd:cd14105     84 VLILELVAGgELFDFLAEKESLSEEEATEFLKQILDGVNYLHTKNIAHFDLKPENIMLLDKNVPipRIKLIDFGLAHKIE 163

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1809 PDEAQYCKYGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDLCHEAK 1888
Cdd:cd14105    164 DGNEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGDTKQETLANITAVNYDFDDEYFSNTSELAK 243

                          250       260
                   ....*....|....*....|....*
gi 1207186029 1889 GFVIKLLVAD-RLRPDANECLRHPW 1912
Cdd:cd14105    244 DFIRQLLVKDpRKRMTIQESLRHPW 268

Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DAPKs mediate cell death and act as tumor suppressors. They are necessary to induce cell death and their overexpression leads to death-associated changes including membrane blebbing, cell rounding, and formation of autophagic vesicles. Vertebrates contain three subfamily members with different domain architecture, localization, and function. DAPK2, also called DAPK-related protein 1 (DRP-1), is a Ca2+/calmodulin (CaM)-regulated protein containing an N-terminal kinase domain, a CaM autoinhibitory site and a dimerization module. It lacks the cytoskeletal binding regions of DAPK1 and the exogenous protein has been shown to be soluble and cytoplasmic. FLAG-tagged DAPK2, however, accumulated within membrane-enclosed autophagic vesicles. It is unclear where endogenous DAPK2 is localized. DAPK2 participates in TNF-alpha and FAS-receptor induced cell death and enhances neutrophilic maturation in myeloid leukemic cells. It contributes to the induction of anoikis and its down-regulation is implicated in the beta-catenin induced resistance of malignant epithelial cells to anoikis. The DAPK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271098 [Multi-domain] Cd Length: 269 Bit Score: 221.37 E-value: 2.03e-64

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1656 RRLTDYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISAR---AKRKASAL----RELNILSHLDHERILYFHDAFEKK 1728
Cdd:cd14196      1 QKVEDFYDIGEELGSGQFAIVKKCREKSTGLEYAAKFIKKRqsrASRRGVSReeieREVSILRQVLHPNIITLHDVYENR 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1729 NAVIIITELCHE-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSD--QIRICDFGNAV 1805
Cdd:cd14196     81 TDVVLILELVSGgELFDFLAQKESLSEEEATSFIKQILDGVNYLHTKKIAHFDLKPENIMLLDKNIPipHIKLIDFGLAH 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1806 KfMPDEAQYCK-YGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDLC 1884
Cdd:cd14196    161 E-IEDGVEFKNiFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGDTKQETLANITAVSYDFDEEFFSHTS 239

                          250       260
                   ....*....|....*....|....*....
gi 1207186029 1885 HEAKGFVIKLLVAD-RLRPDANECLRHPW 1912
Cdd:cd14196    240 ELAKDFIRKLLVKEtRKRLTIQEALRHPW 268

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK phosphorylates myosin regulatory light chain and controls the contraction of all muscle types. In vertebrates, different MLCKs function in smooth (MLCK1), skeletal (MLCK2), and cardiac (MLCK3) muscles. A fourth protein, MLCK4, has also been identified through comprehensive genome analysis although it has not been biochemically characterized. The MLCK1 gene expresses three transcripts in a cell-specific manner: a short MLCK1 which contains three immunoglobulin (Ig)-like and one fibronectin type III (FN3) domains, PEVK and actin-binding regions, and a kinase domain near the C-terminus; a long MLCK1 containing six additional Ig-like domains at the N-terminus compared to the short MLCK1; and the C-terminal Ig module. MLCK2, MLCK3, and MLCK4 share a simpler domain architecture of a single kinase domain near the C-terminus and the absence of Ig-like or FN3 domains. The MLCK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271005 [Multi-domain] Cd Length: 250 Bit Score: 218.63 E-value: 8.64e-64

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKIVP-YEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLHSLI 3386
Cdd:cd14103      3 RGKFGTVYRCVEKATGKELAAKFIKcRKAKDREDVRNEIEIMNQLRHPRLLQLYDAFETPREMVLVMEYVAGGELFERVV 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3387 D-RFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIV--TYMNVVKIIDFGSAQTFNP------LFlkqfsppiG 3457
Cdd:cd14103     83 DdDFELTERDCILFMRQICEGVQYMHKQGILHLDLKPENILCvsRTGNQIKIIDFGLARKYDPdkklkvLF--------G 154

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3458 TLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLS-KLYQNVSQSASLFIKKILCSY 3536
Cdd:cd14103    155 TPEFVAPEVVNYEPISYATDMWSVGVICYVLLSGLSPFMGDNDAETLANVTRAKWDFDdEAFDDISDEAKDFISKLLVKD 234

                          250
                   ....*....|....*.
gi 1207186029 3537 PWARPTIKDCFTNSWL 3552
Cdd:cd14103    235 PRKRMSAAQCLQHPWL 250

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK phosphorylates myosin regulatory light chain and controls the contraction of all muscle types. In vertebrates, different MLCKs function in smooth (MLCK1), skeletal (MLCK2), and cardiac (MLCK3) muscles. A fourth protein, MLCK4, has also been identified through comprehensive genome analysis although it has not been biochemically characterized. MLCK4 (or MYLK4 or SgK085) contains a single kinase domain near the C-terminus. The MLCK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271095 [Multi-domain] Cd Length: 261 Bit Score: 218.63 E-value: 1.18e-63

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1659 TDYYDVHKE--IGRGAFSYVKRVIQKAGKLEYAAKFISARA-KRKASALRELNILSHLDHERILYFHDAFEKKNAVIIIT 1735
Cdd:cd14193      1 NSYYNVNKEeiLGGGRFGQVHKCEEKSSGLKLAAKIIKARSqKEKEEVKNEIEVMNQLNHANLIQLYDAFESRNDIVLVM 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1736 ELCHE-ELLDRLTKKSTIL-ESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSDQIRICDFGNAVKFMPDEAQ 1813
Cdd:cd14193     81 EYVDGgELFDRIIDENYNLtELDTILFIKQICEGIQYMHQMYILHLDLKPENILCVSREANQVKIIDFGLARRYKPREKL 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1814 YCKYGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDLCHEAKGFVIK 1893
Cdd:cd14193    161 RVNFGTPEFLAPEVVNYEFVSFPTDMWSLGVIAYMLLSGLSPFLGEDDNETLNNILACQWDFEDEEFADISEEAKDFISK 240

                          250       260
                   ....*....|....*....|
gi 1207186029 1894 LLVADR-LRPDANECLRHPW 1912
Cdd:cd14193    241 LLIKEKsWRMSASEALKHPW 260

Catalytic domain of the Giant Serine/Threonine Kinase Titin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Titin, also called connectin, is a muscle-specific elastic protein and is the largest known protein to date. It contains multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains, and a single kinase domain near the C-terminus. It spans half of the sarcomere, the repeating contractile unit of striated muscle, and performs mechanical and catalytic functions. Titin contributes to the passive force generated when muscle is stretched during relaxation. Its kinase domain phosphorylates and regulates the muscle protein telethonin, which is required for sarcomere formation in differentiating myocytes. In addition, titin binds many sarcomere proteins and acts as a molecular scaffold for filament formation during myofibrillogenesis. The Titin subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271006 [Multi-domain] Cd Length: 277 Bit Score: 219.35 E-value: 1.26e-63

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITE-LCHE 1740
Cdd:cd14104      2 YMIAEELGRGQFGIVHRCVETSSKKTYMAKFVKVKGADQVLVKKEISILNIARHRNILRLHESFESHEELVMIFEfISGV 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1741 ELLDRLTKKSTIL-ESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSDQIRICDFGNAVKFMPDEAQYCKYGT 1819
Cdd:cd14104     82 DIFERITTARFELnEREIVSYVRQVCEALEFLHSKNIGHFDIRPENIIYCTRRGSYIKIIEFGQSRQLKPGDKFRLQYTS 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1820 PEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDLCHEAKGFVIKLLVADR 1899
Cdd:cd14104    162 AEFYAPEVHQHESVSTATDMWSLGCLVYVLLSGINPFEAETNQQTIENIRNAEYAFDDEAFKNISIEALDFVDRLLVKER 241

                          250       260       270
                   ....*....|....*....|....*....|....*.
gi 1207186029 1900 -LRPDANECLRHPWFKtlNKGKSISTESLKKFLSRR 1934
Cdd:cd14104    242 kSRMTAQEALNHPWLK--QGMETVSSKDIKTTRHRR 275

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK3 (or MYLK3) phosphorylates myosin regulatory light chain 2 and controls the contraction of cardiac muscles. It is expressed specifically in both the atrium and ventricle of the heart and its expression is regulated by the cardiac protein Nkx2-5. MLCK3 plays an important role in cardiogenesis by regulating the assembly of cardiac sarcomeres, the repeating contractile unit of striated muscle. MLCK3 contains a single kinase domain near the C-terminus and a unique N-terminal half, and unlike MLCK1/2, it does not appear to be regulated by Ca2+/calmodulin. The MLCK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271094 [Multi-domain] Cd Length: 261 Bit Score: 216.37 E-value: 9.35e-63

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1659 TDYYDV--HKEIGRGAFSYVKRVIQKAGKLEYAAKFISAR-AKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIIT 1735
Cdd:cd14192      1 NSYYAVcpHEVLGGGRFGQVHKCTELSTGLTLAAKIIKVKgAKEREEVKNEINIMNQLNHVNLIQLYDAFESKTNLTLIM 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1736 ELCHE-ELLDRLTKKSTIL-ESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSDQIRICDFGNAVKFMPDEAQ 1813
Cdd:cd14192     81 EYVDGgELFDRITDESYQLtELDAILFTRQICEGVHYLHQHYILHLDLKPENILCVNSTGNQIKIIDFGLARRYKPREKL 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1814 YCKYGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDLCHEAKGFVIK 1893
Cdd:cd14192    161 KVNFGTPEFLAPEVVNYDFVSFPTDMWSVGVITYMLLSGLSPFLGETDAETMNNIVNCKWDFDAEAFENLSEEAKDFISR 240

                          250       260
                   ....*....|....*....|.
gi 1207186029 1894 LLVADR-LRPDANECLRHPWF 1913
Cdd:cd14192    241 LLVKEKsCRMSATQCLKHEWL 261

Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DAPKs mediate cell death and act as tumor suppressors. They are necessary to induce cell death and their overexpression leads to death-associated changes including membrane blebbing, cell rounding, and formation of autophagic vesicles. Vertebrates contain three subfamily members with different domain architecture, localization, and function. DAPK1 is the prototypical member of the subfamily and is also simply referred to as DAPK. It is Ca2+/calmodulin (CaM)-regulated and actin-associated protein that contains an N-terminal kinase domain followed by an autoinhibitory CaM binding region and a large C-terminal extension with multiple functional domains including ankyrin (ANK) repeats, a cytoskeletal binding domain, a Death domain, and a serine-rich tail. Loss of DAPK1 expression, usually because of DNA methylation, is implicated in many tumor types. DAPK1 is highly abundant in the brain and has also been associated with neurodegeneration. The DAPK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271096 [Multi-domain] Cd Length: 269 Bit Score: 214.50 E-value: 4.88e-62

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1658 LTDYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFI-------SARAKRKASALRELNILSHLDHERILYFHDAFEKKNA 1730
Cdd:cd14194      3 VDDYYDTGEELGSGQFAVVKKCREKSTGLQYAAKFIkkrrtksSRRGVSREDIEREVSILKEIQHPNVITLHEVYENKTD 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1731 VIIITELCHE-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSDQ--IRICDFGNAVKF 1807
Cdd:cd14194     83 VILILELVAGgELFDFLAEKESLTEEEATEFLKQILNGVYYLHSLQIAHFDLKPENIMLLDRNVPKprIKIIDFGLAHKI 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1808 mpDEAQYCK--YGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDLCH 1885
Cdd:cd14194    163 --DFGNEFKniFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGDTKQETLANVSAVNYEFEDEYFSNTSA 240

                          250       260
                   ....*....|....*....|....*...
gi 1207186029 1886 EAKGFVIKLLVAD-RLRPDANECLRHPW 1912
Cdd:cd14194    241 LAKDFIRRLLVKDpKKRMTIQDSLQHPW 268

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK2 (or MYLK2) phosphorylates myosin regulatory light chain and controls the contraction of skeletal muscles. MLCK2 contains a single kinase domain near the C-terminus followed by a regulatory segment containing an autoinhibitory Ca2+/calmodulin binding site. The MLCK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271092 [Multi-domain] Cd Length: 261 Bit Score: 208.24 E-value: 6.23e-60

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1659 TDYYDVH-KEI-GRGAFSYVKRVIQKAGKLEYAAKFISAR-AKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIIT 1735
Cdd:cd14190      1 SSTFSIHsKEVlGGGKFGKVHTCTEKRTGLKLAAKVINKQnSKDKEMVLLEIQVMNQLNHRNLIQLYEAIETPNEIVLFM 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1736 ELCHE-ELLDRLTKKSTIL-ESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSDQIRICDFGNAVKFMPDEAQ 1813
Cdd:cd14190     81 EYVEGgELFERIVDEDYHLtEVDAMVFVRQICEGIQFMHQMRVLHLDLKPENILCVNRTGHQVKIIDFGLARRYNPREKL 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1814 YCKYGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDLCHEAKGFVIK 1893
Cdd:cd14190    161 KVNFGTPEFLSPEVVNYDQVSFPTDMWSMGVITYMLLSGLSPFLGDDDTETLNNVLMGNWYFDEETFEHVSDEAKDFVSN 240

                          250       260
                   ....*....|....*....|.
gi 1207186029 1894 LLVADR-LRPDANECLRHPWF 1913
Cdd:cd14190    241 LIIKERsARMSATQCLKHPWL 261

Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DAPKs mediate cell death and act as tumor suppressors. They are necessary to induce cell death and their overexpression leads to death-associated changes including membrane blebbing, cell rounding, and formation of autophagic vesicles. Vertebrates contain three subfamily members with different domain architecture, localization, and function. DAPK3, also called DAP-like kinase (DLK) and zipper-interacting protein kinase (ZIPk), contains an N-terminal kinase domain and a C-terminal region with nuclear localization signals (NLS) and a leucine zipper motif that mediates homodimerization and interaction with other leucine zipper proteins. It interacts with Par-4, a protein that contains a death domain and interacts with actin filaments. DAPK3 is present in both the cytoplasm and nucleus. Its co-expression with Par-4 results in the co-localization of the two proteins to actin filaments. In addition to cell death, DAPK3 is also implicated in mediating cell motility and the contraction of smooth muscles. The DAPK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271097 [Multi-domain] Cd Length: 271 Bit Score: 203.31 E-value: 3.66e-58

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1660 DYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFI-------SARAKRKASALRELNILSHLDHERILYFHDAFEKKNAVI 1732
Cdd:cd14195      5 DHYEMGEELGSGQFAIVRKCREKGTGKEYAAKFIkkrrlssSRRGVSREEIEREVNILREIQHPNIITLHDIFENKTDVV 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1733 IITELCHE-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHS--SDQIRICDFGNAVKFMP 1809
Cdd:cd14195     85 LILELVSGgELFDFLAEKESLTEEEATQFLKQILDGVHYLHSKRIAHFDLKPENIMLLDKNvpNPRIKLIDFGIAHKIEA 164

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1810 DEAQYCKYGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDLCHEAKG 1889
Cdd:cd14195    165 GNEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGETKQETLTNISAVNYDFDEEYFSNTSELAKD 244

                          250       260
                   ....*....|....*....|....*.
gi 1207186029 1890 FVIKLLVAD-RLRPDANECLRHPWFK 1914
Cdd:cd14195    245 FIRRLLVKDpKKRMTIAQSLEHSWIK 270

The catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related Apoptosis-inducing protein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DRAKs were named based on their similarity (around 50% identity) to the kinase domain of DAPKs. They contain an N-terminal kinase domain and a C-terminal regulatory domain. Vertebrates contain two subfamily members, DRAK1 and DRAK2 (also called STK17B). Both DRAKs are localized to the nucleus, autophosphorylate themselves, and phosphorylate myosin light chain as a substrate. DRAK2 has been implicated in inducing or enhancing apoptosis in beta cells, fibroblasts, and lymphoid cells, where it is highly expressed. It is involved in regulating many immune processes including the germinal center (GC) reaction, responses to thymus-dependent antigens, activated T cell survival, memory T cell responses. It may be involved in the development of autoimmunity. The DRAK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271100 [Multi-domain] Cd Length: 270 Bit Score: 202.07 E-value: 9.73e-58

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1654 KMRRLTDYYDV-HKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKR---KASALRELNILSHL-DHERILYFHDAFEKK 1728
Cdd:cd14198      1 SMDNFNNFYILtSKELGRGKFAVVRQCISKSTGQEYAAKFLKKRRRGqdcRAEILHEIAVLELAkSNPRVVNLHEVYETT 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1729 NAVIIITE---------LCHEELLDRLTkkstilESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSS-DQIRI 1798
Cdd:cd14198     81 SEIILILEyaaggeifnLCVPDLAEMVS------ENDIIRLIRQILEGVYYLHQNNIVHLDLKPQNILLSSIYPlGDIKI 154

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1799 CDFGNAVKFMPDEAQYCKYGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEES 1878
Cdd:cd14198    155 VDFGMSRKIGHACELREIMGTPEYLAPEILNYDPITTATDMWNIGVIAYMLLTHESPFVGEDNQETFLNISQVNVDYSEE 234

                          250       260       270
                   ....*....|....*....|....*....|....*.
gi 1207186029 1879 MFTDLCHEAKGFVIKLLV-ADRLRPDANECLRHPWF 1913
Cdd:cd14198    235 TFSSVSQLATDFIQKLLVkNPEKRPTAEICLSHSWL 270

C-terminal kinase domain of the Large Serine/Threonine Kinase and Rho Guanine Nucleotide Exchange Factor, Kalirin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Kalirin, also called Duo or Duet, is a large multidomain protein containing a series of spectrin-like repeats, two each of RhoGEF and SH3 domains, an immunoglobulin-like (Ig) domain and a C-terminal kinase. As a GEF, it activates Rac1, RhoA, and RhoG. It is highly expressed in neurons and is required for spine formation. The kalirin gene produces at least 10 isoforms from alternative promoter use and splicing. Of the major isoforms (Kalirin-7, -9, and -12), only kalirin-12 contains the C-terminal kinase domain. Kalirin-12 is highly expressed during embryonic development and it plays an important role in axon outgrowth. The Kalirin subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271017 [Multi-domain] Cd Length: 248 Bit Score: 200.57 E-value: 1.57e-57

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITELCHE-ELLDRL 1746
Cdd:cd14115      1 IGRGRFSIVKKCLHKATRKDVAVKFVSKKMKKKEQAAHEAALLQHLQHPQYITLHDTYESPTSYILVLELMDDgRLLDYL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1747 TKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMA-DHSSDQIRICDFGNAVKFMPDEAQYCKYGTPEFVAP 1825
Cdd:cd14115     81 MNHDELMEEKVAFYIRDIMEALQYLHNCRVAHLDIKPENLLIDlRIPVPRVKLIDLEDAVQISGHRHVHHLLGNPEFAAP 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1826 EIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDLCHEAKGFVIKLLVAD-RLRPDA 1904
Cdd:cd14115    161 EVIQGTPVSLATDIWSIGVLTYVMLSGVSPFLDESKEETCINVCRVDFSFPDEYFGDVSQAARDFINVILQEDpRRRPTA 240


                   ....*...
gi 1207186029 1905 NECLRHPW 1912
Cdd:cd14115    241 ATCLQHPW 248

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK1 (or MYLK1) phosphorylates myosin regulatory light chain and controls the contraction of smooth muscles. The MLCK1 gene expresses three transcripts in a cell-specific manner: a short MLCK1 which contains three immunoglobulin (Ig)-like and one fibronectin type III (FN3) domains, PEVK and actin-binding regions, and a kinase domain near the C-terminus followed by a regulatory segment containing an autoinhibitory Ca2+/calmodulin binding site; a long MLCK1 containing six additional Ig-like domains at the N-terminus compared to the short MLCK1; and the C-terminal Ig module which results in the expression of telokin in phasic smooth muscles, leading to Ca2+ desensitization by cyclic nucleotides of smooth muscle force. MLCK1 is also responsible for myosin regulatory light chain phosphorylation in nonmuscle cells and may play a role in regulating myosin II ATPase activity. The MLCK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271093 [Multi-domain] Cd Length: 259 Bit Score: 199.07 E-value: 8.08e-57

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1659 TDYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISA-RAKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITEL 1737
Cdd:cd14191      1 SDFYDIEERLGSGKFGQVFRLVEKKTKKVWAGKFFKAySAKEKENIRQEISIMNCLHHPKLVQCVDAFEEKANIVMVLEM 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1738 CHE-ELLDRLTKKS-TILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSDQIRICDFGNAVKFMPDEAQYC 1815
Cdd:cd14191     81 VSGgELFERIIDEDfELTERECIKYMRQISEGVEYIHKQGIVHLDLKPENIMCVNKTGTKIKLIDFGLARRLENAGSLKV 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1816 KYGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDLCHEAKGFVIKLL 1895
Cdd:cd14191    161 LFGTPEFVAPEVINYEPIGYATDMWSIGVICYILVSGLSPFMGDNDNETLANVTSATWDFDDEAFDEISDDAKDFISNLL 240

                          250
                   ....*....|....*....
gi 1207186029 1896 VAD-RLRPDANECLRHPWF 1913
Cdd:cd14191    241 KKDmKARLTCTQCLQHPWL 259

Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DAPKs mediate cell death and act as tumor suppressors. They are necessary to induce cell death and their overexpression leads to death-associated changes including membrane blebbing, cell rounding, and formation of autophagic vesicles. Vertebrates contain three subfamily members with different domain architecture, localization, and function. DAPK1 is the prototypical member of the subfamily and is also simply referred to as DAPK. DAPK2 is also called DAPK-related protein 1 (DRP-1), while DAPK3 has also been named DAP-like kinase (DLK) and zipper-interacting protein kinase (ZIPk). These proteins are ubiquitously expressed in adult tissues, are capable of cross talk with each other, and may act synergistically in regulating cell death. The DAPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271007 [Multi-domain] Cd Length: 269 Bit Score: 195.01 E-value: 2.78e-55

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPE-------SKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLI 3372
Cdd:cd14105      7 YDIGEELGSGQFAVVKKCREKSTGLEYAAKFIKKRRSkasrrgvSREDIEREVSILRQVLHPNIITLHDVFENKTDVVLI 86

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3373 SECCSGKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNV----VKIIDFGSAQTFNPlf 3448
Cdd:cd14105     87 LELVAGGELFDFLAEKESLSEEEATEFLKQILDGVNYLHTKNIAHFDLKPENIMLLDKNVpiprIKLIDFGLAHKIED-- 164

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3449 LKQFSPPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDL-SKLYQNVSQSASL 3527
Cdd:cd14105    165 GNEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGDTKQETLANITAVNYDFdDEYFSNTSELAKD 244

                          250       260
                   ....*....|....*....|....*
gi 1207186029 3528 FIKKILCSYPWARPTIKDCFTNSWL 3552
Cdd:cd14105    245 FIRQLLVKDPRKRMTIQESLRHPWI 269

Catalytic domain of the Serine/Threonine kinase, Aurora kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Aurora kinases are key regulators of mitosis and are essential for the accurate and equal division of genomic material from parent to daughter cells. Yeast contains only one Aurora kinase while most higher eukaryotes have two. Vertebrates contain at least 2 Aurora kinases (A and B); mammals contains a third Aurora kinase gene (C). Aurora-A regulates cell cycle events from the late S-phase through the M-phase including centrosome maturation, mitotic entry, centrosome separation, spindle assembly, chromosome alignment, cytokinesis, and mitotic exit. Aurora-A activation depends on its autophosphorylation and binding to the microtubule-associated protein TPX2. Aurora-B is most active at the transition during metaphase to the end of mitosis. It is critical for accurate chromosomal segregation, cytokinesis, protein localization to the centrosome and kinetochore, correct microtubule-kinetochore attachments, and regulation of the mitotic checkpoint. Aurora-C is mainly expressed in meiotically dividing cells; it was originally discovered in mice as a testis-specific STK called Aie1. Both Aurora-B and -C are chromosomal passenger proteins that can form complexes with INCENP and survivin, and they may have redundant cellular functions. The Aurora subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270909 [Multi-domain] Cd Length: 253 Bit Score: 194.23 E-value: 2.81e-55

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKIVPYEPESKQTVLQ----EYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLH 3383
Cdd:cd14007     10 KGKFGNVYLAREKKSGFIVALKVISKSQLQKSGLEHqlrrEIEIQSHLRHPNILRLYGYFEDKKRIYLILEYAPNGELYK 89

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3384 SLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSA--------QTFnplflkqfspp 3455
Cdd:cd14007     90 ELKKQKRFDEKEAAKYIYQLALALDYLHSKNIIHRDIKPENILLGSNGELKLADFGWSvhapsnrrKTF----------- 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3456 IGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLSKlyqNVSQSASLFIKKILCS 3535
Cdd:cd14007    159 CGTLDYLPPEMVEGKEYDYKVDIWSLGVLCYELLVGKPPFESKSHQETYKRIQNVDIKFPS---SVSPEAKDLISKLLQK 235

                          250
                   ....*....|....*...
gi 1207186029 3536 YPWARPTIKDCFTNSWLQ 3553
Cdd:cd14007    236 DPSKRLSLEQVLNHPWIK 253

The catalytic domain of the Giant Serine/Threonine Kinases, Twitchin and Projectin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. Twitchin and Projectin are both associated with thick filaments. Twitchin is localized in the outer parts of A-bands and is involved in regulating muscle contraction. It interacts with the myofibrillar proteins myosin and actin in a phosphorylation-dependent manner, and may be involved in regulating the myosin cross-bridge cycle. The kinase activity of Twitchen is activated by Ca2+ and the Ca2+ binding protein S100A1. Projectin is associated with the end of thick filaments and is a component of flight muscle connecting filaments. The kinase domain of Projectin may play roles in autophosphorylation and transphosphorylation, which impact the formation of myosin filaments. The Twitchin-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271016 [Multi-domain] Cd Length: 259 Bit Score: 188.95 E-value: 2.46e-53

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVPY-EPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSG 3378
Cdd:cd14114      4 YDILEELGTGAFGVVHRCTERATGNNFAAKFIMTpHESDKETVRKEIQIMNQLHHPKLINLHDAFEDDNEMVLILEFLSG 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3379 KELLHSLIDR-FRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTY--MNVVKIIDFGSAQTFNPLFLKQFSpp 3455
Cdd:cd14114     84 GELFERIAAEhYKMSEAEVINYMRQVCEGLCHMHENNIVHLDIKPENIMCTTkrSNEVKLIDFGLATHLDPKESVKVT-- 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3456 IGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAA--KFDLSKlYQNVSQSASLFIKKIL 3533
Cdd:cd14114    162 TGTAEFAAPEIVEREPVGFYTDMWAVGVLSYVLLSGLSPFAGENDDETLRNVKSCdwNFDDSA-FSGISEEAKDFIRKLL 240

                          250
                   ....*....|....*....
gi 1207186029 3534 CSYPWARPTIKDCFTNSWL 3552
Cdd:cd14114    241 LADPNKRMTIHQALEHPWL 259

C-terminal kinase domain of the Large Serine/Threonine Kinase and Rho Guanine Nucleotide Exchange Factor, Triple functional domain protein; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Triple functional domain protein (Trio), also called PTPRF-interacting protein, is a large multidomain protein containing a series of spectrin-like repeats, two each of RhoGEF and SH3 domains, an immunoglobulin-like (Ig) domain and a C-terminal kinase. Trio plays important roles in neuronal cell migration and axon guidance. It was originally identified as an interacting partner of the of the receptor-like tyrosine phosphatase (RPTP) LAR (leukocyte-antigen-related protein), a family of receptors that function in the signaling to the actin cytoskeleton during development. Trio functions as a GEF for Rac1, RhoG, and RhoA, and is involved in the regulation of lamellipodia formation, mediating Rac1-dependent cell spreading and migration. The Trio subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271015 [Multi-domain] Cd Length: 263 Bit Score: 189.03 E-value: 3.09e-53

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1661 YYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITELCHE 1740
Cdd:cd14113      8 FYSEVAELGRGRFSVVKKCDQRGTKRAVATKFVNKKLMKRDQVTHELGVLQSLQHPQLVGLLDTFETPTSYILVLEMADQ 87

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1741 -ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMaDHSSDQ--IRICDFGNAVKFMPDEAQYCKY 1817
Cdd:cd14113     88 gRLLDYVVRWGNLTEEKIRFYLREILEALQYLHNCRIAHLDLKPENILV-DQSLSKptIKLADFGDAVQLNTTYYIHQLL 166

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1818 GTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDLCHEAKGFVIKLLVA 1897
Cdd:cd14113    167 GSPEFAAPEIILGNPVSLTSDLWSIGVLTYVLLSGVSPFLDESVEETCLNICRLDFSFPDDYFKGVSQKAKDFVCFLLQM 246

                          250
                   ....*....|....*..
gi 1207186029 1898 DRL-RPDANECLRHPWF 1913
Cdd:cd14113    247 DPAkRPSAALCLQEQWL 263

Catalytic domain of AMP-activated protein kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The AMPK-like subfamily is composed of AMPK, MARK, BRSK, NUAK, MELK, SNRK, TSSK, and SIK, among others. LKB1 serves as a master upstream kinase that activates AMPK and most AMPK-like kinases. AMPK, also called SNF1 (sucrose non-fermenting1) in yeasts and SnRK1 (SNF1-related kinase1) in plants, is a heterotrimeric enzyme composed of a catalytic alpha subunit and two regulatory subunits, beta and gamma. It is a stress-activated kinase that serves as master regulator of glucose and lipid metabolism by monitoring carbon and energy supplies, via sensing the cell's AMP:ATP ratio. MARKs phosphorylate tau and related microtubule-associated proteins (MAPs), and regulates microtubule-based intracellular transport. They are involved in embryogenesis, epithelial cell polarization, cell signaling, and neuronal differentiation. BRSKs play important roles in establishing neuronal polarity. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. The AMPK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270905 [Multi-domain] Cd Length: 252 Bit Score: 188.11 E-value: 4.60e-53

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3299 PYTFMDEKARGRFGVIRECRENATGNLYMAKIVPYE---PESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISEC 3375
Cdd:cd14003      1 NYELGKTLGEGSFGKVKLARHKLTGEKVAIKIIDKSklkEEIEEKIKREIEIMKLLNHPNIIKLYEVIETENKIYLVMEY 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3376 CSGKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNP-LFLKQFsp 3454
Cdd:cd14003     81 ASGGELFDYIVNNGRLSEDEARRFFQQLISAVDYCHSNGIVHRDLKLENILLDKNGNLKIIDFGLSNEFRGgSLLKTF-- 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3455 pIGTLDYMSPEMLKGD-VVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLSKlyqNVSQSASLFIKKIL 3533
Cdd:cd14003    159 -CGTPAYAAPEVLLGRkYDGPKADVWSLGVILYAMLTGYLPFDDDNDSKLFRKILKGKYPIPS---HLSPDARDLIRRML 234

                          250
                   ....*....|....*...
gi 1207186029 3534 CSYPWARPTIKDCFTNSW 3551
Cdd:cd14003    235 VVDPSKRITIEEILNHPW 252

Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related Apoptosis-inducing protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DRAKs, also called STK17, were named based on their similarity (around 50% identity) to the kinase domain of DAPKs. They contain an N-terminal kinase domain and a C-terminal regulatory domain. Vertebrates contain two subfamily members, DRAK1 and DRAK2. Both DRAKs are localized to the nucleus, autophosphorylate themselves, and phosphorylate myosin light chain as a substrate. They may play a role in apoptotic signaling. The DRAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271008 [Multi-domain] Cd Length: 268 Bit Score: 187.56 E-value: 8.97e-53

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3307 ARGRFGVIRECRENATGNLYMAKIVPYEPESKQT---VLQEYDILK-SLHHEKIMALHEAYVTPRYLVLISECCSGKELL 3382
Cdd:cd14106     17 GRGKFAVVRKCIHKETGKEYAAKFLRKRRRGQDCrneILHEIAVLElCKDCPRVVNLHEVYETRSELILILELAAGGELQ 96

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3383 HSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNV---VKIIDFGSAQTFNPlfLKQFSPPIGTL 3459
Cdd:cd14106     97 TLLDEEECLTEADVRRLMRQILEGVQYLHERNIVHLDLKPQNILLTSEFPlgdIKLCDFGISRVIGE--GEEIREILGTP 174

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3460 DYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLSK-LYQNVSQSASLFIKKILCSYPW 3538
Cdd:cd14106    175 DYVAPEILSYEPISLATDMWSIGVLTYVLLTGHSPFGGDDKQETFLNISQCNLDFPEeLFKDVSPLAIDFIKRLLVKDPE 254

                          250
                   ....*....|....
gi 1207186029 3539 ARPTIKDCFTNSWL 3552
Cdd:cd14106    255 KRLTAKECLEHPWL 268

Pseudokinase domain, first repeat, of the Giant Serine/Threonine Kinase Uncoordinated protein 89; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. The nematode Unc-89 gene, through alternative promoter use and splicing, encodes at least six major isoforms (Unc-89A to Unc-89F) of giant muscle proteins that are homologs for the vetebrate obscurin. In flies, five isoforms of Unc-89 have been detected: four in the muscles of adult flies (two in the indirect flight muscle and two in other muscles) and another isoform in the larva. Unc-89 in nematodes is required for normal muscle cell architecture. In flies, it is necessary for the development of a symmetrical sarcomere in the flight muscles. Unc-89 proteins contain several adhesion and signaling domains including multiple copies of the immunoglobulin (Ig) domain, as well as fibronectin type III (FN3), SH3, RhoGEF, and PH domains. The nematode Unc-89 isoforms D, C, D, and F contain two kinase domain with B and F having two complete kinase domains while the first repeat of C and D are partial domains. Homology modeling suggests that the first kinase repeat of Unc-89 may be catalytically inactive, a pseudokinase, while the second kinase repeat may be active. The pseudokinase domain may function as a regulatory domain or a protein interaction domain. The Unc-89 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271011 [Multi-domain] Cd Length: 255 Bit Score: 184.64 E-value: 6.93e-52

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1660 DYYDV-HKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAkrkaSALRELNILSHLDHERILYFHDAFE-KKNAVIIITEL 1737
Cdd:cd14109      3 ELYEIgEEDEKRAAQGAPFHVTERSTGRNFLAQLRYGDP----FLMREVDIHNSLDHPNIVQMHDAYDdEKLAVTVIDNL 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1738 CHEELLDR---LTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADhssDQIRICDFGNAVKFMPDEAQY 1814
Cdd:cd14109     79 ASTIELVRdnlLPGKDYYTERQVAVFVRQLLLALKHMHDLGIAHLDLRPEDILLQD---DKLKLADFGQSRRLLRGKLTT 155

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1815 CKYGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDLCHEAKGFVIKL 1894
Cdd:cd14109    156 LIYGSPEFVSPEIVNSYPVTLATDMWSVGVLTYVLLGGISPFLGDNDRETLTNVRSGKWSFDSSPLGNISDDARDFIKKL 235

                          250       260
                   ....*....|....*....|
gi 1207186029 1895 LV-ADRLRPDANECLRHPWF 1913
Cdd:cd14109    236 LVyIPESRLTVDEALNHPWF 255

Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DAPKs mediate cell death and act as tumor suppressors. They are necessary to induce cell death and their overexpression leads to death-associated changes including membrane blebbing, cell rounding, and formation of autophagic vesicles. Vertebrates contain three subfamily members with different domain architecture, localization, and function. DAPK1 is the prototypical member of the subfamily and is also simply referred to as DAPK. It is Ca2+/calmodulin (CaM)-regulated and actin-associated protein that contains an N-terminal kinase domain followed by an autoinhibitory CaM binding region and a large C-terminal extension with multiple functional domains including ankyrin (ANK) repeats, a cytoskeletal binding domain, a Death domain, and a serine-rich tail. Loss of DAPK1 expression, usually because of DNA methylation, is implicated in many tumor types. DAPK1 is highly abundant in the brain and has also been associated with neurodegeneration. The DAPK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271096 [Multi-domain] Cd Length: 269 Bit Score: 181.76 E-value: 1.22e-50

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPE-------SKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLI 3372
Cdd:cd14194      7 YDTGEELGSGQFAVVKKCREKSTGLQYAAKFIKKRRTkssrrgvSREDIEREVSILKEIQHPNVITLHEVYENKTDVILI 86

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3373 SECCSGKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNV----VKIIDFGSAQTFNplF 3448
Cdd:cd14194     87 LELVAGGELFDFLAEKESLTEEEATEFLKQILNGVYYLHSLQIAHFDLKPENIMLLDRNVpkprIKIIDFGLAHKID--F 164

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3449 LKQFSPPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLSK-LYQNVSQSASL 3527
Cdd:cd14194    165 GNEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGDTKQETLANVSAVNYEFEDeYFSNTSALAKD 244

                          250       260
                   ....*....|....*....|....*
gi 1207186029 3528 FIKKILCSYPWARPTIKDCFTNSWL 3552
Cdd:cd14194    245 FIRRLLVKDPKKRMTIQDSLQHPWI 269

Catalytic domain of the Giant Serine/Threonine Kinase Titin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Titin, also called connectin, is a muscle-specific elastic protein and is the largest known protein to date. It contains multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains, and a single kinase domain near the C-terminus. It spans half of the sarcomere, the repeating contractile unit of striated muscle, and performs mechanical and catalytic functions. Titin contributes to the passive force generated when muscle is stretched during relaxation. Its kinase domain phosphorylates and regulates the muscle protein telethonin, which is required for sarcomere formation in differentiating myocytes. In addition, titin binds many sarcomere proteins and acts as a molecular scaffold for filament formation during myofibrillogenesis. The Titin subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271006 [Multi-domain] Cd Length: 277 Bit Score: 181.98 E-value: 1.24e-50

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGK 3379
Cdd:cd14104      2 YMIAEELGRGQFGIVHRCVETSSKKTYMAKFVKVKGADQVLVKKEISILNIARHRNILRLHESFESHEELVMIFEFISGV 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3380 ELLHSLID-RFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYM--NVVKIIDFGSAQTFNP--LFLKQFSP 3454
Cdd:cd14104     82 DIFERITTaRFELNEREIVSYVRQVCEALEFLHSKNIGHFDIRPENIIYCTRrgSYIKIIEFGQSRQLKPgdKFRLQYTS 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3455 PigtlDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDL-SKLYQNVSQSASLFIKKIL 3533
Cdd:cd14104    162 A----EFYAPEVHQHESVSTATDMWSLGCLVYVLLSGINPFEAETNQQTIENIRNAEYAFdDEAFKNISIEALDFVDRLL 237

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|...
gi 1207186029 3534 CSYPWARPTIKDCFTNSWLQdaylMRLRR-QTLTFTTTRLKEF 3575
Cdd:cd14104    238 VKERKSRMTAQEALNHPWLK----QGMETvSSKDIKTTRHRRY 276

Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related Apoptosis-inducing protein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DRAKs were named based on their similarity (around 50% identity) to the kinase domain of DAPKs. They contain an N-terminal kinase domain and a C-terminal regulatory domain. Vertebrates contain two subfamily members, DRAK1 (also called STK17A) and DRAK2. Both DRAKs are localized to the nucleus, autophosphorylate themselves, and phosphorylate myosin light chain as a substrate. Rabbit DRAK1 has been shown to induce apoptosis in osteoclasts and overexpressio of human DRAK1 induces apoptosis in cultured fibroblast cells. DRAK1 may be involved in apoptotic signaling. The DRAK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271099 [Multi-domain] Cd Length: 271 Bit Score: 180.13 E-value: 4.61e-50

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1658 LTDYYDVH--KEIGRGAFSYVKRVIQKAGKLEYAAKFIsaRAKRKASALR-----ELNILS-HLDHERILYFHDAFEKKN 1729
Cdd:cd14197      5 FQERYSLSpgRELGRGKFAVVRKCVEKDSGKEFAAKFM--RKRRKGQDCRmeiihEIAVLElAQANPWVINLHEVYETAS 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1730 AVIIITELCHE-ELLDRLT--KKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSS-DQIRICDFGNAV 1805
Cdd:cd14197     83 EMILVLEYAAGgEIFNQCVadREEAFKEKDVKRLMKQILEGVSFLHNNNVVHLDLKPQNILLTSESPlGDIKIVDFGLSR 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1806 KFMPDEAQYCKYGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDLCH 1885
Cdd:cd14197    163 ILKNSEELREIMGTPEYVAPEILSYEPISTATDMWSIGVLAYVMLTGISPFLGDDKQETFLNISQMNVSYSEEEFEHLSE 242

                          250       260
                   ....*....|....*....|....*....
gi 1207186029 1886 EAKGFVIKLLVAD-RLRPDANECLRHPWF 1913
Cdd:cd14197    243 SAIDFIKTLLIKKpENRATAEDCLKHPWL 271

Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DAPKs mediate cell death and act as tumor suppressors. They are necessary to induce cell death and their overexpression leads to death-associated changes including membrane blebbing, cell rounding, and formation of autophagic vesicles. Vertebrates contain three subfamily members with different domain architecture, localization, and function. DAPK2, also called DAPK-related protein 1 (DRP-1), is a Ca2+/calmodulin (CaM)-regulated protein containing an N-terminal kinase domain, a CaM autoinhibitory site and a dimerization module. It lacks the cytoskeletal binding regions of DAPK1 and the exogenous protein has been shown to be soluble and cytoplasmic. FLAG-tagged DAPK2, however, accumulated within membrane-enclosed autophagic vesicles. It is unclear where endogenous DAPK2 is localized. DAPK2 participates in TNF-alpha and FAS-receptor induced cell death and enhances neutrophilic maturation in myeloid leukemic cells. It contributes to the induction of anoikis and its down-regulation is implicated in the beta-catenin induced resistance of malignant epithelial cells to anoikis. The DAPK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271098 [Multi-domain] Cd Length: 269 Bit Score: 179.38 E-value: 6.86e-50

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVP--YEPESKQTVLQ-----EYDILKSLHHEKIMALHEAYVTPRYLVLI 3372
Cdd:cd14196      7 YDIGEELGSGQFAIVKKCREKSTGLEYAAKFIKkrQSRASRRGVSReeierEVSILRQVLHPNIITLHDVYENRTDVVLI 86

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3373 SECCSGKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNV----VKIIDFGSAQTFNPLF 3448
Cdd:cd14196     87 LELVSGGELFDFLAQKESLSEEEATSFIKQILDGVNYLHTKKIAHFDLKPENIMLLDKNIpiphIKLIDFGLAHEIEDGV 166

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3449 lkQFSPPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDL-SKLYQNVSQSASL 3527
Cdd:cd14196    167 --EFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGDTKQETLANITAVSYDFdEEFFSHTSELAKD 244

                          250       260
                   ....*....|....*....|....*
gi 1207186029 3528 FIKKILCSYPWARPTIKDCFTNSWL 3552
Cdd:cd14196    245 FIRKLLVKETRKRLTIQEALRHPWI 269

Catalytic domain of AMP-activated protein kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The AMPK-like subfamily is composed of AMPK, MARK, BRSK, NUAK, MELK, SNRK, TSSK, and SIK, among others. LKB1 serves as a master upstream kinase that activates AMPK and most AMPK-like kinases. AMPK, also called SNF1 (sucrose non-fermenting1) in yeasts and SnRK1 (SNF1-related kinase1) in plants, is a heterotrimeric enzyme composed of a catalytic alpha subunit and two regulatory subunits, beta and gamma. It is a stress-activated kinase that serves as master regulator of glucose and lipid metabolism by monitoring carbon and energy supplies, via sensing the cell's AMP:ATP ratio. MARKs phosphorylate tau and related microtubule-associated proteins (MAPs), and regulates microtubule-based intracellular transport. They are involved in embryogenesis, epithelial cell polarization, cell signaling, and neuronal differentiation. BRSKs play important roles in establishing neuronal polarity. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. The AMPK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270905 [Multi-domain] Cd Length: 252 Bit Score: 178.87 E-value: 6.99e-50

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISaRAKRKASAL----RELNILSHLDHERILYFHDAFEKKNAVIIITEL 1737
Cdd:cd14003      2 YELGKTLGEGSFGKVKLARHKLTGEKVAIKIID-KSKLKEEIEekikREIEIMKLLNHPNIIKLYEVIETENKIYLVMEY 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1738 C-HEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDFGNAVKFMPDEAQYCK 1816
Cdd:cd14003     81 AsGGELFDYIVNNGRLSEDEARRFFQQLISAVDYCHSNGIVHRDLKLENILL--DKNGNLKIIDFGLSNEFRGGSLLKTF 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1817 YGTPEFVAPEIVNQTPV-SKATDIWPIGVLTYLCLTGVSPFAGENDRssvlNIRNYNVAFEESMFTDLCHEAKGFVIKLL 1895
Cdd:cd14003    159 CGTPAYAAPEVLLGRKYdGPKADVWSLGVILYAMLTGYLPFDDDNDS----KLFRKILKGKYPIPSHLSPDARDLIRRML 234

                          250
                   ....*....|....*...
gi 1207186029 1896 VAD-RLRPDANECLRHPW 1912
Cdd:cd14003    235 VVDpSKRITIEEILNHPW 252

Catalytic domain of bacterial Serine/Threonine kinases, PknB and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes many bacterial eukaryotic-type STKs including Staphylococcus aureus PknB (also called PrkC or Stk1), Bacillus subtilis PrkC, and Mycobacterium tuberculosis Pkn proteins (PknB, PknD, PknE, PknF, PknL, and PknH), among others. S. aureus PknB is the only eukaryotic-type STK present in this species, although many microorganisms encode for several such proteins. It is important for the survival and pathogenesis of S. aureus as it is involved in the regulation of purine and pyrimidine biosynthesis, cell wall metabolism, autolysis, virulence, and antibiotic resistance. M. tuberculosis PknB is essential for growth and it acts on diverse substrates including proteins involved in peptidoglycan synthesis, cell division, transcription, stress responses, and metabolic regulation. B. subtilis PrkC is located at the inner membrane of endospores and functions to trigger spore germination. Bacterial STKs in this subfamily show varied domain architectures. The well-characterized members such as S. aureus and M. tuberculosis PknB, and B. subtilis PrkC, contain an N-terminal cytosolic kinase domain, a transmembrane (TM) segment, and mutliple C-terminal extracellular PASTA domains. The PknB subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270916 [Multi-domain] Cd Length: 260 Bit Score: 173.93 E-value: 3.99e-48

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3307 ARGRFGVIRECRENATGNLYMAKIVPYE----PESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELL 3382
Cdd:cd14014      9 GRGGMGEVYRARDTLLGRPVAIKVLRPElaedEEFRERFLREARALARLSHPNIVRVYDVGEDDGRPYIVMEYVEGGSLA 88

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3383 HSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLKQFSPPIGTLDYM 3462
Cdd:cd14014     89 DLLRERGPLPPREALRILAQIADALAAAHRAGIVHRDIKPANILLTEDGRVKLTDFGIARALGDSGLTQTGSVLGTPAYM 168

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3463 SPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAET-EARIQAAKFDLSKLYQNVSQSASLFIKKILCSYPWARP 3541
Cdd:cd14014    169 APEQARGGPVDPRSDIYSLGVVLYELLTGRPPFDGDSPAAVlAKHLQEAPPPPSPLNPDVPPALDAIILRALAKDPEERP 248


                   .
gi 1207186029 3542 T 3542
Cdd:cd14014    249 Q 249

Catalytic domain of the Serine/Threonine Kinases, Polo-like kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. PLKs derive their names from homology to polo, a kinase first identified in Drosophila. There are five mammalian PLKs (PLK1-5) from distinct genes. There is good evidence that PLK1 may function as an oncogene while PLK2-5 have tumor suppressive properties. PLK1 functions as a positive regulator of mitosis, meiosis, and cytokinesis. PLK2 functions in G1 progression, S-phase arrest, and centriole duplication. PLK3 regulates angiogenesis and responses to DNA damage. PLK4 is required for late mitotic progression, cell survival, and embryonic development. PLK5 was first identified as a pseudogene containing a stop codon within the kinase domain, however, both murine and human genes encode expressed proteins. PLK5 functions in cell cycle arrest.

Pssm-ID: 271001 [Multi-domain] Cd Length: 258 Bit Score: 172.74 E-value: 1.13e-47

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1660 DYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFIS----ARAKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIIT 1735
Cdd:cd14099      1 KRYRRGKFLGKGGFAKCYEVTDMSTGKVYAGKVVPksslTKPKQREKLKSEIKIHRSLKHPNIVKFHDCFEDEENVYILL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1736 ELCH-EELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSsdQIRICDFGNAVKFMPDEAqy 1814
Cdd:cd14099     81 ELCSnGSLMELLKRRKALTEPEVRYFMRQILSGVKYLHSNRIIHRDLKLGNLFLDENM--NVKIGDFGLAARLEYDGE-- 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1815 CKY---GTPEFVAPEIVN-QTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMftDLCHEAKGF 1890
Cdd:cd14099    157 RKKtlcGTPNYIAPEVLEkKKGHSFEVDIWSLGVILYTLLVGKPPFETSDVKETYKRIKKNEYSFPSHL--SISDEAKDL 234

                          250       260
                   ....*....|....*....|....
gi 1207186029 1891 VIKLLVAD-RLRPDANECLRHPWF 1913
Cdd:cd14099    235 IRSMLQPDpTKRPSLDEILSHPFF 258

Catalytic domain of the Serine/Threonine kinase, Aurora kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Aurora kinases are key regulators of mitosis and are essential for the accurate and equal division of genomic material from parent to daughter cells. Yeast contains only one Aurora kinase while most higher eukaryotes have two. Vertebrates contain at least 2 Aurora kinases (A and B); mammals contains a third Aurora kinase gene (C). Aurora-A regulates cell cycle events from the late S-phase through the M-phase including centrosome maturation, mitotic entry, centrosome separation, spindle assembly, chromosome alignment, cytokinesis, and mitotic exit. Aurora-A activation depends on its autophosphorylation and binding to the microtubule-associated protein TPX2. Aurora-B is most active at the transition during metaphase to the end of mitosis. It is critical for accurate chromosomal segregation, cytokinesis, protein localization to the centrosome and kinetochore, correct microtubule-kinetochore attachments, and regulation of the mitotic checkpoint. Aurora-C is mainly expressed in meiotically dividing cells; it was originally discovered in mice as a testis-specific STK called Aie1. Both Aurora-B and -C are chromosomal passenger proteins that can form complexes with INCENP and survivin, and they may have redundant cellular functions. The Aurora subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270909 [Multi-domain] Cd Length: 253 Bit Score: 172.27 E-value: 1.22e-47

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFIS----ARAKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITEL 1737
Cdd:cd14007      2 FEIGKPLGKGKFGNVYLAREKKSGFIVALKVISksqlQKSGLEHQLRREIEIQSHLRHPNILRLYGYFEDKKRIYLILEY 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1738 C-HEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDFGNAVKFMPDEAQ-YC 1815
Cdd:cd14007     82 ApNGELYKELKKQKRFDEKEAAKYIYQLALALDYLHSKNIIHRDIKPENILL--GSNGELKLADFGWSVHAPSNRRKtFC 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1816 kyGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTdlchEAKGFVIKLL 1895
Cdd:cd14007    160 --GTLDYLPPEMVEGKEYDYKVDIWSLGVLCYELLVGKPPFESKSHQETYKRIQNVDIKFPSSVSP----EAKDLISKLL 233

                          250       260
                   ....*....|....*....|
gi 1207186029 1896 VAD-RLRPDANECLRHPWFK 1914
Cdd:cd14007    234 QKDpSKRLSLEQVLNHPWIK 253

The catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related Apoptosis-inducing protein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DRAKs were named based on their similarity (around 50% identity) to the kinase domain of DAPKs. They contain an N-terminal kinase domain and a C-terminal regulatory domain. Vertebrates contain two subfamily members, DRAK1 and DRAK2 (also called STK17B). Both DRAKs are localized to the nucleus, autophosphorylate themselves, and phosphorylate myosin light chain as a substrate. DRAK2 has been implicated in inducing or enhancing apoptosis in beta cells, fibroblasts, and lymphoid cells, where it is highly expressed. It is involved in regulating many immune processes including the germinal center (GC) reaction, responses to thymus-dependent antigens, activated T cell survival, memory T cell responses. It may be involved in the development of autoimmunity. The DRAK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271100 [Multi-domain] Cd Length: 270 Bit Score: 172.03 E-value: 2.39e-47

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3305 EKARGRFGVIRECRENATGNLYMAKIVPYE---PESKQTVLQEYDILK-SLHHEKIMALHEAYVTPRYLVLISECCSGKE 3380
Cdd:cd14198     15 ELGRGKFAVVRQCISKSTGQEYAAKFLKKRrrgQDCRAEILHEIAVLElAKSNPRVVNLHEVYETTSEIILILEYAAGGE 94

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3381 LL-HSLID-RFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNV---VKIIDFGSAQTF-NPLFLKQFsp 3454
Cdd:cd14198     95 IFnLCVPDlAEMVSENDIIRLIRQILEGVYYLHQNNIVHLDLKPQNILLSSIYPlgdIKIVDFGMSRKIgHACELREI-- 172

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3455 pIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLSK-LYQNVSQSASLFIKKIL 3533
Cdd:cd14198    173 -MGTPEYLAPEILNYDPITTATDMWNIGVIAYMLLTHESPFVGEDNQETFLNISQVNVDYSEeTFSSVSQLATDFIQKLL 251

                          250
                   ....*....|....*....
gi 1207186029 3534 CSYPWARPTIKDCFTNSWL 3552
Cdd:cd14198    252 VKNPEKRPTAEICLSHSWL 270

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type II; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. CaMKs contain an N-terminal catalytic domain followed by a regulatory domain that harbors a CaM binding site. In addition, CaMKII contains a C-terminal association domain that facilitates oligomerization. There are four CaMKII proteins (alpha, beta, gamma, delta) encoded by different genes; each gene undergoes alternative splicing to produce more than 30 isoforms. CaMKII-alpha and -beta are enriched in neurons while CaMKII-gamma and -delta are predominant in myocardium. CaMKII is a signaling molecule that translates upstream calcium and reactive oxygen species (ROS) signals into downstream responses that play important roles in synaptic function and cardiovascular physiology. It is a major component of the postsynaptic density and is critical in regulating synaptic plasticity including long-term potentiation. It is critical in regulating ion channels and proteins involved in myocardial excitation-contraction and excitation-transcription coupling. Excessive CaMKII activity promotes processes that contribute to heart failure and arrhythmias. The CaMKII subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270988 [Multi-domain] Cd Length: 292 Bit Score: 172.61 E-value: 3.77e-47

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1660 DYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFI-----SARAKRKASalRELNILSHLDHERILYFHDAFEKKNAVIII 1734
Cdd:cd14086      1 DEYDLKEELGKGAFSVVRRCVQKSTGQEFAAKIIntkklSARDHQKLE--REARICRLLKHPNIVRLHDSISEEGFHYLV 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1735 TELCH-EELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSDQ-IRICDFGNAVKFMPDEA 1812
Cdd:cd14086     79 FDLVTgGELFEDIVAREFYSEADASHCIQQILESVNHCHQNGIVHRDLKPENLLLASKSKGAaVKLADFGLAIEVQGDQQ 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1813 QYCKY-GTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDLCHEAKGFV 1891
Cdd:cd14086    159 AWFGFaGTPGYLSPEVLRKDPYGKPVDIWACGVILYILLVGYPPFWDEDQHRLYAQIKAGAYDYPSPEWDTVTPEAKDLI 238

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1892 IKLLVAD-RLRPDANECLRHPWFKTLNKGKSI-----STESLKKFLSRRK 1935
Cdd:cd14086    239 NQMLTVNpAKRITAAEALKHPWICQRDRVASMvhrqeTVDCLKKFNARRK 288

Catalytic kinase domain, first repeat, of the Giant Serine/Threonine Kinase Obscurin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Obscurin, approximately 800 kDa in size, is one of three giant proteins expressed in vetebrate striated muscle, together with titin and nebulin. It is a multidomain protein composed of tandem adhesion and signaling domains, including 49 immunoglobulin (Ig) and 2 fibronectin type III (FN3) domains at the N-terminus followed by a more complex region containing more Ig domains, a conserved SH3 domain near a RhoGEF and PH domains, non-modular regions, as well as IQ and phosphorylation motifs. The obscurin gene also encode two kinase domains, which are not expressed as part of the 800 kDa protein, but as a smaller, alternatively spliced product present mainly in the heart muscle, also called obscurin-MLCK. Obscurin is localized at the peripheries of Z-disks and M-lines, where it is able to communicate with the surrounding myoplasm. It interacts with diverse proteins including sAnk1, myosin, titin, and MyBP-C. It may act as a scaffold for the assembly of elements of the contractile apparatus. The obscurin subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271009 [Multi-domain] Cd Length: 257 Bit Score: 170.84 E-value: 4.32e-47

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGK 3379
Cdd:cd14107      4 YEVKEEIGRGTFGFVKRVTHKGNGECCAAKFIPLRSSTRARAFQERDILARLSHRRLTCLLDQFETRKTLILILELCSSE 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3380 ELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTY--MNVVKIIDFGSAQTFNPLFLkQFSpPIG 3457
Cdd:cd14107     84 ELLDRLFLKGVVTEAEVKLYIQQVLEGIGYLHGMNILHLDIKPDNILMVSptREDIKICDFGFAQEITPSEH-QFS-KYG 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3458 TLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFT-ENDPAeTEARIQAAKFDLSK-LYQNVSQSASLFIKKILCS 3535
Cdd:cd14107    162 SPEFVAPEIVHQEPVSAATDIWALGVIAYLSLTCHSPFAgENDRA-TLLNVAEGVVSWDTpEITHLSEDAKDFIKRVLQP 240

                          250
                   ....*....|....*..
gi 1207186029 3536 YPWARPTIKDCFTNSWL 3552
Cdd:cd14107    241 DPEKRPSASECLSHEWF 257

Catalytic kinase domain, second repeat, of the Giant Serine/Threonine Kinase Uncoordinated protein 89; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The nematode Unc-89 gene, through alternative promoter use and splicing, encodes at least six major isoforms (Unc-89A to Unc-89F) of giant muscle proteins that are homologs for the vetebrate obscurin. In flies, five isoforms of Unc-89 have been detected: four in the muscles of adult flies (two in the indirect flight muscle and two in other muscles) and another isoform in the larva. Unc-89 in nematodes is required for normal muscle cell architecture. In flies, it is necessary for the development of a symmetrical sarcomere in the flight muscles. Unc-89 proteins contain several adhesion and signaling domains including multiple copies of the immunoglobulin (Ig) domain, as well as fibronectin type III (FN3), SH3, RhoGEF, and PH domains. The nematode Unc-89 isoforms D, C, D, and F contain two kinase domain with B and F having two complete kinase domains while the first repeat of C and D are partial domains. Homology modeling suggests that the first kinase repeat of Unc-89 may be catalytically inactive, a pseudokinase, while the second kinase repeat may be active. The Unc-89 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271014 [Multi-domain] Cd Length: 259 Bit Score: 170.40 E-value: 6.40e-47

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3296 PQKPYTFMDEKARGRFGVIRECRENA--TGNLYMAKIVPYEPESKQTVlQEYDILKSLHHEKIMALHEAYVTPRYLVLIS 3373
Cdd:cd14112      1 PTGRFSFGSEIFRGRFSVIVKAVDSTteTDAHCAVKIFEVSDEASEAV-REFESLRTLQHENVQRLIAAFKPSNFAYLVM 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3374 ECCSgKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMN--VVKIIDFGSAQTFNPLFLKq 3451
Cdd:cd14112     80 EKLQ-EDVFTRFSSNDYYSEEQVATTVRQILDALHYLHFKGIAHLDVQPDNIMFQSVRswQVKLVDFGRAQKVSKLGKV- 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3452 fsPPIGTLDYMSPEMLKGD-VVGPPADIWSIGILTYIMLSGRLPFT--ENDPAETEARIQAAKFDLSKLYQNVSQSASLF 3528
Cdd:cd14112    158 --PVDGDTDWASPEFHNPEtPITVQSDIWGLGVLTFCLLSGFHPFTseYDDEEETKENVIFVKCRPNLIFVEATQEALRF 235

                          250       260
                   ....*....|....*....|....
gi 1207186029 3529 IKKILCSYPWARPTIKDCFTNSWL 3552
Cdd:cd14112    236 ATWALKKSPTRRMRTDEALEHRWL 259

Catalytic domain of the Serine/Threonine Kinase, Death-Associated Protein Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DAPKs mediate cell death and act as tumor suppressors. They are necessary to induce cell death and their overexpression leads to death-associated changes including membrane blebbing, cell rounding, and formation of autophagic vesicles. Vertebrates contain three subfamily members with different domain architecture, localization, and function. DAPK3, also called DAP-like kinase (DLK) and zipper-interacting protein kinase (ZIPk), contains an N-terminal kinase domain and a C-terminal region with nuclear localization signals (NLS) and a leucine zipper motif that mediates homodimerization and interaction with other leucine zipper proteins. It interacts with Par-4, a protein that contains a death domain and interacts with actin filaments. DAPK3 is present in both the cytoplasm and nucleus. Its co-expression with Par-4 results in the co-localization of the two proteins to actin filaments. In addition to cell death, DAPK3 is also implicated in mediating cell motility and the contraction of smooth muscles. The DAPK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271097 [Multi-domain] Cd Length: 271 Bit Score: 170.95 E-value: 6.71e-47

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIV-------PYEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLI 3372
Cdd:cd14195      7 YEMGEELGSGQFAIVRKCREKGTGKEYAAKFIkkrrlssSRRGVSREEIEREVNILREIQHPNIITLHDIFENKTDVVLI 86

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3373 SECCSGKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNV----VKIIDFGSAQTFNPlf 3448
Cdd:cd14195     87 LELVSGGELFDFLAEKESLTEEEATQFLKQILDGVHYLHSKRIAHFDLKPENIMLLDKNVpnprIKLIDFGIAHKIEA-- 164

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3449 LKQFSPPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLSKLY-QNVSQSASL 3527
Cdd:cd14195    165 GNEFKNIFGTPEFVAPEIVNYEPLGLEADMWSIGVITYILLSGASPFLGETKQETLTNISAVNYDFDEEYfSNTSELAKD 244

                          250       260
                   ....*....|....*....|....*.
gi 1207186029 3528 FIKKILCSYPWARPTIKDCFTNSWLQ 3553
Cdd:cd14195    245 FIRRLLVKDPKKRMTIAQSLEHSWIK 270

Catalytic domain of AGC family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. AGC kinases regulate many cellular processes including division, growth, survival, metabolism, motility, and differentiation. Many are implicated in the development of various human diseases. Members of this family include cAMP-dependent Protein Kinase (PKA), cGMP-dependent Protein Kinase (PKG), Protein Kinase C (PKC), Protein Kinase B (PKB), G protein-coupled Receptor Kinase (GRK), Serum- and Glucocorticoid-induced Kinase (SGK), and 70 kDa ribosomal Protein S6 Kinase (p70S6K or S6K), among others. AGC kinases share an activation mechanism based on the phosphorylation of up to three sites: the activation loop (A-loop), the hydrophobic motif (HM) and the turn motif. Phosphorylation at the A-loop is required of most AGC kinases, which results in a disorder-to-order transition of the A-loop. The ordered conformation results in the access of substrates and ATP to the active site. A subset of AGC kinases with C-terminal extensions containing the HM also requires phosphorylation at this site. Phosphorylation at the HM allows the C-terminal extension to form an ordered structure that packs into the hydrophobic pocket of the catalytic domain, which then reconfigures the kinase into an active bi-lobed state. In addition, growth factor-activated AGC kinases such as PKB, p70S6K, RSK, MSK, PKC, and SGK, require phosphorylation at the turn motif (also called tail or zipper site), located N-terminal to the HM at the C-terminal extension. The AGC family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and Phosphoinositide 3-Kinase.

Pssm-ID: 270693 [Multi-domain] Cd Length: 250 Bit Score: 168.46 E-value: 2.48e-46

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKIVpyepeSKQTVLQ---------EYDILKSLHHEKIMALHEAYVTPRYLVLISECCSG 3378
Cdd:cd05123      3 KGSFGKVLLVRKKDTGKLYAMKVL-----RKKEIIKrkevehtlnERNILERVNHPFIVKLHYAFQTEEKLYLVLDYVPG 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3379 KELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLKQFSpPIGT 3458
Cdd:cd05123     78 GELFSHLSKEGRFPEERARFYAAEIVLALEYLHSLGIIYRDLKPENILLDSDGHIKLTDFGLAKELSSDGDRTYT-FCGT 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3459 LDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLSklyQNVSQSASLFIKKILCSYPW 3538
Cdd:cd05123    157 PEYLAPEVLLGKGYGKAVDWWSLGVLLYEMLTGKPPFYAENRKEIYEKILKSPLKFP---EYVSPEAKSLISGLLQKDPT 233


                   ..
gi 1207186029 3539 AR 3540
Cdd:cd05123    234 KR 235

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK2 (or MYLK2) phosphorylates myosin regulatory light chain and controls the contraction of skeletal muscles. MLCK2 contains a single kinase domain near the C-terminus followed by a regulatory segment containing an autoinhibitory Ca2+/calmodulin binding site. The MLCK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271092 [Multi-domain] Cd Length: 261 Bit Score: 168.94 E-value: 2.49e-46

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3309 GRFGVIRECRENATGNLYMAKIVPYE-PESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLHSLID 3387
Cdd:cd14190     15 GKFGKVHTCTEKRTGLKLAAKVINKQnSKDKEMVLLEIQVMNQLNHRNLIQLYEAIETPNEIVLFMEYVEGGELFERIVD 94

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3388 R-FRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIV--TYMNVVKIIDFGSAQTFNPLflKQFSPPIGTLDYMSP 3464
Cdd:cd14190     95 EdYHLTEVDAMVFVRQICEGIQFMHQMRVLHLDLKPENILCvnRTGHQVKIIDFGLARRYNPR--EKLKVNFGTPEFLSP 172

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3465 EMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAK--FDlSKLYQNVSQSASLFIKKILCSYPWARPT 3542
Cdd:cd14190    173 EVVNYDQVSFPTDMWSMGVITYMLLSGLSPFLGDDDTETLNNVLMGNwyFD-EETFEHVSDEAKDFVSNLIIKERSARMS 251

                          250
                   ....*....|
gi 1207186029 3543 IKDCFTNSWL 3552
Cdd:cd14190    252 ATQCLKHPWL 261

Catalytic domain of Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. PKs make up a large family of serine/threonine kinases (STKs), protein tyrosine kinases (PTKs), and dual-specificity PKs that phosphorylate both serine/threonine and tyrosine residues of target proteins. Majority of protein phosphorylation occurs on serine residues while only 1% occurs on tyrosine residues. Protein phosphorylation is a mechanism by which a wide variety of cellular proteins, such as enzymes and membrane channels, are reversibly regulated in response to certain stimuli. PKs often function as components of signal transduction pathways in which one kinase activates a second kinase, which in turn, may act on other kinases; this sequential action transmits a signal from the cell surface to target proteins, which results in cellular responses. The PK family is one of the largest known protein families with more than 100 homologous yeast enzymes and more than 500 human proteins. A fraction of PK family members are pseudokinases that lack crucial residues for catalytic activity. The mutiplicity of kinases allows for specific regulation according to substrate, tissue distribution, and cellular localization. PKs regulate many cellular processes including proliferation, division, differentiation, motility, survival, metabolism, cell-cycle progression, cytoskeletal rearrangement, immunity, and neuronal functions. Many kinases are implicated in the development of various human diseases including different types of cancer. The PK family is part of a larger superfamily that includes the catalytic domains of RIO kinases, aminoglycoside phosphotransferase, choline kinase, phosphoinositide 3-kinase (PI3K), and actin-fragmin kinase.

Pssm-ID: 270622 [Multi-domain] Cd Length: 215 Bit Score: 167.06 E-value: 2.91e-46

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKIVP--YEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELlHSL 3385
Cdd:cd00180      3 KGSFGKVYKARDKETGKKVAVKVIPkeKLKKLLEELLREIEILKKLNHPNIVKLYDVFETENFLYLVMEYCEGGSL-KDL 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3386 IDRFRY--SEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTF-NPLFLKQFSPPIGTLDYM 3462
Cdd:cd00180     82 LKENKGplSEEEALSILRQLLSALEYLHSNGIIHRDLKPENILLDSDGTVKLADFGLAKDLdSDDSLLKTTGGTTPPYYA 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3463 SPEMLKGDVVGPPADIWSIGILTYIMlsgrlpftendpaeteariqaakfdlsklyqnvsQSASLFIKKILCSYPWARPT 3542
Cdd:cd00180    162 PPELLGGRYYGPKVDIWSLGVILYEL----------------------------------EELKDLIRRMLQYDPKKRPS 207


                   ....*
gi 1207186029 3543 IKDCF 3547
Cdd:cd00180    208 AKELL 212

Serine/threonine protein kinase [Signal transduction mechanisms];

Pssm-ID: 440281 [Multi-domain] Cd Length: 482 Bit Score: 174.82 E-value: 6.59e-46

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3303 MDEKARGRFGVIRECRENATGNLYMA-----------KIVPYE----PESKQTVLQEYDILKSLHHEKIMALHEAYVTPR 3367
Cdd:COG0515      1 MSALLLGRYRILRLLGRGGMGVVYLArdlrlgrpvalKVLRPElaadPEARERFRREARALARLNHPNIVRVYDVGEEDG 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3368 YLVLISECCSGKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPL 3447
Cdd:COG0515     81 RPYLVMEYVEGESLADLLRRRGPLPPAEALRILAQLAEALAAAHAAGIVHRDIKPANILLTPDGRVKLIDFGIARALGGA 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3448 FLKQFSPPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKF-DLSKLYQNVSQSAS 3526
Cdd:COG0515    161 TLTQTGTVVGTPGYMAPEQARGEPVDPRSDVYSLGVTLYELLTGRPPFDGDSPAELLRAHLREPPpPPSELRPDLPPALD 240

                          250
                   ....*....|....*
gi 1207186029 3527 LFIKKILCSYPWARP 3541
Cdd:COG0515    241 AIVLRALAKDPEERY 255

C-terminal catalytic domain of the Serine/Threonine Kinases, Ribosomal S6 kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. Mammals possess four RSK isoforms (RSK1-4) from distinct genes. RSK proteins are also referred to as MAP kinase-activated protein kinases (MAPKAPKs), 90 kDa ribosomal protein S6 kinases (p90-RSKs), or p90S6Ks. The RSK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270993 [Multi-domain] Cd Length: 291 Bit Score: 168.20 E-value: 1.12e-45

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISaraKRKASALRELNIL-SHLDHERILYFHDAFEKKNAVIIITELCH- 1739
Cdd:cd14091      2 YEIKEEIGKGSYSVCKRCIHKATGKEYAVKIID---KSKRDPSEEIEILlRYGQHPNIITLRDVYDDGNSVYLVTELLRg 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1740 EELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSD--QIRICDFGNAvKFMPDEAQY--- 1814
Cdd:cd14091     79 GELLDRILRQKFFSEREASAVMKTLTKTVEYLHSQGVVHRDLKPSNILYADESGDpeSLRICDFGFA-KQLRAENGLlmt 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1815 -CkYgTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFA-GENDRSSVL--NIRNYNVAFEESMFTDLCHEAKGF 1890
Cdd:cd14091    158 pC-Y-TANFVAPEVLKKQGYDAACDIWSLGVLLYTMLAGYTPFAsGPNDTPEVIlaRIGSGKIDLSGGNWDHVSDSAKDL 235

                          250       260
                   ....*....|....*....|....*
gi 1207186029 1891 VIKLL-VADRLRPDANECLRHPWFK 1914
Cdd:cd14091    236 VRKMLhVDPSQRPTAAQVLQHPWIR 260

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270985 [Multi-domain] Cd Length: 259 Bit Score: 166.78 E-value: 1.19e-45

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1658 LTDYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARA-KRKASALR-ELNILSHLDHERILYFHDAFEKKNAVIIIT 1735
Cdd:cd14083      1 IRDKYEFKEVLGTGAFSEVVLAEDKATGKLVAIKCIDKKAlKGKEDSLEnEIAVLRKIKHPNIVQLLDIYESKSHLYLVM 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1736 ELCHE-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSD-QIRICDFGnaVKFMPDE-- 1811
Cdd:cd14083     81 ELVTGgELFDRIVEKGSYTEKDASHLIRQVLEAVDYLHSLGIVHRDLKPENLLYYSPDEDsKIMISDFG--LSKMEDSgv 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1812 -AQYCkyGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDLCHEAKGF 1890
Cdd:cd14083    159 mSTAC--GTPGYVAPEVLAQKPYGKAVDCWSIGVISYILLCGYPPFYDENDSKLFAQILKAEYEFDSPYWDDISDSAKDF 236

                          250       260
                   ....*....|....*....|...
gi 1207186029 1891 VIKLLVAD-RLRPDANECLRHPW 1912
Cdd:cd14083    237 IRHLMEKDpNKRYTCEQALEHPW 259

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK phosphorylates myosin regulatory light chain and controls the contraction of all muscle types. In vertebrates, different MLCKs function in smooth (MLCK1), skeletal (MLCK2), and cardiac (MLCK3) muscles. A fourth protein, MLCK4, has also been identified through comprehensive genome analysis although it has not been biochemically characterized. MLCK4 (or MYLK4 or SgK085) contains a single kinase domain near the C-terminus. The MLCK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271095 [Multi-domain] Cd Length: 261 Bit Score: 166.63 E-value: 1.39e-45

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3309 GRFGVIRECRENATGNLYMAKIVPYE-PESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLHSLID 3387
Cdd:cd14193     15 GRFGQVHKCEEKSSGLKLAAKIIKARsQKEKEEVKNEIEVMNQLNHANLIQLYDAFESRNDIVLVMEYVDGGELFDRIID 94

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3388 R-FRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTY--MNVVKIIDFGSAQTFNPLflKQFSPPIGTLDYMSP 3464
Cdd:cd14193     95 EnYNLTELDTILFIKQICEGIQYMHQMYILHLDLKPENILCVSreANQVKIIDFGLARRYKPR--EKLRVNFGTPEFLAP 172

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3465 EMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLS-KLYQNVSQSASLFIKKILCSYPWARPTI 3543
Cdd:cd14193    173 EVVNYEFVSFPTDMWSLGVIAYMLLSGLSPFLGEDDNETLNNILACQWDFEdEEFADISEEAKDFISKLLIKEKSWRMSA 252


                   ....*....
gi 1207186029 3544 KDCFTNSWL 3552
Cdd:cd14193    253 SEALKHPWL 261

Catalytic domain of STE family Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. This family is composed of STKs, and some dual-specificity PKs that phosphorylate both threonine and tyrosine residues of target proteins. Most members are kinases involved in mitogen-activated protein kinase (MAPK) signaling cascades, acting as MAPK kinases (MAPKKs), MAPKK kinases (MAPKKKs), or MAPKKK kinases (MAP4Ks). The MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising of the MAPK, which is phosphorylated and activated by a MAPKK, which itself is phosphorylated and activated by a MAPKKK. Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAPKKK to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Other STE family members include p21-activated kinases (PAKs) and class III myosins, among others. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain, which can phosphorylate several cytoskeletal proteins, conventional myosin regulatory light chains, as well as autophosphorylate the C-terminal motor domain. They play an important role in maintaining the structural integrity of photoreceptor cell microvilli. The STE family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270692 [Multi-domain] Cd Length: 254 Bit Score: 166.22 E-value: 1.83e-45

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVPYE-PESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSG 3378
Cdd:cd05122      2 FEILEKIGKGGFGVVYKARHKKTGQIVAIKKINLEsKEKKESILNEIAILKKCKHPNIVKYYGSYLKKDELWIVMEFCSG 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3379 ---KELLHSLIDRFrySEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPlfLKQFSPP 3455
Cdd:cd05122     82 gslKDLLKNTNKTL--TEQQIAYVCKEVLKGLEYLHSHGIIHRDIKAANILLTSDGEVKLIDFGLSAQLSD--GKTRNTF 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3456 IGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPaeTEARIQAAKFDLSKLYQNVSQSASL--FIKKIL 3533
Cdd:cd05122    158 VGTPYWMAPEVIQGKPYGFKADIWSLGITAIEMAEGKPPYSELPP--MKALFLIATNGPPGLRNPKKWSKEFkdFLKKCL 235

                          250
                   ....*....|.
gi 1207186029 3534 CSYPWARPTIK 3544
Cdd:cd05122    236 QKDPEKRPTAE 246

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK3 (or MYLK3) phosphorylates myosin regulatory light chain 2 and controls the contraction of cardiac muscles. It is expressed specifically in both the atrium and ventricle of the heart and its expression is regulated by the cardiac protein Nkx2-5. MLCK3 plays an important role in cardiogenesis by regulating the assembly of cardiac sarcomeres, the repeating contractile unit of striated muscle. MLCK3 contains a single kinase domain near the C-terminus and a unique N-terminal half, and unlike MLCK1/2, it does not appear to be regulated by Ca2+/calmodulin. The MLCK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271094 [Multi-domain] Cd Length: 261 Bit Score: 165.52 E-value: 3.69e-45

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3309 GRFGVIRECRENATGNLYMAKIVPYE-PESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLHSLID 3387
Cdd:cd14192     15 GRFGQVHKCTELSTGLTLAAKIIKVKgAKEREEVKNEINIMNQLNHVNLIQLYDAFESKTNLTLIMEYVDGGELFDRITD 94

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3388 -RFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYM--NVVKIIDFGSAQTFNPLflKQFSPPIGTLDYMSP 3464
Cdd:cd14192     95 eSYQLTELDAILFTRQICEGVHYLHQHYILHLDLKPENILCVNStgNQIKIIDFGLARRYKPR--EKLKVNFGTPEFLAP 172

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3465 EMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDL-SKLYQNVSQSASLFIKKILCSYPWARPTI 3543
Cdd:cd14192    173 EVVNYDFVSFPTDMWSVGVITYMLLSGLSPFLGETDAETMNNIVNCKWDFdAEAFENLSEEAKDFISRLLVKEKSCRMSA 252


                   ....*....
gi 1207186029 3544 KDCFTNSWL 3552
Cdd:cd14192    253 TQCLKHEWL 261

Catalytic domain of the Serine/Threonine kinases, Liver Kinase B1, Calmodulin Dependent Protein Kinase Kinase, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Both LKB1 and CaMKKs can phosphorylate and activate AMP-activated protein kinase (AMPK). LKB1, also called STK11, serves as a master upstream kinase that activates AMPK and most AMPK-like kinases. LKB1 and AMPK are part of an energy-sensing pathway that links cell energy to metabolism and cell growth. They play critical roles in the establishment and maintenance of cell polarity, cell proliferation, cytoskeletal organization, as well as T-cell metabolism, including T-cell development, homeostasis, and effector function. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMPK. Vertebrates contain two CaMKKs, CaMKK1 (or alpha) and CaMKK2 (or beta). CaMKK1 is involved in the regulation of glucose uptake in skeletal muscles. CaMKK2 is involved in regulating energy balance, glucose metabolism, adiposity, hematopoiesis, inflammation, and cancer. The LKB1/CaMKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270910 [Multi-domain] Cd Length: 267 Bit Score: 165.42 E-value: 4.57e-45

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKIVP----------YEPESK-----QTVLQEYDILKSLHHEKIMALHEAYVTPR----Y 3368
Cdd:cd14008      3 RGSFGKVKLALDTETGQLYAIKIFNksrlrkrregKNDRGKiknalDDVRREIAIMKKLDHPNIVRLYEVIDDPEsdklY 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3369 LVLisECCSGKELLH--SLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNP 3446
Cdd:cd14008     83 LVL--EYCEGGPVMEldSGDRVPPLPEETARKYFRDLVLGLEYLHENGIVHRDIKPENLLLTADGTVKISDFGVSEMFED 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3447 lFLKQFSPPIGTLDYMSPEMLKGDVV---GPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKF------DLSKL 3517
Cdd:cd14008    161 -GNDTLQKTAGTPAFLAPELCDGDSKtysGKAADIWALGVTLYCLVFGRLPFNGDNILELYEAIQNQNDefpippELSPE 239

                          250       260       270
                   ....*....|....*....|....*....|....*
gi 1207186029 3518 YQNvsqsaslFIKKILCSYPWARPTIKDCFTNSWL 3552
Cdd:cd14008    240 LKD-------LLRRMLEKDPEKRITLKEIKEHPWV 267

Catalytic domain of the Protein Serine/Threonine kinase H1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PSKH1 is an autophosphorylating STK that is expressed ubiquitously and exhibits multiple intracellular localizations including the centrosome, Golgi apparatus, and splice factor compartments. It contains a catalytic kinase domain and an N-terminal SH4-like motif that is acylated to facilitate membrane attachment. PSKH1 plays a rile in the maintenance of the Golgi apparatus, an important organelle within the secretory pathway. It may also function as a novel splice factor and a regulator of prostate cancer cell growth. The PSKH1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270989 [Multi-domain] Cd Length: 259 Bit Score: 164.24 E-value: 1.05e-44

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITELCHE- 1740
Cdd:cd14087      3 YDIKALIGRGSFSRVVRVEHRVTRQPYAIKMIETKCRGREVCESELNVLRRVRHTNIIQLIEVFETKERVYMVMELATGg 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1741 ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSD-QIRICDFG--NAVKFMPDEAQYCKY 1817
Cdd:cd14087     83 ELFDRIIAKGSFTERDATRVLQMVLDGVKYLHGLGITHRDLKPENLLYYHPGPDsKIMITDFGlaSTRKKGPNCLMKTTC 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1818 GTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDLCHEAKGFVIKLLVA 1897
Cdd:cd14087    163 GTPEYIAPEILLRKPYTQSVDMWAVGVIAYILLSGTMPFDDDNRTRLYRQILRAKYSYSGEPWPSVSNLAKDFIDRLLTV 242

                          250
                   ....*....|....*.
gi 1207186029 1898 DRL-RPDANECLRHPW 1912
Cdd:cd14087    243 NPGeRLSATQALKHPW 258

Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma subunit; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phosphorylase kinase (PhK) catalyzes the phosphorylation of inactive phosphorylase b to form the active phosphorylase a. It coordinates hormonal, metabolic, and neuronal signals to initiate the breakdown of glycogen stores, which enables the maintenance of blood-glucose homeostasis during fasting, and is also used as a source of energy for muscle contraction. PhK is one of the largest and most complex protein kinases, composed of a heterotetramer containing four molecules each of four subunit types: one catalytic (gamma) and three regulatory (alpha, beta, and delta). Each subunit has tissue-specific isoforms or splice variants. Vertebrates contain two isoforms of the gamma subunit (gamma 1 and gamma 2). The gamma subunit, when isolated, is constitutively active and does not require phosphorylation of the A-loop for activity. The regulatory subunits restrain this kinase activity until signals are received to relieve this inhibition. For example, the kinase is activated in response to hormonal stimulation, after autophosphorylation or phosphorylation by cAMP-dependent kinase of the alpha and beta subunits. The high-affinity binding of ADP to the beta subunit also stimulates kinase activity, whereas calcium relieves inhibition by binding to the delta (calmodulin) subunit. The PhKG subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270995 [Multi-domain] Cd Length: 272 Bit Score: 164.45 E-value: 1.11e-44

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1666 KEI-GRGAFSYVKRVIQKAGKLEYAAKFISARAKR---------KASALRELNILSHLD-HERILYFHDAFEKKNAVIII 1734
Cdd:cd14093      8 KEIlGRGVSSTVRRCIEKETGQEFAVKIIDITGEKsseneaeelREATRREIEILRQVSgHPNIIELHDVFESPTFIFLV 87

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1735 TELCHE-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADhsSDQIRICDFGNAVKFMPDEAQ 1813
Cdd:cd14093     88 FELCRKgELFDYLTEVVTLSEKKTRRIMRQLFEAVEFLHSLNIVHRDLKPENILLDD--NLNVKISDFGFATRLDEGEKL 165

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1814 YCKYGTPEFVAPEIV------NQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDLCHEA 1887
Cdd:cd14093    166 RELCGTPGYLAPEVLkcsmydNAPGYGKEVDMWACGVIMYTLLAGCPPFWHRKQMVMLRNIMEGKYEFGSPEWDDISDTA 245

                          250       260
                   ....*....|....*....|....*..
gi 1207186029 1888 KGFVIKLLVAD-RLRPDANECLRHPWF 1913
Cdd:cd14093    246 KDLISKLLVVDpKKRLTAEEALEHPFF 272

Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Checkpoint Kinase 2 (Chk2) plays an important role in cellular responses to DNA double-strand breaks and related lesions. It is phosphorylated and activated by ATM kinase, resulting in its dissociation from sites of damage to phosphorylate downstream targets such as BRCA1, p53, cell cycle transcription factor E2F1, the promyelocytic leukemia protein (PML) involved in apoptosis, and CDC25 phosphatases, among others. Mutations in Chk2 is linked to a variety of cancers including familial breast cancer, myelodysplastic syndromes, prostate cancer, lung cancer, and osteosarcomas. Chk2 contains an N-terminal SQ/TQ cluster domain (SCD), a central forkhead-associated (FHA) domain, and a C-terminal catalytic kinase domain. The Chk2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270986 [Multi-domain] Cd Length: 275 Bit Score: 162.95 E-value: 4.28e-44

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1656 RRLTDYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISAR---------AKRKASALRELNILSHLDHERILYFHDAFE 1726
Cdd:cd14084      2 KELRKKYIMSRTLGSGACGEVKLAYDKSTCKKVAIKIINKRkftigsrreINKPRNIETEIEILKKLSHPCIIKIEDFFD 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1727 KKNAVIIITELCHE-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSD-QIRICDFGNA 1804
Cdd:cd14084     82 AEDDYYIVLELMEGgELFDRVVSNKRLKEAICKLYFYQMLLAVKYLHSNGIIHRDLKPENVLLSSQEEEcLIKITDFGLS 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1805 vKFMpDEAQYCKY--GTPEFVAPEIVN---QTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLN-IRNYNVAFEES 1878
Cdd:cd14084    162 -KIL-GETSLMKTlcGTPTYLAPEVLRsfgTEGYTRAVDCWSLGVILFICLSGYPPFSEEYTQMSLKEqILSGKYTFIPK 239

                          250       260       270
                   ....*....|....*....|....*....|....*
gi 1207186029 1879 MFTDLCHEAKGFVIKLLVAD-RLRPDANECLRHPW 1912
Cdd:cd14084    240 AWKNVSEEAKDLVKKMLVVDpSRRPSIEEALEHPW 274

Catalytic domain of Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. PKs make up a large family of serine/threonine kinases (STKs), protein tyrosine kinases (PTKs), and dual-specificity PKs that phosphorylate both serine/threonine and tyrosine residues of target proteins. Majority of protein phosphorylation occurs on serine residues while only 1% occurs on tyrosine residues. Protein phosphorylation is a mechanism by which a wide variety of cellular proteins, such as enzymes and membrane channels, are reversibly regulated in response to certain stimuli. PKs often function as components of signal transduction pathways in which one kinase activates a second kinase, which in turn, may act on other kinases; this sequential action transmits a signal from the cell surface to target proteins, which results in cellular responses. The PK family is one of the largest known protein families with more than 100 homologous yeast enzymes and more than 500 human proteins. A fraction of PK family members are pseudokinases that lack crucial residues for catalytic activity. The mutiplicity of kinases allows for specific regulation according to substrate, tissue distribution, and cellular localization. PKs regulate many cellular processes including proliferation, division, differentiation, motility, survival, metabolism, cell-cycle progression, cytoskeletal rearrangement, immunity, and neuronal functions. Many kinases are implicated in the development of various human diseases including different types of cancer. The PK family is part of a larger superfamily that includes the catalytic domains of RIO kinases, aminoglycoside phosphotransferase, choline kinase, phosphoinositide 3-kinase (PI3K), and actin-fragmin kinase.

Pssm-ID: 270622 [Multi-domain] Cd Length: 215 Bit Score: 159.74 E-value: 9.90e-44

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYVKRVIQKAGKLEYAAKFI--SARAKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITELCHE-ELLD 1744
Cdd:cd00180      1 LGKGSFGKVYKARDKETGKKVAVKVIpkEKLKKLLEELLREIEILKKLNHPNIVKLYDVFETENFLYLVMEYCEGgSLKD 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1745 RLTKKSTIL-ESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDFGNAVKFMPDEAQYCKYGTPEFV 1823
Cdd:cd00180     81 LLKENKGPLsEEEALSILRQLLSALEYLHSNGIIHRDLKPENILL--DSDGTVKLADFGLAKDLDSDDSLLKTTGGTTPP 158

                          170       180
                   ....*....|....*....|....*..
gi 1207186029 1824 ---APEIVNQTPVSKATDIWPIGVLTY 1847
Cdd:cd00180    159 yyaPPELLGGRYYGPKVDIWSLGVILY 185

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Nek family is composed of 11 different mammalian members (Nek1-11) with similarity to the catalytic domain of Aspergillus nidulans NIMA kinase, the founding member of the Nek family, which was identified in a screen for cell cycle mutants that were prevented from entering mitosis. Neks contain a conserved N-terminal catalytic domain and a more divergent C-terminal regulatory region of various sizes and structures. They are involved in the regulation of downstream processes following the activation of Cdc2, and many of their functions are cell cycle-related. They play critical roles in microtubule dynamics during ciliogenesis and mitosis. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270855 [Multi-domain] Cd Length: 258 Bit Score: 159.17 E-value: 5.67e-43

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVPY---EPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECC 3376
Cdd:cd08215      2 YEKIRVIGKGSFGSAYLVRRKSDGKLYVLKEIDLsnmSEKEREEALNEVKLLSKLKHPNIVKYYESFEENGKLCIVMEYA 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3377 SGKeLLHSLIDRFR-----YSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFG----------SA 3441
Cdd:cd08215     82 DGG-DLAQKIKKQKkkgqpFPEEQILDWFVQICLALKYLHSRKILHRDLKTQNIFLTKDGVVKLGDFGiskvlesttdLA 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3442 QTFnplflkqfsppIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFD-LSKLYqn 3520
Cdd:cd08215    161 KTV-----------VGTPYYLSPELCENKPYNYKSDIWALGCVLYELCTLKHPFEANNLPALVYKIVKGQYPpIPSQY-- 227

                          250       260
                   ....*....|....*....|....*
gi 1207186029 3521 vSQSASLFIKKILCSYPWARPTIKD 3545
Cdd:cd08215    228 -SSELRDLVNSMLQKDPEKRPSANE 251

C-terminal kinase domain of the Large Serine/Threonine Kinase and Rho Guanine Nucleotide Exchange Factor, Triple functional domain protein; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Triple functional domain protein (Trio), also called PTPRF-interacting protein, is a large multidomain protein containing a series of spectrin-like repeats, two each of RhoGEF and SH3 domains, an immunoglobulin-like (Ig) domain and a C-terminal kinase. Trio plays important roles in neuronal cell migration and axon guidance. It was originally identified as an interacting partner of the of the receptor-like tyrosine phosphatase (RPTP) LAR (leukocyte-antigen-related protein), a family of receptors that function in the signaling to the actin cytoskeleton during development. Trio functions as a GEF for Rac1, RhoG, and RhoA, and is involved in the regulation of lamellipodia formation, mediating Rac1-dependent cell spreading and migration. The Trio subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271015 [Multi-domain] Cd Length: 263 Bit Score: 157.06 E-value: 3.54e-42

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGK 3379
Cdd:cd14113      9 YSEVAELGRGRFSVVKKCDQRGTKRAVATKFVNKKLMKRDQVTHELGVLQSLQHPQLVGLLDTFETPTSYILVLEMADQG 88

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3380 ELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIV---TYMNVVKIIDFGSAQTFNPLFLkqFSPPI 3456
Cdd:cd14113     89 RLLDYVVRWGNLTEEKIRFYLREILEALQYLHNCRIAHLDLKPENILVdqsLSKPTIKLADFGDAVQLNTTYY--IHQLL 166

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3457 GTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLSKLY-QNVSQSASLFIKKILCS 3535
Cdd:cd14113    167 GSPEFAAPEIILGNPVSLTSDLWSIGVLTYVLLSGVSPFLDESVEETCLNICRLDFSFPDDYfKGVSQKAKDFVCFLLQM 246

                          250
                   ....*....|....*..
gi 1207186029 3536 YPWARPTIKDCFTNSWL 3552
Cdd:cd14113    247 DPAKRPSAALCLQEQWL 263

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type IV; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKIV is found predominantly in neurons and immune cells. It is activated by the binding of calcium/CaM and phosphorylation by CaMKK (alpha or beta). The CaMKK-CaMKIV cascade participates in regulating several transcription factors like CREB, MEF2, and retinoid orphan receptors. It also is implicated in T-cell development and signaling, cytokine secretion, and signaling through Toll-like receptors, and is thus, pivotal in immune response and inflammation. The CaMKIV subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270987 [Multi-domain] Cd Length: 294 Bit Score: 157.68 E-value: 5.30e-42

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1658 LTDYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKAsALRELNILSHLDHERILYFHDAFEKKNAVIIITEL 1737
Cdd:cd14085      1 LEDFFEIESELGRGATSVVYRCRQKGTQKPYAVKKLKKTVDKKI-VRTEIGVLLRLSHPNIIKLKEIFETPTEISLVLEL 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1738 CHE-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSDQ-IRICDFGNAvKFMPDEAQY- 1814
Cdd:cd14085     80 VTGgELFDRIVEKGYYSERDAADAVKQILEAVAYLHENGIVHRDLKPENLLYATPAPDApLKIADFGLS-KIVDQQVTMk 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1815 --CkyGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGEN-DRSSVLNIRNYNVAFEESMFTDLCHEAKGFV 1891
Cdd:cd14085    159 tvC--GTPGYCAPEILRGCAYGPEVDMWSVGVITYILLCGFEPFYDERgDQYMFKRILNCDYDFVSPWWDDVSLNAKDLV 236

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*...
gi 1207186029 1892 IKLLVAD-RLRPDANECLRHPWFKTLNKGKSI---STESLKKFLSRRK 1935
Cdd:cd14085    237 KKLIVLDpKKRLTTQQALQHPWVTGKAANFAHmdtAQKKLQEFNARRK 284

Catalytic kinase domain, second repeat, of Giant Serine/Threonine Kinase Striated muscle preferentially expressed protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Striated muscle preferentially expressed gene (SPEG) generates 4 different isoforms through alternative promoter use and splicing in a tissue-specific manner: SPEGalpha and SPEGbeta are expressed in cardiac and skeletal striated muscle; Aortic Preferentially Expressed Protein-1 (APEG-1) is expressed in vascular smooth muscle; and Brain preferentially expressed gene (BPEG) is found in the brain and aorta. SPEG proteins have mutliple immunoglobulin (Ig), 2 fibronectin type III (FN3), and two kinase domains. They are necessary for cardiac development and survival. The SPEG subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271013 [Multi-domain] Cd Length: 257 Bit Score: 155.75 E-value: 8.25e-42

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITELC-HE 1740
Cdd:cd14111      5 YTFLDEKARGRFGVIRRCRENATGKNFPAKIVPYQAEEKQGVLQEYEILKSLHHERIMALHEAYITPRYLVLIAEFCsGK 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1741 ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADhsSDQIRICDFGNAVKFMPDEAQYC--KYG 1818
Cdd:cd14111     85 ELLHSLIDRFRYSEDDVVGYLVQILQGLEYLHGRRVLHLDIKPDNIMVTN--LNAIKIVDFGSAQSFNPLSLRQLgrRTG 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1819 TPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIrnYNVAFEES-MFTDLCHEAKGFVIKLL-V 1896
Cdd:cd14111    163 TLEYMAPEMVKGEPVGPPADIWSIGVLTYIMLSGRSPFEDQDPQETEAKI--LVAKFDAFkLYPNVSQSASLFLKKVLsS 240

                          250
                   ....*....|....*.
gi 1207186029 1897 ADRLRPDANECLRHPW 1912
Cdd:cd14111    241 YPWSRPTTKDCFAHAW 256

Catalytic domain of the Serine/Threonine Kinase, Phosphoinositide-dependent kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PDK1 carries an N-terminal catalytic domain and a C-terminal pleckstrin homology (PH) domain that binds phosphoinositides. It phosphorylates the activation loop of AGC kinases that are regulated by PI3K such as PKB, SGK, and PKC, among others, and is crucial for their activation. Thus, it contributes in regulating many processes including metabolism, growth, proliferation, and survival. PDK1 also has the ability to autophosphorylate and is constitutively active in mammalian cells. It is essential for normal embryo development and is important in regulating cell volume. The PDK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270733 [Multi-domain] Cd Length: 278 Bit Score: 156.22 E-value: 1.02e-41

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVpyepeSK---------QTVLQEYDILKSLHHEKIMALHEAYVTPR--Y 3368
Cdd:cd05581      3 FKFGKPLGEGSYSTVVLAKEKETGKEYAIKVL-----DKrhiikekkvKYVTIEKEVLSRLAHPGIVKLYYTFQDESklY 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3369 LVLisECCSGKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNP-- 3446
Cdd:cd05581     78 FVL--EYAPNGDLLEYIRKYGSLDEKCTRFYTAEIVLALEYLHSKGIIHRDLKPENILLDEDMHIKITDFGTAKVLGPds 155

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3447 ----LFLKQFSPP----------IGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKF 3512
Cdd:cd05581    156 spesTKGDADSQIaynqaraasfVGTAEYVSPELLNEKPAGKSSDLWALGCIIYQMLTGKPPFRGSNEYLTFQKIVKLEY 235

                          250       260       270
                   ....*....|....*....|....*....|....*.
gi 1207186029 3513 DLSklyQNVSQSASLFIKKILCSYPWARPTIKDCFT 3548
Cdd:cd05581    236 EFP---ENFPPDAKDLIQKLLVLDPSKRLGVNENGG 268

Catalytic domain of the yeast Serine/Threonine Kinases, Rad53 and Cds1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Rad53 and Cds1 are the checkpoint kinase 2 (Chk2) homologs found in budding and fission yeast, respectively. They play a central role in the cell's response to DNA lesions to prevent genome rearrangements and maintain genome integrity. They are phosphorylated in response to DNA damage and incomplete replication, and are essential for checkpoint control. They help promote DNA repair by stalling the cell cycle prior to mitosis in the presence of DNA damage. The Rad53/Cds1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271000 [Multi-domain] Cd Length: 265 Bit Score: 155.71 E-value: 1.08e-41

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKI-----VPYEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISE 3374
Cdd:cd14098      2 YQIIDRLGSGTFAEVKKAVEVETGKMRAIKQivkrkVAGNDKNLQLFQREINILKSLEHPGIVRLIDWYEDDQHIYLVME 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3375 CCSGKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMN--VVKIIDFGSAQ-TFNPLFLKQ 3451
Cdd:cd14098     82 YVEGGDLMDFIMAWGAIPEQHARELTKQILEAMAYTHSMGITHRDLKPENILITQDDpvIVKISDFGLAKvIHTGTFLVT 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3452 FsppIGTLDYMSPEMLKG-DVVGPP-----ADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLSKLYQ-NVSQS 3524
Cdd:cd14098    162 F---CGTMAYLAPEILMSkEQNLQGgysnlVDMWSVGCLVYVMLTGALPFDGSSQLPVEKRIRKGRYTQPPLVDfNISEE 238

                          250       260
                   ....*....|....*....|....*..
gi 1207186029 3525 ASLFIKKILCSYPWARPTIKDCFTNSW 3551
Cdd:cd14098    239 AIDFILRLLDVDPEKRMTAAQALDHPW 265

C-terminal kinase domain of the Large Serine/Threonine Kinase and Rho Guanine Nucleotide Exchange Factor, Kalirin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Kalirin, also called Duo or Duet, is a large multidomain protein containing a series of spectrin-like repeats, two each of RhoGEF and SH3 domains, an immunoglobulin-like (Ig) domain and a C-terminal kinase. As a GEF, it activates Rac1, RhoA, and RhoG. It is highly expressed in neurons and is required for spine formation. The kalirin gene produces at least 10 isoforms from alternative promoter use and splicing. Of the major isoforms (Kalirin-7, -9, and -12), only kalirin-12 contains the C-terminal kinase domain. Kalirin-12 is highly expressed during embryonic development and it plays an important role in axon outgrowth. The Kalirin subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271017 [Multi-domain] Cd Length: 248 Bit Score: 155.12 E-value: 1.20e-41

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKIVPYEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLHSLID 3387
Cdd:cd14115      3 RGRFSIVKKCLHKATRKDVAVKFVSKKMKKKEQAAHEAALLQHLQHPQYITLHDTYESPTSYILVLELMDDGRLLDYLMN 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3388 RFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTY---MNVVKIIDFGSAQTFNPLFlkQFSPPIGTLDYMSP 3464
Cdd:cd14115     83 HDELMEEKVAFYIRDIMEALQYLHNCRVAHLDIKPENLLIDLripVPRVKLIDLEDAVQISGHR--HVHHLLGNPEFAAP 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3465 EMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLSKLY-QNVSQSASLFIKKILCSYPWARPTI 3543
Cdd:cd14115    161 EVIQGTPVSLATDIWSIGVLTYVMLSGVSPFLDESKEETCINVCRVDFSFPDEYfGDVSQAARDFINVILQEDPRRRPTA 240


                   ....*...
gi 1207186029 3544 KDCFTNSW 3551
Cdd:cd14115    241 ATCLQHPW 248

Protein kinase domain;

Pssm-ID: 459660 [Multi-domain] Cd Length: 217 Bit Score: 152.40 E-value: 3.71e-41

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPESK---QTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECC 3376
Cdd:pfam00069    1 YEVLRKLGSGSFGTVYKAKHRDTGKIVAIKKIKKEKIKKkkdKNILREIKILKKLNHPNIVRLYDAFEDKDNLYLVLEYV 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3377 SGKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSrrilhldikpeniivtYMNVVkiidfgsaqtfnplflkqfsppi 3456
Cdd:pfam00069   81 EGGSLFDLLSEKGAFSEREAKFIMKQILEGLESGSS----------------LTTFV----------------------- 121

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3457 GTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLSKLYQNVSQSASLFIKKILCSY 3536
Cdd:pfam00069  122 GTPWYMAPEVLGGNPYGPKVDVWSLGCILYELLTGKPPFPGINGNEIYELIIDQPYAFPELPSNLSEEAKDLLKKLLKKD 201

                          250
                   ....*....|....*.
gi 1207186029 3537 PWARPTIKDCFTNSWL 3552
Cdd:pfam00069  202 PSKRLTATQALQHPWF 217

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I alpha; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-alpha subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271069 [Multi-domain] Cd Length: 263 Bit Score: 154.03 E-value: 4.15e-41

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1658 LTDYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARA--KRKASALRELNILSHLDHERILYFHDAFEKKNAVIIIT 1735
Cdd:cd14167      1 IRDIYDFREVLGTGAFSEVVLAEEKRTQKLVAIKCIAKKAleGKETSIENEIAVLHKIKHPNIVALDDIYESGGHLYLIM 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1736 ELCHE-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSD-QIRICDFGNAVKFMPDEAQ 1813
Cdd:cd14167     81 QLVSGgELFDRIVEKGFYTERDASKLIFQILDAVKYLHDMGIVHRDLKPENLLYYSLDEDsKIMISDFGLSKIEGSGSVM 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1814 YCKYGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDLCHEAKGFVIK 1893
Cdd:cd14167    161 STACGTPGYVAPEVLAQKPYSKAVDCWSIGVIAYILLCGYPPFYDENDAKLFEQILKAEYEFDSPYWDDISDSAKDFIQH 240

                          250       260
                   ....*....|....*....|
gi 1207186029 1894 LLVAD-RLRPDANECLRHPW 1912
Cdd:cd14167    241 LMEKDpEKRFTCEQALQHPW 260

Catalytic domain of bacterial Serine/Threonine kinases, PknB and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes many bacterial eukaryotic-type STKs including Staphylococcus aureus PknB (also called PrkC or Stk1), Bacillus subtilis PrkC, and Mycobacterium tuberculosis Pkn proteins (PknB, PknD, PknE, PknF, PknL, and PknH), among others. S. aureus PknB is the only eukaryotic-type STK present in this species, although many microorganisms encode for several such proteins. It is important for the survival and pathogenesis of S. aureus as it is involved in the regulation of purine and pyrimidine biosynthesis, cell wall metabolism, autolysis, virulence, and antibiotic resistance. M. tuberculosis PknB is essential for growth and it acts on diverse substrates including proteins involved in peptidoglycan synthesis, cell division, transcription, stress responses, and metabolic regulation. B. subtilis PrkC is located at the inner membrane of endospores and functions to trigger spore germination. Bacterial STKs in this subfamily show varied domain architectures. The well-characterized members such as S. aureus and M. tuberculosis PknB, and B. subtilis PrkC, contain an N-terminal cytosolic kinase domain, a transmembrane (TM) segment, and mutliple C-terminal extracellular PASTA domains. The PknB subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270916 [Multi-domain] Cd Length: 260 Bit Score: 153.13 E-value: 8.17e-41

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFI----SARAKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITEL 1737
Cdd:cd14014      2 YRLVRLLGRGGMGEVYRARDTLLGRPVAIKVLrpelAEDEEFRERFLREARALARLSHPNIVRVYDVGEDDGRPYIVMEY 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1738 CH-EELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADhsSDQIRICDFGNAVKFMPDEAQYCK 1816
Cdd:cd14014     82 VEgGSLADLLRERGPLPPREALRILAQIADALAAAHRAGIVHRDIKPANILLTE--DGRVKLTDFGIARALGDSGLTQTG 159

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1207186029 1817 --YGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNY 1871
Cdd:cd14014    160 svLGTPAYMAPEQARGGPVDPRSDIYSLGVVLYELLTGRPPFDGDSPAAVLAKHLQE 216

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I gamma; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-gamma subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271068 [Multi-domain] Cd Length: 285 Bit Score: 153.61 E-value: 1.08e-40

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFIS-ARAKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITELCHE 1740
Cdd:cd14166      5 FIFMEVLGSGAFSEVYLVKQRSTGKLYALKCIKkSPLSRDSSLENEIAVLKRIKHENIVTLEDIYESTTHYYLVMQLVSG 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1741 -ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNIL-MADHSSDQIRICDFGNAvKFMPDEAQYCKYG 1818
Cdd:cd14166     85 gELFDRILERGVYTEKDASRVINQVLSAVKYLHENGIVHRDLKPENLLyLTPDENSKIMITDFGLS-KMEQNGIMSTACG 163

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1819 TPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDLCHEAKGFVIKLLVAD 1898
Cdd:cd14166    164 TPGYVAPEVLAQKPYSKAVDCWSIGVITYILLCGYPPFYEETESRLFEKIKEGYYEFESPFWDDISESAKDFIRHLLEKN 243

                          250
                   ....*....|....*
gi 1207186029 1899 -RLRPDANECLRHPW 1912
Cdd:cd14166    244 pSKRYTCEKALSHPW 258

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase Kinase Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPKKKs (MKKKs or MAP3Ks) are also called MAP/ERK kinase kinases (MEKKs) in some cases. They phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. This subfamily is composed of the Apoptosis Signal-regulating Kinases ASK1 (or MAPKKK5) and ASK2 (or MAPKKK6), MEKK1, MEKK2, MEKK3, MEKK4, as well as plant and fungal MAPKKKs. Also included in this subfamily are the cell division control proteins Schizosaccharomyces pombe Cdc7 and Saccharomyces cerevisiae Cdc15. The MAPKKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270783 [Multi-domain] Cd Length: 258 Bit Score: 151.90 E-value: 1.66e-40

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1666 KEIGRGAFSYVKRVIQKAGKLEYAAK--FISARAKRKASAL-RELNILSHLDHERILYFHDAFEKKNAVIIITELCHE-E 1741
Cdd:cd06606      6 ELLGKGSFGSVYLALNLDTGELMAVKevELSGDSEEELEALeREIRILSSLKHPNIVRYLGTERTENTLNIFLEYVPGgS 85

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1742 LLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMAdhSSDQIRICDFGNAVKF---MPDEAQYCKYG 1818
Cdd:cd06606     86 LASLLKKFGKLPEPVVRKYTRQILEGLEYLHSNGIVHRDIKGANILVD--SDGVVKLADFGCAKRLaeiATGEGTKSLRG 163

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1819 TPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLnirnYNVAFEES---MFTDLCHEAKGFVIKLL 1895
Cdd:cd06606    164 TPYWMAPEVIRGEGYGRAADIWSLGCTVIEMATGKPPWSELGNPVAAL----FKIGSSGEpppIPEHLSEEAKDFLRKCL 239

                          250
                   ....*....|....*....
gi 1207186029 1896 VAD-RLRPDANECLRHPWF 1913
Cdd:cd06606    240 QRDpKKRPTADELLQHPFL 258

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409405 [Multi-domain] Cd Length: 91 Bit Score: 145.33 E-value: 2.02e-40

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1123 PLFTRKLDVLEVIEGRNARFDCKVSGTPPPQVIWSHFDRPLEEN-EDIRILKEGGRHSLIISHVSNEDEGLYTVAARNSH 1201
Cdd:cd05744      1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDsAHKMLVRENGRHSLIIEPVTKRDAGIYTCIARNRA 80

                           90
                   ....*....|.
gi 1207186029 1202 GEDECAAELYV 1212
Cdd:cd05744     81 GENSFNAELVV 91

Catalytic domain of STE family Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. This family is composed of STKs, and some dual-specificity PKs that phosphorylate both threonine and tyrosine residues of target proteins. Most members are kinases involved in mitogen-activated protein kinase (MAPK) signaling cascades, acting as MAPK kinases (MAPKKs), MAPKK kinases (MAPKKKs), or MAPKKK kinases (MAP4Ks). The MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising of the MAPK, which is phosphorylated and activated by a MAPKK, which itself is phosphorylated and activated by a MAPKKK. Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAPKKK to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Other STE family members include p21-activated kinases (PAKs) and class III myosins, among others. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain, which can phosphorylate several cytoskeletal proteins, conventional myosin regulatory light chains, as well as autophosphorylate the C-terminal motor domain. They play an important role in maintaining the structural integrity of photoreceptor cell microvilli. The STE family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270692 [Multi-domain] Cd Length: 254 Bit Score: 151.59 E-value: 2.29e-40

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1661 YYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISAR-AKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITELCH 1739
Cdd:cd05122      1 LFEILEKIGKGGFGVVYKARHKKTGQIVAIKKINLEsKEKKESILNEIAILKKCKHPNIVKYYGSYLKKDELWIVMEFCS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1740 ----EELLDrlTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMadhSSD-QIRICDFGNAVKFMPDEAQY 1814
Cdd:cd05122     81 ggslKDLLK--NTNKTLTEQQIAYVCKEVLKGLEYLHSHGIIHRDIKAANILL---TSDgEVKLIDFGLSAQLSDGKTRN 155

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1815 CKYGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFaGENDRSSVLNIRNYNVA--FEESMFTDLchEAKGFVI 1892
Cdd:cd05122    156 TFVGTPYWMAPEVIQGKPYGFKADIWSLGITAIEMAEGKPPY-SELPPMKALFLIATNGPpgLRNPKKWSK--EFKDFLK 232

                          250       260
                   ....*....|....*....|..
gi 1207186029 1893 KLLVAD-RLRPDANECLRHPWF 1913
Cdd:cd05122    233 KCLQKDpEKRPTAEQLLKHPFI 254

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-beta subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271071 [Multi-domain] Cd Length: 277 Bit Score: 152.35 E-value: 2.31e-40

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASAL--RELNILSHLDHERILYFHDAFEKKNAVIIITELCH 1739
Cdd:cd14169      5 YELKEKLGEGAFSEVVLAQERGSQRLVALKCIPKKALRGKEAMveNEIAVLRRINHENIVSLEDIYESPTHLYLAMELVT 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1740 E-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSD-QIRICDFGNAvKFMPDEAQYCKY 1817
Cdd:cd14169     85 GgELFDRIIERGSYTEKDASQLIGQVLQAVKYLHQLGIVHRDLKPENLLYATPFEDsKIMISDFGLS-KIEAQGMLSTAC 163

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1818 GTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDLCHEAKGFVIKLLVA 1897
Cdd:cd14169    164 GTPGYVAPELLEQKPYGKAVDVWAIGVISYILLCGYPPFYDENDSELFNQILKAEYEFDSPYWDDISESAKDFIRHLLER 243

                          250
                   ....*....|....*.
gi 1207186029 1898 D-RLRPDANECLRHPW 1912
Cdd:cd14169    244 DpEKRFTCEQALQHPW 259

Catalytic domain of Brain-specific serine/threonine-protein kinases 1 and 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BRSK1, also called SAD-B or SAD1 (Synapses of Amphids Defective homolog 1), and BRSK2, also called SAD-A, are highly expressed in mammalian forebrain. They play important roles in establishing neuronal polarity. BRSK1/2 double knock-out mice die soon after birth, showing thin cerebral cortices due to disordered subplate layers and neurons that lack distinct axons and dendrites. BRSK1 regulates presynaptic neurotransmitter release. Its activity fluctuates during cell cysle progression and it acts as a regulator of centrosome duplication. BRSK2 is also abundant in pancreatic islets, where it is involved in the regulation of glucose-stimulated insulin secretion. The BRSK1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270983 [Multi-domain] Cd Length: 255 Bit Score: 150.87 E-value: 3.43e-40

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKIVPYEPESKQTVLQ----EYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLH 3383
Cdd:cd14081     11 KGQTGLVKLAKHCVTGQKVAIKIVNKEKLSKESVLMkverEIAIMKLIEHPNVLKLYDVYENKKYLYLVLEYVSGGELFD 90

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3384 SLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLKQFSppIGTLDYMS 3463
Cdd:cd14081     91 YLVKKGRLTEKEARKFFRQIISALDYCHSHSICHRDLKPENLLLDEKNNIKIADFGMASLQPEGSLLETS--CGSPHYAC 168

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3464 PEMLKGDVV-GPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLSklyQNVSQSASLFIKKILCSYPWARPT 3542
Cdd:cd14081    169 PEVIKGEKYdGRKADIWSCGVILYALLVGALPFDDDNLRQLLEKVKRGVFHIP---HFISPDAQDLLRRMLEVNPEKRIT 245

                          250
                   ....*....|
gi 1207186029 3543 IKDCFTNSWL 3552
Cdd:cd14081    246 IEEIKKHPWF 255

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK1 (or MYLK1) phosphorylates myosin regulatory light chain and controls the contraction of smooth muscles. The MLCK1 gene expresses three transcripts in a cell-specific manner: a short MLCK1 which contains three immunoglobulin (Ig)-like and one fibronectin type III (FN3) domains, PEVK and actin-binding regions, and a kinase domain near the C-terminus followed by a regulatory segment containing an autoinhibitory Ca2+/calmodulin binding site; a long MLCK1 containing six additional Ig-like domains at the N-terminus compared to the short MLCK1; and the C-terminal Ig module which results in the expression of telokin in phasic smooth muscles, leading to Ca2+ desensitization by cyclic nucleotides of smooth muscle force. MLCK1 is also responsible for myosin regulatory light chain phosphorylation in nonmuscle cells and may play a role in regulating myosin II ATPase activity. The MLCK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271093 [Multi-domain] Cd Length: 259 Bit Score: 150.92 E-value: 4.94e-40

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIV-PYEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSG 3378
Cdd:cd14191      4 YDIEERLGSGKFGQVFRLVEKKTKKVWAGKFFkAYSAKEKENIRQEISIMNCLHHPKLVQCVDAFEEKANIVMVLEMVSG 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3379 KELLHSLIDR-FRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYM--NVVKIIDFGSAQTF-NPLFLKQFsp 3454
Cdd:cd14191     84 GELFERIIDEdFELTERECIKYMRQISEGVEYIHKQGIVHLDLKPENIMCVNKtgTKIKLIDFGLARRLeNAGSLKVL-- 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3455 pIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLS-KLYQNVSQSASLFIKKIL 3533
Cdd:cd14191    162 -FGTPEFVAPEVINYEPIGYATDMWSIGVICYILVSGLSPFMGDNDNETLANVTSATWDFDdEAFDEISDDAKDFISNLL 240

                          250
                   ....*....|....*....
gi 1207186029 3534 CSYPWARPTIKDCFTNSWL 3552
Cdd:cd14191    241 KKDMKARLTCTQCLQHPWL 259

Protein kinase domain;

Pssm-ID: 459660 [Multi-domain] Cd Length: 217 Bit Score: 148.93 E-value: 5.11e-40

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFI---SARAKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITELC 1738
Cdd:pfam00069    1 YEVLRKLGSGSFGTVYKAKHRDTGKIVAIKKIkkeKIKKKKDKNILREIKILKKLNHPNIVRLYDAFEDKDNLYLVLEYV 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1739 H-EELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDilhldikpdnilmadhssdqiricdfgnavkfmpdeaQYCky 1817
Cdd:pfam00069   81 EgGSLFDLLSEKGAFSEREAKFIMKQILEGLESGSSLT-------------------------------------TFV-- 121

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1818 GTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNynvafEESMFTDLCH----EAKGFVIK 1893
Cdd:pfam00069  122 GTPWYMAPEVLGGNPYGPKVDVWSLGCILYELLTGKPPFPGINGNEIYELIID-----QPYAFPELPSnlseEAKDLLKK 196

                          250       260
                   ....*....|....*....|.
gi 1207186029 1894 LLVAD-RLRPDANECLRHPWF 1913
Cdd:pfam00069  197 LLKKDpSKRLTATQALQHPWF 217

Catalytic domain of the Serine/Threonine Kinase, Phosphoinositide-dependent kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PDK1 carries an N-terminal catalytic domain and a C-terminal pleckstrin homology (PH) domain that binds phosphoinositides. It phosphorylates the activation loop of AGC kinases that are regulated by PI3K such as PKB, SGK, and PKC, among others, and is crucial for their activation. Thus, it contributes in regulating many processes including metabolism, growth, proliferation, and survival. PDK1 also has the ability to autophosphorylate and is constitutively active in mammalian cells. It is essential for normal embryo development and is important in regulating cell volume. The PDK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270733 [Multi-domain] Cd Length: 278 Bit Score: 151.21 E-value: 5.99e-40

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISA----RAKRKASALRELNILSHLDHERI--LYFHdaFEKKNAVIIIT 1735
Cdd:cd05581      3 FKFGKPLGEGSYSTVVLAKEKETGKEYAIKVLDKrhiiKEKKVKYVTIEKEVLSRLAHPGIvkLYYT--FQDESKLYFVL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1736 ELC-HEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMAD--HssdqIRICDFGNA-------- 1804
Cdd:cd05581     81 EYApNGDLLEYIRKYGSLDEKCTRFYTAEIVLALEYLHSKGIIHRDLKPENILLDEdmH----IKITDFGTAkvlgpdss 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1805 ------VKFMPDEAQYCK----YGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVA 1874
Cdd:cd05581    157 pestkgDADSQIAYNQARaasfVGTAEYVSPELLNEKPAGKSSDLWALGCIIYQMLTGKPPFRGSNEYLTFQKIVKLEYE 236

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*.
gi 1207186029 1875 FEESMFTDlcheAKGFVIKLLVAD---RL----RPDANECLRHPWF 1913
Cdd:cd05581    237 FPENFPPD----AKDLIQKLLVLDpskRLgvneNGGYDELKAHPFF 278

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase Kinase Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPKKKs (MKKKs or MAP3Ks) are also called MAP/ERK kinase kinases (MEKKs) in some cases. They phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. This subfamily is composed of the Apoptosis Signal-regulating Kinases ASK1 (or MAPKKK5) and ASK2 (or MAPKKK6), MEKK1, MEKK2, MEKK3, MEKK4, as well as plant and fungal MAPKKKs. Also included in this subfamily are the cell division control proteins Schizosaccharomyces pombe Cdc7 and Saccharomyces cerevisiae Cdc15. The MAPKKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270783 [Multi-domain] Cd Length: 258 Bit Score: 149.98 E-value: 8.27e-40

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKIVPYEPESKQTV---LQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELlHS 3384
Cdd:cd06606     10 KGSFGSVYLALNLDTGELMAVKEVELSGDSEEELealEREIRILSSLKHPNIVRYLGTERTENTLNIFLEYVPGGSL-AS 88

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3385 LIDRF-RYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSA-QTFNPLFLKQFSPPIGTLDYM 3462
Cdd:cd06606     89 LLKKFgKLPEPVVRKYTRQILEGLEYLHSNGIVHRDIKGANILVDSDGVVKLADFGCAkRLAEIATGEGTKSLRGTPYWM 168

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3463 SPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTE-NDPAETEARIQAAKfDLSKLYQNVSQSASLFIKKILCSYPWARP 3541
Cdd:cd06606    169 APEVIRGEGYGRAADIWSLGCTVIEMATGKPPWSElGNPVAALFKIGSSG-EPPPIPEHLSEEAKDFLRKCLQRDPKKRP 247


                   ....
gi 1207186029 3542 TIKD 3545
Cdd:cd06606    248 TADE 251

Catalytic domain of the Serine/Threonine kinases, Liver Kinase B1, Calmodulin Dependent Protein Kinase Kinase, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Both LKB1 and CaMKKs can phosphorylate and activate AMP-activated protein kinase (AMPK). LKB1, also called STK11, serves as a master upstream kinase that activates AMPK and most AMPK-like kinases. LKB1 and AMPK are part of an energy-sensing pathway that links cell energy to metabolism and cell growth. They play critical roles in the establishment and maintenance of cell polarity, cell proliferation, cytoskeletal organization, as well as T-cell metabolism, including T-cell development, homeostasis, and effector function. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMPK. Vertebrates contain two CaMKKs, CaMKK1 (or alpha) and CaMKK2 (or beta). CaMKK1 is involved in the regulation of glucose uptake in skeletal muscles. CaMKK2 is involved in regulating energy balance, glucose metabolism, adiposity, hematopoiesis, inflammation, and cancer. The LKB1/CaMKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270910 [Multi-domain] Cd Length: 267 Bit Score: 148.86 E-value: 2.69e-39

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYVKRVIQKAGKLEYAAKFISARAKRK-----------ASAL----RELNILSHLDHERI--LY--FHDAFEKK 1728
Cdd:cd14008      1 LGRGSFGKVKLALDTETGQLYAIKIFNKSRLRKrregkndrgkiKNALddvrREIAIMKKLDHPNIvrLYevIDDPESDK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1729 naVIIITELCHE---ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMAdhSSDQIRICDFGNAv 1805
Cdd:cd14008     81 --LYLVLEYCEGgpvMELDSGDRVPPLPEETARKYFRDLVLGLEYLHENGIVHRDIKPENLLLT--ADGTVKISDFGVS- 155

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1806 KFMPDEAQYCK--YGTPEFVAPEI--VNQTPVS-KATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMf 1880
Cdd:cd14008    156 EMFEDGNDTLQktAGTPAFLAPELcdGDSKTYSgKAADIWALGVTLYCLVFGRLPFNGDNILELYEAIQNQNDEFPIPP- 234

                          250       260       270
                   ....*....|....*....|....*....|....
gi 1207186029 1881 tDLCHEAKGFVIKLLVAD-RLRPDANECLRHPWF 1913
Cdd:cd14008    235 -ELSPELKDLLRRMLEKDpEKRITLKEIKEHPWV 267

Pseudokinase domain, first repeat, of the Giant Serine/Threonine Kinase Uncoordinated protein 89; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. The nematode Unc-89 gene, through alternative promoter use and splicing, encodes at least six major isoforms (Unc-89A to Unc-89F) of giant muscle proteins that are homologs for the vetebrate obscurin. In flies, five isoforms of Unc-89 have been detected: four in the muscles of adult flies (two in the indirect flight muscle and two in other muscles) and another isoform in the larva. Unc-89 in nematodes is required for normal muscle cell architecture. In flies, it is necessary for the development of a symmetrical sarcomere in the flight muscles. Unc-89 proteins contain several adhesion and signaling domains including multiple copies of the immunoglobulin (Ig) domain, as well as fibronectin type III (FN3), SH3, RhoGEF, and PH domains. The nematode Unc-89 isoforms D, C, D, and F contain two kinase domain with B and F having two complete kinase domains while the first repeat of C and D are partial domains. Homology modeling suggests that the first kinase repeat of Unc-89 may be catalytically inactive, a pseudokinase, while the second kinase repeat may be active. The pseudokinase domain may function as a regulatory domain or a protein interaction domain. The Unc-89 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271011 [Multi-domain] Cd Length: 255 Bit Score: 148.04 E-value: 4.04e-39

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3304 DEKaRGRFGVIRECRENATGNLYMAKIVPYEPeskqTVLQEYDILKSLHHEKIMALHEAYVT-PRYLVLISECCSGKELL 3382
Cdd:cd14109     11 DEK-RAAQGAPFHVTERSTGRNFLAQLRYGDP----FLMREVDIHNSLDHPNIVQMHDAYDDeKLAVTVIDNLASTIELV 85

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3383 HSLIDRFR--YSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYmNVVKIIDFGSAQTFNPLFLkqFSPPIGTLD 3460
Cdd:cd14109     86 RDNLLPGKdyYTERQVAVFVRQLLLALKHMHDLGIAHLDLRPEDILLQD-DKLKLADFGQSRRLLRGKL--TTLIYGSPE 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3461 YMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDL-SKLYQNVSQSASLFIKKILCSYPWA 3539
Cdd:cd14109    163 FVSPEIVNSYPVTLATDMWSVGVLTYVLLGGISPFLGDNDRETLTNVRSGKWSFdSSPLGNISDDARDFIKKLLVYIPES 242

                          250
                   ....*....|...
gi 1207186029 3540 RPTIKDCFTNSWL 3552
Cdd:cd14109    243 RLTVDEALNHPWF 255

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I delta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-delta subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271070 [Multi-domain] Cd Length: 301 Bit Score: 149.04 E-value: 5.99e-39

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1653 RKMRRLTDYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARA-KRKASALR-ELNILSHLDHERILYFHDAFEKKNA 1730
Cdd:cd14168      3 KQVEDIKKIFEFKEVLGTGAFSEVVLAEERATGKLFAVKCIPKKAlKGKESSIEnEIAVLRKIKHENIVALEDIYESPNH 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1731 VIIITELCHE-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNIL-MADHSSDQIRICDFGNAVKFM 1808
Cdd:cd14168     83 LYLVMQLVSGgELFDRIVEKGFYTEKDASTLIRQVLDAVYYLHRMGIVHRDLKPENLLyFSQDEESKIMISDFGLSKMEG 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1809 PDEAQYCKYGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDLCHEAK 1888
Cdd:cd14168    163 KGDVMSTACGTPGYVAPEVLAQKPYSKAVDCWSIGVIAYILLCGYPPFYDENDSKLFEQILKADYEFDSPYWDDISDSAK 242

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1207186029 1889 GFVIKLLVAD-RLRPDANECLRHPWF---KTLNKG--KSISTESLKKFlSRRKWQRSL 1940
Cdd:cd14168    243 DFIRNLMEKDpNKRYTCEQALRHPWIagdTALCKNihESVSAQIRKNF-AKSKWRQAF 299

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type II; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. CaMKs contain an N-terminal catalytic domain followed by a regulatory domain that harbors a CaM binding site. In addition, CaMKII contains a C-terminal association domain that facilitates oligomerization. There are four CaMKII proteins (alpha, beta, gamma, delta) encoded by different genes; each gene undergoes alternative splicing to produce more than 30 isoforms. CaMKII-alpha and -beta are enriched in neurons while CaMKII-gamma and -delta are predominant in myocardium. CaMKII is a signaling molecule that translates upstream calcium and reactive oxygen species (ROS) signals into downstream responses that play important roles in synaptic function and cardiovascular physiology. It is a major component of the postsynaptic density and is critical in regulating synaptic plasticity including long-term potentiation. It is critical in regulating ion channels and proteins involved in myocardial excitation-contraction and excitation-transcription coupling. Excessive CaMKII activity promotes processes that contribute to heart failure and arrhythmias. The CaMKII subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270988 [Multi-domain] Cd Length: 292 Bit Score: 147.57 E-value: 1.43e-38

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPESK---QTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECC 3376
Cdd:cd14086      3 YDLKEELGKGAFSVVRRCVQKSTGQEFAAKIINTKKLSArdhQKLEREARICRLLKHPNIVRLHDSISEEGFHYLVFDLV 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3377 SGKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMN---VVKIIDFGSA---QTFNPLFLK 3450
Cdd:cd14086     83 TGGELFEDIVAREFYSEADASHCIQQILESVNHCHQNGIVHRDLKPENLLLASKSkgaAVKLADFGLAievQGDQQAWFG 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3451 qFSppiGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDL-SKLYQNVSQSASLFI 3529
Cdd:cd14086    163 -FA---GTPGYLSPEVLRKDPYGKPVDIWACGVILYILLVGYPPFWDEDQHRLYAQIKAGAYDYpSPEWDTVTPEAKDLI 238

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*...
gi 1207186029 3530 KKILCSYPWARPTIKDCFTNSWL--QDAYLMRLRRQTltfTTTRLKEF 3575
Cdd:cd14086    239 NQMLTVNPAKRITAAEALKHPWIcqRDRVASMVHRQE---TVDCLKKF 283

Catalytic domain of Fungal Halotolerance protein 4-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of HAL4, Saccharomyces cerevisiae Ptk2/Stk2, and similar fungal proteins. Proteins in this subfamily are involved in regulating ion transporters. In budding and fission yeast, HAL4 promotes potassium ion uptake, which increases cellular resistance to other cations such as sodium, lithium, and calcium ions. HAL4 stabilizes the major high-affinity K+ transporter Trk1 at the plasma membrane under low K+ conditions, which prevents endocytosis and vacuolar degradation. Budding yeast Ptk2 phosphorylates and regulates the plasma membrane H+ ATPase, Pma1. The HAL4-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270896 [Multi-domain] Cd Length: 265 Bit Score: 146.68 E-value: 1.47e-38

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3307 ARGRFGVIREC--RENATGNLYMAKIV--PYEPESKQ----TVLQEYDILKSLHHEKIMALHEAYVTP-RYLVLISECCS 3377
Cdd:cd13994      2 GKGATSVVRIVtkKNPRSGVLYAVKEYrrRDDESKRKdyvkRLTSEYIISSKLHHPNIVKVLDLCQDLhGKWCLVMEYCP 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3378 GKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLKQ---FSP 3454
Cdd:cd13994     82 GGDLFTLIEKADSLSLEEKDCFFKQILRGVAYLHSHGIAHRDLKPENILLDEDGVLKLTDFGTAEVFGMPAEKEspmSAG 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3455 PIGTLDYMSPE-MLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPaeTEARIQAAKFDLSKLYQNVSQSASLF----- 3528
Cdd:cd13994    162 LCGSEPYMAPEvFTSGSYDGRAVDVWSCGIVLFALFTGRFPWRSAKK--SDSAYKAYEKSGDFTNGPYEPIENLLpsecr 239

                          250       260
                   ....*....|....*....|....*.
gi 1207186029 3529 --IKKILCSYPWARPTIKDCFTNSWL 3552
Cdd:cd13994    240 rlIYRMLHPDPEKRITIDEALNDPWV 265

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Nek family is composed of 11 different mammalian members (Nek1-11) with similarity to the catalytic domain of Aspergillus nidulans NIMA kinase, the founding member of the Nek family, which was identified in a screen for cell cycle mutants that were prevented from entering mitosis. Neks contain a conserved N-terminal catalytic domain and a more divergent C-terminal regulatory region of various sizes and structures. They are involved in the regulation of downstream processes following the activation of Cdc2, and many of their functions are cell cycle-related. They play critical roles in microtubule dynamics during ciliogenesis and mitosis. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270855 [Multi-domain] Cd Length: 258 Bit Score: 146.07 E-value: 1.69e-38

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISAR---AKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITELC 1738
Cdd:cd08215      2 YEKIRVIGKGSFGSAYLVRRKSDGKLYVLKEIDLSnmsEKEREEALNEVKLLSKLKHPNIVKYYESFEENGKLCIVMEYA 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1739 -----HEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHssDQIRICDFGNAvKFMPDEAQ 1813
Cdd:cd08215     82 dggdlAQKIKKQKKKGQPFPEEQILDWFVQICLALKYLHSRKILHRDLKTQNIFLTKD--GVVKLGDFGIS-KVLESTTD 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1814 YCK--YGTPEFVAPEIVNQTPVSKATDIWPIGVLTY-LClTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDlchEAKGF 1890
Cdd:cd08215    159 LAKtvVGTPYYLSPELCENKPYNYKSDIWALGCVLYeLC-TLKHPFEANNLPALVYKIVKGQYPPIPSQYSS---ELRDL 234

                          250       260
                   ....*....|....*....|..
gi 1207186029 1891 VIKLLVAD-RLRPDANECLRHP 1911
Cdd:cd08215    235 VNSMLQKDpEKRPSANEILSSP 256

Catalytic domain of the Serine/Threonine Kinase, Death-associated protein kinase-Related Apoptosis-inducing protein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DRAKs were named based on their similarity (around 50% identity) to the kinase domain of DAPKs. They contain an N-terminal kinase domain and a C-terminal regulatory domain. Vertebrates contain two subfamily members, DRAK1 (also called STK17A) and DRAK2. Both DRAKs are localized to the nucleus, autophosphorylate themselves, and phosphorylate myosin light chain as a substrate. Rabbit DRAK1 has been shown to induce apoptosis in osteoclasts and overexpressio of human DRAK1 induces apoptosis in cultured fibroblast cells. DRAK1 may be involved in apoptotic signaling. The DRAK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271099 [Multi-domain] Cd Length: 271 Bit Score: 146.62 E-value: 1.80e-38

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3305 EKARGRFGVIRECRENATGNLYMAKIVPYE---PESKQTVLQEYDILK-SLHHEKIMALHEAYVTPRYLVLISECCSGKE 3380
Cdd:cd14197     16 ELGRGKFAVVRKCVEKDSGKEFAAKFMRKRrkgQDCRMEIIHEIAVLElAQANPWVINLHEVYETASEMILVLEYAAGGE 95

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3381 LLHSLI-DRFR-YSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTY---MNVVKIIDFGSAQTFNPLflKQFSPP 3455
Cdd:cd14197     96 IFNQCVaDREEaFKEKDVKRLMKQILEGVSFLHNNNVVHLDLKPQNILLTSespLGDIKIVDFGLSRILKNS--EELREI 173

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3456 IGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLS-KLYQNVSQSASLFIKKILC 3534
Cdd:cd14197    174 MGTPEYVAPEILSYEPISTATDMWSIGVLAYVMLTGISPFLGDDKQETFLNISQMNVSYSeEEFEHLSESAIDFIKTLLI 253

                          250
                   ....*....|....*...
gi 1207186029 3535 SYPWARPTIKDCFTNSWL 3552
Cdd:cd14197    254 KKPENRATAEDCLKHPWL 271

Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 2 subunit; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phosphorylase kinase (PhK) catalyzes the phosphorylation of inactive phosphorylase b to form the active phosphorylase a. It coordinates hormonal, metabolic, and neuronal signals to initiate the breakdown of glycogen stores, which enables the maintenance of blood-glucose homeostasis during fasting, and is also used as a source of energy for muscle contraction. PhK is one of the largest and most complex protein kinases, composed of a heterotetramer containing four molecules each of four subunit types: one catalytic (gamma) and three regulatory (alpha, beta, and delta). The gamma 2 subunit (PhKG2) is also referred to as the testis/liver gamma isoform. Mutations in its gene cause autosomal-recessive glycogenosis of the liver. The gamma subunit, when isolated, is constitutively active and does not require phosphorylation of the A-loop for activity. The regulatory subunits restrain this kinase activity until signals are received to relieve this inhibition. For example, the kinase is activated in response to hormonal stimulation, after autophosphorylation or phosphorylation by cAMP-dependent kinase of the alpha and beta subunits. The high-affinity binding of ADP to the beta subunit also stimulates kinase activity, whereas calcium relieves inhibition by binding to the delta (calmodulin) subunit. The PhKG2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271083 [Multi-domain] Cd Length: 279 Bit Score: 147.04 E-value: 1.81e-38

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKR---------KASALRELNILSHL-DHERILYFHDAFEKKNAV 1731
Cdd:cd14181     12 YDPKEVIGRGVSSVVRRCVHRHTGQEFAVKIIEVTAERlspeqleevRSSTLKEIHILRQVsGHPSIITLIDSYESSTFI 91

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1732 IIITELCHE-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSsdQIRICDFGNAVKFMPD 1810
Cdd:cd14181     92 FLVFDLMRRgELFDYLTEKVTLSEKETRSIMRSLLEAVSYLHANNIVHRDLKPENILLDDQL--HIKLSDFGFSCHLEPG 169

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1811 EAQYCKYGTPEFVAPEIV------NQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDLC 1884
Cdd:cd14181    170 EKLRELCGTPGYLAPEILkcsmdeTHPGYGKEVDLWACGVILFTLLAGSPPFWHRRQMLMLRMIMEGRYQFSSPEWDDRS 249

                          250       260       270
                   ....*....|....*....|....*....|
gi 1207186029 1885 HEAKGFVIKLLVAD-RLRPDANECLRHPWF 1913
Cdd:cd14181    250 STVKDLISRLLVVDpEIRLTAEQALQHPFF 279

Catalytic domain of CMGC family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The CMGC family consists of Cyclin-Dependent protein Kinases (CDKs), Mitogen-activated protein kinases (MAPKs) such as Extracellular signal-regulated kinase (ERKs), c-Jun N-terminal kinases (JNKs), and p38, and other kinases. CDKs belong to a large subfamily of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. MAPKs serve as important mediators of cellular responses to extracellular signals. They control critical cellular functions including differentiation, proliferation, migration, and apoptosis. They are also implicated in the pathogenesis of many diseases including multiple types of cancer, stroke, diabetes, and chronic inflammation. Other members of the CMGC family include casein kinase 2 (CK2), Dual-specificity tYrosine-phosphorylated and -Regulated Kinase (DYRK), Glycogen Synthase Kinase 3 (GSK3), among many others. The CMGC family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270688 [Multi-domain] Cd Length: 249 Bit Score: 144.68 E-value: 4.23e-38

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASALRELNILSHL----DHERILYFHDAFE--KKNAVIIIT 1735
Cdd:cd05118      1 YEVLRKIGEGAFGTVWLARDKVTGEKVAIKKIKNDFRHPKAALREIKLLKHLndveGHPNIVKLLDVFEhrGGNHLCLVF 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1736 ELCHEELLDRLTKKSTIL-ESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMaDHSSDQIRICDFGNAVKFMPDEaqY 1814
Cdd:cd05118     81 ELMGMNLYELIKDYPRGLpLDLIKSYLYQLLQALDFLHSNGIIHRDLKPENILI-NLELGQLKLADFGLARSFTSPP--Y 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1815 CKYGTP-EFVAPE-IVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRnynvafeESMFTDlchEAKGFVI 1892
Cdd:cd05118    158 TPYVATrWYRAPEvLLGAKPYGSSIDIWSLGCILAELLTGRPLFPGDSEVDQLAKIV-------RLLGTP---EALDLLS 227

                          250       260
                   ....*....|....*....|..
gi 1207186029 1893 KLLVAD-RLRPDANECLRHPWF 1913
Cdd:cd05118    228 KMLKYDpAKRITASQALAHPYF 249

Catalytic kinase domain, second repeat, of the Giant Serine/Threonine Kinase Uncoordinated protein 89; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The nematode Unc-89 gene, through alternative promoter use and splicing, encodes at least six major isoforms (Unc-89A to Unc-89F) of giant muscle proteins that are homologs for the vetebrate obscurin. In flies, five isoforms of Unc-89 have been detected: four in the muscles of adult flies (two in the indirect flight muscle and two in other muscles) and another isoform in the larva. Unc-89 in nematodes is required for normal muscle cell architecture. In flies, it is necessary for the development of a symmetrical sarcomere in the flight muscles. Unc-89 proteins contain several adhesion and signaling domains including multiple copies of the immunoglobulin (Ig) domain, as well as fibronectin type III (FN3), SH3, RhoGEF, and PH domains. The nematode Unc-89 isoforms D, C, D, and F contain two kinase domain with B and F having two complete kinase domains while the first repeat of C and D are partial domains. Homology modeling suggests that the first kinase repeat of Unc-89 may be catalytically inactive, a pseudokinase, while the second kinase repeat may be active. The Unc-89 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271014 [Multi-domain] Cd Length: 259 Bit Score: 144.98 E-value: 4.60e-38

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1659 TDYYDVHKEIGRGAFSYVKRVIQKAGKLEY--AAKfISARAKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITE 1736
Cdd:cd14112      2 TGRFSFGSEIFRGRFSVIVKAVDSTTETDAhcAVK-IFEVSDEASEAVREFESLRTLQHENVQRLIAAFKPSNFAYLVME 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1737 LCHEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSDQIRICDFGNAVKFMPdEAQYCK 1816
Cdd:cd14112     81 KLQEDVFTRFSSNDYYSEEQVATTVRQILDALHYLHFKGIAHLDVQPDNIMFQSVRSWQVKLVDFGRAQKVSK-LGKVPV 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1817 YGTPEFVAPEIVN-QTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSvlNIRNyNVAFE----ESMFTDLCHEAKGFV 1891
Cdd:cd14112    160 DGDTDWASPEFHNpETPITVQSDIWGLGVLTFCLLSGFHPFTSEYDDEE--ETKE-NVIFVkcrpNLIFVEATQEALRFA 236

                          250       260
                   ....*....|....*....|..
gi 1207186029 1892 IKLLV-ADRLRPDANECLRHPW 1912
Cdd:cd14112    237 TWALKkSPTRRMRTDEALEHRW 258

Catalytic domain of testis-specific serine/threonine kinases and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK1 and TSSK2 are expressed specifically in meiotic and postmeiotic spermatogenic cells, respectively. TSSK3 has been reported to be expressed in the interstitial Leydig cells of adult testis. TSSK4, also called TSSK5, is expressed in testis from haploid round spermatids to mature spermatozoa. TSSK6, also called SSTK, is expressed at the head of elongated sperm. TSSK1/TSSK2 double knock-out and TSSK6 null mice are sterile without manifesting other defects, making these kinases viable targets for male contraception. The TSSK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270982 [Multi-domain] Cd Length: 262 Bit Score: 145.02 E-value: 5.51e-38

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRV--IQKAGKLEYAAKFISaraKRKASA------L-RELNILSHLDHERILYFHDAFEKKNAVI 1732
Cdd:cd14080      2 YRLGKTIGEGSYSKVKLAeyTKSGLKEKVACKIID---KKKAPKdflekfLpRELEILRKLRHPNIIQVYSIFERGSKVF 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1733 IITELC-HEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMAdhSSDQIRICDFGNAVKFMPDE 1811
Cdd:cd14080     79 IFMEYAeHGDLLEYIQKRGALSESQARIWFRQLALAVQYLHSLDIAHRDLKCENILLD--SNNNVKLSDFGFARLCPDDD 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1812 AQ-----YCkyGTPEFVAPEIVNQTPVS-KATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMfTDLCH 1885
Cdd:cd14080    157 GDvlsktFC--GSAAYAAPEILQGIPYDpKKYDIWSLGVILYIMLCGSMPFDDSNIKKMLKDQQNRKVRFPSSV-KKLSP 233

                          250       260
                   ....*....|....*....|....*....
gi 1207186029 1886 EAKGFVIKLLVAD-RLRPDANECLRHPWF 1913
Cdd:cd14080    234 ECKDLIDQLLEPDpTKRATIEEILNHPWL 262

Catalytic domain of the Serine/Threonine Kinases, Polo-like kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. PLKs derive their names from homology to polo, a kinase first identified in Drosophila. There are five mammalian PLKs (PLK1-5) from distinct genes. There is good evidence that PLK1 may function as an oncogene while PLK2-5 have tumor suppressive properties. PLK1 functions as a positive regulator of mitosis, meiosis, and cytokinesis. PLK2 functions in G1 progression, S-phase arrest, and centriole duplication. PLK3 regulates angiogenesis and responses to DNA damage. PLK4 is required for late mitotic progression, cell survival, and embryonic development. PLK5 was first identified as a pseudogene containing a stop codon within the kinase domain, however, both murine and human genes encode expressed proteins. PLK5 functions in cell cycle arrest.

Pssm-ID: 271001 [Multi-domain] Cd Length: 258 Bit Score: 143.85 E-value: 9.84e-38

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKIVP----YEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLH 3383
Cdd:cd14099     11 KGGFAKCYEVTDMSTGKVYAGKVVPksslTKPKQREKLKSEIKIHRSLKHPNIVKFHDCFEDEENVYILLELCSNGSLME 90

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3384 SLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVT-YMNvVKIIDFGSAQTFNPLFLKQFSppI-GTLDY 3461
Cdd:cd14099     91 LLKRRKALTEPEVRYFMRQILSGVKYLHSNRIIHRDLKLGNLFLDeNMN-VKIGDFGLAARLEYDGERKKT--LcGTPNY 167

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3462 MSPEMLKGDVV-GPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLSKlYQNVSQSASLFIKKILCSYPWAR 3540
Cdd:cd14099    168 IAPEVLEKKKGhSFEVDIWSLGVILYTLLVGKPPFETSDVKETYKRIKKNEYSFPS-HLSISDEAKDLIRSMLQPDPTKR 246

                          250
                   ....*....|..
gi 1207186029 3541 PTIKDCFTNSWL 3552
Cdd:cd14099    247 PSLDEILSHPFF 258

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270985 [Multi-domain] Cd Length: 259 Bit Score: 144.05 E-value: 9.96e-38

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3298 KPYTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEP-ESKQTVLQ-EYDILKSLHHEKIMALHEAYVTPRYLVLISEC 3375
Cdd:cd14083      3 DKYEFKEVLGTGAFSEVVLAEDKATGKLVAIKCIDKKAlKGKEDSLEnEIAVLRKIKHPNIVQLLDIYESKSHLYLVMEL 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3376 CSGKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIvtYMNV-----VKIIDFGSAQTFNPLFLk 3450
Cdd:cd14083     83 VTGGELFDRIVEKGSYTEKDASHLIRQVLEAVDYLHSLGIVHRDLKPENLL--YYSPdedskIMISDFGLSKMEDSGVM- 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3451 qfSPPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDL-SKLYQNVSQSASLFI 3529
Cdd:cd14083    160 --STACGTPGYVAPEVLAQKPYGKAVDCWSIGVISYILLCGYPPFYDENDSKLFAQILKAEYEFdSPYWDDISDSAKDFI 237

                          250       260
                   ....*....|....*....|..
gi 1207186029 3530 KKILCSYPWARPTIKDCFTNSW 3551
Cdd:cd14083    238 RHLMEKDPNKRYTCEQALEHPW 259

Catalytic kinase domain, first repeat, of Giant Serine/Threonine Kinase Striated muscle preferentially expressed protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Striated muscle preferentially expressed gene (SPEG) generates 4 different isoforms through alternative promoter use and splicing in a tissue-specific manner: SPEGalpha and SPEGbeta are expressed in cardiac and skeletal striated muscle; Aortic Preferentially Expressed Protein-1 (APEG-1) is expressed in vascular smooth muscle; and Brain preferentially expressed gene (BPEG) is found in the brain and aorta. SPEG proteins have mutliple immunoglobulin (Ig), 2 fibronectin type III (FN3), and two kinase domains. They are necessary for cardiac development and survival. The SPEG subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271010 [Multi-domain] Cd Length: 255 Bit Score: 143.89 E-value: 1.04e-37

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSgK 3379
Cdd:cd14108      4 YDIHKEIGRGAFSYLRRVKEKSSDLSFAAKFIPVRAKKKTSARRELALLAELDHKSIVRFHDAFEKRRVVIIVTELCH-E 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3380 ELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIV--TYMNVVKIIDFGSAQTFNP---LFLKqfsp 3454
Cdd:cd14108     83 ELLERITKRPTVCESEVRSYMRQLLEGIEYLHQNDVLHLDLKPENLLMadQKTDQVRICDFGNAQELTPnepQYCK---- 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3455 pIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFT-ENDPAE-TEARIQAAKFDlSKLYQNVSQSASLFIKKI 3532
Cdd:cd14108    159 -YGTPEFVAPEIVNQSPVSKVTDIWPVGVIAYLCLTGISPFVgENDRTTlMNIRNYNVAFE-ESMFKDLCREAKGFIIKV 236

                          250       260
                   ....*....|....*....|
gi 1207186029 3533 LCSYPwARPTIKDCFTNSWL 3552
Cdd:cd14108    237 LVSDR-LRPDAEETLEHPWF 255

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase (also called Doublecortin-like and CAM kinase-like); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL (or DCAMKL) proteins belong to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. In addition, DCKL proteins contain a C-terminal kinase domain with similarity to CAMKs. They are involved in the regulation of cAMP signaling. Vertebrates contain three DCKL proteins (DCKL1-3); DCKL1 and 2 also contain a serine, threonine, and proline rich domain (SP), while DCKL3 contains only a single DCX domain instead of tandem domains. The DCKL subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270997 [Multi-domain] Cd Length: 258 Bit Score: 143.62 E-value: 1.28e-37

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3309 GRFGVIRECRENATGNLYMAKIV-PYEPESKQTVLQ-EYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLHSLI 3386
Cdd:cd14095     11 GNFAVVKECRDKATDKEYALKIIdKAKCKGKEHMIEnEVAILRRVKHPNIVQLIEEYDTDTELYLVMELVKGGDLFDAIT 90

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3387 DRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIV----TYMNVVKIIDFGSAQTF-NPLFlkqfsPPIGTLDY 3461
Cdd:cd14095     91 SSTKFTERDASRMVTDLAQALKYLHSLSIVHRDIKPENLLVveheDGSKSLKLADFGLATEVkEPLF-----TVCGTPTY 165

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3462 MSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETE--ARIQAAKFD-LSKLYQNVSQSASLFIKKILCSYPW 3538
Cdd:cd14095    166 VAPEILAETGYGLKVDIWAAGVITYILLCGFPPFRSPDRDQEElfDLILAGEFEfLSPYWDNISDSAKDLISRMLVVDPE 245

                          250
                   ....*....|...
gi 1207186029 3539 ARPTIKDCFTNSW 3551
Cdd:cd14095    246 KRYSAGQVLDHPW 258

Catalytic domain of AGC family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. AGC kinases regulate many cellular processes including division, growth, survival, metabolism, motility, and differentiation. Many are implicated in the development of various human diseases. Members of this family include cAMP-dependent Protein Kinase (PKA), cGMP-dependent Protein Kinase (PKG), Protein Kinase C (PKC), Protein Kinase B (PKB), G protein-coupled Receptor Kinase (GRK), Serum- and Glucocorticoid-induced Kinase (SGK), and 70 kDa ribosomal Protein S6 Kinase (p70S6K or S6K), among others. AGC kinases share an activation mechanism based on the phosphorylation of up to three sites: the activation loop (A-loop), the hydrophobic motif (HM) and the turn motif. Phosphorylation at the A-loop is required of most AGC kinases, which results in a disorder-to-order transition of the A-loop. The ordered conformation results in the access of substrates and ATP to the active site. A subset of AGC kinases with C-terminal extensions containing the HM also requires phosphorylation at this site. Phosphorylation at the HM allows the C-terminal extension to form an ordered structure that packs into the hydrophobic pocket of the catalytic domain, which then reconfigures the kinase into an active bi-lobed state. In addition, growth factor-activated AGC kinases such as PKB, p70S6K, RSK, MSK, PKC, and SGK, require phosphorylation at the turn motif (also called tail or zipper site), located N-terminal to the HM at the C-terminal extension. The AGC family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and Phosphoinositide 3-Kinase.

Pssm-ID: 270693 [Multi-domain] Cd Length: 250 Bit Score: 143.43 E-value: 1.34e-37

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYVKRVIQKAGKLEYAAKFISARA--KRK--ASALRELNILSHLDHERI--LYFhdAFEKKNAVIIITELCHE- 1740
Cdd:cd05123      1 LGKGSFGKVLLVRKKDTGKLYAMKVLRKKEiiKRKevEHTLNERNILERVNHPFIvkLHY--AFQTEEKLYLVLDYVPGg 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1741 ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSsdQIRICDFGNAVKFMPDEAQ---YCky 1817
Cdd:cd05123     79 ELFSHLSKEGRFPEERARFYAAEIVLALEYLHSLGIIYRDLKPENILLDSDG--HIKLTDFGLAKELSSDGDRtytFC-- 154

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1818 GTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTdlchEAKGFVIKLLVA 1897
Cdd:cd05123    155 GTPEYLAPEVLLGKGYGKAVDWWSLGVLLYEMLTGKPPFYAENRKEIYEKILKSPLKFPEYVSP----EAKSLISGLLQK 230

                          250       260
                   ....*....|....*....|
gi 1207186029 1898 D---RL-RPDANECLRHPWF 1913
Cdd:cd05123    231 DptkRLgSGGAEEIKAHPFF 250

C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, in response to various stimuli such as growth factors, hormones, neurotransmitters, cellular stress, and pro-inflammatory cytokines. This triggers phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) in the C-terminal extension of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. MSKs are predominantly nuclear proteins. They are widely expressed in many tissues including heart, brain, lung, liver, kidney, and pancreas. There are two isoforms of MSK, called MSK1 and MSK2. The MSK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270994 [Multi-domain] Cd Length: 311 Bit Score: 145.14 E-value: 1.52e-37

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYVKRVIQKAGKLEYAAKFISarakRKASALRELNILSHLD-HERILYFHDAFEKKNAVIIITELCH-EELLDR 1745
Cdd:cd14092     14 LGDGSFSVCRKCVHKKTGQEFAVKIVS----RRLDTSREVQLLRLCQgHPNIVKLHEVFQDELHTYLVMELLRgGELLER 89

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1746 LTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSD-QIRICDFGNAvKFMPdEAQYCKygTPEFV- 1823
Cdd:cd14092     90 IRKKKRFTESEASRIMRQLVSAVSFMHSKGVVHRDLKPENLLFTDEDDDaEIKIVDFGFA-RLKP-ENQPLK--TPCFTl 165

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1824 ---APEIVNQTPV----SKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLN----IRNYNVAFEESMFTDLCHEAKGFVI 1892
Cdd:cd14092    166 pyaAPEVLKQALStqgyDESCDLWSLGVILYTMLSGQVPFQSPSRNESAAEimkrIKSGDFSFDGEEWKNVSSEAKSLIQ 245

                          250       260       270
                   ....*....|....*....|....*....|....*...
gi 1207186029 1893 KLLVAD---RLRpdANECLRHPWfktLNKGKSISTESL 1927
Cdd:cd14092    246 GLLTVDpskRLT--MSELRNHPW---LQGSSSPSSTPL 278

C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, in response to various stimuli such as growth factors, hormones, neurotransmitters, cellular stress, and pro-inflammatory cytokines. This triggers phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) in the C-terminal extension of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. MSKs are predominantly nuclear proteins. They are widely expressed in many tissues including heart, brain, lung, liver, kidney, and pancreas. There are two isoforms of MSK, called MSK1 and MSK2. The MSK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270994 [Multi-domain] Cd Length: 311 Bit Score: 145.14 E-value: 1.68e-37

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3309 GRFGVIRECRENATGNLYMAKIVpyepeSKQ-TVLQEYDILKSLH-HEKIMALHEAYVTPRYLVLISECCSGKELLHSLI 3386
Cdd:cd14092     17 GSFSVCRKCVHKKTGQEFAVKIV-----SRRlDTSREVQLLRLCQgHPNIVKLHEVFQDELHTYLVMELLRGGELLERIR 91

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3387 DRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMN---VVKIIDFGSAQtfnplfLK----QFSPPIGTL 3459
Cdd:cd14092     92 KKKRFTESEASRIMRQLVSAVSFMHSKGVVHRDLKPENLLFTDEDddaEIKIVDFGFAR------LKpenqPLKTPCFTL 165

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3460 DYMSPEMLKGDVVGP----PADIWSIGILTYIMLSGRLPF----TENDPAETEARIQAAKFDLSKL-YQNVSQSASLFIK 3530
Cdd:cd14092    166 PYAAPEVLKQALSTQgydeSCDLWSLGVILYTMLSGQVPFqspsRNESAAEIMKRIKSGDFSFDGEeWKNVSSEAKSLIQ 245

                          250       260
                   ....*....|....*....|....*
gi 1207186029 3531 KILCSYPWARPTIKDCFTNSWLQDA 3555
Cdd:cd14092    246 GLLTVDPSKRLTMSELRNHPWLQGS 270

Catalytic kinase domain, second repeat, of the Giant Serine/Threonine Kinase Obscurin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Obscurin, approximately 800 kDa in size, is one of three giant proteins expressed in vetebrate striated muscle, together with titin and nebulin. It is a multidomain protein composed of tandem adhesion and signaling domains, including 49 immunoglobulin (Ig) and 2 fibronectin type III (FN3) domains at the N-terminus followed by a more complex region containing more Ig domains, a conserved SH3 domain near a RhoGEF and PH domains, non-modular regions, as well as IQ and phosphorylation motifs. The obscurin gene also encode two kinase domains, which are not expressed as part of the 800 kDa protein, but as a smaller, alternatively spliced product present mainly in the heart muscle, also called obscurin-MLCK. Obscurin is localized at the peripheries of Z-disks and M-lines, where it is able to communicate with the surrounding myoplasm. It interacts with diverse proteins including sAnk1, myosin, titin, and MyBP-C. It may act as a scaffold for the assembly of elements of the contractile apparatus. The obscurin subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271012 [Multi-domain] Cd Length: 257 Bit Score: 143.13 E-value: 2.21e-37

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITELCH-E 1740
Cdd:cd14110      5 YAFQTEINRGRFSVVRQCEEKRSGQMLAAKIIPYKPEDKQLVLREYQVLRRLSHPRIAQLHSAYLSPRHLVLIEELCSgP 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1741 ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHssDQIRICDFGNAVKFMPDEA---QYCKY 1817
Cdd:cd14110     85 ELLYNLAERNSYSEAEVTDYLWQILSAVDYLHSRRILHLDLRSENMIITEK--NLLKIVDLGNAQPFNQGKVlmtDKKGD 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1818 GTpEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESmFTDLCHEAKGFVIKLLVA 1897
Cdd:cd14110    163 YV-ETMAPELLEGQGAGPQTDIWAIGVTAFIMLSADYPVSSDLNWERDRNIRKGKVQLSRC-YAGLSGGAVNFLKSTLCA 240

                          250
                   ....*....|....*.
gi 1207186029 1898 DRL-RPDANECLRHPW 1912
Cdd:cd14110    241 KPWgRPTASECLQNPW 256

Catalytic domain of the Serine/Threonine Kinase, cGMP-dependent protein kinase (cGK or PKG); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mammals have two cGK isoforms from different genes, cGKI and cGKII. cGKI exists as two splice variants, cGKI-alpha and cGKI-beta. cGK consists of an N-terminal regulatory domain containing a dimerization and an autoinhibitory pseudosubstrate region, two cGMP-binding domains, and a C-terminal catalytic domain. Binding of cGMP to both binding sites releases the inhibition of the catalytic center by the pseudosubstrate region, allowing autophosphorylation and activation of the kinase. cGKI is a soluble protein expressed in all smooth muscles, platelets, cerebellum, and kidney. It is also expressed at lower concentrations in other tissues. cGKII is a membrane-bound protein that is most abundantly expressed in the intestine. It is also present in the brain nuclei, adrenal cortex, kidney, lung, and prostate. cGKI is involved in the regulation of smooth muscle tone, smooth cell proliferation, and platelet activation. cGKII plays a role in the regulation of secretion, such as renin secretion by the kidney and aldosterone secretion by the adrenal. It also regulates bone growth and the circadian rhythm. The cGK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270724 [Multi-domain] Cd Length: 262 Bit Score: 142.75 E-value: 2.90e-37

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3307 ARGRFGVIRECRENATGNLYMAKIVP----YEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELL 3382
Cdd:cd05572      2 GVGGFGRVELVQLKSKGRTFALKCVKkrhiVQTRQQEHIFSEKEILEECNSPFIVKLYRTFKDKKYLYMLMEYCLGGELW 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3383 HSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQ---------TFnplflkqfs 3453
Cdd:cd05572     82 TILRDRGLFDEYTARFYTACVVLAFEYLHSRGIIYRDLKPENLLLDSNGYVKLVDFGFAKklgsgrktwTF--------- 152

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3454 ppIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTEN--DPAETEARIQAAKFDLsKLYQNVSQSASLFIKK 3531
Cdd:cd05572    153 --CGTPEYVAPEIILNKGYDFSVDYWSLGILLYELLTGRPPFGGDdeDPMKIYNIILKGIDKI-EFPKYIDKNAKNLIKQ 229


                   ....*....
gi 1207186029 3532 ILCSYPWAR 3540
Cdd:cd05572    230 LLRRNPEER 238

Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 1 subunit; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phosphorylase kinase (PhK) catalyzes the phosphorylation of inactive phosphorylase b to form the active phosphorylase a. It coordinates hormonal, metabolic, and neuronal signals to initiate the breakdown of glycogen stores, which enables the maintenance of blood-glucose homeostasis during fasting, and is also used as a source of energy for muscle contraction. PhK is one of the largest and most complex protein kinases, composed of a heterotetramer containing four molecules each of four subunit types: one catalytic (gamma) and three regulatory (alpha, beta, and delta). The gamma 1 subunit (PhKG1) is also referred to as the muscle gamma isoform. The gamma subunit, when isolated, is constitutively active and does not require phosphorylation of the A-loop for activity. The regulatory subunits restrain this kinase activity until signals are received to relieve this inhibition. For example, the kinase is activated in response to hormonal stimulation, after autophosphorylation or phosphorylation by cAMP-dependent kinase of the alpha and beta subunits. The high-affinity binding of ADP to the beta subunit also stimulates kinase activity, whereas calcium relieves inhibition by binding to the delta (calmodulin) subunit. The PhKG1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271084 [Multi-domain] Cd Length: 276 Bit Score: 142.36 E-value: 6.36e-37

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASA----------LRELNILSHLD-HERILYFHDAFEKKNA 1730
Cdd:cd14182      5 YEPKEILGRGVSSVVRRCIHKPTRQEYAVKIIDITGGGSFSPeevqelreatLKEIDILRKVSgHPNIIQLKDTYETNTF 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1731 VIIITELCHE-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSdqIRICDFGNAVKFMP 1809
Cdd:cd14182     85 FFLVFDLMKKgELFDYLTEKVTLSEKETRKIMRALLEVICALHKLNIVHRDLKPENILLDDDMN--IKLTDFGFSCQLDP 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1810 DEAQYCKYGTPEFVAPEIV------NQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDL 1883
Cdd:cd14182    163 GEKLREVCGTPGYLAPEIIecsmddNHPGYGKEVDMWSTGVIMYTLLAGSPPFWHRKQMLMLRMIMSGNYQFGSPEWDDR 242

                          250       260       270
                   ....*....|....*....|....*....|..
gi 1207186029 1884 CHEAKGFVIKLLVAD-RLRPDANECLRHPWFK 1914
Cdd:cd14182    243 SDTVKDLISRFLVVQpQKRYTAEEALAHPFFQ 274

C-terminal catalytic domain of the Serine/Threonine Kinases, Ribosomal S6 kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. Mammals possess four RSK isoforms (RSK1-4) from distinct genes. RSK proteins are also referred to as MAP kinase-activated protein kinases (MAPKAPKs), 90 kDa ribosomal protein S6 kinases (p90-RSKs), or p90S6Ks. The RSK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270993 [Multi-domain] Cd Length: 291 Bit Score: 142.39 E-value: 7.73e-37

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVPyepESKQTVLQEYDILKSL-HHEKIMALHEAYVTPRYLVLISECCSG 3378
Cdd:cd14091      2 YEIKEEIGKGSYSVCKRCIHKATGKEYAVKIID---KSKRDPSEEIEILLRYgQHPNIITLRDVYDDGNSVYLVTELLRG 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3379 KELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIvtYMN------VVKIIDFGsaqtfnplFLKQF 3452
Cdd:cd14091     79 GELLDRILRQKFFSEREASAVMKTLTKTVEYLHSQGVVHRDLKPSNIL--YADesgdpeSLRICDFG--------FAKQL 148

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3453 SP-------PIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPF--TEND-PAETEARIQAAKFDLS-KLYQNV 3521
Cdd:cd14091    149 RAengllmtPCYTANFVAPEVLKKQGYDAACDIWSLGVLLYTMLAGYTPFasGPNDtPEVILARIGSGKIDLSgGNWDHV 228

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1207186029 3522 SQSASLFIKKILCSYPWARPTIKDCFTNSWLQDAYLMRLRRQTLTFTTTRLKEFLEQ 3578
Cdd:cd14091    229 SDSAKDLVRKMLHVDPSQRPTAAQVLQHPWIRNRDSLPQRQLTDPQDAALVKGAVAA 285

Catalytic domain of Serine/Threonine Kinase 36; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK36, also called Fused (or Fu) kinase, is involved in the Hedgehog signaling pathway. It is activated by the Smoothened (SMO) signal transducer, resulting in the stabilization of GLI transcription factors and the phosphorylation of SUFU to facilitate the nuclear accumulation of GLI. In Drosophila, Fused kinase is maternally required for proper segmentation during embryonic development and for the development of legs and wings during the larval stage. In mice, STK36 is not necessary for embryonic development, although mice deficient in STK36 display growth retardation postnatally. The STK36 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270904 [Multi-domain] Cd Length: 253 Bit Score: 141.24 E-value: 8.42e-37

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1660 DYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRK---ASALRELNILSHLDHERILYFHDAFEKKNAVIIITE 1736
Cdd:cd14002      1 ENYHVLELIGEGSFGKVYKGRRKYTGQVVALKFIPKRGKSEkelRNLRQEIEILRKLNHPNIIEMLDSFETKKEFVVVTE 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1737 LCHEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMAdhSSDQIRICDFGNA------------ 1804
Cdd:cd14002     81 YAQGELFQILEDDGTLPEEEVRSIAKQLVSALHYLHSNRIIHRDMKPQNILIG--KGGVVKLCDFGFAramscntlvlts 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1805 VKfmpdeaqyckyGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDLc 1884
Cdd:cd14002    159 IK-----------GTPLYMAPELVQEQPYDHTADLWSLGCILYELFVGQPPFYTNSIYQLVQMIVKDPVKWPSNMSPEF- 226

                          250       260
                   ....*....|....*....|....*...
gi 1207186029 1885 heaKGFVIKLLVAD-RLRPDANECLRHP 1911
Cdd:cd14002    227 ---KSFLQGLLNKDpSKRLSWPDLLEHP 251

C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 2 (also called 90kDa ribosomal protein S6 kinase 3 or Ribosomal protein S6 kinase alpha-3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSK2 is also called p90RSK3, RPS6KA3, S6K-alpha-3, or MAPK-activated protein kinase 1b (MAPKAPK-1b). RSK2 is expressed highly in the regions of the brain with high synaptic activity. It plays a role in the maintenance and consolidation of excitatory synapses. It is a specific modulator of phospholipase D in calcium-regulated exocytosis. Mutations in the RSK2 gene, RPS6KA3, cause Coffin-Lowry syndrome (CLS), a rare syndromic form of X-linked mental retardation characterized by growth and psychomotor retardation and skeletal abnormalities. RSK2 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. The RSK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271078 [Multi-domain] Cd Length: 339 Bit Score: 144.01 E-value: 9.24e-37

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1650 SILRKMRR----LTDYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISaRAKRKASALRELnILSHLDHERILYFHDAF 1725
Cdd:cd14176      5 SIVQQLHRnsiqFTDGYEVKEDIGVGSYSVCKRCIHKATNMEFAVKIID-KSKRDPTEEIEI-LLRYGQHPNIITLKDVY 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1726 EKKNAVIIITELCHE-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSS--DQIRICDFG 1802
Cdd:cd14176     83 DDGKYVYVVTELMKGgELLDKILRQKFFSEREASAVLFTITKTVEYLHAQGVVHRDLKPSNILYVDESGnpESIRICDFG 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1803 NAVKFMPDEAQY---CKygTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFA-GENDRSSVLNIRNYNVAFEES 1878
Cdd:cd14176    163 FAKQLRAENGLLmtpCY--TANFVAPEVLERQGYDAACDIWSLGVLLYTMLTGYTPFAnGPDDTPEEILARIGSGKFSLS 240

                          250       260       270
                   ....*....|....*....|....*....|....*..
gi 1207186029 1879 --MFTDLCHEAKGFVIKLLVAD-RLRPDANECLRHPW 1912
Cdd:cd14176    241 ggYWNSVSDTAKDLVSKMLHVDpHQRLTAALVLRHPW 277

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I gamma; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-gamma subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271068 [Multi-domain] Cd Length: 285 Bit Score: 142.05 E-value: 1.11e-36

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3297 QKPYTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPESKQTVLQ-EYDILKSLHHEKIMALHEAYVTPRYLVLISEC 3375
Cdd:cd14166      2 RETFIFMEVLGSGAFSEVYLVKQRSTGKLYALKCIKKSPLSRDSSLEnEIAVLKRIKHENIVTLEDIYESTTHYYLVMQL 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3376 CSGKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIvtYMN-----VVKIIDFG-SAQTFNPLfl 3449
Cdd:cd14166     82 VSGGELFDRILERGVYTEKDASRVINQVLSAVKYLHENGIVHRDLKPENLL--YLTpdensKIMITDFGlSKMEQNGI-- 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3450 kqFSPPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDL-SKLYQNVSQSASLF 3528
Cdd:cd14166    158 --MSTACGTPGYVAPEVLAQKPYSKAVDCWSIGVITYILLCGYPPFYEETESRLFEKIKEGYYEFeSPFWDDISESAKDF 235

                          250       260
                   ....*....|....*....|....
gi 1207186029 3529 IKKILCSYPWARPTIKDCFTNSWL 3552
Cdd:cd14166    236 IRHLLEKNPSKRYTCEKALSHPWI 259

Catalytic domain of Cyclin-Dependent protein Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. CDKs are partly regulated by their subcellular localization, which defines substrate phosphorylation and the resulting specific function. CDK1, CDK2, CDK4, and CDK6 have well-defined functions in the cell cycle, such as the regulation of the early G1 phase by CDK4 or CDK6, the G1/S phase transition by CDK2, or the entry of mitosis by CDK1. They also exhibit overlapping cyclin specificity and functions in certain conditions. Knockout mice with a single CDK deleted remain viable with specific phenotypes, showing that some CDKs can compensate for each other. For example, CDK4 can compensate for the loss of CDK6, however, double knockout mice with both CDK4 and CDK6 deleted die in utero. CDK8 and CDK9 are mainly involved in transcription while CDK5 is implicated in neuronal function. CDK7 plays essential roles in both the cell cycle as a CDK-Activating Kinase (CAK) and in transcription as a component of the general transcription factor TFIIH. The CDK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270823 [Multi-domain] Cd Length: 282 Bit Score: 140.70 E-value: 2.69e-36

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPESK---QTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECC 3376
Cdd:cd07829      1 YEKLEKLGEGTYGVVYKAKDKKTGEIVALKKIRLDNEEEgipSTALREISLLKELKHPNIVKLLDVIHTENKLYLVFEYC 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3377 SgkELLHSLIDRFRY--SEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFN-PlfLKQFS 3453
Cdd:cd07829     81 D--QDLKKYLDKRPGplPPNLIKSIMYQLLRGLAYCHSHRILHRDLKPQNLLINRDGVLKLADFGLARAFGiP--LRTYT 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3454 PPIGTLDYMSPEMLKGD-VVGPPADIWSIGILTYIMLSGRLPFtendPAETE----ARI--------------------Q 3508
Cdd:cd07829    157 HEVVTLWYRAPEILLGSkHYSTAVDIWSVGCIFAELITGKPLF----PGDSEidqlFKIfqilgtpteeswpgvtklpdY 232

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3509 AAKF------DLSKLYQNVSQSASLFIKKILCSYPWARPTIKDCFTNSWL 3552
Cdd:cd07829    233 KPTFpkwpknDLEKVLPRLDPEGIDLLSKMLQYNPAKRISAKEALKHPYF 282

Catalytic domain of Plant dual-specificity Mitogen-Activated Protein Kinase Kinases and similar proteins; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include MAPKKs from plants, kinetoplastids, alveolates, and mycetozoa. The MAPKK, LmxPK4, from Leishmania mexicana, is important in differentiation and virulence. Dictyostelium discoideum MEK1 is required for proper chemotaxis; MEK1 null mutants display severe defects in cell polarization and directional movement. Plants contain multiple MAPKKs like other eukaryotes. The Arabidopsis genome encodes for 10 MAPKKs while poplar and rice contain 13 MAPKKs each. The functions of these proteins have not been fully elucidated. There is evidence to suggest that MAPK cascades are involved in plant stress responses. In Arabidopsis, MKK3 plays a role in pathogen signaling; MKK2 is involved in cold and salt stress signaling; MKK4/MKK5 participates in innate immunity; and MKK7 regulates basal and systemic acquired resistance. The MAPKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 132954 [Multi-domain] Cd Length: 264 Bit Score: 140.03 E-value: 3.04e-36

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKIVPY--EPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELlHSL 3385
Cdd:cd06623     11 QGSSGVVYKVRHKPTGKIYALKKIHVdgDEEFRKQLLRELKTLRSCESPYVVKCYGAFYKEGEISIVLEYMDGGSL-ADL 89

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3386 IDRFRYSEDDVVAYIV-QILQGLDYLHS-RRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLfLKQFSPPIGTLDYMS 3463
Cdd:cd06623     90 LKKVGKIPEPVLAYIArQILKGLDYLHTkRHIIHRDIKPSNLLINSKGEVKIADFGISKVLENT-LDQCNTFVGTVTYMS 168

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3464 PEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQA-AKFDLSKL-YQNVSQSASLFIKKILCSYPWARP 3541
Cdd:cd06623    169 PERIQGESYSYAADIWSLGLTLLECALGKFPFLPPGQPSFFELMQAiCDGPPPSLpAEEFSPEFRDFISACLQKDPKKRP 248

                          250
                   ....*....|..
gi 1207186029 3542 TIKDCFTNSWLQ 3553
Cdd:cd06623    249 SAAELLQHPFIK 260

C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 1 (also called Ribosomal protein S6 kinase alpha-1 or 90kDa ribosomal protein S6 kinase 1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSK1 is also called S6K-alpha-1, RPS6KA1, p90RSK1 or MAPK-activated protein kinase 1a (MAPKAPK-1a). It is a component of the insulin transduction pathway, regulating the function of IRS1. It also interacts with PKA and promotes its inactivation. RSK1 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. The RSK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271077 [Multi-domain] Cd Length: 291 Bit Score: 140.55 E-value: 3.49e-36

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1660 DYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISaRAKRKASALRELnILSHLDHERILYFHDAFEKKNAVIIITELCH 1739
Cdd:cd14175      1 DGYVVKETIGVGSYSVCKRCVHKATNMEYAVKVID-KSKRDPSEEIEI-LLRYGQHPNIITLKDVYDDGKHVYLVTELMR 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1740 E-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSD--QIRICDFGNAVKFMPDEAQY-- 1814
Cdd:cd14175     79 GgELLDKILRQKFFSEREASSVLHTICKTVEYLHSQGVVHRDLKPSNILYVDESGNpeSLRICDFGFAKQLRAENGLLmt 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1815 -CKygTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFA---GENDRSSVLNIRNYNVAFEESMFTDLCHEAKGF 1890
Cdd:cd14175    159 pCY--TANFVAPEVLKRQGYDEGCDIWSLGILLYTMLAGYTPFAngpSDTPEEILTRIGSGKFTLSGGNWNTVSDAAKDL 236

                          250       260
                   ....*....|....*....|...
gi 1207186029 1891 VIKLLVAD-RLRPDANECLRHPW 1912
Cdd:cd14175    237 VSKMLHVDpHQRLTAKQVLQHPW 259

C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 4 (also called Ribosomal protein S6 kinase alpha-6 or 90kDa ribosomal protein S6 kinase 6); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSK4 is also called S6K-alpha-6, RPS6KA6, p90RSK6 or pp90RSK4. RSK4 is a substrate of ERK and is a modulator of p53-dependent proliferation arrest in human cells. Deletion of the RSK4 gene, RPS6KA6, frequently occurs in patients of X-linked deafness type 3, mental retardation and choroideremia. Studies of RSK4 in cancer cells and tissues suggest that it may be oncogenic or tumor suppressive depending on many factors. RSK4 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. The RSK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271079 [Multi-domain] Cd Length: 295 Bit Score: 140.54 E-value: 4.06e-36

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1657 RLTDYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISaRAKRKASALRELnILSHLDHERILYFHDAFEKKNAVIIITE 1736
Cdd:cd14177      1 QFTDVYELKEDIGVGSYSVCKRCIHRATNMEFAVKIID-KSKRDPSEEIEI-LMRYGQHPNIITLKDVYDDGRYVYLVTE 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1737 LCHE-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSS--DQIRICDFGNAVKFMPDEAQ 1813
Cdd:cd14177     79 LMKGgELLDRILRQKFFSEREASAVLYTITKTVDYLHCQGVVHRDLKPSNILYMDDSAnaDSIRICDFGFAKQLRGENGL 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1814 Y---CKygTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFA-GENDRSS--VLNIRNYNVAFEESMFTDLCHEA 1887
Cdd:cd14177    159 LltpCY--TANFVAPEVLMRQGYDAACDIWSLGVLLYTMLAGYTPFAnGPNDTPEeiLLRIGSGKFSLSGGNWDTVSDAA 236

                          250       260
                   ....*....|....*....|....*.
gi 1207186029 1888 KGFVIKLLVAD-RLRPDANECLRHPW 1912
Cdd:cd14177    237 KDLLSHMLHVDpHQRYTAEQVLKHSW 262

C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 3 (also called Ribosomal protein S6 kinase alpha-2 or 90kDa ribosomal protein S6 kinase 2); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSK3 is also called S6K-alpha-2, RPS6KA2, p90RSK2 or MAPK-activated protein kinase 1c (MAPKAPK-1c). RSK3 binds muscle A-kinase anchoring protein (mAKAP)-b directly and regulates concentric cardiac myocyte growth. The RSK3 gene, RPS6KA2, is a putative tumor suppressor gene in sporadic epithelial ovarian cancer and variations to the gene may be associated with rectal cancer risk. RSK3 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. The RSK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271080 [Multi-domain] Cd Length: 293 Bit Score: 139.38 E-value: 1.05e-35

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1658 LTDYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISaRAKRKASALRELnILSHLDHERILYFHDAFEKKNAVIIITEL 1737
Cdd:cd14178      1 FTDGYEIKEDIGIGSYSVCKRCVHKATSTEYAVKIID-KSKRDPSEEIEI-LLRYGQHPNIITLKDVYDDGKFVYLVMEL 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1738 CHE-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSS--DQIRICDFGNAVKFMPDEAQY 1814
Cdd:cd14178     79 MRGgELLDRILRQKCFSEREASAVLCTITKTVEYLHSQGVVHRDLKPSNILYMDESGnpESIRICDFGFAKQLRAENGLL 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1815 ---CKygTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFA-GENDRSS--VLNIRNYNVAFEESMFTDLCHEAK 1888
Cdd:cd14178    159 mtpCY--TANFVAPEVLKRQGYDAACDIWSLGILLYTMLAGFTPFAnGPDDTPEeiLARIGSGKYALSGGNWDSISDAAK 236

                          250       260
                   ....*....|....*....|....*
gi 1207186029 1889 GFVIKLLVAD-RLRPDANECLRHPW 1912
Cdd:cd14178    237 DIVSKMLHVDpHQRLTAPQVLRHPW 261

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase (also called Doublecortin-like and CAM kinase-like); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL (or DCAMKL) proteins belong to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. In addition, DCKL proteins contain a C-terminal kinase domain with similarity to CAMKs. They are involved in the regulation of cAMP signaling. Vertebrates contain three DCKL proteins (DCKL1-3); DCKL1 and 2 also contain a serine, threonine, and proline rich domain (SP), while DCKL3 contains only a single DCX domain instead of tandem domains. The DCKL subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270997 [Multi-domain] Cd Length: 258 Bit Score: 138.23 E-value: 1.14e-35

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFIS-ARAKRKASALR-ELNILSHLDHERILYFHDAFEKKNAVIIITELCH 1739
Cdd:cd14095      2 YDIGRVIGDGNFAVVKECRDKATDKEYALKIIDkAKCKGKEHMIEnEVAILRRVKHPNIVQLIEEYDTDTELYLVMELVK 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1740 E-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSDQIRI--CDFGNAVKFmpDEAQYCK 1816
Cdd:cd14095     82 GgDLFDAITSSTKFTERDASRMVTDLAQALKYLHSLSIVHRDIKPENLLVVEHEDGSKSLklADFGLATEV--KEPLFTV 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1817 YGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVL--NIRNYNVAFEESMFTDLCHEAKGFVIKL 1894
Cdd:cd14095    160 CGTPTYVAPEILAETGYGLKVDIWAAGVITYILLCGFPPFRSPDRDQEELfdLILAGEFEFLSPYWDNISDSAKDLISRM 239

                          250
                   ....*....|....*....
gi 1207186029 1895 LVAD-RLRPDANECLRHPW 1912
Cdd:cd14095    240 LVVDpEKRYSAGQVLDHPW 258

Catalytic domain of the Serine/Threonine kinase, Checkpoint kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Chk1 is implicated in many major checkpoints of the cell cycle, providing a link between upstream sensors and the cell cycle engine. It plays an important role in DNA damage response and maintaining genomic stability. Chk1 acts as an effector of the sensor kinase, ATR (ATM and Rad3-related), a member of the PI3K family, which is activated upon DNA replication stress. Chk1 delays mitotic entry in response to replication blocks by inhibiting cyclin dependent kinase (Cdk) activity. In addition, Chk1 contributes to the function of centrosome and spindle-based checkpoints, inhibits firing of origins of DNA replication (Ori), and represses transcription of cell cycle proteins including cyclin B and Cdk1. The Chk1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270971 [Multi-domain] Cd Length: 261 Bit Score: 137.85 E-value: 1.34e-35

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3298 KPYTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPESK---QTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISE 3374
Cdd:cd14069      1 EDWDLVQTLGEGAFGEVFLAVNRNTEEAVAVKFVDMKRAPGdcpENIKKEVCIQKMLSHKNVVRFYGHRREGEFQYLFLE 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3375 CCSGKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTF-NPLFLKQFS 3453
Cdd:cd14069     81 YASGGELFDKIEPDVGMPEDVAQFYFQQLMAGLKYLHSCGITHRDIKPENLLLDENDNLKISDFGLATVFrYKGKERLLN 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3454 PPIGTLDYMSPEMLKGDVV-GPPADIWSIGILTYIMLSGRLPF---TENDPaETEARIQAAKFDLSKLYQnVSQSASLFI 3529
Cdd:cd14069    161 KMCGTLPYVAPELLAKKKYrAEPVDVWSCGIVLFAMLAGELPWdqpSDSCQ-EYSDWKENKKTYLTPWKK-IDTAALSLL 238

                          250       260
                   ....*....|....*....|...
gi 1207186029 3530 KKILCSYPWARPTIKDCFTNSWL 3552
Cdd:cd14069    239 RKILTENPNKRITIEDIKKHPWY 261

Catalytic domain of the yeast Serine/Threonine Kinases, Rad53 and Cds1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Rad53 and Cds1 are the checkpoint kinase 2 (Chk2) homologs found in budding and fission yeast, respectively. They play a central role in the cell's response to DNA lesions to prevent genome rearrangements and maintain genome integrity. They are phosphorylated in response to DNA damage and incomplete replication, and are essential for checkpoint control. They help promote DNA repair by stalling the cell cycle prior to mitosis in the presence of DNA damage. The Rad53/Cds1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271000 [Multi-domain] Cd Length: 265 Bit Score: 137.61 E-value: 2.28e-35

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISAR----AKRKASAL-RELNILSHLDHERILYFHDAFEKKNAVIIITE 1736
Cdd:cd14098      2 YQIIDRLGSGTFAEVKKAVEVETGKMRAIKQIVKRkvagNDKNLQLFqREINILKSLEHPGIVRLIDWYEDDQHIYLVME 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1737 LCHE-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSDQIRICDFGNAVKFMPDEAQYC 1815
Cdd:cd14098     82 YVEGgDLMDFIMAWGAIPEQHARELTKQILEAMAYTHSMGITHRDLKPENILITQDDPVIVKISDFGLAKVIHTGTFLVT 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1816 KYGTPEFVAPEIVNQTPV------SKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDLCHEAKG 1889
Cdd:cd14098    162 FCGTMAYLAPEILMSKEQnlqggySNLVDMWSVGCLVYVMLTGALPFDGSSQLPVEKRIRKGRYTQPPLVDFNISEEAID 241

                          250       260
                   ....*....|....*....|....
gi 1207186029 1890 FVIKLLVAD-RLRPDANECLRHPW 1912
Cdd:cd14098    242 FILRLLDVDpEKRMTAAQALDHPW 265

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Nek2 subfamily includes Aspergillus nidulans NIMA kinase, the founding member of the Nek family, which was identified in a screen for cell cycle mutants prevented from entering mitosis. NIMA is essential for mitotic entry and progression through mitosis, and its degradation is essential for mitotic exit. NIMA is involved in nuclear membrane fission. Vertebrate Nek2 is a cell cycle-regulated STK, localized in centrosomes and kinetochores, that regulates centrosome splitting at the G2/M phase. It also interacts with other mitotic kinases such as Polo-like kinase 1 and may play a role in spindle checkpoint. An increase in the expression of the human NEK2 gene is strongly associated with the progression of non-Hodgkin lymphoma. Nek2 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. It The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270857 [Multi-domain] Cd Length: 265 Bit Score: 136.52 E-value: 5.37e-35

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVPY----EPESKQTVlQEYDILKSLHHEKIMALHEAYVTPR----YLVL 3371
Cdd:cd08217      2 YEVLETIGKGSFGTVRKVRRKSDGKILVWKEIDYgkmsEKEKQQLV-SEVNILRELKHPNIVRYYDRIVDRAnttlYIVM 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3372 isECCSGKELlHSLI-----DRFRYSEDDVVAYIVQILQGLDYLHSR-----RILHLDIKPENIIVTYMNVVKIIDFG-- 3439
Cdd:cd08217     81 --EYCEGGDL-AQLIkkckkENQYIPEEFIWKIFTQLLLALYECHNRsvgggKILHRDLKPANIFLDSDNNVKLGDFGla 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3440 --------SAQTFnplflkqfsppIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAK 3511
Cdd:cd08217    158 rvlshdssFAKTY-----------VGTPYYMSPELLNEQSYDEKSDIWSLGCLIYELCALHPPFQAANQLELAKKIKEGK 226

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|
gi 1207186029 3512 FD-LSKLYqnvSQSASLFIKKILCSYPWARPTIKDCFTNS 3550
Cdd:cd08217    227 FPrIPSRY---SSELNEVIKSMLNVDPDKRPSVEELLQLP 263

Catalytic domain of Serine/Threonine Kinase 33; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK33 is highly expressed in the testis and is present in low levels in most tissues. It may be involved in spermatogenesis and organ ontogenesis. It interacts with and phosphorylates vimentin and may be involved in regulating intermediate filament cytoskeletal dynamics. Its role in promoting the cell viability of KRAS-dependent cancer cells is under debate; some studies have found STK33 to promote cancer cell viability, while other studies have found it to be non-essential. KRAS is the most commonly mutated human oncogene, thus, studies on the role of STK33 in KRAS mutant cancer cells are important. The STK33 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270999 [Multi-domain] Cd Length: 266 Bit Score: 136.14 E-value: 5.99e-35

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISaRAKRKASAL----RELNILSHLDHERILYFHDAFEKKNAVIIITEL 1737
Cdd:cd14097      3 YTFGRKLGQGSFGVVIEATHKETQTKWAIKKIN-REKAGSSAVklleREVDILKHVNHAHIIHLEEVFETPKRMYLVMEL 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1738 CHE-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSDQ-----IRICDFGNAVKFM--- 1808
Cdd:cd14097     82 CEDgELKELLLRKGFFSENETRHIIQSLASAVAYLHKNDIVHRDLKLENILVKSSIIDNndklnIKVTDFGLSVQKYglg 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1809 PDEAQ-YCkyGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDLCHEA 1887
Cdd:cd14097    162 EDMLQeTC--GTPIYMAPEVISAHGYSQQCDIWSIGVIMYMLLCGEPPFVAKSEEKLFEEIRKGDLTFTQSVWQSVSDAA 239

                          250       260
                   ....*....|....*....|....*.
gi 1207186029 1888 KGFVIKLLVAD-RLRPDANECLRHPW 1912
Cdd:cd14097    240 KNVLQQLLKVDpAHRMTASELLDNPW 265

Catalytic domain of Cell division control protein 7-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily include Schizosaccharomyces pombe Cdc7, Saccharomyces cerevisiae Cdc15, Arabidopsis thaliana mitogen-activated protein kinase kinase kinase (MAPKKK) epsilon, and related proteins. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Fission yeast Cdc7 is essential for cell division by playing a key role in the initiation of septum formation and cytokinesis. Budding yeast Cdc15 functions to coordinate mitotic exit with cytokinesis. Arabidopsis MAPKKK epsilon is required for pollen development in the plasma membrane. The Cdc7-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270797 [Multi-domain] Cd Length: 254 Bit Score: 135.43 E-value: 7.51e-35

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYV-KRVIQKAGklEYAA-KFISaRAKRKASALR----ELNILSHLDHERILYFHDAFEKKNAVIIIT 1735
Cdd:cd06627      2 YQLGDLIGRGAFGSVyKGLNLNTG--EFVAiKQIS-LEKIPKSDLKsvmgEIDLLKKLNHPNIVKYIGSVKTKDSLYIIL 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1736 ELCHE-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSdqIRICDFGNAVKFMPDEAQY 1814
Cdd:cd06627     79 EYVENgSLASIIKKFGKFPESLVAVYIYQVLEGLAYLHEQGVIHRDIKGANILTTKDGL--VKLADFGVATKLNEVEKDE 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1815 CK-YGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIrnynVAFEESMF-TDLCHEAKGFVI 1892
Cdd:cd06627    157 NSvVGTPYWMAPEVIEMSGVTTASDIWSVGCTVIELLTGNPPYYDLQPMAALFRI----VQDDHPPLpENISPELRDFLL 232

                          250       260
                   ....*....|....*....|..
gi 1207186029 1893 KLLVAD-RLRPDANECLRHPWF 1913
Cdd:cd06627    233 QCFQKDpTLRPSAKELLKHPWL 254

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 3 (also called Doublecortin-like and CAM kinase-like 3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL3 (or DCAMKL3) belongs to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. DCKL3 contains a single DCX domain (instead of a tandem) and a C-terminal kinase domain with similarity to CAMKs. It has been shown to interact with tubulin and JIP1/2. The DCKL3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271087 [Multi-domain] Cd Length: 258 Bit Score: 135.85 E-value: 7.53e-35

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3309 GRFGVIRECRENATGNLYMAKIVPYEP-ESKQTVLQ-EYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLHSLI 3386
Cdd:cd14185     11 GNFAVVKECRHWNENQEYAMKIIDKSKlKGKEDMIEsEILIIKSLSHPNIVKLFEVYETEKEIYLILEYVRGGDLFDAII 90

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3387 DRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTY----MNVVKIIDFGSAQ-TFNPLFlkqfsPPIGTLDY 3461
Cdd:cd14185     91 ESVKFTEHDAALMIIDLCEALVYIHSKHIVHRDLKPENLLVQHnpdkSTTLKLADFGLAKyVTGPIF-----TVCGTPTY 165

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3462 MSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPF--TENDPAETEARIQAAKFD-LSKLYQNVSQSASLFIKKILCSYPW 3538
Cdd:cd14185    166 VAPEILSEKGYGLEVDMWAAGVILYILLCGFPPFrsPERDQEELFQIIQLGHYEfLPPYWDNISEAAKDLISRLLVVDPE 245

                          250
                   ....*....|...
gi 1207186029 3539 ARPTIKDCFTNSW 3551
Cdd:cd14185    246 KRYTAKQVLQHPW 258

Catalytic domain of Rho-associated coiled-coil containing protein kinase (ROCK)- and Nuclear Dbf2-Related (NDR)-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily include ROCK and ROCK-like proteins such as DMPK, MRCK, and CRIK, as well as NDR and NDR-like proteins such as LATS, CBK1 and Sid2p. ROCK and CRIK are effectors of the small GTPase Rho, while MRCK is an effector of the small GTPase Cdc42. NDR and NDR-like kinases contain an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Proteins in this subfamily are involved in regulating many cellular functions including contraction, motility, division, proliferation, apoptosis, morphogenesis, and cytokinesis. The ROCK/NDR-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270725 [Multi-domain] Cd Length: 350 Bit Score: 137.80 E-value: 1.19e-34

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3307 ARGRFGVIRECRENATGNLYMAKIVpyepeSKQTVLQ---------EYDILKSLHHEKIMALHEAYVTPRYLVLISECCS 3377
Cdd:cd05573     10 GRGAFGEVWLVRDKDTGQVYAMKIL-----RKSDMLKreqiahvraERDILADADSPWIVRLHYAFQDEDHLYLVMEYMP 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3378 GKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSA--------------QT 3443
Cdd:cd05573     85 GGDLMNLLIKYDVFPEETARFYIAELVLALDSLHKLGFIHRDIKPDNILLDADGHIKLADFGLCtkmnksgdresylnDS 164

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3444 FNPLFLKQ--------------FSPPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQA 3509
Cdd:cd05573    165 VNTLFQDNvlarrrphkqrrvrAYSAVGTPDYIAPEVLRGTGYGPECDWWSLGVILYEMLYGFPPFYSDSLVETYSKIMN 244

                          250       260
                   ....*....|....*....|....*..
gi 1207186029 3510 AKFDLS-KLYQNVSQSASLFIKKILCS 3535
Cdd:cd05573    245 WKESLVfPDDPDVSPEAIDLIRRLLCD 271

Catalytic domain of Microtubule-associated serine/threonine (MAST) kinase-like proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes MAST kinases, MAST-like (MASTL) kinases (also called greatwall kinase or Gwl), and fungal kinases with similarity to Saccharomyces cerevisiae Rim15 and Schizosaccharomyces pombe cek1. MAST kinases contain an N-terminal domain of unknown function, a central catalytic domain, and a C-terminal PDZ domain that mediates protein-protein interactions. MASTL kinases carry only a catalytic domain which contains a long insert relative to other kinases. The fungal kinases in this subfamily harbor other domains in addition to a central catalytic domain, which like in MASTL, also contains an insert relative to MAST kinases. Rim15 contains a C-terminal signal receiver (REC) domain while cek1 contains an N-terminal PAS domain. MAST kinases are cytoskeletal associated kinases of unknown function that are also expressed at neuromuscular junctions and postsynaptic densities. MASTL/Gwl is involved in the regulation of mitotic entry, mRNA stabilization, and DNA checkpoint recovery. The fungal proteins Rim15 and cek1 are involved in the regulation of meiosis and mitosis, respectively. The MAST-like kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270731 [Multi-domain] Cd Length: 272 Bit Score: 134.27 E-value: 3.22e-34

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKIVP----YEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELlH 3383
Cdd:cd05579      3 RGAYGRVYLAKKKSTGDLYAIKVIKkrdmIRKNQVDSVLAERNILSQAQNPFVVKLYYSFQGKKNLYLVMEYLPGGDL-Y 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3384 SLIDRFRYSEDDVVA-YIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFG--------------SAQTFNPLF 3448
Cdd:cd05579     82 SLLENVGALDEDVARiYIAEIVLALEYLHSHGIIHRDLKPDNILIDANGHLKLTDFGlskvglvrrqiklsIQKKSNGAP 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3449 LKQFSPPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLSKlYQNVSQSASLF 3528
Cdd:cd05579    162 EKEDRRIVGTPDYLAPEILLGQGHGKTVDWWSLGVILYEFLVGIPPFHAETPEEIFQNILNGKIEWPE-DPEVSDEAKDL 240

                          250
                   ....*....|...
gi 1207186029 3529 IKKILCSYPWARP 3541
Cdd:cd05579    241 ISKLLTPDPEKRL 253

Catalytic domain of Serine/Threonine Kinase 33; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK33 is highly expressed in the testis and is present in low levels in most tissues. It may be involved in spermatogenesis and organ ontogenesis. It interacts with and phosphorylates vimentin and may be involved in regulating intermediate filament cytoskeletal dynamics. Its role in promoting the cell viability of KRAS-dependent cancer cells is under debate; some studies have found STK33 to promote cancer cell viability, while other studies have found it to be non-essential. KRAS is the most commonly mutated human oncogene, thus, studies on the role of STK33 in KRAS mutant cancer cells are important. The STK33 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270999 [Multi-domain] Cd Length: 266 Bit Score: 133.44 E-value: 5.47e-34

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3298 KPYTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPESKQTVL---QEYDILKSLHHEKIMALHEAYVTPRYLVLISE 3374
Cdd:cd14097      1 KIYTFGRKLGQGSFGVVIEATHKETQTKWAIKKINREKAGSSAVKlleREVDILKHVNHAHIIHLEEVFETPKRMYLVME 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3375 CCSGKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNV-------VKIIDFGSAQTFNPL 3447
Cdd:cd14097     81 LCEDGELKELLLRKGFFSENETRHIIQSLASAVAYLHKNDIVHRDLKLENILVKSSIIdnndklnIKVTDFGLSVQKYGL 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3448 FLKQFSPPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLSKL-YQNVSQSAS 3526
Cdd:cd14097    161 GEDMLQETCGTPIYMAPEVISAHGYSQQCDIWSIGVIMYMLLCGEPPFVAKSEEKLFEEIRKGDLTFTQSvWQSVSDAAK 240

                          250       260
                   ....*....|....*....|....*.
gi 1207186029 3527 LFIKKILCSYPWARPTIKDCFTNSWL 3552
Cdd:cd14097    241 NVLQQLLKVDPAHRMTASELLDNPWI 266

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK4, also called SAK or STK18, is structurally different from other PLKs in that it contains only one polo box that can form two adjacent polo boxes and a functional PDB by homodimerization. It is required for late mitotic progression, cell survival, and embryonic development. It localizes to centrosomes and is required for centriole duplication and chromosomal stability. Overexpression of PLK4 may be associated with colon tumors. The PLK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271088 [Multi-domain] Cd Length: 256 Bit Score: 132.29 E-value: 9.62e-34

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASALR----ELNILSHLDHERILYFHDAFEKKNAVIIITEL 1737
Cdd:cd14186      3 FKVLNLLGKGSFACVYRARSLHTGLEVAIKMIDKKAMQKAGMVQrvrnEVEIHCQLKHPSILELYNYFEDSNYVYLVLEM 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1738 CHEELLDRLTK--KSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMAdhSSDQIRICDFGNAVKF-MPDEAQY 1814
Cdd:cd14186     83 CHNGEMSRYLKnrKKPFTEDEARHFMHQIVTGMLYLHSHGILHRDLTLSNLLLT--RNMNIKIADFGLATQLkMPHEKHF 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1815 CKYGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFagenDRSSVLNIRNYNVAFEESMFTDLCHEAKGFVIKL 1894
Cdd:cd14186    161 TMCGTPNYISPEIATRSAHGLESDVWSLGCMFYTLLVGRPPF----DTDTVKNTLNKVVLADYEMPAFLSREAQDLIHQL 236

                          250
                   ....*....|....*....
gi 1207186029 1895 LVAD-RLRPDANECLRHPW 1912
Cdd:cd14186    237 LRKNpADRLSLSSVLDHPF 255

Catalytic domain of Microtubule-associated serine/threonine (MAST) kinase-like proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes MAST kinases, MAST-like (MASTL) kinases (also called greatwall kinase or Gwl), and fungal kinases with similarity to Saccharomyces cerevisiae Rim15 and Schizosaccharomyces pombe cek1. MAST kinases contain an N-terminal domain of unknown function, a central catalytic domain, and a C-terminal PDZ domain that mediates protein-protein interactions. MASTL kinases carry only a catalytic domain which contains a long insert relative to other kinases. The fungal kinases in this subfamily harbor other domains in addition to a central catalytic domain, which like in MASTL, also contains an insert relative to MAST kinases. Rim15 contains a C-terminal signal receiver (REC) domain while cek1 contains an N-terminal PAS domain. MAST kinases are cytoskeletal associated kinases of unknown function that are also expressed at neuromuscular junctions and postsynaptic densities. MASTL/Gwl is involved in the regulation of mitotic entry, mRNA stabilization, and DNA checkpoint recovery. The fungal proteins Rim15 and cek1 are involved in the regulation of meiosis and mitosis, respectively. The MAST-like kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270731 [Multi-domain] Cd Length: 272 Bit Score: 132.73 E-value: 1.12e-33

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKA----SALRELNILSHLDHERILYFHDAFEKKNAVIIITELCHEELL 1743
Cdd:cd05579      1 ISRGAYGRVYLAKKKSTGDLYAIKVIKKRDMIRKnqvdSVLAERNILSQAQNPFVVKLYYSFQGKKNLYLVMEYLPGGDL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1744 DRLTKKSTIL-ESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMAdhSSDQIRICDFG---------------NAVKF 1807
Cdd:cd05579     81 YSLLENVGALdEDVARIYIAEIVLALEYLHSHGIIHRDLKPDNILID--ANGHLKLTDFGlskvglvrrqiklsiQKKSN 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1808 MPDEAQYCK-YGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMftDLCHE 1886
Cdd:cd05579    159 GAPEKEDRRiVGTPDYLAPEILLGQGHGKTVDWWSLGVILYEFLVGIPPFHAETPEEIFQNILNGKIEWPEDP--EVSDE 236

                          250       260       270
                   ....*....|....*....|....*....|....*
gi 1207186029 1887 AKGFVIKLLVADRL-RPDAN---ECLRHPWFKTLN 1917
Cdd:cd05579    237 AKDLISKLLTPDPEkRLGAKgieEIKNHPFFKGID 271

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-beta subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271071 [Multi-domain] Cd Length: 277 Bit Score: 132.32 E-value: 1.89e-33

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEP-ESKQTVLQ-EYDILKSLHHEKIMALHEAYVTPRYLVLISECCS 3377
Cdd:cd14169      5 YELKEKLGEGAFSEVVLAQERGSQRLVALKCIPKKAlRGKEAMVEnEIAVLRRINHENIVSLEDIYESPTHLYLAMELVT 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3378 GKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENII-VTYMNVVKII--DFGSAQTFNPLFLkqfSP 3454
Cdd:cd14169     85 GGELFDRIIERGSYTEKDASQLIGQVLQAVKYLHQLGIVHRDLKPENLLyATPFEDSKIMisDFGLSKIEAQGML---ST 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3455 PIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDL-SKLYQNVSQSASLFIKKIL 3533
Cdd:cd14169    162 ACGTPGYVAPELLEQKPYGKAVDVWAIGVISYILLCGYPPFYDENDSELFNQILKAEYEFdSPYWDDISESAKDFIRHLL 241

                          250
                   ....*....|....*....
gi 1207186029 3534 CSYPWARPTIKDCFTNSWL 3552
Cdd:cd14169    242 ERDPEKRFTCEQALQHPWI 260

Catalytic domain of the Serine/Threonine Kinase, Citron Rho-interacting kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CRIK (also called citron kinase) is an effector of the small GTPase Rho. It plays an important function during cytokinesis and affects its contractile process. CRIK-deficient mice show severe ataxia and epilepsy as a result of abnormal cytokinesis and massive apoptosis in neuronal precursors. A Down syndrome critical region protein TTC3 interacts with CRIK and inhibits CRIK-dependent neuronal differentiation and neurite extension. CRIK contains a catalytic domain, a central coiled-coil domain, and a C-terminal region containing a Rho-binding domain (RBD), a zinc finger, and a pleckstrin homology (PH) domain, in addition to other motifs. The CRIK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270752 [Multi-domain] Cd Length: 328 Bit Score: 133.59 E-value: 2.55e-33

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLY-MAKIVPYEPESKQTVLQ---EYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLh 3383
Cdd:cd05601     11 RGHFGEVQVVKEKATGDIYaMKVLKKSETLAQEEVSFfeeERDIMAKANSPWITKLQYAFQDSENLYLVMEYHPGGDLL- 89

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3384 SLIDRF--RYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLKQFSPPIGTLDY 3461
Cdd:cd05601     90 SLLSRYddIFEESMARFYLAELVLAIHSLHSMGYVHRDIKPENILIDRTGHIKLADFGSAAKLSSDKTVTSKMPVGTPDY 169

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3462 MSPEML------KGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLSK-LYQNVSQSASLFIKKILC 3534
Cdd:cd05601    170 IAPEVLtsmnggSKGTYGVECDWWSLGIVAYEMLYGKTPFTEDTVIKTYSNIMNFKKFLKFpEDPKVSESAVDLIKGLLT 249


                   .
gi 1207186029 3535 S 3535
Cdd:cd05601    250 D 250

Catalytic domain of RCK1-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of fungal STKs including Saccharomyces cerevisiae RCK1 and RCK2, Schizosaccharomyces pombe Sty1-regulated kinase 1 (Srk1), and similar proteins. RCK1, RCK2 (or Rck2p), and Srk1 are MAPK-activated protein kinases. RCK1 and RCK2 are involved in oxidative and metal stress resistance in budding yeast. RCK2 also regulates rapamycin sensitivity in both S. cerevisiae and Candida albicans. Srk1 is activated by Sty1/Spc1 and is involved in negatively regulating cell cycle progression by inhibiting Cdc25. The RCK1-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270998 [Multi-domain] Cd Length: 295 Bit Score: 132.56 E-value: 2.57e-33

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1659 TDYYDVHKeIGRGAFSYVKR--------------VIQKAGKLEYAAKfisarAKRKASALRELNILSHLDHERILYFHDA 1724
Cdd:cd14096      1 ENYRLINK-IGEGAFSNVYKavplrntgkpvaikVVRKADLSSDNLK-----GSSRANILKEVQIMKRLSHPNIVKLLDF 74

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1725 FEKKNAVIIITELCHE-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMA-----------DHS 1792
Cdd:cd14096     75 QESDEYYYIVLELADGgEIFHQIVRLTYFSEDLSRHVITQVASAVKYLHEIGVVHRDIKPENLLFEpipfipsivklRKA 154

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1793 SD--------------------QIRICDFGNAVKFMPDEAQY-CkyGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLT 1851
Cdd:cd14096    155 DDdetkvdegefipgvggggigIVKLADFGLSKQVWDSNTKTpC--GTVGYTAPEVVKDERYSKKVDMWALGCVLYTLLC 232

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1207186029 1852 GVSPFAGENDRSSVLNIRNYNVAFEESMFTDLCHEAKGFVIKLLVAD-RLRPDANECLRHPW 1912
Cdd:cd14096    233 GFPPFYDESIETLTEKISRGDYTFLSPWWDEISKSAKDLISHLLTVDpAKRYDIDEFLAHPW 294

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type IV; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKIV is found predominantly in neurons and immune cells. It is activated by the binding of calcium/CaM and phosphorylation by CaMKK (alpha or beta). The CaMKK-CaMKIV cascade participates in regulating several transcription factors like CREB, MEF2, and retinoid orphan receptors. It also is implicated in T-cell development and signaling, cytokine secretion, and signaling through Toll-like receptors, and is thus, pivotal in immune response and inflammation. The CaMKIV subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270987 [Multi-domain] Cd Length: 294 Bit Score: 131.87 E-value: 3.70e-33

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVPyEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGK 3379
Cdd:cd14085      5 FEIESELGRGATSVVYRCRQKGTQKPYAVKKLK-KTVDKKIVRTEIGVLLRLSHPNIIKLKEIFETPTEISLVLELVTGG 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3380 ELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYM---NVVKIIDFGSAQTFNPLFLkqFSPPI 3456
Cdd:cd14085     84 ELFDRIVEKGYYSERDAADAVKQILEAVAYLHENGIVHRDLKPENLLYATPapdAPLKIADFGLSKIVDQQVT--MKTVC 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3457 GTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPF-TENDPAETEARIQAAKFD-LSKLYQNVSQSASLFIKKILC 3534
Cdd:cd14085    162 GTPGYCAPEILRGCAYGPEVDMWSVGVITYILLCGFEPFyDERGDQYMFKRILNCDYDfVSPWWDDVSLNAKDLVKKLIV 241

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|.
gi 1207186029 3535 SYPWARPTIKDCFTNSWLQDAylmRLRRQTLTFTTTRLKEF 3575
Cdd:cd14085    242 LDPKKRLTTQQALQHPWVTGK---AANFAHMDTAQKKLQEF 279

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 1 (also called Doublecortin-like and CAM kinase-like 1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL1 (or DCAMKL1) belongs to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. In addition, DCKL1 contains a serine, threonine, and proline rich domain (SP) and a C-terminal kinase domain with similarity to CAMKs. DCKL1 interacts with tubulin, glucocorticoid receptor, dynein, JIP1/2, caspases (3 and 8), and calpain, among others. It plays roles in neurogenesis, neuronal migration, retrograde transport, and neuronal apoptosis. The DCKL1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271085 [Multi-domain] Cd Length: 268 Bit Score: 130.50 E-value: 6.25e-33

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1658 LTDYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASAL--RELNILSHLDHERILYFHDAFEKKNAVIIIT 1735
Cdd:cd14183      4 ISERYKVGRTIGDGNFAVVKECVERSTGREYALKIINKSKCRGKEHMiqNEVSILRRVKHPNIVLLIEEMDMPTELYLVM 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1736 ELCHE-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHS--SDQIRICDFGNAVkfMPDEA 1812
Cdd:cd14183     84 ELVKGgDLFDAITSTNKYTERDASGMLYNLASAIKYLHSLNIVHRDIKPENLLVYEHQdgSKSLKLGDFGLAT--VVDGP 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1813 QYCKYGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVL--NIRNYNVAFEESMFTDLCHEAKGF 1890
Cdd:cd14183    162 LYTVCGTPTYVAPEIIAETGYGLKVDIWAAGVITYILLCGFPPFRGSGDDQEVLfdQILMGQVDFPSPYWDNVSDSAKEL 241

                          250       260
                   ....*....|....*....|...
gi 1207186029 1891 VIKLLVAD-RLRPDANECLRHPW 1912
Cdd:cd14183    242 ITMMLQVDvDQRYSALQVLEHPW 264

Serine/threonine protein kinase [Signal transduction mechanisms];

Pssm-ID: 440281 [Multi-domain] Cd Length: 482 Bit Score: 135.91 E-value: 6.86e-33

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASAL----RELNILSHLDHERILYFHDAFEKKNAVIIITEL 1737
Cdd:COG0515      9 YRILRLLGRGGMGVVYLARDLRLGRPVALKVLRPELAADPEARerfrREARALARLNHPNIVRVYDVGEEDGRPYLVMEY 88

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1738 CH-EELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADhsSDQIRICDFGnAVKFMPDEAQYCK 1816
Cdd:COG0515     89 VEgESLADLLRRRGPLPPAEALRILAQLAEALAAAHAAGIVHRDIKPANILLTP--DGRVKLIDFG-IARALGGATLTQT 165

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1207186029 1817 ---YGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRN 1870
Cdd:COG0515    166 gtvVGTPGYMAPEQARGEPVDPRSDVYSLGVTLYELLTGRPPFDGDSPAELLRAHLR 222

Catalytic domain of the Serine/Threonine kinases, Autophagy-related protein 1 and Unc-51-like kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes yeast ATG1 and metazoan homologs including vertebrate ULK1-3. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. It is involved in nutrient sensing and signaling, the assembly of autophagy factors and the execution of autophagy. In metazoans, ATG1 homologs display additional functions. Unc-51 and ULKs have been implicated in neuronal and axonal development. The ATG1/ULK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270911 [Multi-domain] Cd Length: 251 Bit Score: 129.26 E-value: 1.03e-32

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKIVPYE---PESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLHS 3384
Cdd:cd14009      3 RGSFATVWKGRHKQTGEVVAIKEISRKklnKKLQENLESEIAILKSIKHPNIVRLYDVQKTEDFIYLVLEYCAGGDLSQY 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3385 LIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMN---VVKIIDFGSAQTFNPLFLKQF---SPPigt 3458
Cdd:cd14009     83 IRKRGRLPEAVARHFMQQLASGLKFLRSKNIIHRDLKPQNLLLSTSGddpVLKIADFGFARSLQPASMAETlcgSPL--- 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3459 ldYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLS-KLYQNVSQSASLFIKKILCSYP 3537
Cdd:cd14009    160 --YMAPEILQFQKYDAKADLWSVGAILFEMLVGKPPFRGSNHVQLLRNIERSDAVIPfPIAAQLSPDCKDLLRRLLRRDP 237

                          250
                   ....*....|....
gi 1207186029 3538 WARPTIKDCFTNSW 3551
Cdd:cd14009    238 AERISFEEFFAHPF 251

Catalytic domain of the Alpha subunit of the Serine/Threonine Kinase, AMP-activated protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. AMPK, also called SNF1 (sucrose non-fermenting1) in yeasts and SnRK1 (SNF1-related kinase1) in plants, is a heterotrimeric enzyme composed of a catalytic alpha subunit and two regulatory subunits, beta and gamma. It is a stress-activated kinase that serves as master regulator of glucose and lipid metabolism by monitoring carbon and energy supplies, via sensing the cell's AMP:ATP ratio. In response to decreased ATP levels, it enhances energy-producing processes and inhibits energy-consuming pathways. Once activated, AMPK phosphorylates a broad range of downstream targets, with effects in carbohydrate metabolism and uptake, lipid and fatty acid biosynthesis, carbon energy storage, and inflammation, among others. Defects in energy homeostasis underlie many human diseases including Type 2 diabetes, obesity, heart disease, and cancer. As a result, AMPK has emerged as a therapeutic target in the treatment of these diseases. The AMPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270981 [Multi-domain] Cd Length: 256 Bit Score: 128.93 E-value: 1.43e-32

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3299 PYTFMDEKARGRFGVIRECRENATGNLYMAKIVPYE----PESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISE 3374
Cdd:cd14079      3 NYILGKTLGVGSFGKVKLAEHELTGHKVAVKILNRQkiksLDMEEKIRREIQILKLFRHPHIIRLYEVIETPTDIFMVME 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3375 CCSGKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFG-SAQTFNPLFLKQfs 3453
Cdd:cd14079     83 YVSGGELFDYIVQKGRLSEDEARRFFQQIISGVEYCHRHMVVHRDLKPENLLLDSNMNVKIADFGlSNIMRDGEFLKT-- 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3454 pPIGTLDYMSPEMLKGDV-VGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFdlsKLYQNVSQSASLFIKKI 3532
Cdd:cd14079    161 -SCGSPNYAAPEVISGKLyAGPEVDVWSCGVILYALLCGSLPFDDEHIPNLFKKIKSGIY---TIPSHLSPGARDLIKRM 236

                          250       260
                   ....*....|....*....|
gi 1207186029 3533 LCSYPWARPTIKDCFTNSWL 3552
Cdd:cd14079    237 LVVDPLKRITIPEIRQHPWF 256

Catalytic domain of the Serine/Threonine Kinase, SNF1-related kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SNRK is a kinase highly expressed in testis and brain that is found inactive in cells that lack the LKB1 tumour suppressor protein kinase. The regulatory subunits STRAD and MO25 are required for LKB1 to activate SNRK. The SNRK mRNA is increased 3-fold when granule neurons are cultured in low potassium, and may thus play a role in the survival responses in these cells. In some vertebrates, a second SNRK gene (snrkb or snrk-1) has been sequenced and/or identified. Snrk-1 is expressed specifically in embryonic zebrafish vasculature; it plays an essential role in angioblast differentiation, maintenance, and migration. The SNRK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270976 [Multi-domain] Cd Length: 258 Bit Score: 129.07 E-value: 1.47e-32

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIV---PYEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECC 3376
Cdd:cd14074      5 YDLEETLGRGHFAVVKLARHVFTGEKVAVKVIdktKLDDVSKAHLFQEVRCMKLVQHPNVVRLYEVIDTQTKLYLILELG 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3377 SGKELlHSLIDRFR--YSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIV-TYMNVVKIIDFGSAQTFNPLflKQFS 3453
Cdd:cd14074     85 DGGDM-YDYIMKHEngLNEDLARKYFRQIVSAISYCHKLHVVHRDLKPENVVFfEKQGLVKLTDFGFSNKFQPG--EKLE 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3454 PPIGTLDYMSPEMLKGDVVGPPA-DIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLSklyQNVSQSASLFIKKI 3532
Cdd:cd14074    162 TSCGSLAYSAPEILLGDEYDAPAvDIWSLGVILYMLVCGQPPFQEANDSETLTMIMDCKYTVP---AHVSPECKDLIRRM 238

                          250       260
                   ....*....|....*....|
gi 1207186029 3533 LCSYPWARPTIKDCFTNSWL 3552
Cdd:cd14074    239 LIRDPKKRASLEEIENHPWL 258

Catalytic domain of testis-specific serine/threonine kinase 4 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK4, also called TSSK5, is expressed in testis from haploid round spermatids to mature spermatozoa. It phosphorylates Cre-Responsive Element Binding protein (CREB), facilitating the binding of CREB to the specific cis cAMP responsive element (CRE), which is important in activating genes related to germ cell differentiation. Mutations in the human TSSK4 gene is associated with infertile Chinese men with impaired spermatogenesis. The TSSK4-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271064 [Multi-domain] Cd Length: 259 Bit Score: 128.95 E-value: 1.64e-32

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISaraKRKASA-------LRELNILSHLDHERILYFHDAFEKKNAVIII 1734
Cdd:cd14162      2 YIVGKTLGHGSYAVVKKAYSTKHKCKVAIKIVS---KKKAPEdylqkflPREIEVIKGLKHPNLICFYEAIETTSRVYII 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1735 TELCHE-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHssDQIRICDFGNAVKFM-PDEA 1812
Cdd:cd14162     79 MELAENgDLLDYIRKNGALPEPQARRWFRQLVAGVEYCHSKGVVHRDLKCENLLLDKN--NNLKITDFGFARGVMkTKDG 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1813 Q------YCkyGTPEFVAPEIVNQTPVS-KATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNyNVAFEESmfTDLCH 1885
Cdd:cd14162    157 KpklsetYC--GSYAYASPEILRGIPYDpFLSDIWSMGVVLYTMVYGRLPFDDSNLKVLLKQVQR-RVVFPKN--PTVSE 231

                          250       260
                   ....*....|....*....|....*...
gi 1207186029 1886 EAKGFVIKLLVADRLRPDANECLRHPWF 1913
Cdd:cd14162    232 ECKDLILRMLSPVKKRITIEEIKRDPWF 259

Catalytic domain of Cyclin-Dependent protein Kinase Like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDKL1-5 and similar proteins. Some CDKLs, like CDKL1 and CDKL3, may be implicated in transformation and others, like CDKL3 and CDKL5, are associated with mental retardation when impaired. CDKL2 plays a role in learning and memory. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270827 [Multi-domain] Cd Length: 288 Bit Score: 129.74 E-value: 1.77e-32

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAK---IVPYEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECC 3376
Cdd:cd07833      3 YEVLGVVGEGAYGVVLKCRNKATGEIVAIKkfkESEDDEDVKKTALREVKVLRQLRHENIVNLKEAFRRKGRLYLVFEYV 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3377 sGKELLHsLIDRFRY--SEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQtfnplFLKQFSP 3454
Cdd:cd07833     83 -ERTLLE-LLEASPGglPPDAVRSYIWQLLQAIAYCHSHNIIHRDIKPENILVSESGVLKLCDFGFAR-----ALTARPA 155

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3455 P-----IGTLDYMSPEMLKGDV-VGPPADIWSIGILTYIMLSGRLPFT-END---------------PAETE-----ARI 3507
Cdd:cd07833    156 SpltdyVATRWYRAPELLVGDTnYGKPVDVWAIGCIMAELLDGEPLFPgDSDidqlyliqkclgplpPSHQElfssnPRF 235

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1207186029 3508 QAAKF-------DLSKLYQNVSQSASL-FIKKILCSYPWARPTIKDCftnswLQDAYL 3557
Cdd:cd07833    236 AGVAFpepsqpeSLERRYPGKVSSPALdFLKACLRMDPKERLTCDEL-----LQHPYF 288

Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii FA2 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Chlamydomonas reinhardtii FA2 was discovered in a genetic screen for deflagellation-defective mutants. It is essential for basal-body/centriole-associated microtubule severing, and plays a role in cell cycle progression. No cellular function has yet been ascribed to CNK4. The Chlamydomonas reinhardtii FA2-like subfamily belongs to the (NIMA)-related kinase (Nek) family, which includes seven different Chlamydomonas Neks (CNKs 1-6 and Fa2). This subfamily contains FA2 and CNK4. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270868 [Multi-domain] Cd Length: 256 Bit Score: 128.30 E-value: 2.61e-32

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFI---SARAKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITELC 1738
Cdd:cd08529      2 FEILNKLGKGSFGVVYKVVRKVDGRVYALKQIdisRMSRKMREEAIDEARVLSKLNSPYVIKYYDSFVDKGKLNIVMEYA 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1739 HEELLDRLTKK---STILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDFGNAvKFMPDEAQYC 1815
Cdd:cd08529     82 ENGDLHSLIKSqrgRPLPEDQIWKFFIQTLLGLSHLHSKKILHRDIKSMNIFL--DKGDNVKIGDLGVA-KILSDTTNFA 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1816 K--YGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNI-RNYNVAFEESMFTDLCHeakgFVI 1892
Cdd:cd08529    159 QtiVGTPYYLSPELCEDKPYNEKSDVWALGCVLYELCTGKHPFEAQNQGALILKIvRGKYPPISASYSQDLSQ----LID 234

                          250       260
                   ....*....|....*....|
gi 1207186029 1893 KLLVAD-RLRPDANECLRHP 1911
Cdd:cd08529    235 SCLTKDyRQRPDTTELLRNP 254

Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Checkpoint Kinase 2 (Chk2) plays an important role in cellular responses to DNA double-strand breaks and related lesions. It is phosphorylated and activated by ATM kinase, resulting in its dissociation from sites of damage to phosphorylate downstream targets such as BRCA1, p53, cell cycle transcription factor E2F1, the promyelocytic leukemia protein (PML) involved in apoptosis, and CDC25 phosphatases, among others. Mutations in Chk2 is linked to a variety of cancers including familial breast cancer, myelodysplastic syndromes, prostate cancer, lung cancer, and osteosarcomas. Chk2 contains an N-terminal SQ/TQ cluster domain (SCD), a central forkhead-associated (FHA) domain, and a C-terminal catalytic kinase domain. The Chk2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270986 [Multi-domain] Cd Length: 275 Bit Score: 128.28 E-value: 3.71e-32

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3341 VLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDI 3420
Cdd:cd14084     58 IETEIEILKKLSHPCIIKIEDFFDAEDDYYIVLELMEGGELFDRVVSNKRLKEAICKLYFYQMLLAVKYLHSNGIIHRDL 137

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3421 KPENIIVTYMN---VVKIIDFGSAQTF-NPLFLKQFSppiGTLDYMSPEMLK--GDV-VGPPADIWSIGILTYIMLSGRL 3493
Cdd:cd14084    138 KPENVLLSSQEeecLIKITDFGLSKILgETSLMKTLC---GTPTYLAPEVLRsfGTEgYTRAVDCWSLGVILFICLSGYP 214

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1207186029 3494 PFTEnDPAETEARIQAAK----FDlSKLYQNVSQSASLFIKKILCSYPWARPTIKDCFTNSWL 3552
Cdd:cd14084    215 PFSE-EYTQMSLKEQILSgkytFI-PKAWKNVSEEAKDLVKKMLVVDPSRRPSIEEALEHPWL 275

Catalytic domain of the Serine/Threonine Kinase, Calcium/calmodulin-dependent serine protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CASK belongs to the MAGUK (membrane-associated guanylate kinase) protein family, which functions as multiple domain adaptor proteins and is characterized by the presence of a core of three domains: PDZ, SH3, and guanylate kinase (GuK). The enzymatically inactive GuK domain in MAGUK proteins mediates protein-protein interactions and associates intramolecularly with the SH3 domain. In addition, CASK contains a catalytic kinase and two L27 domains. It is highly expressed in the nervous system and plays roles in synaptic protein targeting, neural development, and regulation of gene expression. Binding partners include parkin (a Parkinson's disease molecule), neurexin (adhesion molecule), syndecans, calcium channel proteins, CINAP (nucleosome assembly protein), transcription factor Tbr-1, and the cytoplasmic adaptor proteins Mint1, Veli/mLIN-7/MALS, SAP97, caskin, and CIP98. Deletion or mutations in the CASK gene have been implicated in X-linked mental retardation. The CASK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270996 [Multi-domain] Cd Length: 300 Bit Score: 128.81 E-value: 4.98e-32

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1658 LTDYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASAL------RELNILSHLDHERILYFHDAFEKKNAV 1731
Cdd:cd14094      1 FEDVYELCEVIGKGPFSVVRRCIHRETGQQFAVKIVDVAKFTSSPGLstedlkREASICHMLKHPHIVELLETYSSDGML 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1732 IIITE------LCHEeLLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMAD-HSSDQIRICDFGNA 1804
Cdd:cd14094     81 YMVFEfmdgadLCFE-IVKRADAGFVYSEAVASHYMRQILEALRYCHDNNIIHRDVKPHCVLLASkENSAPVKLGGFGVA 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1805 VKFMPDEAQYC-KYGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNyNVAFEESMFTDL 1883
Cdd:cd14094    160 IQLGESGLVAGgRVGTPHFMAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFYGTKERLFEGIIKG-KYKMNPRQWSHI 238

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1884 CHEAKGFVIKLLVAD-RLRPDANECLRHPWFKtlNKGKSIS-------TESLKKFLSRRK 1935
Cdd:cd14094    239 SESAKDLVRRMLMLDpAERITVYEALNHPWIK--ERDRYAYrihlpetVEQLRKFNARRK 296

Catalytic subunit of the Serine/Threonine Kinases, cAMP-dependent protein kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the cAMP-dependent protein kinases, PKA and PRKX, and similar proteins. The inactive PKA holoenzyme is a heterotetramer composed of two phosphorylated and active catalytic subunits with a dimer of regulatory (R) subunits. Activation is achieved through the binding of the important second messenger cAMP to the R subunits, which leads to the dissociation of PKA into the R dimer and two active subunits. PKA is present ubiquitously in cells and interacts with many different downstream targets. It plays a role in the regulation of diverse processes such as growth, development, memory, metabolism, gene expression, immunity, and lipolysis. PRKX is also reulated by the R subunit and is is present in many tissues including fetal and adult brain, kidney, and lung. It is implicated in granulocyte/macrophage lineage differentiation, renal cell epithelial migration, and tubular morphogenesis in the developing kidney. The PKA-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270732 [Multi-domain] Cd Length: 290 Bit Score: 128.47 E-value: 6.07e-32

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3309 GRFGVIRECRENATGNLYMAKIVPYEP--ESKQT--VLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLHS 3384
Cdd:cd05580     12 GSFGRVRLVKHKDSGKYYALKILKKAKiiKLKQVehVLNEKRILSEVRHPFIVNLLGSFQDDRNLYMVMEYVPGGELFSL 91

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3385 LIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGsaqtfnplFLKQFSPP----IGTLD 3460
Cdd:cd05580     92 LRRSGRFPNDVAKFYAAEVVLALEYLHSLDIVYRDLKPENLLLDSDGHIKITDFG--------FAKRVKDRtytlCGTPE 163

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1207186029 3461 YMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLSKlyqNVSQSASLFIKKIL 3533
Cdd:cd05580    164 YLAPEIILSKGHGKAVDWWALGILIYEMLAGYPPFFDENPMKIYEKILEGKIRFPS---FFDPDAKDLIKRLL 233

Catalytic domain of Cell division control protein 7-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily include Schizosaccharomyces pombe Cdc7, Saccharomyces cerevisiae Cdc15, Arabidopsis thaliana mitogen-activated protein kinase kinase kinase (MAPKKK) epsilon, and related proteins. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Fission yeast Cdc7 is essential for cell division by playing a key role in the initiation of septum formation and cytokinesis. Budding yeast Cdc15 functions to coordinate mitotic exit with cytokinesis. Arabidopsis MAPKKK epsilon is required for pollen development in the plasma membrane. The Cdc7-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270797 [Multi-domain] Cd Length: 254 Bit Score: 126.96 E-value: 6.80e-32

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVPYE---PESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECC 3376
Cdd:cd06627      2 YQLGDLIGRGAFGSVYKGLNLNTGEFVAIKQISLEkipKSDLKSVMGEIDLLKKLNHPNIVKYIGSVKTKDSLYIILEYV 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3377 SGKELlHSLIDRF-RYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLKQFSpP 3455
Cdd:cd06627     82 ENGSL-ASIIKKFgKFPESLVAVYIYQVLEGLAYLHEQGVIHRDIKGANILTTKDGLVKLADFGVATKLNEVEKDENS-V 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3456 IGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIqaAKFDLSKLYQNVSQSASLFIKKILCS 3535
Cdd:cd06627    160 VGTPYWMAPEVIEMSGVTTASDIWSVGCTVIELLTGNPPYYDLQPMAALFRI--VQDDHPPLPENISPELRDFLLQCFQK 237

                          250
                   ....*....|....*..
gi 1207186029 3536 YPWARPTIKDCFTNSWL 3552
Cdd:cd06627    238 DPTLRPSAKELLKHPWL 254

Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii CNK2 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Chlamydomonas reinhardtii CNK2 has both cilliary and cell cycle functions. It influences flagellar length through promoting flagellar disassembly, and it regulates cell size, through influencing the size threshold at which cells commit to mitosis. This subfamily belongs to the (NIMA)-related kinase (Nek) family, which includes seven different Chlamydomonas Neks (CNKs 1-6 and Fa2). This subfamily includes CNK1, and -2. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270869 [Multi-domain] Cd Length: 256 Bit Score: 127.12 E-value: 7.10e-32

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKIVPYEPES---KQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLHS 3384
Cdd:cd08530     10 KGSYGSVYKVKRLSDNQVYALKEVNLGSLSqkeREDSVNEIRLLASVNHPNIIRYKEAFLDGNRLCIVMEYAPFGDLSKL 89

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3385 LIDRFR----YSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLKQfspPIGTLD 3460
Cdd:cd08530     90 ISKRKKkrrlFPEDDIWRIFIQMLRGLKALHDQKILHRDLKSANILLSAGDLVKIGDLGISKVLKKNLAKT---QIGTPL 166

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3461 YMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDlsKLYQNVSQSASLFIKKILCSYPWAR 3540
Cdd:cd08530    167 YAAPEVWKGRPYDYKSDIWSLGCLLYEMATFRPPFEARTMQELRYKVCRGKFP--PIPPVYSQDLQQIIRSLLQVNPKKR 244


                   ....*
gi 1207186029 3541 PTIKD 3545
Cdd:cd08530    245 PSCDK 249

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I alpha; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-alpha subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271069 [Multi-domain] Cd Length: 263 Bit Score: 127.07 E-value: 8.37e-32

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEP-ESKQTVLQ-EYDILKSLHHEKIMALHEAYVTPRYLVLISECCS 3377
Cdd:cd14167      5 YDFREVLGTGAFSEVVLAEEKRTQKLVAIKCIAKKAlEGKETSIEnEIAVLHKIKHPNIVALDDIYESGGHLYLIMQLVS 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3378 GKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMN---VVKIIDFGSAQTFNPLFLkqFSP 3454
Cdd:cd14167     85 GGELFDRIVEKGFYTERDASKLIFQILDAVKYLHDMGIVHRDLKPENLLYYSLDedsKIMISDFGLSKIEGSGSV--MST 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3455 PIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDL-SKLYQNVSQSASLFIKKIL 3533
Cdd:cd14167    163 ACGTPGYVAPEVLAQKPYSKAVDCWSIGVIAYILLCGYPPFYDENDAKLFEQILKAEYEFdSPYWDDISDSAKDFIQHLM 242

                          250
                   ....*....|....*....
gi 1207186029 3534 CSYPWARPTIKDCFTNSWL 3552
Cdd:cd14167    243 EKDPEKRFTCEQALQHPWI 261

Catalytic domain of the Serine/Threonine Kinase, NIM1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NIM1 is a widely-expressed kinase belonging to the AMP-activated protein kinase (AMPK) subfamily. Although present in most tissues, NIM1 kinase activity is only observed in the brain and testis. NIM1 is capable of autophosphorylating and activating itself, but may be present in other tissues in the inactive form. The physiological function of NIM1 has yet to be elucidated. The NIM1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270977 [Multi-domain] Cd Length: 255 Bit Score: 126.68 E-value: 9.29e-32

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3343 QEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKP 3422
Cdd:cd14075     50 REISSMEKLHHPNIIRLYEVVETLSKLHLVMEYASGGELYTKISTEGKLSESEAKPLFAQIVSAVKHMHENNIIHRDLKA 129

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3423 ENIIVTYMNVVKIIDFGSAQTFNPL-FLKQF--SPPigtldYMSPEMLKGD-VVGPPADIWSIGILTYIMLSGRLPFTEN 3498
Cdd:cd14075    130 ENVFYASNNCVKVGDFGFSTHAKRGeTLNTFcgSPP-----YAAPELFKDEhYIGIYVDIWALGVLLYFMVTGVMPFRAE 204

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1207186029 3499 DPAETEARIQAAKFDLSklyQNVSQSASLFIKKILCSYPWARPTIKDCFTNSWL 3552
Cdd:cd14075    205 TVAKLKKCILEGTYTIP---SYVSEPCQELIRGILQPVPSDRYSIDEIKNSEWL 255

Catalytic domain of the Serine/Threonine kinase, Liver Kinase B1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LKB1, also called STK11, was first identified as a tumor suppressor responsible for Peutz-Jeghers syndrome, a disorder that leads to an increased risk of spontaneous epithelial cancer. It serves as a master upstream kinase that activates AMP-activated protein kinase (AMPK) and most AMPK-like kinases. LKB1 and AMPK are part of an energy-sensing pathway that links cell energy to metabolism and cell growth. They play critical roles in the establishment and maintenance of cell polarity, cell proliferation, cytoskeletal organization, as well as T-cell metabolism, including T-cell development, homeostasis, and effector function. To be activated, LKB1 requires the adaptor proteins STe20-Related ADaptor (STRAD) and mouse protein 25 (MO25). The LKB1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271021 [Multi-domain] Cd Length: 255 Bit Score: 126.22 E-value: 1.27e-31

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYVKRVIQKAGKLEYAAKFISARAKRK-----ASALRELNILSHLDHERILYFHDAF--EKKNAVIIITELCH- 1739
Cdd:cd14119      1 LGEGSYGKVKEVLDTETLCRRAVKILKKRKLRRipngeANVKREIQILRRLNHRNVIKLVDVLynEEKQKLYMVMEYCVg 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1740 --EELLDRLT-KKSTILESEirSSVRQLLEGINYLHQLDILHLDIKPDNILMadhSSDQI-RICDFGNAV---KFMPDEA 1812
Cdd:cd14119     81 glQEMLDSAPdKRLPIWQAH--GYFVQLIDGLEYLHSQGIIHKDIKPGNLLL---TTDGTlKISDFGVAEaldLFAEDDT 155

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1813 QYCKYGTPEFVAPEIVN--QTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDLCHEAKGf 1890
Cdd:cd14119    156 CTTSQGSPAFQPPEIANgqDSFSGFKVDIWSAGVTLYNMTTGKYPFEGDNIYKLFENIGKGEYTIPDDVDPDLQDLLRG- 234

                          250       260
                   ....*....|....*....|....
gi 1207186029 1891 vikLLVAD-RLRPDANECLRHPWF 1913
Cdd:cd14119    235 ---MLEKDpEKRFTIEQIRQHPWF 255

Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein kinase subfamily 2, group 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The SnRKs form three different subfamilies designated SnRK1-3. SnRK2 is represented in this cd. SnRK2s are involved in plant response to abiotic stresses and abscisic acid (ABA)-dependent plant development. The SnRK2s subfamily is in turn classed into three subgroups, all 3 of which are represented in this CD. Group 1 comprises kinases not activated by ABA, group 2 - kinases not activated or activated very weakly by ABA (depending on plant species), and group 3 - kinases strongly activated by ABA. The SnRKs belong to a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271135 [Multi-domain] Cd Length: 257 Bit Score: 126.25 E-value: 1.46e-31

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGK 3379
Cdd:cd14665      2 YELVKDIGSGNFGVARLMRDKQTKELVAVKYIERGEKIDENVQREIINHRSLRHPNIVRFKEVILTPTHLAIVMEYAAGG 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3380 ELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIV--TYMNVVKIIDFGSAQTfnPLFLKQFSPPIG 3457
Cdd:cd14665     82 ELFERICNAGRFSEDEARFFFQQLISGVSYCHSMQICHRDLKLENTLLdgSPAPRLKICDFGYSKS--SVLHSQPKSTVG 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3458 TLDYMSPE-MLKGDVVGPPADIWSIGILTYIMLSGRLPFteNDPAE------TEARIQAAKFDLSKlYQNVSQSASLFIK 3530
Cdd:cd14665    160 TPAYIAPEvLLKKEYDGKIADVWSCGVTLYVMLVGAYPF--EDPEEprnfrkTIQRILSVQYSIPD-YVHISPECRHLIS 236

                          250       260
                   ....*....|....*....|.
gi 1207186029 3531 KILCSYPWARPTIKDCFTNSW 3551
Cdd:cd14665    237 RIFVADPATRITIPEIRNHEW 257

Catalytic domain of Serine/Threonine Kinase 36; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK36, also called Fused (or Fu) kinase, is involved in the Hedgehog signaling pathway. It is activated by the Smoothened (SMO) signal transducer, resulting in the stabilization of GLI transcription factors and the phosphorylation of SUFU to facilitate the nuclear accumulation of GLI. In Drosophila, Fused kinase is maternally required for proper segmentation during embryonic development and for the development of legs and wings during the larval stage. In mice, STK36 is not necessary for embryonic development, although mice deficient in STK36 display growth retardation postnatally. The STK36 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270904 [Multi-domain] Cd Length: 253 Bit Score: 125.83 E-value: 1.88e-31

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKIVPYEPESKQTVL---QEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGkELLHS 3384
Cdd:cd14002     11 EGSFGKVYKGRRKYTGQVVALKFIPKRGKSEKELRnlrQEIEILRKLNHPNIIEMLDSFETKKEFVVVTEYAQG-ELFQI 89

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3385 LIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQ--TFNPLFLKQFSppiGTLDYM 3462
Cdd:cd14002     90 LEDDGTLPEEEVRSIAKQLVSALHYLHSNRIIHRDMKPQNILIGKGGVVKLCDFGFARamSCNTLVLTSIK---GTPLYM 166

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1207186029 3463 SPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETearIQAAKFDLSKLYQNVSQSASLFIKKILCSYPWAR 3540
Cdd:cd14002    167 APELVQEQPYDHTADLWSLGCILYELFVGQPPFYTNSIYQL---VQMIVKDPVKWPSNMSPEFKSFLQGLLNKDPSKR 241

Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NUAK proteins are classified as AMP-activated protein kinase (AMPK)-related kinases, which like AMPK are activated by the major tumor suppressor LKB1. Vertebrates contain two NUAK proteins, called NUAK1 and NUAK2. NUAK1, also called ARK5 (AMPK-related protein kinase 5), regulates cell proliferation and displays tumor suppression through direct interaction and phosphorylation of p53. It is also involved in cell senescence and motility. High NUAK1 expression is associated with invasiveness of nonsmall cell lung cancer (NSCLC) and breast cancer cells. NUAK2, also called SNARK (Sucrose, non-fermenting 1/AMP-activated protein kinase-related kinase), is involved in energy metabolism. It is activated by hyperosmotic stress, DNA damage, and nutrients such as glucose and glutamine. NUAK2-knockout mice develop obesity, altered serum lipid profiles, hyperinsulinaemia, hyperglycaemia, and impaired glucose tolerance. The NUAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270975 [Multi-domain] Cd Length: 254 Bit Score: 125.19 E-value: 3.01e-31

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISaRAKRKASA-----LRELNILSHLDHERILYFHDAFEKKNAVIIITE 1736
Cdd:cd14073      3 YELLETLGKGTYGKVKLAIERATGREVAIKSIK-KDKIEDEQdmvriRREIEIMSSLNHPHIIRIYEVFENKDKIVIVME 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1737 LCHE-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSdqIRICDFGNAVKFMPDE--AQ 1813
Cdd:cd14073     82 YASGgELYDYISERRRLPEREARRIFRQIVSAVHYCHKNGVVHRDLKLENILLDQNGN--AKIADFGLSNLYSKDKllQT 159

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*...
gi 1207186029 1814 YCkyGTPEFVAPEIVNQTP-VSKATDIWPIGVLTYLCLTGVSPFAGEN 1860
Cdd:cd14073    160 FC--GSPLYASPEIVNGTPyQGPEVDCWSLGVLLYTLVYGTMPFDGSD 205

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 2 (also called Doublecortin-like and CAM kinase-like 2); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL2 (or DCAMKL2) belongs to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. In addition, DCKL2 contains a serine, threonine, and proline rich domain (SP) and a C-terminal kinase domain with similarity to CAMKs. DCKL2 has been shown to interact with tubulin, JIP1/2, JNK, neurabin 2, and actin. It is associated with the terminal segments of axons and dendrites, and may function as a phosphorylation-dependent switch to control microtubule dynamics in neuronal growth cones. The DCKL2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271086 [Multi-domain] Cd Length: 259 Bit Score: 125.53 E-value: 3.01e-31

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1660 DYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASAL--RELNILSHLDHERILYFHDAFEKKNAVIIITEL 1737
Cdd:cd14184      1 EKYKIGKVIGDGNFAVVKECVERSTGKEFALKIIDKAKCCGKEHLieNEVSILRRVKHPNIIMLIEEMDTPAELYLVMEL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1738 CHE-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHS--SDQIRICDFGNAVkfMPDEAQY 1814
Cdd:cd14184     81 VKGgDLFDAITSSTKYTERDASAMVYNLASALKYLHGLCIVHRDIKPENLLVCEYPdgTKSLKLGDFGLAT--VVEGPLY 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1815 CKYGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVL--NIRNYNVAFEESMFTDLCHEAKGFVI 1892
Cdd:cd14184    159 TVCGTPTYVAPEIIAETGYGLKVDIWAAGVITYILLCGFPPFRSENNLQEDLfdQILLGKLEFPSPYWDNITDSAKELIS 238

                          250       260
                   ....*....|....*....|.
gi 1207186029 1893 KLL-VADRLRPDANECLRHPW 1912
Cdd:cd14184    239 HMLqVNVEARYTAEQILSHPW 259

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK2, also called Snk (serum-inducible kinase), functions in G1 progression, S-phase arrest, and centriole duplication. Its gene is responsive to both growth factors and cellular stress, is a transcriptional target of p53, and activates a G2-M checkpoint. The PLK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271090 [Multi-domain] Cd Length: 255 Bit Score: 125.12 E-value: 3.57e-31

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3307 ARGRFGVIRECRENATGNLYMAKIVPY----EPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELL 3382
Cdd:cd14188     10 GKGGFAKCYEMTDLTTNKVYAAKIIPHsrvsKPHQREKIDKEIELHRILHHKHVVQFYHYFEDKENIYILLEYCSRRSMA 89

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3383 HSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLKQFSpPIGTLDYM 3462
Cdd:cd14188     90 HILKARKVLTEPEVRYYLRQIVSGLKYLHEQEILHRDLKLGNFFINENMELKVGDFGLAARLEPLEHRRRT-ICGTPNYL 168

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3463 SPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLSklyQNVSQSASLFIKKILCSYPWARPT 3542
Cdd:cd14188    169 SPEVLNKQGHGCESDIWALGCVMYTMLLGRPPFETTNLKETYRCIREARYSLP---SSLLAPAKHLIASMLSKNPEDRPS 245


                   ...
gi 1207186029 3543 IKD 3545
Cdd:cd14188    246 LDE 248

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK3, also called Prk or Fnk (FGF-inducible kinase), regulates angiogenesis and responses to DNA damage. Activated PLK3 mediates Chk2 phosphorylation by ATM and the resulting checkpoint activation. PLK3 phosphorylates DNA polymerase delta and may be involved in DNA repair. It also inhibits Cdc25c, thereby regulating the onset of mitosis. The PLK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271091 [Multi-domain] Cd Length: 255 Bit Score: 124.65 E-value: 4.08e-31

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKIVPY----EPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLH 3383
Cdd:cd14189     11 KGGFARCYEMTDLATNKTYAVKVIPHsrvaKPHQREKIVNEIELHRDLHHKHVVKFSHHFEDAENIYIFLELCSRKSLAH 90

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3384 SLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPlfLKQFSPPI-GTLDYM 3462
Cdd:cd14189     91 IWKARHTLLEPEVRYYLKQIISGLKYLHLKGILHRDLKLGNFFINENMELKVGDFGLAARLEP--PEQRKKTIcGTPNYL 168

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3463 SPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLSklyQNVSQSASLFIKKILCSYPWARPT 3542
Cdd:cd14189    169 APEVLLRQGHGPESDVWSLGCVMYTLLCGNPPFETLDLKETYRCIKQVKYTLP---ASLSLPARHLLAGILKRNPGDRLT 245


                   .
gi 1207186029 3543 I 3543
Cdd:cd14189    246 L 246

Catalytic domain of the Serine/Threonine Kinase, Calcium/calmodulin-dependent serine protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CASK belongs to the MAGUK (membrane-associated guanylate kinase) protein family, which functions as multiple domain adaptor proteins and is characterized by the presence of a core of three domains: PDZ, SH3, and guanylate kinase (GuK). The enzymatically inactive GuK domain in MAGUK proteins mediates protein-protein interactions and associates intramolecularly with the SH3 domain. In addition, CASK contains a catalytic kinase and two L27 domains. It is highly expressed in the nervous system and plays roles in synaptic protein targeting, neural development, and regulation of gene expression. Binding partners include parkin (a Parkinson's disease molecule), neurexin (adhesion molecule), syndecans, calcium channel proteins, CINAP (nucleosome assembly protein), transcription factor Tbr-1, and the cytoplasmic adaptor proteins Mint1, Veli/mLIN-7/MALS, SAP97, caskin, and CIP98. Deletion or mutations in the CASK gene have been implicated in X-linked mental retardation. The CASK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270996 [Multi-domain] Cd Length: 300 Bit Score: 125.73 E-value: 5.97e-31

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKIVPYEPESKQTVL------QEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKEL 3381
Cdd:cd14094     13 KGPFSVVRRCIHRETGQQFAVKIVDVAKFTSSPGLstedlkREASICHMLKHPHIVELLETYSSDGMLYMVFEFMDGADL 92

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3382 LHSLIDR----FRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNV---VKIIDFGSAQTFNPLFLKQfSP 3454
Cdd:cd14094     93 CFEIVKRadagFVYSEAVASHYMRQILEALRYCHDNNIIHRDVKPHCVLLASKENsapVKLGGFGVAIQLGESGLVA-GG 171

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3455 PIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPF--TENDPAEteaRIQAAKFDLS-KLYQNVSQSASLFIKK 3531
Cdd:cd14094    172 RVGTPHFMAPEVVKREPYGKPVDVWGCGVILFILLSGCLPFygTKERLFE---GIIKGKYKMNpRQWSHISESAKDLVRR 248

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*....
gi 1207186029 3532 ILCSYPWARPTIKDCFTNSWLQDAYLMrLRRQTLTFTTTRLKEFLEQQQ 3580
Cdd:cd14094    249 MLMLDPAERITVYEALNHPWIKERDRY-AYRIHLPETVEQLRKFNARRK 296

Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma subunit; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phosphorylase kinase (PhK) catalyzes the phosphorylation of inactive phosphorylase b to form the active phosphorylase a. It coordinates hormonal, metabolic, and neuronal signals to initiate the breakdown of glycogen stores, which enables the maintenance of blood-glucose homeostasis during fasting, and is also used as a source of energy for muscle contraction. PhK is one of the largest and most complex protein kinases, composed of a heterotetramer containing four molecules each of four subunit types: one catalytic (gamma) and three regulatory (alpha, beta, and delta). Each subunit has tissue-specific isoforms or splice variants. Vertebrates contain two isoforms of the gamma subunit (gamma 1 and gamma 2). The gamma subunit, when isolated, is constitutively active and does not require phosphorylation of the A-loop for activity. The regulatory subunits restrain this kinase activity until signals are received to relieve this inhibition. For example, the kinase is activated in response to hormonal stimulation, after autophosphorylation or phosphorylation by cAMP-dependent kinase of the alpha and beta subunits. The high-affinity binding of ADP to the beta subunit also stimulates kinase activity, whereas calcium relieves inhibition by binding to the delta (calmodulin) subunit. The PhKG subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270995 [Multi-domain] Cd Length: 272 Bit Score: 124.77 E-value: 6.03e-31

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKIV--------PYEPES-KQTVLQEYDILKSLH-HEKIMALHEAYVTPRYLVLISECCS 3377
Cdd:cd14093     13 RGVSSTVRRCIEKETGQEFAVKIIditgekssENEAEElREATRREIEILRQVSgHPNIIELHDVFESPTFIFLVFELCR 92

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3378 GKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNP-LFLKQFsppI 3456
Cdd:cd14093     93 KGELFDYLTEVVTLSEKKTRRIMRQLFEAVEFLHSLNIVHRDLKPENILLDDNLNVKISDFGFATRLDEgEKLREL---C 169

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3457 GTLDYMSPEMLKGDVV------GPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDL-SKLYQNVSQSASLFI 3529
Cdd:cd14093    170 GTPGYLAPEVLKCSMYdnapgyGKEVDMWACGVIMYTLLAGCPPFWHRKQMVMLRNIMEGKYEFgSPEWDDISDTAKDLI 249

                          250       260
                   ....*....|....*....|...
gi 1207186029 3530 KKILCSYPWARPTIKDCFTNSWL 3552
Cdd:cd14093    250 SKLLVVDPKKRLTAEEALEHPFF 272

Catalytic domain of Dual-specificity tYrosine-phosphorylated and -Regulated Kinase-like protein kinases; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. This subfamily is composed of the dual-specificity DYRKs and YAK1, as well as the S/T kinases (STKs), HIPKs. DYRKs and YAK1 autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. Proteins in this subfamily play important roles in cell proliferation, differentiation, survival, growth, and development. The DYRK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271035 [Multi-domain] Cd Length: 262 Bit Score: 124.30 E-value: 7.07e-31

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASALRELNILSHL------DHERILYFHDAFEKKNAVIIIT 1735
Cdd:cd14133      1 YEVLEVLGKGTFGQVVKCYDLLTGEEVALKIIKNNKDYLDQSLDEIRLLELLnkkdkaDKYHIVRLKDVFYFKNHLCIVF 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1736 ELCHEELLD--RLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSDQIRICDFGNAVkFMPDeAQ 1813
Cdd:cd14133     81 ELLSQNLYEflKQNKFQYLSLPRIRKIAQQILEALVFLHSLGLIHCDLKPENILLASYSRCQIKIIDFGSSC-FLTQ-RL 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1814 YCKYGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESM----------FTDl 1883
Cdd:cd14133    159 YSYIQSRYYRAPEVILGLPYDEKIDMWSLGCILAELYTGEPLFPGASEVDQLARIIGTIGIPPAHMldqgkaddelFVD- 237

                          250       260       270
                   ....*....|....*....|....*....|.
gi 1207186029 1884 cheakgFVIKLLVADRL-RPDANECLRHPWF 1913
Cdd:cd14133    238 ------FLKKLLEIDPKeRPTASQALSHPWL 262

C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 3 (also called Ribosomal protein S6 kinase alpha-2 or 90kDa ribosomal protein S6 kinase 2); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSK3 is also called S6K-alpha-2, RPS6KA2, p90RSK2 or MAPK-activated protein kinase 1c (MAPKAPK-1c). RSK3 binds muscle A-kinase anchoring protein (mAKAP)-b directly and regulates concentric cardiac myocyte growth. The RSK3 gene, RPS6KA2, is a putative tumor suppressor gene in sporadic epithelial ovarian cancer and variations to the gene may be associated with rectal cancer risk. RSK3 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. The RSK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271080 [Multi-domain] Cd Length: 293 Bit Score: 125.13 E-value: 7.68e-31

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVPyepESKQTVLQEYDIL-KSLHHEKIMALHEAYVTPRYLVLISECCSG 3378
Cdd:cd14178      5 YEIKEDIGIGSYSVCKRCVHKATSTEYAVKIID---KSKRDPSEEIEILlRYGQHPNIITLKDVYDDGKFVYLVMELMRG 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3379 KELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIvtYMN------VVKIIDFGSAQTF---NPLFL 3449
Cdd:cd14178     82 GELLDRILRQKCFSEREASAVLCTITKTVEYLHSQGVVHRDLKPSNIL--YMDesgnpeSIRICDFGFAKQLraeNGLLM 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3450 KqfspPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFT---ENDPAETEARIQAAKFDLS-KLYQNVSQSA 3525
Cdd:cd14178    160 T----PCYTANFVAPEVLKRQGYDAACDIWSLGILLYTMLAGFTPFAngpDDTPEEILARIGSGKYALSgGNWDSISDAA 235

                          250       260
                   ....*....|....*....|....*..
gi 1207186029 3526 SLFIKKILCSYPWARPTIKDCFTNSWL 3552
Cdd:cd14178    236 KDIVSKMLHVDPHQRLTAPQVLRHPWI 262

Catalytic domain of testis-specific serine/threonine kinases and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK1 and TSSK2 are expressed specifically in meiotic and postmeiotic spermatogenic cells, respectively. TSSK3 has been reported to be expressed in the interstitial Leydig cells of adult testis. TSSK4, also called TSSK5, is expressed in testis from haploid round spermatids to mature spermatozoa. TSSK6, also called SSTK, is expressed at the head of elongated sperm. TSSK1/TSSK2 double knock-out and TSSK6 null mice are sterile without manifesting other defects, making these kinases viable targets for male contraception. The TSSK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270982 [Multi-domain] Cd Length: 262 Bit Score: 123.45 E-value: 1.44e-30

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3344 EYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPE 3423
Cdd:cd14080     52 ELEILRKLRHPNIIQVYSIFERGSKVFIFMEYAEHGDLLEYIQKRGALSESQARIWFRQLALAVQYLHSLDIAHRDLKCE 131

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3424 NIIVTYMNVVKIIDFGSAQTF----NPLFLKQFSppiGTLDYMSPEMLKG---DvvGPPADIWSIGILTYIMLSGRLPFT 3496
Cdd:cd14080    132 NILLDSNNNVKLSDFGFARLCpdddGDVLSKTFC---GSAAYAAPEILQGipyD--PKKYDIWSLGVILYIMLCGSMPFD 206

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1207186029 3497 ENDPAETEARIQAAKFDLSKLYQNVSQSASLFIKKILCSYPWARPTIKDCFTNSWL 3552
Cdd:cd14080    207 DSNIKKMLKDQQNRKVRFPSSVKKLSPECKDLIDQLLEPDPTKRATIEEILNHPWL 262

C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 2 (also called 90kDa ribosomal protein S6 kinase 3 or Ribosomal protein S6 kinase alpha-3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSK2 is also called p90RSK3, RPS6KA3, S6K-alpha-3, or MAPK-activated protein kinase 1b (MAPKAPK-1b). RSK2 is expressed highly in the regions of the brain with high synaptic activity. It plays a role in the maintenance and consolidation of excitatory synapses. It is a specific modulator of phospholipase D in calcium-regulated exocytosis. Mutations in the RSK2 gene, RPS6KA3, cause Coffin-Lowry syndrome (CLS), a rare syndromic form of X-linked mental retardation characterized by growth and psychomotor retardation and skeletal abnormalities. RSK2 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. The RSK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271078 [Multi-domain] Cd Length: 339 Bit Score: 125.52 E-value: 1.61e-30

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVPyepESKQTVLQEYDIL-KSLHHEKIMALHEAYVTPRYLVLISECCSG 3378
Cdd:cd14176     21 YEVKEDIGVGSYSVCKRCIHKATNMEFAVKIID---KSKRDPTEEIEILlRYGQHPNIITLKDVYDDGKYVYVVTELMKG 97

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3379 KELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIvtYMN------VVKIIDFGSAQTF---NPLFL 3449
Cdd:cd14176     98 GELLDKILRQKFFSEREASAVLFTITKTVEYLHAQGVVHRDLKPSNIL--YVDesgnpeSIRICDFGFAKQLraeNGLLM 175

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3450 KqfspPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFT---ENDPAETEARIQAAKFDLSKLYQN-VSQSA 3525
Cdd:cd14176    176 T----PCYTANFVAPEVLERQGYDAACDIWSLGVLLYTMLTGYTPFAngpDDTPEEILARIGSGKFSLSGGYWNsVSDTA 251

                          250       260
                   ....*....|....*....|....*..
gi 1207186029 3526 SLFIKKILCSYPWARPTIKDCFTNSWL 3552
Cdd:cd14176    252 KDLVSKMLHVDPHQRLTAALVLRHPWI 278

Catalytic domain of CMGC family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The CMGC family consists of Cyclin-Dependent protein Kinases (CDKs), Mitogen-activated protein kinases (MAPKs) such as Extracellular signal-regulated kinase (ERKs), c-Jun N-terminal kinases (JNKs), and p38, and other kinases. CDKs belong to a large subfamily of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. MAPKs serve as important mediators of cellular responses to extracellular signals. They control critical cellular functions including differentiation, proliferation, migration, and apoptosis. They are also implicated in the pathogenesis of many diseases including multiple types of cancer, stroke, diabetes, and chronic inflammation. Other members of the CMGC family include casein kinase 2 (CK2), Dual-specificity tYrosine-phosphorylated and -Regulated Kinase (DYRK), Glycogen Synthase Kinase 3 (GSK3), among many others. The CMGC family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270688 [Multi-domain] Cd Length: 249 Bit Score: 122.73 E-value: 1.62e-30

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPESKQTVLQEYDILKSL----HHEKIMALHEAYVTP--RYLVLIS 3373
Cdd:cd05118      1 YEVLRKIGEGAFGTVWLARDKVTGEKVAIKKIKNDFRHPKAALREIKLLKHLndveGHPNIVKLLDVFEHRggNHLCLVF 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3374 ECCSgkELLHSLIDRF--RYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMN-VVKIIDFGSAQTFNPlflK 3450
Cdd:cd05118     81 ELMG--MNLYELIKDYprGLPLDLIKSYLYQLLQALDFLHSNGIIHRDLKPENILINLELgQLKLADFGLARSFTS---P 155

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1207186029 3451 QFSPPIGTLDYMSPEMLKGD-VVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARI 3507
Cdd:cd05118    156 PYTPYVATRWYRAPEVLLGAkPYGSSIDIWSLGCILAELLTGRPLFPGDSEVDQLAKI 213

Catalytic domain of Cyclin-Dependent protein Kinase Like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDKL1-5 and similar proteins. Some CDKLs, like CDKL1 and CDKL3, may be implicated in transformation and others, like CDKL3 and CDKL5, are associated with mental retardation when impaired. CDKL2 plays a role in learning and memory. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270827 [Multi-domain] Cd Length: 288 Bit Score: 123.97 E-value: 1.87e-30

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKA-GKLEYAAKFISARAKR--KASALRELNILSHLDHERILYFHDAFEKKNAVIIITELC 1738
Cdd:cd07833      3 YEVLGVVGEGAYGVVLKCRNKAtGEIVAIKKFKESEDDEdvKKTALREVKVLRQLRHENIVNLKEAFRRKGRLYLVFEYV 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1739 HEELLDRLTKKSTILESE-IRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSdqIRICDFGNAvKFMPDEAQ--YC 1815
Cdd:cd07833     83 ERTLLELLEASPGGLPPDaVRSYIWQLLQAIAYCHSHNIIHRDIKPENILVSESGV--LKLCDFGFA-RALTARPAspLT 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1816 KY-GTPEFVAPEI-VNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRN--------------YNVAFEESM 1879
Cdd:cd07833    160 DYvATRWYRAPELlVGDTNYGKPVDVWAIGCIMAELLDGEPLFPGDSDIDQLYLIQKclgplppshqelfsSNPRFAGVA 239

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*....
gi 1207186029 1880 FTDLCHE--------------AKGFVIKLLVAD-RLRPDANECLRHPWF 1913
Cdd:cd07833    240 FPEPSQPeslerrypgkvsspALDFLKACLRMDpKERLTCDELLQHPYF 288

Catalytic subunit of the Serine/Threonine Kinases, cAMP-dependent protein kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the cAMP-dependent protein kinases, PKA and PRKX, and similar proteins. The inactive PKA holoenzyme is a heterotetramer composed of two phosphorylated and active catalytic subunits with a dimer of regulatory (R) subunits. Activation is achieved through the binding of the important second messenger cAMP to the R subunits, which leads to the dissociation of PKA into the R dimer and two active subunits. PKA is present ubiquitously in cells and interacts with many different downstream targets. It plays a role in the regulation of diverse processes such as growth, development, memory, metabolism, gene expression, immunity, and lipolysis. PRKX is also reulated by the R subunit and is is present in many tissues including fetal and adult brain, kidney, and lung. It is implicated in granulocyte/macrophage lineage differentiation, renal cell epithelial migration, and tubular morphogenesis in the developing kidney. The PKA-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270732 [Multi-domain] Cd Length: 290 Bit Score: 123.84 E-value: 2.25e-30

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFIS----ARAKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITEL 1737
Cdd:cd05580      3 FEFLKTLGTGSFGRVRLVKHKDSGKYYALKILKkakiIKLKQVEHVLNEKRILSEVRHPFIVNLLGSFQDDRNLYMVMEY 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1738 CHE-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSdqIRICDFGNAvKFMPDEAqYCK 1816
Cdd:cd05580     83 VPGgELFSLLRRSGRFPNDVAKFYAAEVVLALEYLHSLDIVYRDLKPENLLLDSDGH--IKITDFGFA-KRVKDRT-YTL 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1817 YGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDlcheAKGFVIKLLV 1896
Cdd:cd05580    159 CGTPEYLAPEIILSKGHGKAVDWWALGILIYEMLAGYPPFFDENPMKIYEKILEGKIRFPSFFDPD----AKDLIKRLLV 234

                          250       260
                   ....*....|....*....|....*..
gi 1207186029 1897 ADR------LRPDANECLRHPWFKTLN 1917
Cdd:cd05580    235 VDLtkrlgnLKNGVEDIKNHPWFAGID 261

Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein kinase subfamily 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The SnRKs form three different subfamilies designated SnRK1-3. SnRK3 is represented in this cd. The SnRK3 group contains members also known as CBL-interacting protein kinase, salt overly sensitive 2, SOS3-interacting proteins and protein kinase S. These kinases interact with calcium-binding proteins such as SOS3, SCaBPs, and CBL proteins, and are involved in responses to salt stress and in sugar and ABA signaling. The SnRKs belong to a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271133 [Multi-domain] Cd Length: 256 Bit Score: 122.51 E-value: 2.36e-30

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3309 GRFGVIRECRENATGNLYMAKIVpyepeSKQTVLQ---------EYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGK 3379
Cdd:cd14663     11 GTFAKVKFARNTKTGESVAIKII-----DKEQVARegmveqikrEIAIMKLLRHPNIVELHEVMATKTKIFFVMELVTGG 85

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3380 ELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFG-SA--QTFNPLFLKQFSppI 3456
Cdd:cd14663     86 ELFSKIAKNGRLKEDKARKYFQQLIDAVDYCHSRGVFHRDLKPENLLLDEDGNLKISDFGlSAlsEQFRQDGLLHTT--C 163

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3457 GTLDYMSPEMLKGD-VVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLSKLYqnvSQSASLFIKKILCS 3535
Cdd:cd14663    164 GTPNYVAPEVLARRgYDGAKADIWSCGVILFVLLAGYLPFDDENLMALYRKIMKGEFEYPRWF---SPGAKSLIKRILDP 240

                          250
                   ....*....|....*.
gi 1207186029 3536 YPWARPTIKDCFTNSW 3551
Cdd:cd14663    241 NPSTRITVEQIMASPW 256

C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK1 plays a role in the regulation of translational control and transcriptional activation. It phosphorylates the transcription factors, CREB and NFkB. It also phosphorylates the nucleosomal proteins H3 and HMG-14. Increased phosphorylation of MSK1 is associated with the development of cerebral ischemic/hypoxic preconditioning. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. The MSK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271081 [Multi-domain] Cd Length: 310 Bit Score: 124.00 E-value: 2.64e-30

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3309 GRFGVIRECRENATGNLYMAKIVPYEPESKQTvlQEYDILKSLH-HEKIMALHEAYVTPRYLVLISECCSGKELLHSLID 3387
Cdd:cd14179     18 GSFSICRKCLHKKTNQEYAVKIVSKRMEANTQ--REIAALKLCEgHPNIVKLHEVYHDQLHTFLVMELLKGGELLERIKK 95

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3388 RFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMN---VVKIIDFGSAQtFNPLFLKQFSPPIGTLDYMSP 3464
Cdd:cd14179     96 KQHFSETEASHIMRKLVSAVSHMHDVGVVHRDLKPENLLFTDESdnsEIKIIDFGFAR-LKPPDNQPLKTPCFTLHYAAP 174

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3465 EMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPA-------ETEARIQAAKFDLS-KLYQNVSQSASLFIKKILCSY 3536
Cdd:cd14179    175 ELLNYNGYDESCDLWSLGVILYTMLSGQVPFQCHDKSltctsaeEIMKKIKQGDFSFEgEAWKNVSQEAKDLIQGLLTVD 254

                          250
                   ....*....|....*...
gi 1207186029 3537 PWARPTIKDCFTNSWLQD 3554
Cdd:cd14179    255 PNKRIKMSGLRYNEWLQD 272

Catalytic domain of the Serine/Threonine Kinases, MAP/microtubule affinity-regulating kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MARKs, also called Partitioning-defective 1 (Par1) proteins, function as regulators of diverse cellular processes in nematodes, Drosophila, yeast, and vertebrates. They are involved in embryogenesis, epithelial cell polarization, cell signaling, and neuronal differentiation. MARKs phosphorylate tau and related microtubule-associated proteins (MAPs), and regulates microtubule-based intracellular transport. Vertebrates contain four isoforms, namely MARK1 (or Par1c), MARK2 (or Par1b), MARK3 (Par1a), and MARK4 (or MARKL1). Known substrates of MARKs include the cell cycle-regulating phosphatase Cdc25, tyrosine phosphatase PTPH1, MAPK scaffolding protein KSR1, class IIa histone deacetylases, and plakophilin 2. The MARK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270974 [Multi-domain] Cd Length: 253 Bit Score: 122.24 E-value: 2.79e-30

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIV---PYEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECC 3376
Cdd:cd14072      2 YRLLKTIGKGNFAKVKLARHVLTGREVAIKIIdktQLNPSSLQKLFREVRIMKILNHPNIVKLFEVIETEKTLYLVMEYA 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3377 SGKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNP-LFLKQF--S 3453
Cdd:cd14072     82 SGGEVFDYLVAHGRMKEKEARAKFRQIVSAVQYCHQKRIVHRDLKAENLLLDADMNIKIADFGFSNEFTPgNKLDTFcgS 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3454 PPigtldYMSPEMLKGDVV-GPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLSkLYqnVSQSASLFIKKI 3532
Cdd:cd14072    162 PP-----YAAPELFQGKKYdGPEVDVWSLGVILYTLVSGSLPFDGQNLKELRERVLRGKYRIP-FY--MSTDCENLLKKF 233

                          250       260
                   ....*....|....*....|
gi 1207186029 3533 LCSYPWARPTIKDCFTNSWL 3552
Cdd:cd14072    234 LVLNPSKRGTLEQIMKDRWM 253

Catalytic domain of Plant dual-specificity Mitogen-Activated Protein Kinase Kinases and similar proteins; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include MAPKKs from plants, kinetoplastids, alveolates, and mycetozoa. The MAPKK, LmxPK4, from Leishmania mexicana, is important in differentiation and virulence. Dictyostelium discoideum MEK1 is required for proper chemotaxis; MEK1 null mutants display severe defects in cell polarization and directional movement. Plants contain multiple MAPKKs like other eukaryotes. The Arabidopsis genome encodes for 10 MAPKKs while poplar and rice contain 13 MAPKKs each. The functions of these proteins have not been fully elucidated. There is evidence to suggest that MAPK cascades are involved in plant stress responses. In Arabidopsis, MKK3 plays a role in pathogen signaling; MKK2 is involved in cold and salt stress signaling; MKK4/MKK5 participates in innate immunity; and MKK7 regulates basal and systemic acquired resistance. The MAPKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 132954 [Multi-domain] Cd Length: 264 Bit Score: 122.70 E-value: 3.11e-30

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1666 KEIGRGAFSYVKRVIQKAGKLEYAAKFI---SARAKRKAsALRELNILSHLDHERILYFHDAFEKKNAVIIITELCHEEL 1742
Cdd:cd06623      7 KVLGQGSSGVVYKVRHKPTGKIYALKKIhvdGDEEFRKQ-LLRELKTLRSCESPYVVKCYGAFYKEGEISIVLEYMDGGS 85

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1743 LDRLTKKS-TILESEIRSSVRQLLEGINYLHQ-LDILHLDIKPDNILMadHSSDQIRICDFGNAvKFMPDEAQYCK--YG 1818
Cdd:cd06623     86 LADLLKKVgKIPEPVLAYIARQILKGLDYLHTkRHIIHRDIKPSNLLI--NSKGEVKIADFGIS-KVLENTLDQCNtfVG 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1819 TPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGeNDRSSVLNIRNYnVAFEES------MFTDlchEAKGFVI 1892
Cdd:cd06623    163 TVTYMSPERIQGESYSYAADIWSLGLTLLECALGKFPFLP-PGQPSFFELMQA-ICDGPPpslpaeEFSP---EFRDFIS 237

                          250       260
                   ....*....|....*....|...
gi 1207186029 1893 KLLVAD-RLRPDANECLRHPWFK 1914
Cdd:cd06623    238 ACLQKDpKKRPSAAELLQHPFIK 260

C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK1 plays a role in the regulation of translational control and transcriptional activation. It phosphorylates the transcription factors, CREB and NFkB. It also phosphorylates the nucleosomal proteins H3 and HMG-14. Increased phosphorylation of MSK1 is associated with the development of cerebral ischemic/hypoxic preconditioning. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. The MSK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271081 [Multi-domain] Cd Length: 310 Bit Score: 123.61 E-value: 3.61e-30

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1666 KEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKrkASALRELNILSHLD-HERILYFHDAFEKKNAVIIITELCHE-ELL 1743
Cdd:cd14179     13 KPLGEGSFSICRKCLHKKTNQEYAVKIVSKRME--ANTQREIAALKLCEgHPNIVKLHEVYHDQLHTFLVMELLKGgELL 90

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1744 DRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSD-QIRICDFGNAvKFMPDEAQYCKygTP-- 1820
Cdd:cd14179     91 ERIKKKQHFSETEASHIMRKLVSAVSHMHDVGVVHRDLKPENLLFTDESDNsEIKIIDFGFA-RLKPPDNQPLK--TPcf 167

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1821 --EFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGEnDRS----SVLN----IRNYNVAFEESMFTDLCHEAKGF 1890
Cdd:cd14179    168 tlHYAAPELLNYNGYDESCDLWSLGVILYTMLSGQVPFQCH-DKSltctSAEEimkkIKQGDFSFEGEAWKNVSQEAKDL 246


                   ....*...
gi 1207186029 1891 VIKLLVAD 1898
Cdd:cd14179    247 IQGLLTVD 254

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 2 (also called Doublecortin-like and CAM kinase-like 2); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL2 (or DCAMKL2) belongs to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. In addition, DCKL2 contains a serine, threonine, and proline rich domain (SP) and a C-terminal kinase domain with similarity to CAMKs. DCKL2 has been shown to interact with tubulin, JIP1/2, JNK, neurabin 2, and actin. It is associated with the terminal segments of axons and dendrites, and may function as a phosphorylation-dependent switch to control microtubule dynamics in neuronal growth cones. The DCKL2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271086 [Multi-domain] Cd Length: 259 Bit Score: 122.06 E-value: 3.70e-30

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3309 GRFGVIRECRENATGNLYMAKIVPYEP--ESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLHSLI 3386
Cdd:cd14184     12 GNFAVVKECVERSTGKEFALKIIDKAKccGKEHLIENEVSILRRVKHPNIIMLIEEMDTPAELYLVMELVKGGDLFDAIT 91

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3387 DRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIV-TYMN---VVKIIDFGSAQTFN-PLFlkqfsPPIGTLDY 3461
Cdd:cd14184     92 SSTKYTERDASAMVYNLASALKYLHGLCIVHRDIKPENLLVcEYPDgtkSLKLGDFGLATVVEgPLY-----TVCGTPTY 166

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3462 MSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPF-TENDPAETE-ARIQAAKFDL-SKLYQNVSQSASLFIKKILCSYPW 3538
Cdd:cd14184    167 VAPEIIAETGYGLKVDIWAAGVITYILLCGFPPFrSENNLQEDLfDQILLGKLEFpSPYWDNITDSAKELISHMLQVNVE 246

                          250
                   ....*....|...
gi 1207186029 3539 ARPTIKDCFTNSW 3551
Cdd:cd14184    247 ARYTAEQILSHPW 259

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Nek2 subfamily includes Aspergillus nidulans NIMA kinase, the founding member of the Nek family, which was identified in a screen for cell cycle mutants prevented from entering mitosis. NIMA is essential for mitotic entry and progression through mitosis, and its degradation is essential for mitotic exit. NIMA is involved in nuclear membrane fission. Vertebrate Nek2 is a cell cycle-regulated STK, localized in centrosomes and kinetochores, that regulates centrosome splitting at the G2/M phase. It also interacts with other mitotic kinases such as Polo-like kinase 1 and may play a role in spindle checkpoint. An increase in the expression of the human NEK2 gene is strongly associated with the progression of non-Hodgkin lymphoma. Nek2 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. It The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270857 [Multi-domain] Cd Length: 265 Bit Score: 122.26 E-value: 4.48e-30

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARA---KRKASALRELNILSHLDHERIL-YFHDAFEKKNAVI-IITE 1736
Cdd:cd08217      2 YEVLETIGKGSFGTVRKVRRKSDGKILVWKEIDYGKmseKEKQQLVSEVNILRELKHPNIVrYYDRIVDRANTTLyIVME 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1737 LCHEELLDRLTKK-----STILESEIRSSVRQLLEGINYLHQLD-----ILHLDIKPDNI-LMADHSsdqIRICDFGNAv 1805
Cdd:cd08217     82 YCEGGDLAQLIKKckkenQYIPEEFIWKIFTQLLLALYECHNRSvgggkILHRDLKPANIfLDSDNN---VKLGDFGLA- 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1806 KFMPDEAQYCK--YGTPEFVAPEIVNQTPVSKATDIWPIGVLTY-LClTGVSPFAGENDRSSVLNIRNYNVAFEESMFTD 1882
Cdd:cd08217    158 RVLSHDSSFAKtyVGTPYYMSPELLNEQSYDEKSDIWSLGCLIYeLC-ALHPPFQAANQLELAKKIKEGKFPRIPSRYSS 236

                          250       260       270
                   ....*....|....*....|....*....|.
gi 1207186029 1883 LCHEakgfVIK--LLVADRLRPDANECLRHP 1911
Cdd:cd08217    237 ELNE----VIKsmLNVDPDKRPSVEELLQLP 263

C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 1 (also called Ribosomal protein S6 kinase alpha-1 or 90kDa ribosomal protein S6 kinase 1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSK1 is also called S6K-alpha-1, RPS6KA1, p90RSK1 or MAPK-activated protein kinase 1a (MAPKAPK-1a). It is a component of the insulin transduction pathway, regulating the function of IRS1. It also interacts with PKA and promotes its inactivation. RSK1 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. The RSK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271077 [Multi-domain] Cd Length: 291 Bit Score: 122.44 E-value: 6.36e-30

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVPyepESKQTVLQEYDILKSL-HHEKIMALHEAYVTPRYLVLISECCSG 3378
Cdd:cd14175      3 YVVKETIGVGSYSVCKRCVHKATNMEYAVKVID---KSKRDPSEEIEILLRYgQHPNIITLKDVYDDGKHVYLVTELMRG 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3379 KELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIvtYMN------VVKIIDFGSAQTF---NPLFL 3449
Cdd:cd14175     80 GELLDKILRQKFFSEREASSVLHTICKTVEYLHSQGVVHRDLKPSNIL--YVDesgnpeSLRICDFGFAKQLraeNGLLM 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3450 KqfspPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFT---ENDPAETEARIQAAKFDLS-KLYQNVSQSA 3525
Cdd:cd14175    158 T----PCYTANFVAPEVLKRQGYDEGCDIWSLGILLYTMLAGYTPFAngpSDTPEEILTRIGSGKFTLSgGNWNTVSDAA 233

                          250       260
                   ....*....|....*....|....*..
gi 1207186029 3526 SLFIKKILCSYPWARPTIKDCFTNSWL 3552
Cdd:cd14175    234 KDLVSKMLHVDPHQRLTAKQVLQHPWI 260

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 3 (also called Doublecortin-like and CAM kinase-like 3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL3 (or DCAMKL3) belongs to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. DCKL3 contains a single DCX domain (instead of a tandem) and a C-terminal kinase domain with similarity to CAMKs. It has been shown to interact with tubulin and JIP1/2. The DCKL3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271087 [Multi-domain] Cd Length: 258 Bit Score: 120.82 E-value: 9.30e-30

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1661 YYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFI-SARAKRKASALR-ELNILSHLDHERILYFHDAFEKKNAVIIITELC 1738
Cdd:cd14185      1 HYEIGRTIGDGNFAVVKECRHWNENQEYAMKIIdKSKLKGKEDMIEsEILIIKSLSHPNIVKLFEVYETEKEIYLILEYV 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1739 HE-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMaDHSSDQ---IRICDFGNAVKFMPDEAQY 1814
Cdd:cd14185     81 RGgDLFDAIIESVKFTEHDAALMIIDLCEALVYIHSKHIVHRDLKPENLLV-QHNPDKsttLKLADFGLAKYVTGPIFTV 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1815 CkyGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPF-AGENDRSSVLN-IRNYNVAFEESMFTDLCHEAKGFVI 1892
Cdd:cd14185    160 C--GTPTYVAPEILSEKGYGLEVDMWAAGVILYILLCGFPPFrSPERDQEELFQiIQLGHYEFLPPYWDNISEAAKDLIS 237

                          250       260
                   ....*....|....*....|.
gi 1207186029 1893 KLLVAD-RLRPDANECLRHPW 1912
Cdd:cd14185    238 RLLVVDpEKRYTAKQVLQHPW 258

Catalytic domain of the Serine/Threonine Kinase, Maternal Embryonic Leucine zipper Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MELK is a cell cycle dependent protein which functions in cytokinesis, cell cycle, apoptosis, cell proliferation, and mRNA processing. It is found upregulated in many types of cancer cells, playing an indispensable role in cancer cell survival. It makes an attractive target in the design of inhibitors for use in the treatment of a wide range of human cancer. The MELK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270980 [Multi-domain] Cd Length: 257 Bit Score: 120.57 E-value: 1.15e-29

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3341 VLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDI 3420
Cdd:cd14078     48 VKTEIEALKNLSHQHICRLYHVIETDNKIFMVLEYCPGGELFDYIVAKDRLSEDEARVFFRQIVSAVAYVHSQGYAHRDL 127

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3421 KPENIIVTYMNVVKIIDFGSAQTFNPLFLKQFSPPIGTLDYMSPEMLKGD-VVGPPADIWSIGILTYIMLSGRLPFTEND 3499
Cdd:cd14078    128 KPENLLLDEDQNLKLIDFGLCAKPKGGMDHHLETCCGSPAYAAPELIQGKpYIGSEADVWSMGVLLYALLCGFLPFDDDN 207

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1207186029 3500 PAETEARIQAAKFDLSKLyqnVSQSASLFIKKILCSYPWARPTIKDCFTNSWL 3552
Cdd:cd14078    208 VMALYRKIQSGKYEEPEW---LSPSSKLLLDQMLQVDPKKRITVKELLNHPWV 257

Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein kinase subfamily 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The SnRKs form three different subfamilies designated SnRK1-3. SnRK2 is represented in this cd. SnRK2s are involved in plant response to abiotic stresses and abscisic acid (ABA)-dependent plant development. The SnRK2s subfamily is in turn classed into three subgroups, all 3 of which are represented in this CD. Group 1 comprises kinases not activated by ABA, group 2 - kinases not activated or activated very weakly by ABA (depending on plant species), and group 3 - kinases strongly activated by ABA. The SnRKs belong to a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271132 [Multi-domain] Cd Length: 257 Bit Score: 120.26 E-value: 1.70e-29

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGK 3379
Cdd:cd14662      2 YELVKDIGSGNFGVARLMRNKETKELVAVKYIERGLKIDENVQREIINHRSLRHPNIIRFKEVVLTPTHLAIVMEYAAGG 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3380 ELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIV--TYMNVVKIIDFGSAQTfnPLFLKQFSPPIG 3457
Cdd:cd14662     82 ELFERICNAGRFSEDEARYFFQQLISGVSYCHSMQICHRDLKLENTLLdgSPAPRLKICDFGYSKS--SVLHSQPKSTVG 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3458 TLDYMSPEML-KGDVVGPPADIWSIGILTYIMLSGRLPFTE-NDPA---ETEARIQAAKFDLSKlYQNVSQSASLFIKKI 3532
Cdd:cd14662    160 TPAYIAPEVLsRKEYDGKVADVWSCGVTLYVMLVGAYPFEDpDDPKnfrKTIQRIMSVQYKIPD-YVRVSQDCRHLLSRI 238

                          250
                   ....*....|....*....
gi 1207186029 3533 LCSYPWARPTIKDCFTNSW 3551
Cdd:cd14662    239 FVANPAKRITIPEIKNHPW 257

C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK2 and MSK1 play nonredundant roles in activating histone H3 kinases, which play pivotal roles in compaction of the chromatin fiber. MSK2 is the required H3 kinase in response to stress stimuli and activation of the p38 MAPK pathway. MSK2 also plays a role in the pathogenesis of psoriasis. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family, similar to 90 kDa ribosomal protein S6 kinases (RSKs). MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. The MSK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271082 [Multi-domain] Cd Length: 309 Bit Score: 121.52 E-value: 1.85e-29

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3309 GRFGVIRECRENATGNLYMAKIVPYEPESK-QTVLQEYDILKSlhHEKIMALHEAYVTPRYLVLISECCSGKELLHSLID 3387
Cdd:cd14180     17 GSFSVCRKCRHRQSGQEYAVKIISRRMEANtQREVAALRLCQS--HPNIVALHEVLHDQYHTYLVMELLRGGELLDRIKK 94

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3388 RFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIV---TYMNVVKIIDFGSAQTFnPLFLKQFSPPIGTLDYMSP 3464
Cdd:cd14180     95 KARFSESEASQLMRSLVSAVSFMHEAGVVHRDLKPENILYadeSDGAVLKVIDFGFARLR-PQGSRPLQTPCFTLQYAAP 173

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3465 EMLKGDVVGPPADIWSIGILTYIMLSGRLPF-------TENDPAETEARIQAAKFDLS-KLYQNVSQSASLFIKKILCSY 3536
Cdd:cd14180    174 ELFSNQGYDESCDLWSLGVILYTMLSGQVPFqskrgkmFHNHAADIMHKIKEGDFSLEgEAWKGVSEEAKDLVRGLLTVD 253

                          250
                   ....*....|....*...
gi 1207186029 3537 PWARPTIKDCFTNSWLQD 3554
Cdd:cd14180    254 PAKRLKLSELRESDWLQG 271

C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 4 (also called Ribosomal protein S6 kinase alpha-6 or 90kDa ribosomal protein S6 kinase 6); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSK4 is also called S6K-alpha-6, RPS6KA6, p90RSK6 or pp90RSK4. RSK4 is a substrate of ERK and is a modulator of p53-dependent proliferation arrest in human cells. Deletion of the RSK4 gene, RPS6KA6, frequently occurs in patients of X-linked deafness type 3, mental retardation and choroideremia. Studies of RSK4 in cancer cells and tissues suggest that it may be oncogenic or tumor suppressive depending on many factors. RSK4 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. The RSK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271079 [Multi-domain] Cd Length: 295 Bit Score: 121.28 E-value: 2.04e-29

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVPyepESKQTVLQEYDILKSL-HHEKIMALHEAYVTPRYLVLISECCSG 3378
Cdd:cd14177      6 YELKEDIGVGSYSVCKRCIHRATNMEFAVKIID---KSKRDPSEEIEILMRYgQHPNIITLKDVYDDGRYVYLVTELMKG 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3379 KELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIvtYM------NVVKIIDFGSAQTF---NPLFL 3449
Cdd:cd14177     83 GELLDRILRQKFFSEREASAVLYTITKTVDYLHCQGVVHRDLKPSNIL--YMddsanaDSIRICDFGFAKQLrgeNGLLL 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3450 KqfspPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTE--ND-PAETEARIQAAKFDLS-KLYQNVSQSA 3525
Cdd:cd14177    161 T----PCYTANFVAPEVLMRQGYDAACDIWSLGVLLYTMLAGYTPFANgpNDtPEEILLRIGSGKFSLSgGNWDTVSDAA 236

                          250       260
                   ....*....|....*....|....*..
gi 1207186029 3526 SLFIKKILCSYPWARPTIKDCFTNSWL 3552
Cdd:cd14177    237 KDLLSHMLHVDPHQRYTAEQVLKHSWI 263

Catalytic domain of the Serine/Threonine Kinases, Salt-Inducible kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SIKs are part of a complex network that regulates Na,K-ATPase to maintain sodium homeostasis and blood pressure. Vertebrates contain three forms of SIKs (SIK1-3) from three distinct genes, which display tissue-specific effects. SIK1, also called SNF1LK, controls steroidogenic enzyme production in adrenocortical cells. In the brain, both SIK1 and SIK2 regulate energy metabolism. SIK2, also called QIK or SNF1LK2, is involved in the regulation of gluconeogenesis in the liver and lipogenesis in adipose tissues, where it phosphorylates the insulin receptor substrate-1. In the liver, SIK3 (also called QSK) regulates cholesterol and bile acid metabolism. In addition, SIK2 plays an important role in the initiation of mitosis and regulates the localization of C-Nap1, a centrosome linker protein. The SIK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270973 [Multi-domain] Cd Length: 253 Bit Score: 119.42 E-value: 2.66e-29

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKIVP---YEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLHS 3384
Cdd:cd14071     10 KGNFAVVKLARHRITKTEVAIKIIDksqLDEENLKKIYREVQIMKMLNHPHIIKLYQVMETKDMLYLVTEYASNGEIFDY 89

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3385 LIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIV-TYMNvVKIIDFGSAQTFNP-LFLKQF--SPPigtld 3460
Cdd:cd14071     90 LAQHGRMSEKEARKKFWQILSAVEYCHKRHIVHRDLKAENLLLdANMN-IKIADFGFSNFFKPgELLKTWcgSPP----- 163

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3461 YMSPEMLKG-DVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLSKLyqnVSQSASLFIKKILCSYPWA 3539
Cdd:cd14071    164 YAAPEVFEGkEYEGPQLDIWSLGVVLYVLVCGALPFDGSTLQTLRDRVLSGRFRIPFF---MSTDCEHLIRRMLVLDPSK 240

                          250
                   ....*....|...
gi 1207186029 3540 RPTIKDCFTNSWL 3552
Cdd:cd14071    241 RLTIEQIKKHKWM 253

Catalytic domain of the Serine/Threonine kinases, Autophagy-related protein 1 and Unc-51-like kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes yeast ATG1 and metazoan homologs including vertebrate ULK1-3. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. It is involved in nutrient sensing and signaling, the assembly of autophagy factors and the execution of autophagy. In metazoans, ATG1 homologs display additional functions. Unc-51 and ULKs have been implicated in neuronal and axonal development. The ATG1/ULK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270911 [Multi-domain] Cd Length: 251 Bit Score: 119.25 E-value: 2.81e-29

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYVKRVIQKAGKLEYAAKFISAR---AKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITELCHEELLD 1744
Cdd:cd14009      1 IGRGSFATVWKGRHKQTGEVVAIKEISRKklnKKLQENLESEIAILKSIKHPNIVRLYDVQKTEDFIYLVLEYCAGGDLS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1745 RLTKKSTIL-ESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSD-QIRICDFGNAvKFMPDE---AQYCkyGT 1819
Cdd:cd14009     81 QYIRKRGRLpEAVARHFMQQLASGLKFLRSKNIIHRDLKPQNLLLSTSGDDpVLKIADFGFA-RSLQPAsmaETLC--GS 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1820 PEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDLCHEAKGFVIKLL---V 1896
Cdd:cd14009    158 PLYMAPEILQFQKYDAKADLWSVGAILFEMLVGKPPFRGSNHVQLLRNIERSDAVIPFPIAAQLSPDCKDLLRRLLrrdP 237

                          250
                   ....*....|....*.
gi 1207186029 1897 ADRLRPDanECLRHPW 1912
Cdd:cd14009    238 AERISFE--EFFAHPF 251

Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK4 is a MAPK kinase kinase that phosphorylates and activates the c-Jun N-terminal kinase (JNK) and p38 MAPK signaling pathways by directly activating their respective MAPKKs, MKK4/MKK7 and MKK3/MKK6. JNK and p38 are collectively known as stress-activated MAPKs, as they are activated in response to a variety of environmental stresses and pro-inflammatory cytokines. MEKK4 also plays roles in the re-polarization of the actin cytoskeleton in response to osmotic stress, in the proper closure of the neural tube, in cardiovascular development, and in immune responses. The MEKK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270796 [Multi-domain] Cd Length: 265 Bit Score: 119.71 E-value: 2.98e-29

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3309 GRFGVIRECRENATGNLYMAKIVPYEPESKQTVLQ---EYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLHSL 3385
Cdd:cd06626     11 GTFGKVYTAVNLDTGELMAMKEIRFQDNDPKTIKEiadEMKVLEGLDHPNLVRYYGVEVHREEVYIFMEYCQEGTLEELL 90

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3386 idRFRYSEDDVV--AYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSA-------QTFNPLFLKQFsppI 3456
Cdd:cd06626     91 --RHGRILDEAVirVYTLQLLEGLAYLHENGIVHRDIKPANIFLDSNGLIKLGDFGSAvklknntTTMAPGEVNSL---V 165

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3457 GTLDYMSPEMLKGDVV---GPPADIWSIGILTYIMLSGRLPFTENDP--------AETEARIQAAKFDLSKLYQNvsqsa 3525
Cdd:cd06626    166 GTPAYMAPEVITGNKGeghGRAADIWSLGCVVLEMATGKRPWSELDNewaimyhvGMGHKPPIPDSLQLSPEGKD----- 240

                          250       260
                   ....*....|....*....|....*..
gi 1207186029 3526 slFIKKILCSYPWARPTIKDCFTNSWL 3552
Cdd:cd06626    241 --FLSRCLESDPKKRPTASELLDHPFI 265

Catalytic domain of the Serine/Threonine Kinase, Plant Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of plant MAPK kinase kinases (MAPKKKs) including Arabidopsis thaliana MEKK1 and MAPKKK3. Arabidopsis thaliana MEKK1 activates MPK4, a MAPK that regulates systemic acquired resistance. MEKK1 also participates in the regulation of temperature-sensitive and tissue-specific cell death. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The plant MEKK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270802 [Multi-domain] Cd Length: 259 Bit Score: 119.43 E-value: 3.01e-29

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKIVPYEP------ESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKEL 3381
Cdd:cd06632     10 SGSFGSVYEGFNGDTGDFFAVKEVSLVDddkksrESVKQLEQEIALLSKLRHPNIVQYYGTEREEDNLYIFLEYVPGGSI 89

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3382 lHSLIDRFRYSEDDVV-AYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSA-QTFNPLFLKQFSppiGTL 3459
Cdd:cd06632     90 -HKLLQRYGAFEEPVIrLYTRQILSGLAYLHSRNTVHRDIKGANILVDTNGVVKLADFGMAkHVEAFSFAKSFK---GSP 165

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3460 DYMSPEML--KGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKfDLSKLYQNVSQSASLFIKKILCSYP 3537
Cdd:cd06632    166 YWMAPEVImqKNSGYGLAVDIWSLGCTVLEMATGKPPWSQYEGVAAIFKIGNSG-ELPPIPDHLSPDAKDFIRLCLQRDP 244


                   ....*..
gi 1207186029 3538 WARPTIK 3544
Cdd:cd06632    245 EDRPTAS 251

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 113.12 E-value: 3.54e-29

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1545 PTFETIMEDLDVNVGETPRFAVVVEGKPVPDILWYKGDTLLSESSHFTFVYDDNECSLVVLNTQADDSGVYTCTAKNLAG 1624
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVATNSAG 80

                           90
                   ....*....|
gi 1207186029 1625 SVSCKAELTV 1634
Cdd:pfam07679   81 EAEASAELTV 90

Catalytic domain of the Serine/Threonine kinase, Aurora-A kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Aurora kinases are key regulators of mitosis and are essential for the accurate and equal division of genomic material from parent to daughter cells. Vertebrates contain at least 2 Aurora kinases (A and B); mammals contains a third Aurora kinase gene (C). Aurora-A regulates cell cycle events from the late S-phase through the M-phase including centrosome maturation, mitotic entry, centrosome separation, spindle assembly, chromosome alignment, cytokinesis, and mitotic exit. Aurora-A activation depends on its autophosphorylation and binding to the microtubule-associated protein TPX2, which also localizes the kinase to spindle microtubules. Aurora-A is overexpressed in many cancer types such as prostate, ovarian, breast, bladder, gastric, and pancreatic. The Aurora subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271018 [Multi-domain] Cd Length: 258 Bit Score: 119.29 E-value: 3.63e-29

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKIVPYEPESKQTV----LQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLH 3383
Cdd:cd14116     15 KGKFGNVYLAREKQSKFILALKVLFKAQLEKAGVehqlRREVEIQSHLRHPNILRLYGYFHDATRVYLILEYAPLGTVYR 94

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3384 SLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFG-SAQTFNplflKQFSPPIGTLDYM 3462
Cdd:cd14116     95 ELQKLSKFDEQRTATYITELANALSYCHSKRVIHRDIKPENLLLGSAGELKIADFGwSVHAPS----SRRTTLCGTLDYL 170

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3463 SPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFdlsKLYQNVSQSASLFIKKILCSYPWARPT 3542
Cdd:cd14116    171 PPEMIEGRMHDEKVDLWSLGVLCYEFLVGKPPFEANTYQETYKRISRVEF---TFPDFVTEGARDLISRLLKHNPSQRPM 247

                          250
                   ....*....|
gi 1207186029 3543 IKDCFTNSWL 3552
Cdd:cd14116    248 LREVLEHPWI 257

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. eIF-2 phosphorylation is induced in response to cellular stresses including virus infection, heat shock, nutrient deficiency, and the accummulation of unfolded proteins, among others. There are four distinct kinases that phosphorylate eIF-2 and control protein synthesis under different stress conditions: General Control Non-derepressible-2 (GCN2) which is activated during amino acid or serum starvation; protein kinase regulated by RNA (PKR) which is activated by double stranded RNA; heme-regulated inhibitor kinase (HRI) which is activated under heme-deficient conditions; and PKR-like endoplasmic reticulum kinase (PERK) which is activated when misfolded proteins accumulate in the ER. The EIF2AK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270898 [Multi-domain] Cd Length: 273 Bit Score: 119.32 E-value: 5.06e-29

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKIVPY--EPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLHSL 3385
Cdd:cd13996     16 SGGFGSVYKVRNKVDGVTYAIKKIRLteKSSASEKVLREVKALAKLNHPNIVRYYTAWVEEPPLYIQMELCEGGTLRDWI 95

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3386 IDRFRYS---EDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYM-NVVKIIDFGSAQTF-------------NPLF 3448
Cdd:cd13996     96 DRRNSSSkndRKLALELFKQILKGVSYIHSKGIVHRDLKPSNIFLDNDdLQVKIGDFGLATSIgnqkrelnnlnnnNNGN 175

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*...
gi 1207186029 3449 LKQFSPPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSgrlPFT 3496
Cdd:cd13996    176 TSNNSVGIGTPLYASPEQLDGENYNEKADIYSLGIILFEMLH---PFK 220

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I delta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-delta subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271070 [Multi-domain] Cd Length: 301 Bit Score: 120.15 E-value: 5.14e-29

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3297 QKPYTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEP-ESKQTVLQ-EYDILKSLHHEKIMALHEAYVTPRYLVLISE 3374
Cdd:cd14168      9 KKIFEFKEVLGTGAFSEVVLAEERATGKLFAVKCIPKKAlKGKESSIEnEIAVLRKIKHENIVALEDIYESPNHLYLVMQ 88

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3375 CCSGKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIvtYMN-----VVKIIDFGSAQTFNPLFL 3449
Cdd:cd14168     89 LVSGGELFDRIVEKGFYTEKDASTLIRQVLDAVYYLHRMGIVHRDLKPENLL--YFSqdeesKIMISDFGLSKMEGKGDV 166

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3450 kqFSPPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLSKLY-QNVSQSASLF 3528
Cdd:cd14168    167 --MSTACGTPGYVAPEVLAQKPYSKAVDCWSIGVIAYILLCGYPPFYDENDSKLFEQILKADYEFDSPYwDDISDSAKDF 244

                          250       260
                   ....*....|....*....|....
gi 1207186029 3529 IKKILCSYPWARPTIKDCFTNSWL 3552
Cdd:cd14168    245 IRNLMEKDPNKRYTCEQALRHPWI 268

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK7 plays essential roles in the cell cycle and in transcription. It associates with cyclin H and MAT1 and acts as a CDK-Activating Kinase (CAK) by phosphorylating and activating cell cycle CDKs (CDK1/2/4/6). In the brain, it activates CDK5. CDK7 is also a component of the general transcription factor TFIIH, which phosphorylates the C-terminal domain (CTD) of RNA polymerase II when it is bound with unphosphorylated DNA, as present in the pre-initiation complex. Following phosphorylation, the CTD dissociates from the DNA which allows transcription initiation. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK7 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270833 [Multi-domain] Cd Length: 298 Bit Score: 119.98 E-value: 5.35e-29

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3309 GRFGVIRECRENATGNLY-MAKIVPYEPESKQ-----TVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKelL 3382
Cdd:cd07841     11 GTYAVVYKARDKETGRIVaIKKIKLGERKEAKdginfTALREIKLLQELKHPNIIGLLDVFGHKSNINLVFEFMETD--L 88

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3383 HSLID--RFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTF-NPlfLKQFSPPIGTL 3459
Cdd:cd07841     89 EKVIKdkSIVLTPADIKSYMLMTLRGLEYLHSNWILHRDLKPNNLLIASDGVLKLADFGLARSFgSP--NRKMTHQVVTR 166

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3460 DYMSPEMLKG-DVVGPPADIWSIG-ILTYIMLsgRLPF--------------------TENDPAE-------TEARIQAA 3510
Cdd:cd07841    167 WYRAPELLFGaRHYGVGVDMWSVGcIFAELLL--RVPFlpgdsdidqlgkifealgtpTEENWPGvtslpdyVEFKPFPP 244

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|.
gi 1207186029 3511 KfDLSKLYQNVSQSASLFIKKILCSYPWARPTIKDCFTNSW 3551
Cdd:cd07841    245 T-PLKQIFPAASDDALDLLQRLLTLNPNKRITARQALEHPY 284

Catalytic domain of Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of MEKK3, MEKK2, and related proteins; all contain an N-terminal PB1 domain, which mediates oligomerization, and a C-terminal catalytic domain. MEKK2 and MEKK3 are MAPK kinase kinases (MAPKKKs or MKKK) that activate MEK5 (also called MKK5), which activates ERK5. The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK3 plays an essential role in embryonic angiogenesis and early heart development. MEKK2 and MEKK3 can also activate the MAPKs, c-Jun N-terminal kinase (JNK) and p38, through their respective MAPKKs. The MEKK3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270795 [Multi-domain] Cd Length: 260 Bit Score: 118.61 E-value: 5.77e-29

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKIVPYEPESKQT-----VLQ-EYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKel 3381
Cdd:cd06625     10 QGAFGQVYLCYDADTGRELAVKQVEIDPINTEAskevkALEcEIQLLKNLQHERIVQYYGCLQDEKSLSIFMEYMPGG-- 87

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3382 lhSLIDRFR----YSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLKQ-FSPPI 3456
Cdd:cd06625     88 --SVKDEIKaygaLTENVTRKYTRQILEGLAYLHSNMIVHRDIKGANILRDSNGNVKLGDFGASKRLQTICSSTgMKSVT 165

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3457 GTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPaeteariQAAKFDLS------KLYQNVSQSASLFIK 3530
Cdd:cd06625    166 GTPYWMSPEVINGEGYGRKADIWSVGCTVVEMLTTKPPWAEFEP-------MAAIFKIAtqptnpQLPPHVSEDARDFLS 238

                          250       260
                   ....*....|....*....|.
gi 1207186029 3531 KILCSYPWARPTIKDCFTNSW 3551
Cdd:cd06625    239 LIFVRNKKQRPSAEELLSHSF 259

Catalytic domain of Rho-associated coiled-coil containing protein kinase (ROCK)- and Nuclear Dbf2-Related (NDR)-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily include ROCK and ROCK-like proteins such as DMPK, MRCK, and CRIK, as well as NDR and NDR-like proteins such as LATS, CBK1 and Sid2p. ROCK and CRIK are effectors of the small GTPase Rho, while MRCK is an effector of the small GTPase Cdc42. NDR and NDR-like kinases contain an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Proteins in this subfamily are involved in regulating many cellular functions including contraction, motility, division, proliferation, apoptosis, morphogenesis, and cytokinesis. The ROCK/NDR-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270725 [Multi-domain] Cd Length: 350 Bit Score: 121.24 E-value: 6.01e-29

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARA--KRKASAL--RELNILSHLDHERILYFHDAFEKKNAVIIITE- 1736
Cdd:cd05573      3 FEVIKVIGRGAFGEVWLVRDKDTGQVYAMKILRKSDmlKREQIAHvrAERDILADADSPWIVRLHYAFQDEDHLYLVMEy 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1737 LCHEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMAdhSSDQIRICDFGNAVKfMPDEAQYCK 1816
Cdd:cd05573     83 MPGGDLMNLLIKYDVFPEETARFYIAELVLALDSLHKLGFIHRDIKPDNILLD--ADGHIKLADFGLCTK-MNKSGDRES 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1817 Y-------------------------------GTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSV 1865
Cdd:cd05573    160 YlndsvntlfqdnvlarrrphkqrrvraysavGTPDYIAPEVLRGTGYGPECDWWSLGVILYEMLYGFPPFYSDSLVETY 239

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1207186029 1866 LNIRNYNVAFEESMFTDLCHEAKGFVIKLLVA--DRLRpDANECLRHPWFKTLN 1917
Cdd:cd05573    240 SKIMNWKESLVFPDDPDVSPEAIDLIRRLLCDpeDRLG-SAEEIKAHPFFKGID 292

Catalytic domain of Cyclin-Dependent protein Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. CDKs are partly regulated by their subcellular localization, which defines substrate phosphorylation and the resulting specific function. CDK1, CDK2, CDK4, and CDK6 have well-defined functions in the cell cycle, such as the regulation of the early G1 phase by CDK4 or CDK6, the G1/S phase transition by CDK2, or the entry of mitosis by CDK1. They also exhibit overlapping cyclin specificity and functions in certain conditions. Knockout mice with a single CDK deleted remain viable with specific phenotypes, showing that some CDKs can compensate for each other. For example, CDK4 can compensate for the loss of CDK6, however, double knockout mice with both CDK4 and CDK6 deleted die in utero. CDK8 and CDK9 are mainly involved in transcription while CDK5 is implicated in neuronal function. CDK7 plays essential roles in both the cell cycle as a CDK-Activating Kinase (CAK) and in transcription as a component of the general transcription factor TFIIH. The CDK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270823 [Multi-domain] Cd Length: 282 Bit Score: 119.12 E-value: 6.42e-29

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1701 ASALRELNILSHLDHERILYFHDAFEKKNAVIIITELCHEEL---LDRLTKKstILESEIRSSVRQLLEGINYLHQLDIL 1777
Cdd:cd07829     43 STALREISLLKELKHPNIVKLLDVIHTENKLYLVFEYCDQDLkkyLDKRPGP--LPPNLIKSIMYQLLRGLAYCHSHRIL 120

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1778 HLDIKPDNILMAdhSSDQIRICDFGNAVKFMPDEAQYckygTPEFV-----APEI-VNQTPVSKATDIWPIGVLTYLCLT 1851
Cdd:cd07829    121 HRDLKPQNLLIN--RDGVLKLADFGLARAFGIPLRTY----THEVVtlwyrAPEIlLGSKHYSTAVDIWSVGCIFAELIT 194

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1852 GVSPFAGENDRS------------------SVLNIRNYNVAFE-------ESMFTDLCHEAKGFVIKLLVAD-RLRPDAN 1905
Cdd:cd07829    195 GKPLFPGDSEIDqlfkifqilgtpteeswpGVTKLPDYKPTFPkwpkndlEKVLPRLDPEGIDLLSKMLQYNpAKRISAK 274


                   ....*...
gi 1207186029 1906 ECLRHPWF 1913
Cdd:cd07829    275 EALKHPYF 282

Catalytic domain of the Serine/Threonine kinase, Protein Kinase D; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKDs are important regulators of many intracellular signaling pathways such as ERK and JNK, and cellular processes including the organization of the trans-Golgi network, membrane trafficking, cell proliferation, migration, and apoptosis. They contain N-terminal cysteine-rich zinc binding C1 (PKC conserved region 1), central PH (Pleckstrin Homology), and C-terminal catalytic kinase domains. Mammals harbor three types of PKDs: PKD1 (or PKCmu), PKD2, and PKD3 (or PKCnu). PKDs are activated in a PKC-dependent manner by many agents including diacylglycerol (DAG), PDGF, neuropeptides, oxidative stress, and tumor-promoting phorbol esters, among others. The PKD subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270984 [Multi-domain] Cd Length: 260 Bit Score: 118.28 E-value: 7.25e-29

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYVKRVIQKAGKLEYAAKFISAR--AKRKASALR-ELNILSHLDHERILYFHDAFEKKNAVIIITELCHEELLD 1744
Cdd:cd14082     11 LGSGQFGIVYGGKHRKTGRDVAIKVIDKLrfPTKQESQLRnEVAILQQLSHPGVVNLECMFETPERVFVVMEKLHGDMLE 90

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1745 RL--TKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSS-DQIRICDFGNAvKFMPdEAQYCK--YGT 1819
Cdd:cd14082     91 MIlsSEKGRLPERITKFLVTQILVALRYLHSKNIVHCDLKPENVLLASAEPfPQVKLCDFGFA-RIIG-EKSFRRsvVGT 168

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1820 PEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSvlNIRNYNVAFEESMFTDLCHEAKGFVIKLL-VAD 1898
Cdd:cd14082    169 PAYLAPEVLRNKGYNRSLDMWSVGVIIYVSLSGTFPFNEDEDIND--QIQNAAFMYPPNPWKEISPDAIDLINNLLqVKM 246

                          250
                   ....*....|....
gi 1207186029 1899 RLRPDANECLRHPW 1912
Cdd:cd14082    247 RKRYSVDKSLSHPW 260

Catalytic domain of the Serine/Threonine kinase, Per-ARNT-Sim (PAS) domain Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PASK (or PASKIN) is a nutrient and energy sensor and thus, plays an important role in maintaining cellular energy homeostasis. It coordinates the utilization of glucose in response to metabolic demand. It contains an N-terminal PAS domain which directly interacts and inhibits a C-terminal catalytic kinase domain. The PAS domain serves as a sensory module for different environmental signals such as light, redox state, and various metabolites. Binding of ligands to the PAS domain causes structural changes which leads to kinase activation and the phosphorylation of substrates to trigger the appropriate cellular response. The PASK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270906 [Multi-domain] Cd Length: 256 Bit Score: 118.26 E-value: 8.48e-29

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1661 YYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFIS---------ARAKRKASALRELNILSHLD---HERILYFHDAFEKK 1728
Cdd:cd14004      1 DYTILKEMGEGAYGQVNLAIYKSKGKEVVIKFIFkerilvdtwVRDRKLGTVPLEIHILDTLNkrsHPNIVKLLDFFEDD 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1729 NAVIIITElCHEE---LLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSdqIRICDFGNAV 1805
Cdd:cd14004     81 EFYYLVME-KHGSgmdLFDFIERKPNMDEKEAKYIFRQVADAVKHLHDQGIVHRDIKDENVILDGNGT--IKLIDFGSAA 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1806 kFMPDEAQYCKYGTPEFVAPEIVNQTP-VSKATDIWPIGVLTYLCLTGVSPFAgENDRSSVLNIRNYNVAFEESMftdlc 1884
Cdd:cd14004    158 -YIKSGPFDTFVGTIDYAAPEVLRGNPyGGKEQDIWALGVLLYTLVFKENPFY-NIEEILEADLRIPYAVSEDLI----- 230

                          250       260       270
                   ....*....|....*....|....*....|
gi 1207186029 1885 heakGFVIKLLVAD-RLRPDANECLRHPWF 1913
Cdd:cd14004    231 ----DLISRMLNRDvGDRPTIEELLTDPWL 256

Catalytic domain of Kin1, Kin2, and simlar Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of yeast Kin1, Kin2, and similar proteins. Fission yeast Kin1 is a membrane-associated kinase that is involved in regulating cell surface cohesiveness during interphase. It also plays a role during mitosis, linking actomyosin ring assembly with septum synthesis and membrane closure to ensure separation of daughter cells. Budding yeast Kin1 and Kin2 act downstream of the Rab-GTPase Sec4 and are associated with the exocytic apparatus; they play roles in the secretory pathway. The Kin1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270979 [Multi-domain] Cd Length: 267 Bit Score: 118.32 E-value: 8.83e-29

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPES----------------KQTVLQEYDILKSLHHEKIMALHEAY 3363
Cdd:cd14077      3 WEFVKTIGAGSMGKVKLAKHIRTGEKCAIKIIPRASNAglkkerekrlekeisrDIRTIREAALSSLLNHPHICRLRDFL 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3364 VTPRYLVLISECCSGKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQT 3443
Cdd:cd14077     83 RTPNHYYMLFEYVDGGQLLDYIISHGKLKEKQARKFARQIASALDYLHRNSIVHRDLKIENILISKSGNIKIIDFGLSNL 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3444 FNPlfLKQFSPPIGTLDYMSPEMLKGD-VVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLSKlyqNVS 3522
Cdd:cd14077    163 YDP--RRLLRTFCGSLYFAAPELLQAQpYTGPEVDVWSFGVVLYVLVCGKVPFDDENMPALHAKIKKGKVEYPS---YLS 237

                          250       260       270
                   ....*....|....*....|....*....|
gi 1207186029 3523 QSASLFIKKILCSYPWARPTIKDCFTNSWL 3552
Cdd:cd14077    238 SECKSLISRMLVVDPKKRATLEQVLNHPWM 267

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. eIF-2 phosphorylation is induced in response to cellular stresses including virus infection, heat shock, nutrient deficiency, and the accummulation of unfolded proteins, among others. There are four distinct kinases that phosphorylate eIF-2 and control protein synthesis under different stress conditions: General Control Non-derepressible-2 (GCN2) which is activated during amino acid or serum starvation; protein kinase regulated by RNA (PKR) which is activated by double stranded RNA; heme-regulated inhibitor kinase (HRI) which is activated under heme-deficient conditions; and PKR-like endoplasmic reticulum kinase (PERK) which is activated when misfolded proteins accumulate in the ER. The EIF2AK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270898 [Multi-domain] Cd Length: 273 Bit Score: 118.55 E-value: 9.31e-29

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKAS--ALRELNILSHLDHERILYFHDAFEKKNAVIIITELCH----EE 1741
Cdd:cd13996     14 LGSGGFGSVYKVRNKVDGVTYAIKKIRLTEKSSASekVLREVKALAKLNHPNIVRYYTAWVEEPPLYIQMELCEggtlRD 93

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1742 LLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMaDHSSDQIRICDFG--------------NAVKF 1807
Cdd:cd13996     94 WIDRRNSSSKNDRKLALELFKQILKGVSYIHSKGIVHRDLKPSNIFL-DNDDLQVKIGDFGlatsignqkrelnnLNNNN 172

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1808 MPDEAQYC-KYGTPEFVAPEIVNQTPVSKATDIWPIGVLTY--LCltgvsPFAGENDRSSVL-NIRNYNvaFEESmFTDL 1883
Cdd:cd13996    173 NGNTSNNSvGIGTPLYASPEQLDGENYNEKADIYSLGIILFemLH-----PFKTAMERSTILtDLRNGI--LPES-FKAK 244

                          250       260
                   ....*....|....*....|....*..
gi 1207186029 1884 CHEAKGFVIKLLVAD-RLRPDANECLR 1909
Cdd:cd13996    245 HPKEADLIQSLLSKNpEERPSAEQLLR 271

Catalytic domain of the Protein Serine/Threonine kinase H1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PSKH1 is an autophosphorylating STK that is expressed ubiquitously and exhibits multiple intracellular localizations including the centrosome, Golgi apparatus, and splice factor compartments. It contains a catalytic kinase domain and an N-terminal SH4-like motif that is acylated to facilitate membrane attachment. PSKH1 plays a rile in the maintenance of the Golgi apparatus, an important organelle within the secretory pathway. It may also function as a novel splice factor and a regulator of prostate cancer cell growth. The PSKH1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270989 [Multi-domain] Cd Length: 259 Bit Score: 118.02 E-value: 1.00e-28

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKIVPYEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLHSLID 3387
Cdd:cd14087     11 RGSFSRVVRVEHRVTRQPYAIKMIETKCRGREVCESELNVLRRVRHTNIIQLIEVFETKERVYMVMELATGGELFDRIIA 90

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3388 RFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNV---VKIIDFGSAQTFNPLFLKQFSPPIGTLDYMSP 3464
Cdd:cd14087     91 KGSFTERDATRVLQMVLDGVKYLHGLGITHRDLKPENLLYYHPGPdskIMITDFGLASTRKKGPNCLMKTTCGTPEYIAP 170

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3465 EMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLS-KLYQNVSQSASLFIKKILCSYPWARPTI 3543
Cdd:cd14087    171 EILLRKPYTQSVDMWAVGVIAYILLSGTMPFDDDNRTRLYRQILRAKYSYSgEPWPSVSNLAKDFIDRLLTVNPGERLSA 250


                   ....*....
gi 1207186029 3544 KDCFTNSWL 3552
Cdd:cd14087    251 TQALKHPWI 259

Catalytic domain of the Serine/Threonine kinase, Per-ARNT-Sim (PAS) domain Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PASK (or PASKIN) is a nutrient and energy sensor and thus, plays an important role in maintaining cellular energy homeostasis. It coordinates the utilization of glucose in response to metabolic demand. It contains an N-terminal PAS domain which directly interacts and inhibits a C-terminal catalytic kinase domain. The PAS domain serves as a sensory module for different environmental signals such as light, redox state, and various metabolites. Binding of ligands to the PAS domain causes structural changes which leads to kinase activation and the phosphorylation of substrates to trigger the appropriate cellular response. The PASK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270906 [Multi-domain] Cd Length: 256 Bit Score: 117.49 E-value: 1.52e-28

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEP-------ESKQ--TVLQEYDILKSLH---HEKIMALHEAYVTPR 3367
Cdd:cd14004      2 YTILKEMGEGAYGQVNLAIYKSKGKEVVIKFIFKERilvdtwvRDRKlgTVPLEIHILDTLNkrsHPNIVKLLDFFEDDE 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3368 YLVLISEC-CSGKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQtfnp 3446
Cdd:cd14004     82 FYYLVMEKhGSGMDLFDFIERKPNMDEKEAKYIFRQVADAVKHLHDQGIVHRDIKDENVILDGNGTIKLIDFGSAA---- 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3447 lFLKQ--FSPPIGTLDYMSPEMLKGD-VVGPPADIWSIGILTYIMLSGRLPFTENDpaET-EARIQAakfdlsklYQNVS 3522
Cdd:cd14004    158 -YIKSgpFDTFVGTIDYAAPEVLRGNpYGGKEQDIWALGVLLYTLVFKENPFYNIE--EIlEADLRI--------PYAVS 226

                          250       260       270
                   ....*....|....*....|....*....|
gi 1207186029 3523 QSASLFIKKILCSYPWARPTIKDCFTNSWL 3552
Cdd:cd14004    227 EDLIDLISRMLNRDVGDRPTIEELLTDPWL 256

Catalytic domain of the Serine/Threonine Kinase, Yank1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily contains uncharacterized STKs with similarity to the human protein designated as Yank1 or STK32A. The Yank1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270730 [Multi-domain] Cd Length: 257 Bit Score: 117.36 E-value: 1.75e-28

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNL----YMAKIVPYEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLH 3383
Cdd:cd05578     10 KGSFGKVCIVQKKDTKKMfamkYMNKQKCIEKDSVRNVLNELEILQELEHPFLVNLWYSFQDEEDMYMVVDLLLGGDLRY 89

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3384 SLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLKQFSPpiGTLDYMS 3463
Cdd:cd05578     90 HLQQKVKFSEETVKFYICEIVLALDYLHSKNIIHRDIKPDNILLDEQGHVHITDFNIATKLTDGTLATSTS--GTKPYMA 167

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3464 PEMLKGDVVGPPADIWSIGILTYIMLSGRLPFtENDPAETEARIQAAKFDLSKLYQNV-SQSASLFIKKILCSYPWAR-P 3541
Cdd:cd05578    168 PEVFMRAGYSFAVDWWSLGVTAYEMLRGKRPY-EIHSRTSIEEIRAKFETASVLYPAGwSEEAIDLINKLLERDPQKRlG 246

                          250
                   ....*....|.
gi 1207186029 3542 TIKDCFTNSWL 3552
Cdd:cd05578    247 DLSDLKNHPYF 257

Catalytic domain of Fungal Halotolerance protein 4-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of HAL4, Saccharomyces cerevisiae Ptk2/Stk2, and similar fungal proteins. Proteins in this subfamily are involved in regulating ion transporters. In budding and fission yeast, HAL4 promotes potassium ion uptake, which increases cellular resistance to other cations such as sodium, lithium, and calcium ions. HAL4 stabilizes the major high-affinity K+ transporter Trk1 at the plasma membrane under low K+ conditions, which prevents endocytosis and vacuolar degradation. Budding yeast Ptk2 phosphorylates and regulates the plasma membrane H+ ATPase, Pma1. The HAL4-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270896 [Multi-domain] Cd Length: 265 Bit Score: 117.02 E-value: 2.78e-28

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYVkRVIQK---AGKLEYAAKFI------SARAKRKASALRELNILSHLDHERILYFHDAFEKKNAVI-IITEL 1737
Cdd:cd13994      1 IGKGATSVV-RIVTKknpRSGVLYAVKEYrrrddeSKRKDYVKRLTSEYIISSKLHHPNIVKVLDLCQDLHGKWcLVMEY 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1738 C-HEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSsdQIRICDFGNAVKF-MPDEAQYC 1815
Cdd:cd13994     80 CpGGDLFTLIEKADSLSLEEKDCFFKQILRGVAYLHSHGIAHRDLKPENILLDEDG--VLKLTDFGTAEVFgMPAEKESP 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1816 K----YGTPEFVAPEIVNQTPVS-KATDIWPIGVLtYLCL-TGVSPFA-----GENDRSSVLNIRNYNVAFE---ESMFT 1881
Cdd:cd13994    158 MsaglCGSEPYMAPEVFTSGSYDgRAVDVWSCGIV-LFALfTGRFPWRsakksDSAYKAYEKSGDFTNGPYEpieNLLPS 236

                          250       260       270
                   ....*....|....*....|....*....|...
gi 1207186029 1882 DLcheaKGFVIKLLVAD-RLRPDANECLRHPWF 1913
Cdd:cd13994    237 EC----RRLIYRMLHPDpEKRITIDEALNDPWV 265

Catalytic domain of RCK1-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of fungal STKs including Saccharomyces cerevisiae RCK1 and RCK2, Schizosaccharomyces pombe Sty1-regulated kinase 1 (Srk1), and similar proteins. RCK1, RCK2 (or Rck2p), and Srk1 are MAPK-activated protein kinases. RCK1 and RCK2 are involved in oxidative and metal stress resistance in budding yeast. RCK2 also regulates rapamycin sensitivity in both S. cerevisiae and Candida albicans. Srk1 is activated by Sty1/Spc1 and is involved in negatively regulating cell cycle progression by inhibiting Cdc25. The RCK1-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270998 [Multi-domain] Cd Length: 295 Bit Score: 117.92 E-value: 2.89e-28

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFG-VIRECRENATGNLYMAKIVP--------YEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLV 3370
Cdd:cd14096      3 YRLINKIGEGAFSnVYKAVPLRNTGKPVAIKVVRkadlssdnLKGSSRANILKEVQIMKRLSHPNIVKLLDFQESDEYYY 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3371 LISECCSGKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTY--------------------- 3429
Cdd:cd14096     83 IVLELADGGEIFHQIVRLTYFSEDLSRHVITQVASAVKYLHEIGVVHRDIKPENLLFEPipfipsivklrkadddetkvd 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3430 ------------MNVVKIIDFGSAQTFNPlflKQFSPPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTE 3497
Cdd:cd14096    163 egefipgvggggIGIVKLADFGLSKQVWD---SNTKTPCGTVGYTAPEVVKDERYSKKVDMWALGCVLYTLLCGFPPFYD 239

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1207186029 3498 NDPAETEARIQAAKFD-LSKLYQNVSQSASLFIKKILCSYPWARPTIKDCFTNSWL 3552
Cdd:cd14096    240 ESIETLTEKISRGDYTfLSPWWDEISKSAKDLISHLLTVDPAKRYDIDEFLAHPWI 295

Catalytic domain of Nuclear Dbf2-Related kinase-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NDR kinases regulate mitosis, cell growth, embryonic development, and neurological processes. They are also required for proper centrosome duplication. Higher eukaryotes contain two NDR isoforms, NDR1 and NDR2. This subfamily also contains fungal NDR-like kinases. NDR kinase contains an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Like many other AGC kinases, NDR kinase requires phosphorylation at two sites, the activation loop (A-loop) and the hydrophobic motif (HM), for activity. The NDR kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270750 [Multi-domain] Cd Length: 324 Bit Score: 118.49 E-value: 3.05e-28

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1666 KEIGRGAFSYVKRVIQKAGKLEYAAKFIsarakRKASALR---------ELNILSHLDHERI--LY--FHDAfekKNAVI 1732
Cdd:cd05599      7 KVIGRGAFGEVRLVRKKDTGHVYAMKKL-----RKSEMLEkeqvahvraERDILAEADNPWVvkLYysFQDE---ENLYL 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1733 IITELCHEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDFGNAVKFMPDEA 1812
Cdd:cd05599     79 IMEFLPGGDMMTLLMKKDTLTEEETRFYIAETVLAIESIHKLGYIHRDIKPDNLLL--DARGHIKLSDFGLCTGLKKSHL 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1813 QYCKYGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDLCHEAKGFVI 1892
Cdd:cd05599    157 AYSTVGTPDYIAPEVFLQKGYGKECDWWSLGVIMYEMLIGYPPFCSDDPQETCRKIMNWRETLVFPPEVPISPEAKDLIE 236

                          250       260
                   ....*....|....*....|....*...
gi 1207186029 1893 KLL--VADRL-RPDANECLRHPWFKTLN 1917
Cdd:cd05599    237 RLLcdAEHRLgANGVEEIKSHPFFKGVD 264

Catalytic domain of an Uncharacterized group of Serine/Threonine kinases with similarity to Calcium/calmodulin-dependent protein kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of uncharacterized STKs with similarity to CaMKs, which are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). CaMKs contain an N-terminal catalytic domain followed by a regulatory domain that harbors a CaM binding site. This uncharacterized subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270990 [Multi-domain] Cd Length: 265 Bit Score: 116.66 E-value: 3.40e-28

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3311 FGVIRECRENATGNLYMAKIVPYEPESK--QTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLHSLIDR 3388
Cdd:cd14088     14 FCEIFRAKDKTTGKLYTCKKFLKRDGRKvrKAAKNEINILKMVKHPNILQLVDVFETRKEYFIFLELATGREVFDWILDQ 93

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3389 FRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIvtYMNVVK-----IIDFGSAQTFNPLfLKQfspPIGTLDYMS 3463
Cdd:cd14088     94 GYYSERDTSNVIRQVLEAVAYLHSLKIVHRNLKLENLV--YYNRLKnskivISDFHLAKLENGL-IKE---PCGTPEYLA 167

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3464 PEMLKGDVVGPPADIWSIGILTYIMLSGRLPF---TENDPAETE-----ARIQAAKFDL-SKLYQNVSQSASLFIKKILC 3534
Cdd:cd14088    168 PEVVGRQRYGRPVDCWAIGVIMYILLSGNPPFydeAEEDDYENHdknlfRKILAGDYEFdSPYWDDISQAAKDLVTRLME 247

                          250
                   ....*....|....*...
gi 1207186029 3535 SYPWARPTIKDCFTNSWL 3552
Cdd:cd14088    248 VEQDQRITAEEAISHEWI 265

Catalytic domain of the Serine/Threonine kinases, Mitogen-activated protein kinase signal-integrating kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK signal-integrating kinases (Mnks) are MAPK-activated protein kinases and is comprised by a group of four proteins, produced by alternative splicing from two genes (Mnk1 and Mnk2). The isoforms of Mnk1 (1a/1b) and Mnk2 (2a/2b) differ at their C-termini, with the a-form having a longer C-terminus containing a MAPK-binding region. All Mnks contain a catalytic kinase domain and a polybasic region at the N-terminus which binds importin and the eukaryotic initiation factor eIF4G. The best characterized Mnk substrate is eIF4G, whose phosphorylation may promote the export of certain mRNAs from the nucleus. Mnk also phosphorylate substrates that bind to AU-rich elements that regulate mRNA stability and translation. Mnks have also been implicated in tyrosine kinase receptor signaling, inflammation, and cell prolieration or survival. The Mnk subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270992 [Multi-domain] Cd Length: 289 Bit Score: 117.13 E-value: 3.60e-28

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1660 DYYDVHKEI-GRGAFSYVKRVIQKAGKLEYAAKFISAR-AKRKASALRELNILSHLD-HERILYFHDAFEKKNAVIIITE 1736
Cdd:cd14090      1 DLYKLTGELlGEGAYASVQTCINLYTGKEYAVKIIEKHpGHSRSRVFREVETLHQCQgHPNILQLIEYFEDDERFYLVFE 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1737 LCHE-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMAdhSSDQI---RICDF--GNAVKFMPD 1810
Cdd:cd14090     81 KMRGgPLLSHIEKRVHFTEQEASLVVRDIASALDFLHDKGIAHRDLKPENILCE--SMDKVspvKICDFdlGSGIKLSST 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1811 EAQYCK-------YGTPEFVAPEIVN-----QTPVSKATDIWPIGVLTYLCLTGVSPFAGEN------DRSSVL------ 1866
Cdd:cd14090    159 SMTPVTtpelltpVGSAEYMAPEVVDafvgeALSYDKRCDLWSLGVILYIMLCGYPPFYGRCgedcgwDRGEACqdcqel 238

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1867 ---NIRNYNVAFEESMFTDLCHEAKGFVIKLLVAD-RLRPDANECLRHPW 1912
Cdd:cd14090    239 lfhSIQEGEYEFPEKEWSHISAEAKDLISHLLVRDaSQRYTAEQVLQHPW 288

Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii CNK2 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Chlamydomonas reinhardtii CNK2 has both cilliary and cell cycle functions. It influences flagellar length through promoting flagellar disassembly, and it regulates cell size, through influencing the size threshold at which cells commit to mitosis. This subfamily belongs to the (NIMA)-related kinase (Nek) family, which includes seven different Chlamydomonas Neks (CNKs 1-6 and Fa2). This subfamily includes CNK1, and -2. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270869 [Multi-domain] Cd Length: 256 Bit Score: 116.34 E-value: 3.65e-28

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARA---KRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITELC 1738
Cdd:cd08530      2 FKVLKKLGKGSYGSVYKVKRLSDNQVYALKEVNLGSlsqKEREDSVNEIRLLASVNHPNIIRYKEAFLDGNRLCIVMEYA 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1739 HEELLDRLTKKST-----ILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADhsSDQIRICDFGNAvKFMPDEAQ 1813
Cdd:cd08530     82 PFGDLSKLISKRKkkrrlFPEDDIWRIFIQMLRGLKALHDQKILHRDLKSANILLSA--GDLVKIGDLGIS-KVLKKNLA 158

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*.
gi 1207186029 1814 YCKYGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGE 1859
Cdd:cd08530    159 KTQIGTPLYAAPEVWKGRPYDYKSDIWSLGCLLYEMATFRPPFEAR 204

Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 1 and 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKL1, also called p42 KKIALRE, is a glial protein that is upregulated in gliosis. It is present in neuroblastoma and A431 human carcinoma cells, and may be implicated in neoplastic transformation. The function of CDKL4 is unknown. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL1/4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270837 [Multi-domain] Cd Length: 286 Bit Score: 117.09 E-value: 3.77e-28

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3309 GRFGVIRECRENATGNLY-MAKIVPYE--PESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSgKELLHSL 3385
Cdd:cd07847     12 GSYGVVFKCRNRETGQIVaIKKFVESEddPVIKKIALREIRMLKQLKHPNLVNLIEVFRRKRKLHLVFEYCD-HTVLNEL 90

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3386 IDRFRYSEDDVVAYIV-QILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPlFLKQFSPPIGTLDYMSP 3464
Cdd:cd07847     91 EKNPRGVPEHLIKKIIwQTLQAVNFCHKHNCIHRDVKPENILITKQGQIKLCDFGFARILTG-PGDDYTDYVATRWYRAP 169

                          170       180
                   ....*....|....*....|....*...
gi 1207186029 3465 EMLKGDVV-GPPADIWSIGILTYIMLSG 3491
Cdd:cd07847    170 ELLVGDTQyGPPVDVWAIGCVFAELLTG 197

N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, in response to various stimuli such as growth factors, hormones, neurotransmitters, cellular stress, and pro-inflammatory cytokines. This triggers phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) in the C-terminal extension of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. MSKs are predominantly nuclear proteins. They are widely expressed in many tissues including heart, brain, lung, liver, kidney, and pancreas. There are two isoforms of MSK, called MSK1 and MSK2. The MSK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270735 [Multi-domain] Cd Length: 268 Bit Score: 116.72 E-value: 3.89e-28

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYV----KRVIQKAGKLeYAAKFIsarakRKASALRELNILSHLDHER-----------ILYFHDAFEKKNAVI 1732
Cdd:cd05583      2 LGTGAYGKVflvrKVGGHDAGKL-YAMKVL-----KKATIVQKAKTAEHTMTERqvleavrqspfLVTLHYAFQTDAKLH 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1733 IITE-LCHEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDFGNAVKFMPDE 1811
Cdd:cd05583     76 LILDyVNGGELFTHLYQREHFTESEVRIYIGEIVLALEHLHKLGIIYRDIKLENILL--DSEGHVVLTDFGLSKEFLPGE 153

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1812 AQ----YCkyGTPEFVAPEIVNQTPV--SKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDLCH 1885
Cdd:cd05583    154 NDraysFC--GTIEYMAPEVVRGGSDghDKAVDWWSLGVLTYELLTGASPFTVDGERNSQSEISKRILKSHPPIPKTFSA 231

                          250       260       270
                   ....*....|....*....|....*....|....*..
gi 1207186029 1886 EAKGFVIKLLVAD---RL---RPDANECLRHPWFKTL 1916
Cdd:cd05583    232 EAKDFILKLLEKDpkkRLgagPRGAHEIKEHPFFKGL 268

Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NUAK proteins are classified as AMP-activated protein kinase (AMPK)-related kinases, which like AMPK are activated by the major tumor suppressor LKB1. Vertebrates contain two NUAK proteins, called NUAK1 and NUAK2. NUAK2, also called SNARK (Sucrose, non-fermenting 1/AMP-activated protein kinase-related kinase), is involved in energy metabolism. It is activated by hyperosmotic stress, DNA damage, and nutrients such as glucose and glutamine. NUAK2-knockout mice develop obesity, altered serum lipid profiles, hyperinsulinaemia, hyperglycaemia, and impaired glucose tolerance. NUAK2 is implicated in regulating actin stress fiber assembly through its association with myosin phosphatase Rho-interacting protein (MRIP), which leads to an increase in myosin regulatory light chain (MLC) phosphorylation. It is also associated with tumor growth, migration, and oncogenicity of melanoma cells. The NUAK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271063 [Multi-domain] Cd Length: 255 Bit Score: 115.82 E-value: 4.54e-28

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLeYAAKFISARAKRKASAL----RELNILSHLDHERILYFHDAFEKKNAVIIITEL 1737
Cdd:cd14161      5 YEFLETLGKGTYGRVKKARDSSGRL-VAIKSIRKDRIKDEQDLlhirREIEIMSSLNHPHIISVYEVFENSSKIVIVMEY 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1738 CHE-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDFGNAVKFMPDE--AQY 1814
Cdd:cd14161     84 ASRgDLYDYISERQRLSELEARHFFRQIVSAVHYCHANGIVHRDLKLENILL--DANGNIKIADFGLSNLYNQDKflQTY 161

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1207186029 1815 CkyGTPEFVAPEIVNQTP-VSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRN 1870
Cdd:cd14161    162 C--GSPLYASPEIVNGRPyIGPEVDSWSLGVLLYILVHGTMPFDGHDYKILVKQISS 216

Catalytic domain of the Serine/Threonine Kinase, Hormonally up-regulated Neu-associated kinase (also called MAK-V); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HUNK/MAK-V was identified from a mammary tumor in an MMTV-neu transgenic mouse. It is required for the metastasis of c-myc-induced mammary tumors, but is not necessary for c-myc-induced primary tumor formation or normal development. It is required for HER2/neu-induced tumor formation and maintenance of the cells' tumorigenic phenotype. It is over-expressed in aggressive subsets of ovary, colon, and breast carcinomas. HUNK interacts with synaptopodin, and may also play a role in synaptic plasticity. The HUNK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270972 [Multi-domain] Cd Length: 262 Bit Score: 116.07 E-value: 4.54e-28

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKIVPYEPESKQTVL-----QEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELL 3382
Cdd:cd14070     12 EGSFAKVREGLHAVTGEKVAIKVIDKKKAKKDSYVtknlrREGRIQQMIRHPNITQLLDILETENSYYLVMELCPGGNLM 91

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3383 HSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLKQ-FSPPIGTLDY 3461
Cdd:cd14070     92 HRIYDKKRLEEREARRYIRQLVSAVEHLHRAGVVHRDLKIENLLLDENDNIKLIDFGLSNCAGILGYSDpFSTQCGSPAY 171

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3462 MSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTEnDPAETEARIQA-AKFDLSKLYQNVSQSASLFIKKILCSYPWAR 3540
Cdd:cd14070    172 AAPELLARKKYGPKVDVWSIGVNMYAMLTGTLPFTV-EPFSLRALHQKmVDKEMNPLPTDLSPGAISFLRSLLEPDPLKR 250

                          250
                   ....*....|..
gi 1207186029 3541 PTIKDCFTNSWL 3552
Cdd:cd14070    251 PNIKQALANRWL 262

N-terminal Catalytic domain of Class III myosin-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Class III myosins are motor proteins with an N-terminal kinase catalytic domain and a C-terminal actin-binding motor domain. Class III myosins are present in the photoreceptors of invertebrates and vertebrates and in the auditory hair cells of mammals. The kinase domain of myosin III can phosphorylate several cytoskeletal proteins, conventional myosin regulatory light chains, and can autophosphorylate the C-terminal motor domain. Myosin III may play an important role in maintaining the structural integrity of photoreceptor cell microvilli. It may also function as a cargo carrier during light-dependent translocation, in photoreceptor cells, of proteins such as transducin and arrestin. The Drosophila class III myosin, called NinaC (Neither inactivation nor afterpotential protein C), is critical in normal adaptation and termination of photoresponse. Vertebrates contain two isoforms of class III myosin, IIIA and IIIB. This subfamily also includes mammalian NIK-like embryo-specific kinase (NESK), Traf2- and Nck-interacting kinase (TNIK), and mitogen-activated protein kinase (MAPK) kinase kinase kinase 4/6. MAP4Ks are involved in some MAPK signaling pathways by activating a MAPK kinase kinase. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. The class III myosin-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270785 [Multi-domain] Cd Length: 275 Bit Score: 116.25 E-value: 6.17e-28

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3296 PQKPYTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPESKQTVLQEYDILKSL-HHEKIMALHEAYVTPRYLV---- 3370
Cdd:cd06608      4 PAGIFELVEVIGEGTYGKVYKARHKKTGQLAAIKIMDIIEDEEEEIKLEINILRKFsNHPNIATFYGAFIKKDPPGgddq 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3371 --LISECCSG---KELLHSLIDRFRYSEDDVVAYIVQ-ILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFG-SAQT 3443
Cdd:cd06608     84 lwLVMEYCGGgsvTDLVKGLRKKGKRLKEEWIAYILReTLRGLAYLHENKVIHRDIKGQNILLTEEAEVKLVDFGvSAQL 163

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3444 FNPLFLKQFSppIGTLDYMSPEMLKGD-----VVGPPADIWSIGILTYIMLSGRLPFTENDPaeTEARIQAAKFDLSKLY 3518
Cdd:cd06608    164 DSTLGRRNTF--IGTPYWMAPEVIACDqqpdaSYDARCDVWSLGITAIELADGKPPLCDMHP--MRALFKIPRNPPPTLK 239

                          250       260       270
                   ....*....|....*....|....*....|....*.
gi 1207186029 3519 QNVSQSASL--FIKKILCSYPWARPTIKDCFTNSWL 3552
Cdd:cd06608    240 SPEKWSKEFndFISECLIKNYEQRPFTEELLEHPFI 275

Catalytic domain of the Serine/Threonine Kinases, Never In Mitosis gene A (NIMA)-related kinase 6 and 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek6 and Nek7 are the shortest Neks, consisting only of the catalytic domain and a very short N-terminal extension. They show distinct expression patterns and both appear to be downstream substrates of Nek9. They are required for mitotic spindle formation and cytokinesis. They may also be regulators of the p70 ribosomal S6 kinase. Nek6/7 is part of a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270863 [Multi-domain] Cd Length: 262 Bit Score: 115.83 E-value: 6.81e-28

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLY-MAKIVPYE---PESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLH 3383
Cdd:cd08224     10 KGQFSVVYRARCLLDGRLVaLKKVQIFEmmdAKARQDCLKEIDLLQQLNHPNIIKYLASFIENNELNIVLELADAGDLSR 89

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3384 sLIDRFR-----YSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLKQFSpPIGT 3458
Cdd:cd08224     90 -LIKHFKkqkrlIPERTIWKYFVQLCSALEHMHSKRIMHRDIKPANVFITANGVVKLGDLGLGRFFSSKTTAAHS-LVGT 167

                          170       180       190
                   ....*....|....*....|....*....|....*..
gi 1207186029 3459 LDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPF 3495
Cdd:cd08224    168 PYYMSPERIREQGYDFKSDIWSLGCLLYEMAALQSPF 204

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK2, also called Snk (serum-inducible kinase), functions in G1 progression, S-phase arrest, and centriole duplication. Its gene is responsive to both growth factors and cellular stress, is a transcriptional target of p53, and activates a G2-M checkpoint. The PLK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271090 [Multi-domain] Cd Length: 255 Bit Score: 115.49 E-value: 7.45e-28

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1666 KEIGRGAFSYVKRVIQKAGKLEYAAKFIS----ARAKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITELCHEE 1741
Cdd:cd14188      7 KVLGKGGFAKCYEMTDLTTNKVYAAKIIPhsrvSKPHQREKIDKEIELHRILHHKHVVQFYHYFEDKENIYILLEYCSRR 86

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1742 LLDRLTKKSTIL-ESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDFGNAVKFMPDEAQ---YCky 1817
Cdd:cd14188     87 SMAHILKARKVLtEPEVRYYLRQIVSGLKYLHEQEILHRDLKLGNFFI--NENMELKVGDFGLAARLEPLEHRrrtIC-- 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1818 GTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTdlchEAKGFVIKLLVA 1897
Cdd:cd14188    163 GTPNYLSPEVLNKQGHGCESDIWALGCVMYTMLLGRPPFETTNLKETYRCIREARYSLPSSLLA----PAKHLIASMLSK 238

                          250
                   ....*....|....*..
gi 1207186029 1898 D-RLRPDANECLRHPWF 1913
Cdd:cd14188    239 NpEDRPSLDEIIRHDFF 255

Catalytic domain of Brain-specific serine/threonine-protein kinases 1 and 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BRSK1, also called SAD-B or SAD1 (Synapses of Amphids Defective homolog 1), and BRSK2, also called SAD-A, are highly expressed in mammalian forebrain. They play important roles in establishing neuronal polarity. BRSK1/2 double knock-out mice die soon after birth, showing thin cerebral cortices due to disordered subplate layers and neurons that lack distinct axons and dendrites. BRSK1 regulates presynaptic neurotransmitter release. Its activity fluctuates during cell cysle progression and it acts as a regulator of centrosome duplication. BRSK2 is also abundant in pancreatic islets, where it is involved in the regulation of glucose-stimulated insulin secretion. The BRSK1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270983 [Multi-domain] Cd Length: 255 Bit Score: 115.43 E-value: 7.64e-28

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVK-RVIQKAGKLeYAAKFISARAKRKASAL----RELNILSHLDHERILYFHDAFEKKNAVIIITE 1736
Cdd:cd14081      3 YRLGKTLGKGQTGLVKlAKHCVTGQK-VAIKIVNKEKLSKESVLmkveREIAIMKLIEHPNVLKLYDVYENKKYLYLVLE 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1737 LCHE-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSsdQIRICDFGNAVKFMPDE--AQ 1813
Cdd:cd14081     82 YVSGgELFDYLVKKGRLTEKEARKFFRQIISALDYCHSHSICHRDLKPENLLLDEKN--NIKIADFGMASLQPEGSllET 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1814 YCkyGTPEFVAPEIVNQTPV-SKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYnvAFEesMFTDLCHEAKGFVI 1892
Cdd:cd14081    160 SC--GSPHYACPEVIKGEKYdGRKADIWSCGVILYALLVGALPFDDDNLRQLLEKVKRG--VFH--IPHFISPDAQDLLR 233

                          250       260
                   ....*....|....*....|..
gi 1207186029 1893 KLLVAD-RLRPDANECLRHPWF 1913
Cdd:cd14081    234 RMLEVNpEKRITIEEIKKHPWF 255

Catalytic domain of the Serine/Threonine kinases, Unc-51-like kinases 1 and 2, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK1 is required for efficient amino acid starvation-induced autophagy and mitochondrial clearance. ULK2 is ubiquitously expressed and is essential in autophagy induction. ULK1 and ULK2 have unique and cell-type specific roles, but also display partially redundant roles in starvation-induced autophagy. They both display neuron-specific functions: ULK1 is involved in non-clathrin-coated endocytosis in growth cones, filopodia extension, and axon branching; ULK2 plays a role in axon development. The ULK1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271022 [Multi-domain] Cd Length: 256 Bit Score: 115.16 E-value: 9.10e-28

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYV-KRVIQKAGKLEYAAKFISARAKRKASAL--RELNILSHLDHERILYFHDAFEKKNAVIIITELCHE-ELL 1743
Cdd:cd14120      1 IGHGAFAVVfKGRHRKKPDLPVAIKCITKKNLSKSQNLlgKEIKILKELSHENVVALLDCQETSSSVYLVMEYCNGgDLA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1744 DRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMAdHSSD--------QIRICDFGNAvKFMPDE---A 1812
Cdd:cd14120     81 DYLQAKGTLSEDTIRVFLQQIAAAMKALHSKGIVHRDLKPQNILLS-HNSGrkpspndiRLKIADFGFA-RFLQDGmmaA 158

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*
gi 1207186029 1813 QYCkyGTPEFVAPE-IVNQTPVSKAtDIWPIGVLTYLCLTGVSPF 1856
Cdd:cd14120    159 TLC--GSPMYMAPEvIMSLQYDAKA-DLWSIGTIVYQCLTGKAPF 200

Catalytic domain of an Uncharacterized group of Serine/Threonine kinases with similarity to Calcium/calmodulin-dependent protein kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of uncharacterized STKs with similarity to CaMKs, which are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). CaMKs contain an N-terminal catalytic domain followed by a regulatory domain that harbors a CaM binding site. This uncharacterized subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270990 [Multi-domain] Cd Length: 265 Bit Score: 115.51 E-value: 1.01e-27

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1660 DYYDVHKEIGRGAFSYVKRVIQK-AGKLEYAAKFIS--ARAKRKAsALRELNILSHLDHERILYFHDAFEKKNAVIIITE 1736
Cdd:cd14088      1 DRYDLGQVIKTEEFCEIFRAKDKtTGKLYTCKKFLKrdGRKVRKA-AKNEINILKMVKHPNILQLVDVFETRKEYFIFLE 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1737 LCH-EELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADH-SSDQIRICDFGNAVKFMPDEAQY 1814
Cdd:cd14088     80 LATgREVFDWILDQGYYSERDTSNVIRQVLEAVAYLHSLKIVHRNLKLENLVYYNRlKNSKIVISDFHLAKLENGLIKEP 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1815 CkyGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGE--------NDRSSVLNIRNYNVAFEESMFTDLCHE 1886
Cdd:cd14088    160 C--GTPEYLAPEVVGRQRYGRPVDCWAIGVIMYILLSGNPPFYDEaeeddyenHDKNLFRKILAGDYEFDSPYWDDISQA 237

                          250       260
                   ....*....|....*....|....*..
gi 1207186029 1887 AKGFVIKLLVADR-LRPDANECLRHPW 1912
Cdd:cd14088    238 AKDLVTRLMEVEQdQRITAEEAISHEW 264

Catalytic domain of the Serine/Threonine Kinases, Salt-Inducible kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SIKs are part of a complex network that regulates Na,K-ATPase to maintain sodium homeostasis and blood pressure. Vertebrates contain three forms of SIKs (SIK1-3) from three distinct genes, which display tissue-specific effects. SIK1, also called SNF1LK, controls steroidogenic enzyme production in adrenocortical cells. In the brain, both SIK1 and SIK2 regulate energy metabolism. SIK2, also called QIK or SNF1LK2, is involved in the regulation of gluconeogenesis in the liver and lipogenesis in adipose tissues, where it phosphorylates the insulin receptor substrate-1. In the liver, SIK3 (also called QSK) regulates cholesterol and bile acid metabolism. In addition, SIK2 plays an important role in the initiation of mitosis and regulates the localization of C-Nap1, a centrosome linker protein. The SIK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270973 [Multi-domain] Cd Length: 253 Bit Score: 114.80 E-value: 1.10e-27

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1661 YYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISaRAKRKASAL----RELNILSHLDHERILYFHDAFEKKNAVIIITE 1736
Cdd:cd14071      1 FYDIERTIGKGNFAVVKLARHRITKTEVAIKIID-KSQLDEENLkkiyREVQIMKMLNHPHIIKLYQVMETKDMLYLVTE 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1737 LC-HEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDFGNAVKFMPDE--AQ 1813
Cdd:cd14071     80 YAsNGEIFDYLAQHGRMSEKEARKKFWQILSAVEYCHKRHIVHRDLKAENLLL--DANMNIKIADFGFSNFFKPGEllKT 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1814 YCkyGTPEFVAPEIVN-QTPVSKATDIWPIGVLTYLCLTGVSPFAGEN---DRSSVLNIRnYNVAFeeSMFTDLCHeakg 1889
Cdd:cd14071    158 WC--GSPPYAAPEVFEgKEYEGPQLDIWSLGVVLYVLVCGALPFDGSTlqtLRDRVLSGR-FRIPF--FMSTDCEH---- 228

                          250       260
                   ....*....|....*....|....*
gi 1207186029 1890 FVIKLLVAD-RLRPDANECLRHPWF 1913
Cdd:cd14071    229 LIRRMLVLDpSKRLTIEQIKKHKWM 253

Catalytic domain of the Serine/Threonine Kinase, Yank1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily contains uncharacterized STKs with similarity to the human protein designated as Yank1 or STK32A. The Yank1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270730 [Multi-domain] Cd Length: 257 Bit Score: 114.66 E-value: 1.33e-27

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYVKRVIQKAGKLEYAAKFISARA--KRKA--SALRELNILSHLDHERILYFHDAFEKKNAVIIITELcheeLL 1743
Cdd:cd05578      8 IGKGSFGKVCIVQKKDTKKMFAMKYMNKQKciEKDSvrNVLNELEILQELEHPFLVNLWYSFQDEEDMYMVVDL----LL 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1744 --D---RLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSsdQIRICDFGNAVKFMPDEAQYCKYG 1818
Cdd:cd05578     84 ggDlryHLQQKVKFSEETVKFYICEIVLALDYLHSKNIIHRDIKPDNILLDEQG--HVHITDFNIATKLTDGTLATSTSG 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1819 TPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGeNDRSSVLNIRNYNVAFEESMFTDLCHEAKGFVIKLLVAD 1898
Cdd:cd05578    162 TKPYMAPEVFMRAGYSFAVDWWSLGVTAYEMLRGKRPYEI-HSRTSIEEIRAKFETASVLYPAGWSEEAIDLINKLLERD 240

                          250
                   ....*....|....*...
gi 1207186029 1899 ---RLRpDANECLRHPWF 1913
Cdd:cd05578    241 pqkRLG-DLSDLKNHPYF 257

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK1 functions as a positive regulator of mitosis, meiosis, and cytokinesis. Its localization changes during mitotic progression; associating first with centrosomes in prophase, with kinetochores in prometaphase and metaphase, at the central spindle in anaphase, and in the midbody during telophase. It carries multiple functions throughout the cell cycle through interactions with differrent substrates at these specific subcellular locations. PLK1 is overexpressed in many human cancers and is associated with poor prognosis. The PLK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271089 [Multi-domain] Cd Length: 265 Bit Score: 115.03 E-value: 1.34e-27

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRF---GVIRECRENA---TGNLYMAKIVP----YEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCS 3377
Cdd:cd14187     11 RGRFlgkGGFAKCYEITdadTKEVFAGKIVPksllLKPHQKEKMSMEIAIHRSLAHQHVVGFHGFFEDNDFVYVVLELCR 90

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3378 GKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQT--FNPLFLKQFSpp 3455
Cdd:cd14187     91 RRSLLELHKRRKALTEPEARYYLRQIILGCQYLHRNRVIHRDLKLGNLFLNDDMEVKIGDFGLATKveYDGERKKTLC-- 168

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3456 iGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLSKlyqNVSQSASLFIKKILCS 3535
Cdd:cd14187    169 -GTPNYIAPEVLSKKGHSFEVDIWSIGCIMYTLLVGKPPFETSCLKETYLRIKKNEYSIPK---HINPVAASLIQKMLQT 244

                          250       260
                   ....*....|....*....|.
gi 1207186029 3536 YPWARPTIKDCFTNSWLQDAY 3556
Cdd:cd14187    245 DPTARPTINELLNDEFFTSGY 265

Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii FA2 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Chlamydomonas reinhardtii FA2 was discovered in a genetic screen for deflagellation-defective mutants. It is essential for basal-body/centriole-associated microtubule severing, and plays a role in cell cycle progression. No cellular function has yet been ascribed to CNK4. The Chlamydomonas reinhardtii FA2-like subfamily belongs to the (NIMA)-related kinase (Nek) family, which includes seven different Chlamydomonas Neks (CNKs 1-6 and Fa2). This subfamily contains FA2 and CNK4. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270868 [Multi-domain] Cd Length: 256 Bit Score: 114.05 E-value: 1.88e-27

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3307 ARGRFGVIRECRENATGNLYMAKIVPYEPES---KQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELlH 3383
Cdd:cd08529      9 GKGSFGVVYKVVRKVDGRVYALKQIDISRMSrkmREEAIDEARVLSKLNSPYVIKYYDSFVDKGKLNIVMEYAENGDL-H 87

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3384 SLIDRFR---YSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNP--LFLKQFsppIGT 3458
Cdd:cd08529     88 SLIKSQRgrpLPEDQIWKFFIQTLLGLSHLHSKKILHRDIKSMNIFLDKGDNVKIGDLGVAKILSDttNFAQTI---VGT 164

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3459 LDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFD-LSKLYqnvSQSASLFIKKILCSYP 3537
Cdd:cd08529    165 PYYLSPELCEDKPYNEKSDVWALGCVLYELCTGKHPFEAQNQGALILKIVRGKYPpISASY---SQDLSQLIDSCLTKDY 241

                          250
                   ....*....|....*
gi 1207186029 3538 WARPTIKDCFTNSWL 3552
Cdd:cd08529    242 RQRPDTTELLRNPSL 256

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs are implicated in the regulation of many cellular processes including growth factor receptor-mediated proliferation, cell polarity, cell motility, cell death and survival, and actin cytoskeleton organization. PAK deregulation is associated with tumor development. PAKs from higher eukaryotes are classified into two groups (I and II), according to their biochemical and structural features. Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). Group II PAKs contain a PBD and a catalytic domain, but lack other motifs found in group I PAKs. Since group II PAKs do not contain an obvious AID, they may be regulated differently from group I PAKs. Group I PAKs interact with the SH3 containing proteins Nck, Grb2 and PIX; no such binding has been demonstrated for group II PAKs. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270789 [Multi-domain] Cd Length: 255 Bit Score: 114.23 E-value: 1.95e-27

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1661 YYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITEL--- 1737
Cdd:cd06614      1 LYKNLEKIGEGASGEVYKATDRATGKEVAIKKMRLRKQNKELIINEILIMKECKHPNIVDYYDSYLVGDELWVVMEYmdg 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1738 -CHEELLDRltKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDFGNAVKFMPdEAQYCK 1816
Cdd:cd06614     81 gSLTDIITQ--NPVRMNESQIAYVCREVLQGLEYLHSQNVIHRDIKSDNILL--SKDGSVKLADFGFAAQLTK-EKSKRN 155

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1817 --YGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNV-AFEESmfTDLCHEAKGFVIK 1893
Cdd:cd06614    156 svVGTPYWMAPEVIKRKDYGPKVDIWSLGIMCIEMAEGEPPYLEEPPLRALFLITTKGIpPLKNP--EKWSPEFKDFLNK 233

                          250       260
                   ....*....|....*....|..
gi 1207186029 1894 LLVAD-RLRPDANECLRHPWFK 1914
Cdd:cd06614    234 CLVKDpEKRPSAEELLQHPFLK 255

Catalytic domain of the Serine/Threonine kinase, Oocyte maturation factor Mos; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mos (or c-Mos) is a germ-cell specific kinase that plays roles in both the release of primary arrest and the induction of secondary arrest in oocytes. It is expressed towards the end of meiosis I and is quickly degraded upon fertilization. It is a component of the cytostatic factor (CSF), which is responsible for metaphase II arrest. In addition, Mos activates a phoshorylation cascade that leads to the activation of the p34 subunit of MPF (mitosis-promoting factor or maturation promoting factor), a cyclin-dependent kinase that is responsible for the release of primary arrest in meiosis I. The Mos subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270881 [Multi-domain] Cd Length: 265 Bit Score: 114.40 E-value: 1.99e-27

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFG-VIRecrenAT--GNLYMAKIV---PYEPESKQTVLQEYDILkSLHHE---KIMALHEAYVTPRYLVLISECCsG 3378
Cdd:cd13979     13 SGGFGsVYK-----ATykGETVAVKIVrrrRKNRASRQSFWAELNAA-RLRHEnivRVLAAETGTDFASLGLIIMEYC-G 85

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3379 KELLHSLIDR--FRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLKQ--FSP 3454
Cdd:cd13979     86 NGTLQQLIYEgsEPLPLAHRILISLDIARALRFCHSHGIVHLDVKPANILISEQGVCKLCDFGCSVKLGEGNEVGtpRSH 165

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|...
gi 1207186029 3455 PIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTE 3497
Cdd:cd13979    166 IGGTYTYRAPELLKGERVTPKADIYSFGITLWQMLTRELPYAG 208

Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK4 is a MAPK kinase kinase that phosphorylates and activates the c-Jun N-terminal kinase (JNK) and p38 MAPK signaling pathways by directly activating their respective MAPKKs, MKK4/MKK7 and MKK3/MKK6. JNK and p38 are collectively known as stress-activated MAPKs, as they are activated in response to a variety of environmental stresses and pro-inflammatory cytokines. MEKK4 also plays roles in the re-polarization of the actin cytoskeleton in response to osmotic stress, in the proper closure of the neural tube, in cardiovascular development, and in immune responses. The MEKK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270796 [Multi-domain] Cd Length: 265 Bit Score: 114.32 E-value: 2.17e-27

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1666 KEIGRGAFSYVKRVIQ-KAGKLeYAAKFIS-ARAKRKA--SALRELNILSHLDHERILYFHDAFEKKNAVIIITELCHEE 1741
Cdd:cd06626      6 NKIGEGTFGKVYTAVNlDTGEL-MAMKEIRfQDNDPKTikEIADEMKVLEGLDHPNLVRYYGVEVHREEVYIFMEYCQEG 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1742 LLDRLTKKSTIL-ESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADhsSDQIRICDFGNAVKF------MPDEAQY 1814
Cdd:cd06626     85 TLEELLRHGRILdEAVIRVYTLQLLEGLAYLHENGIVHRDIKPANIFLDS--NGLIKLGDFGSAVKLknntttMAPGEVN 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1815 CKYGTPEFVAPEIVNQTPVS---KATDIWPIGVLTYLCLTGVSPFAGENDRSSVLnirnYNVAF-------EESMFTDLC 1884
Cdd:cd06626    163 SLVGTPAYMAPEVITGNKGEghgRAADIWSLGCVVLEMATGKRPWSELDNEWAIM----YHVGMghkppipDSLQLSPEG 238

                          250       260
                   ....*....|....*....|....*....
gi 1207186029 1885 HEakgFVIKLLVAD-RLRPDANECLRHPW 1912
Cdd:cd06626    239 KD---FLSRCLESDpKKRPTASELLDHPF 264

Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NUAK proteins are classified as AMP-activated protein kinase (AMPK)-related kinases, which like AMPK are activated by the major tumor suppressor LKB1. Vertebrates contain two NUAK proteins, called NUAK1 and NUAK2. NUAK1, also called ARK5 (AMPK-related protein kinase 5), regulates cell proliferation and displays tumor suppression through direct interaction and phosphorylation of p53. It is also involved in cell senescence and motility. High NUAK1 expression is associated with invasiveness of nonsmall cell lung cancer (NSCLC) and breast cancer cells. NUAK2, also called SNARK (Sucrose, non-fermenting 1/AMP-activated protein kinase-related kinase), is involved in energy metabolism. It is activated by hyperosmotic stress, DNA damage, and nutrients such as glucose and glutamine. NUAK2-knockout mice develop obesity, altered serum lipid profiles, hyperinsulinaemia, hyperglycaemia, and impaired glucose tolerance. The NUAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270975 [Multi-domain] Cd Length: 254 Bit Score: 113.64 E-value: 2.54e-27

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEP-ESKQTVL---QEYDILKSLHHEKIMALHEAYVTPRYLVLISEC 3375
Cdd:cd14073      3 YELLETLGKGTYGKVKLAIERATGREVAIKSIKKDKiEDEQDMVrirREIEIMSSLNHPHIIRIYEVFENKDKIVIVMEY 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3376 CSGKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNP-LFLKQFSp 3454
Cdd:cd14073     83 ASGGELYDYISERRRLPEREARRIFRQIVSAVHYCHKNGVVHRDLKLENILLDQNGNAKIADFGLSNLYSKdKLLQTFC- 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3455 piGTLDYMSPEMLKGD-VVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARI-QAAKFDLSKLyqnvsQSASLFIKKI 3532
Cdd:cd14073    162 --GSPLYASPEIVNGTpYQGPEVDCWSLGVLLYTLVYGTMPFDGSDFKRLVKQIsSGDYREPTQP-----SDASGLIRWM 234

                          250       260
                   ....*....|....*....|
gi 1207186029 3533 LCSYPWARPTIKDCFTNSWL 3552
Cdd:cd14073    235 LTVNPKRRATIEDIANHWWV 254

Catalytic domain of the Serine/Threonine Kinase, Apoptosis signal-regulating kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily are mitogen-activated protein kinase (MAPK) kinase kinases (MAPKKKs or MKKKs) and include ASK1, ASK2, and MAPKKK15. ASK1 (also called MAPKKK5) functions in the c-Jun N-terminal kinase (JNK) and p38 MAPK signaling pathways by directly activating their respective MAPKKs, MKK4/MKK7 and MKK3/MKK6. It plays important roles in cytokine and stress responses, as well as in reactive oxygen species-mediated cellular responses. ASK1 is implicated in various diseases mediated by oxidative stress including inschemic heart disease, hypertension, vessel injury, brain ischemia, Fanconi anemia, asthma, and pulmonary edema, among others. ASK2 (also called MAPKKK6) functions only in a heteromeric complex with ASK1, and can activate ASK1 by direct phosphorylation. The function of MAPKKK15 is still unknown. The ASK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270794 [Multi-domain] Cd Length: 268 Bit Score: 114.04 E-value: 3.32e-27

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKIVPYEPESK-QTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLHSLI 3386
Cdd:cd06624     18 KGTFGVVYAARDLSTQVRIAIKEIPERDSREvQPLHEEIALHSRLSHKNIVQYLGSVSEDGFFKIFMEQVPGGSLSALLR 97

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3387 DRF---RYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIV-TYMNVVKIIDFGSAQTF---NPLfLKQFSppiGTL 3459
Cdd:cd06624     98 SKWgplKDNENTIGYYTKQILEGLKYLHDNKIVHRDIKGDNVLVnTYSGVVKISDFGTSKRLagiNPC-TETFT---GTL 173

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3460 DYMSPEM----LKGdvVGPPADIWSIGILTYIMLSGRLPFTE-NDPaeteariQAAKFDLS--KLY----QNVSQSASLF 3528
Cdd:cd06624    174 QYMAPEVidkgQRG--YGPPADIWSLGCTIIEMATGKPPFIElGEP-------QAAMFKVGmfKIHpeipESLSEEAKSF 244

                          250       260
                   ....*....|....*....|....
gi 1207186029 3529 IKKILCSYPWARPTIKDCFTNSWL 3552
Cdd:cd06624    245 ILRCFEPDPDKRATASDLLQDPFL 268

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ULK4 is a functionally uncharacterized kinase that shows similarity to ATG1/ULKs. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. The ULK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270912 [Multi-domain] Cd Length: 269 Bit Score: 113.93 E-value: 3.69e-27

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSyvkrVIQKA---GKLEYAAkFISARAKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITELC 1738
Cdd:cd14010      2 YVLYDEIGRGKHS----VVYKGrrkGTIEFVA-IKCVDKSKRPEVLNEVRLTHELKHPNVLKFYEWYETSNHLWLVVEYC 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1739 H-EELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDFGNA------------- 1804
Cdd:cd14010     77 TgGDLETLLRQDGNLPESSVRKFGRDLVRGLHYIHSKGIIYCDLKPSNILL--DGNGTLKLSDFGLArregeilkelfgq 154

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1805 ----VKFMPDEAQYCKYGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNY-----NVAF 1875
Cdd:cd14010    155 fsdeGNVNKVSKKQAKRGTPYYMAPELFQGGVHSFASDLWALGCVLYEMFTGKPPFVAESFTELVEKILNEdppppPPKV 234

                          250       260       270
                   ....*....|....*....|....*....|....*....
gi 1207186029 1876 EESMFTDLCHEAKGfvikLLVADRL-RPDANECLRHP-W 1912
Cdd:cd14010    235 SSKPSPDFKSLLKG----LLEKDPAkRLSWDELVKHPfW 269

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPKs serve as important mediators of cellular responses to extracellular signals. They control critical cellular functions including differentiation, proliferation, migration, and apoptosis. They are also implicated in the pathogenesis of many diseases including multiple types of cancer, stroke, diabetes, and chronic inflammation. Typical MAPK pathways involve a triple kinase core cascade comprising of the MAPK, which is phosphorylated and activated by a MAPK kinase (MAP2K or MKK), which itself is phosphorylated and activated by a MAPK kinase kinase (MAP3K or MKKK). Each cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. There are three typical MAPK subfamilies: Extracellular signal-Regulated Kinase (ERK), c-Jun N-terminal Kinase (JNK), and p38. Some MAPKs are atypical in that they are not regulated by MAP2Ks. These include MAPK4, MAPK6, NLK, and ERK7. The MAPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270828 [Multi-domain] Cd Length: 329 Bit Score: 115.32 E-value: 4.55e-27

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISA------RAKRkasALRELNILSHLDHERILYFHDAF-----EKKNA 1730
Cdd:cd07834      2 YELLKPIGSGAYGVVCSAYDKRTGRKVAIKKISNvfddliDAKR---ILREIKILRHLKHENIIGLLDILrppspEEFND 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1731 VIIITELCHEELlDRLTKKSTILESE-IRSSVRQLLEGINYLHQLDILHLDIKPDNILmADHSSDqIRICDFGNAVKFMP 1809
Cdd:cd07834     79 VYIVTELMETDL-HKVIKSPQPLTDDhIQYFLYQILRGLKYLHSAGVIHRDLKPSNIL-VNSNCD-LKICDFGLARGVDP 155

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1810 DEAQYCKygTpEFV------APEIV-NQTPVSKATDIWPIGVLTYLCLTGVSPFAGEN--------------------DR 1862
Cdd:cd07834    156 DEDKGFL--T-EYVvtrwyrAPELLlSSKKYTKAIDIWSVGCIFAELLTRKPLFPGRDyidqlnlivevlgtpseedlKF 232

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1207186029 1863 SSVLNIRNYNVAFEE-------SMFTDLCHEAKGFVIKLLVAD-RLRPDANECLRHPWFKTL 1916
Cdd:cd07834    233 ISSEKARNYLKSLPKkpkkplsEVFPGASPEAIDLLEKMLVFNpKKRITADEALAHPYLAQL 294

Catalytic domain of Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed mainly of MAP3Ks and similar proteins, including TGF-beta Activated Kinase-1 (TAK1, also called MAP3K7), MAP3K12, MAP3K13, Mixed lineage kinase (MLK), MLK-Like mitogen-activated protein Triple Kinase (MLTK), and Raf (Rapidly Accelerated Fibrosarcoma) kinases. MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Also included in this subfamily is the pseudokinase Kinase Suppressor of Ras (KSR), which is a scaffold protein that functions downstream of Ras and upstream of Raf in the Extracellular signal-Regulated Kinase (ERK) pathway.

Pssm-ID: 270901 [Multi-domain] Cd Length: 245 Bit Score: 112.63 E-value: 4.58e-27

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3329 KIVPYEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSG---KELLHSliDRFRYSEDDVVAYIVQILQ 3405
Cdd:cd13999     25 KVEDDNDELLKEFRREVSILSKLRHPNIVQFIGACLSPPPLCIVTEYMPGgslYDLLHK--KKIPLSWSLRLKIALDIAR 102

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3406 GLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLKQfSPPIGTLDYMSPEMLKGDVVGPPADIWSIGILT 3485
Cdd:cd13999    103 GMNYLHSPPIIHRDLKSLNILLDENFTVKIADFGLSRIKNSTTEKM-TGVVGTPRWMAPEVLRGEPYTEKADVYSFGIVL 181

                          170
                   ....*....|....*..
gi 1207186029 3486 YIMLSGRLPFTENDPAE 3502
Cdd:cd13999    182 WELLTGEVPFKELSPIQ 198

Catalytic domain of the Serine/Threonine kinase, Checkpoint kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Chk1 is implicated in many major checkpoints of the cell cycle, providing a link between upstream sensors and the cell cycle engine. It plays an important role in DNA damage response and maintaining genomic stability. Chk1 acts as an effector of the sensor kinase, ATR (ATM and Rad3-related), a member of the PI3K family, which is activated upon DNA replication stress. Chk1 delays mitotic entry in response to replication blocks by inhibiting cyclin dependent kinase (Cdk) activity. In addition, Chk1 contributes to the function of centrosome and spindle-based checkpoints, inhibits firing of origins of DNA replication (Ori), and represses transcription of cell cycle proteins including cyclin B and Cdk1. The Chk1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270971 [Multi-domain] Cd Length: 261 Bit Score: 113.19 E-value: 5.06e-27

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASALR---ELNILSHLDHERILYFHDAFEKKNAVIIITELC 1738
Cdd:cd14069      3 WDLVQTLGEGAFGEVFLAVNRNTEEAVAVKFVDMKRAPGDCPENikkEVCIQKMLSHKNVVRFYGHRREGEFQYLFLEYA 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1739 HE-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHssDQIRICDFGNAVKFMPDEAQ---- 1813
Cdd:cd14069     83 SGgELFDKIEPDVGMPEDVAQFYFQQLMAGLKYLHSCGITHRDIKPENLLLDEN--DNLKISDFGLATVFRYKGKErlln 160

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1207186029 1814 -YCkyGTPEFVAPEIVNQTPV-SKATDIWPIGVLTYLCLTGVSPFAGENDRS 1863
Cdd:cd14069    161 kMC--GTLPYVAPELLAKKKYrAEPVDVWSCGIVLFAMLAGELPWDQPSDSC 210

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK1 is required for efficient amino acid starvation-induced autophagy and mitochondrial clearance. It associates with three autophagy-related proteins (Atg13, FIP200 amd Atg101) to form the ULK1 complex. All fours proteins are essential for autophagosome formation. ULK1 is regulated by both mammalian target-of rapamycin complex 1 (mTORC1) and AMP-activated protein kinase (AMPK). mTORC1 negatively regulates the ULK1 complex in a nutrient-dependent manner while AMPK stimulates autophagy by inhibiting mTORC1. ULK1 also plays neuron-specific roles and is involved in non-clathrin-coated endocytosis in growth cones, filopodia extension, neurite extension, and axon branching. The ULK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271104 [Multi-domain] Cd Length: 267 Bit Score: 113.18 E-value: 5.06e-27

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYV-KRVIQKAGKLEYAAKFISARAKRKASAL--RELNILSHLDHERILYFHDAFEKKNAVIIITELCHE-ELL 1743
Cdd:cd14202     10 IGHGAFAVVfKGRHKEKHDLEVAVKCINKKNLAKSQTLlgKEIKILKELKHENIVALYDFQEIANSVYLVMEYCNGgDLA 89

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1744 DRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILM-------ADHSSDQIRICDFGNAVKFMPDEAQYCK 1816
Cdd:cd14202     90 DYLHTMRTLSEDTIRLFLQQIAGAMKMLHSKGIIHRDLKPQNILLsysggrkSNPNNIRIKIADFGFARYLQNNMMAATL 169

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1817 YGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGendrSSVLNIRNYnvaFE--ESMFTDLCHEAKGFVIKL 1894
Cdd:cd14202    170 CGSPMYMAPEVIMSQHYDAKADLWSIGTIIYQCLTGKAPFQA----SSPQDLRLF---YEknKSLSPNIPRETSSHLRQL 242

                          250       260
                   ....*....|....*....|....
gi 1207186029 1895 LVA-----DRLRPDANECLRHPWF 1913
Cdd:cd14202    243 LLGllqrnQKDRMDFDEFFHHPFL 266

N-terminal catalytic domain of the Serine/Threonine Kinase, 90 kDa ribosomal protein S6 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. Mammals possess four RSK isoforms (RSK1-4) from distinct genes. RSK proteins are also referred to as MAP kinase-activated protein kinases (MAPKAPKs), p90-RSKs, or p90S6Ks. The RSK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270734 [Multi-domain] Cd Length: 317 Bit Score: 114.80 E-value: 5.07e-27

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFG---VIRECRENATGNLYMAKIVpyepesKQTVLQ---------EYDILKSLHHEKIMALHEAYVTPRYLVLISEC 3375
Cdd:cd05582      5 QGSFGkvfLVRKITGPDAGTLYAMKVL------KKATLKvrdrvrtkmERDILADVNHPFIVKLHYAFQTEGKLYLILDF 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3376 CSGKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLKQFSpP 3455
Cdd:cd05582     79 LRGGDLFTRLSKEVMFTEEDVKFYLAELALALDHLHSLGIIYRDLKPENILLDEDGHIKLTDFGLSKESIDHEKKAYS-F 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3456 IGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLSklyQNVSQSASLFIKKILCS 3535
Cdd:cd05582    158 CGTVEYMAPEVVNRRGHTQSADWWSFGVLMFEMLTGSLPFQGKDRKETMTMILKAKLGMP---QFLSPEAQSLLRALFKR 234


                   ....*
gi 1207186029 3536 YPWAR 3540
Cdd:cd05582    235 NPANR 239

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase signal-integrating kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK signal-integrating kinases (Mnks) are MAPK-activated protein kinases and is comprised by a group of four proteins, produced by alternative splicing from two genes (Mnk1 and Mnk2). The isoforms of Mnk1 (1a/1b) and Mnk2 (2a/2b) differ at their C-termini, with the a-form having a longer C-terminus containing a MAPK-binding region. All Mnks contain a catalytic kinase domain and a polybasic region at the N-terminus which binds importin and the eukaryotic initiation factor eIF4G. The best characterized Mnk substrate is eIF4G, whose phosphorylation may promote the export of certain mRNAs from the nucleus. Mnk also phosphorylate substrates that bind to AU-rich elements that regulate mRNA stability and translation. Mnks have also been implicated in tyrosine kinase receptor signaling, inflammation, and cell prolieration or survival. The Mnk subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271075 [Multi-domain] Cd Length: 288 Bit Score: 113.97 E-value: 5.41e-27

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1660 DYYDVHKEI-GRGAFSYVKRVIQKAGKLEYAAKFISAR-AKRKASALRELNILSHLD-HERILYFHDAFEKKNAVIIITE 1736
Cdd:cd14173      1 DVYQLQEEVlGEGAYARVQTCINLITNKEYAVKIIEKRpGHSRSRVFREVEMLYQCQgHRNVLELIEFFEEEDKFYLVFE 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1737 -LCHEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMadHSSDQI---RICDF--GNAVKF--- 1807
Cdd:cd14173     81 kMRGGSILSHIHRRRHFNELEASVVVQDIASALDFLHNKGIAHRDLKPENILC--EHPNQVspvKICDFdlGSGIKLnsd 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1808 -----MPDEAQYCkyGTPEFVAPEIV-----NQTPVSKATDIWPIGVLTYLCLTGVSPFAGEN------DRSSV------ 1865
Cdd:cd14173    159 cspisTPELLTPC--GSAEYMAPEVVeafneEASIYDKRCDLWSLGVILYIMLSGYPPFVGRCgsdcgwDRGEAcpacqn 236

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1207186029 1866 ---LNIRNYNVAFEESMFTDLCHEAKGFVIKLLVAD-RLRPDANECLRHPW 1912
Cdd:cd14173    237 mlfESIQEGKYEFPEKDWAHISCAAKDLISKLLVRDaKQRLSAAQVLQHPW 287

Catalytic domain of cyclin G-Associated Kinase-like proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes cyclin G-Associated Kinase (GAK), Drosophila melanogaster Numb-Associated Kinase (NAK)-like proteins, and similar protein kinases. GAK plays regulatory roles in clathrin-mediated membrane trafficking, the maintenance of centrosome integrity and chromosome congression, neural patterning, survival of neurons, and immune responses. NAK plays a role in asymmetric cell division through its association with Numb. It also regulates the localization of Dlg, a protein essential for septate junction formation. The GAK-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270887 [Multi-domain] Cd Length: 272 Bit Score: 113.20 E-value: 5.69e-27

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAK-FISARAKRKASALRELNILSHL-DHERI--LYFHDAFEKKN--AVIIIT 1735
Cdd:cd13985      2 YQVTKQLGEGGFSYVYLAHDVNTGRRYALKrMYFNDEEQLRVAIKEIEIMKRLcGHPNIvqYYDSAILSSEGrkEVLLLM 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1736 ELCHEELLDRLTK--KSTILESEIRSSVRQLLEGINYLHQLD--ILHLDIKPDNILMADhsSDQIRICDFGNAV-KFMPD 1810
Cdd:cd13985     82 EYCPGSLVDILEKspPSPLSEEEVLRIFYQICQAVGHLHSQSppIIHRDIKIENILFSN--TGRFKLCDFGSATtEHYPL 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1811 ---------EAQYCKYGTPEFVAPEIVN---QTPVSKATDIWPIGVLTYLCLTGVSPFagenDRSSVLNIRNYNVAFEES 1878
Cdd:cd13985    160 eraeevniiEEEIQKNTTPMYRAPEMIDlysKKPIGEKADIWALGCLLYKLCFFKLPF----DESSKLAIVAGKYSIPEQ 235

                          250       260       270
                   ....*....|....*....|....*....|
gi 1207186029 1879 -MFTDLCHEakgFVIKLLVAD-RLRPDANE 1906
Cdd:cd13985    236 pRYSPELHD---LIRHMLTPDpAERPDIFQ 262

Catalytic domain of the Serine/Threonine Kinase, 70 kDa ribosomal protein S6 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p70S6K (or S6K) contains only one catalytic kinase domain, unlike p90 ribosomal S6 kinases (RSKs). It acts as a downstream effector of the STK mTOR (mammalian Target of Rapamycin) and plays a role in the regulation of the translation machinery during protein synthesis. p70S6K also plays a pivotal role in regulating cell size and glucose homeostasis. Its targets include S6, the translation initiation factor eIF3, and the insulin receptor substrate IRS-1, among others. Mammals contain two isoforms of p70S6K, named S6K1 and S6K2 (or S6K-beta). The p70S6K subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270736 [Multi-domain] Cd Length: 323 Bit Score: 114.42 E-value: 6.54e-27

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1666 KEIGRGAFSYVKRVIQKAGKLE---YAAKFIsarakRKASALR----------ELNILSHLDHERILYFHDAFEKKNAVI 1732
Cdd:cd05584      2 KVLGKGGYGKVFQVRKTTGSDKgkiFAMKVL-----KKASIVRnqkdtahtkaERNILEAVKHPFIVDLHYAFQTGGKLY 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1733 IITE-LCHEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMaDHSSdQIRICDFGNAVKFMPDE 1811
Cdd:cd05584     77 LILEyLSGGELFMHLEREGIFMEDTACFYLAEITLALGHLHSLGIIYRDLKPENILL-DAQG-HVKLTDFGLCKESIHDG 154

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1812 AQ---YCkyGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSV-------LNIRNYnvafeesmft 1881
Cdd:cd05584    155 TVthtFC--GTIEYMAPEILTRSGHGKAVDWWSLGALMYDMLTGAPPFTAENRKKTIdkilkgkLNLPPY---------- 222

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|..
gi 1207186029 1882 dLCHEAKGFVIKLL---VADRLRP---DANECLRHPWFKTLN 1917
Cdd:cd05584    223 -LTNEARDLLKKLLkrnVSSRLGSgpgDAEEIKAHPFFRHIN 263

Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NUAK proteins are classified as AMP-activated protein kinase (AMPK)-related kinases, which like AMPK are activated by the major tumor suppressor LKB1. Vertebrates contain two NUAK proteins, called NUAK1 and NUAK2. NUAK2, also called SNARK (Sucrose, non-fermenting 1/AMP-activated protein kinase-related kinase), is involved in energy metabolism. It is activated by hyperosmotic stress, DNA damage, and nutrients such as glucose and glutamine. NUAK2-knockout mice develop obesity, altered serum lipid profiles, hyperinsulinaemia, hyperglycaemia, and impaired glucose tolerance. NUAK2 is implicated in regulating actin stress fiber assembly through its association with myosin phosphatase Rho-interacting protein (MRIP), which leads to an increase in myosin regulatory light chain (MLC) phosphorylation. It is also associated with tumor growth, migration, and oncogenicity of melanoma cells. The NUAK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271063 [Multi-domain] Cd Length: 255 Bit Score: 112.36 E-value: 9.20e-27

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPESKQTVL---QEYDILKSLHHEKIMALHEAYVTPRYLVLISECC 3376
Cdd:cd14161      5 YEFLETLGKGTYGRVKKARDSSGRLVAIKSIRKDRIKDEQDLLhirREIEIMSSLNHPHIISVYEVFENSSKIVIVMEYA 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3377 SGKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNP-LFLKQFSpp 3455
Cdd:cd14161     85 SRGDLYDYISERQRLSELEARHFFRQIVSAVHYCHANGIVHRDLKLENILLDANGNIKIADFGLSNLYNQdKFLQTYC-- 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3456 iGTLDYMSPEMLKGD-VVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFdlsKLYQNVSQSASLfIKKILC 3534
Cdd:cd14161    163 -GSPLYASPEIVNGRpYIGPEVDSWSLGVLLYILVHGTMPFDGHDYKILVKQISSGAY---REPTKPSDACGL-IRWLLM 237

                          250
                   ....*....|....*...
gi 1207186029 3535 SYPWARPTIKDCFTNSWL 3552
Cdd:cd14161    238 VNPERRATLEDVASHWWV 255

Catalytic domain of Mitogen-activated protein kinase kinase kinase kinase (MAP4K) 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes MAP4K3, MAP4K1, MAP4K2, MAP4K5, and related proteins. Vertebrate members contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. MAP4K1, also called haematopoietic progenitor kinase 1 (HPK1), is a hematopoietic-specific STK involved in many cellular signaling cascades including MAPK, antigen receptor, apoptosis, growth factor, and cytokine signaling. It participates in the regulation of T cell receptor signaling and T cell-mediated immune responses. MAP4K2 was referred to as germinal center (GC) kinase because of its preferred location in GC B cells. MAP4K3 plays a role in the nutrient-responsive pathway of mTOR (mammalian target of rapamycin) signaling. It is required in the activation of S6 kinase by amino acids and for the phosphorylation of the mTOR-regulated inhibitor of eukaryotic initiation factor 4E. MAP4K5, also called germinal center kinase-related enzyme (GCKR), has been shown to activate the MAPK c-Jun N-terminal kinase (JNK). The MAP4K3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270788 [Multi-domain] Cd Length: 259 Bit Score: 112.40 E-value: 9.47e-27

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEP-ESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSG 3378
Cdd:cd06613      2 YELIQRIGSGTYGDVYKARNIATGELAAVKVIKLEPgDDFEIIQQEISMLKECRHPNIVAYFGSYLRRDKLWIVMEYCGG 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3379 KellhSLIDRFRYS---EDDVVAYI-VQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFG-SAQTFNPLF-LKQF 3452
Cdd:cd06613     82 G----SLQDIYQVTgplSELQIAYVcRETLKGLAYLHSTGKIHRDIKGANILLTEDGDVKLADFGvSAQLTATIAkRKSF 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3453 sppIGTLDYMSPEMLKGDVVGP---PADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLSKLYQNVSQSASL-- 3527
Cdd:cd06613    158 ---IGTPYWMAPEVAAVERKGGydgKCDIWALGITAIELAELQPPMFDLHPMRALFLIPKSNFDPPKLKDKEKWSPDFhd 234

                          250
                   ....*....|....*
gi 1207186029 3528 FIKKILCSYPWARPT 3542
Cdd:cd06613    235 FIKKCLTKNPKKRPT 249

Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein kinase subfamily 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The SnRKs form three different subfamilies designated SnRK1-3. SnRK3 is represented in this cd. The SnRK3 group contains members also known as CBL-interacting protein kinase, salt overly sensitive 2, SOS3-interacting proteins and protein kinase S. These kinases interact with calcium-binding proteins such as SOS3, SCaBPs, and CBL proteins, and are involved in responses to salt stress and in sugar and ABA signaling. The SnRKs belong to a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271133 [Multi-domain] Cd Length: 256 Bit Score: 112.11 E-value: 1.06e-26

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQ-KAGKlEYAAKFIS----ARAKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITE 1736
Cdd:cd14663      2 YELGRTLGEGTFAKVKFARNtKTGE-SVAIKIIDkeqvAREGMVEQIKREIAIMKLLRHPNIVELHEVMATKTKIFFVME 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1737 LCHE-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDFG-NAV--KFMPDEA 1812
Cdd:cd14663     81 LVTGgELFSKIAKNGRLKEDKARKYFQQLIDAVDYCHSRGVFHRDLKPENLLL--DEDGNLKISDFGlSALseQFRQDGL 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1813 QYCKYGTPEFVAPEIVNQTPVSKA-TDIWPIGVLTYLCLTGVSPFAGENdrSSVLNIRNYNVAFEESMFtdLCHEAKGFV 1891
Cdd:cd14663    159 LHTTCGTPNYVAPEVLARRGYDGAkADIWSCGVILFVLLAGYLPFDDEN--LMALYRKIMKGEFEYPRW--FSPGAKSLI 234

                          250       260
                   ....*....|....*....|..
gi 1207186029 1892 IKLLVAD-RLRPDANECLRHPW 1912
Cdd:cd14663    235 KRILDPNpSTRITVEQIMASPW 256

Catalytic domain of testis-specific serine/threonine kinase 1, TSSK2, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK1 and TSSK2 are expressed specifically in meiotic and postmeiotic spermatogenic cells, respectively. TSSK2 is localized in the sperm neck, equatorial segment, and mid-piece of the sperm tail. Both TSSK1 and TSSK2 phosphorylate their common substrate TSKS (testis-specific-kinase-substrate). TSSK1/TSSK2 double knock-out mice are sterile without manifesting other defects, making these kinases viable targets for male contraception. The TSSK1/2-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271067 [Multi-domain] Cd Length: 263 Bit Score: 111.80 E-value: 1.60e-26

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISaraKRKASA-------LRELNILSHLDHERILYFHDAFEKKNA-VII 1733
Cdd:cd14165      3 YILGINLGEGSYAKVKSAYSERLKCNVAIKIID---KKKAPDdfvekflPRELEILARLNHKSIIKTYEIFETSDGkVYI 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1734 ITELCHE-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSdqIRICDFGNAVKFMPDE- 1811
Cdd:cd14165     80 VMELGVQgDLLEFIKLRGALPEDVARKMFHQLSSAIKYCHELDIVHRDLKCENLLLDKDFN--IKLTDFGFSKRCLRDEn 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1812 ------AQYCkyGTPEFVAPEIVNQTPVS-KATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESmfTDLC 1884
Cdd:cd14165    158 grivlsKTFC--GSAAYAAPEVLQGIPYDpRIYDIWSLGVILYIMVCGSMPYDDSNVKKMLKIQKEHRVRFPRS--KNLT 233

                          250       260       270
                   ....*....|....*....|....*....|
gi 1207186029 1885 HEAKGFVIKLLVAD-RLRPDANECLRHPWF 1913
Cdd:cd14165    234 SECKDLIYRLLQPDvSQRLCIDEVLSHPWL 263

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs are implicated in the regulation of many cellular processes including growth factor receptor-mediated proliferation, cell polarity, cell motility, cell death and survival, and actin cytoskeleton organization. PAK deregulation is associated with tumor development. PAKs from higher eukaryotes are classified into two groups (I and II), according to their biochemical and structural features. Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). Group II PAKs contain a PBD and a catalytic domain, but lack other motifs found in group I PAKs. Since group II PAKs do not contain an obvious AID, they may be regulated differently from group I PAKs. Group I PAKs interact with the SH3 containing proteins Nck, Grb2 and PIX; no such binding has been demonstrated for group II PAKs. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270789 [Multi-domain] Cd Length: 255 Bit Score: 111.15 E-value: 2.05e-26

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGK 3379
Cdd:cd06614      2 YKNLEKIGEGASGEVYKATDRATGKEVAIKKMRLRKQNKELIINEILIMKECKHPNIVDYYDSYLVGDELWVVMEYMDGG 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3380 ELLHSLIDRFRYSEDDVVAYIV-QILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLKQFSpPIGT 3458
Cdd:cd06614     82 SLTDIITQNPVRMNESQIAYVCrEVLQGLEYLHSQNVIHRDIKSDNILLSKDGSVKLADFGFAAQLTKEKSKRNS-VVGT 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3459 LDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAetEARIQAAKFDLSKLY--QNVSQSASLFIKKILCSY 3536
Cdd:cd06614    161 PYWMAPEVIKRKDYGPKVDIWSLGIMCIEMAEGEPPYLEEPPL--RALFLITTKGIPPLKnpEKWSPEFKDFLNKCLVKD 238


                   ....*.
gi 1207186029 3537 PWARPT 3542
Cdd:cd06614    239 PEKRPS 244

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK3 mRNA is up-regulated in fibroblasts after Ras-induced senescence, and its overexpression induces both autophagy and senescence in a fibroblast cell line. ULK3, through its kinase activity, positively regulates Gli proteins, mediators of the Sonic hedgehog (Shh) signaling pathway that is implicated in tissue homeostasis maintenance and neurogenesis. It is inhibited by binding to Suppressor of Fused (Sufu). The ULK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271023 [Multi-domain] Cd Length: 252 Bit Score: 110.84 E-value: 2.29e-26

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYVKRVIQKAGKLEYAA-KFISARAKRKASA---LRELNILSHLDHERILYFHDAFEKKNAVIIITELCHEELL 1743
Cdd:cd14121      3 LGSGTYATVYKAYRKSGAREVVAvKCVSKSSLNKASTenlLTEIELLKKLKHPHIVELKDFQWDEEHIYLIMEYCSGGDL 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1744 DRLTKKSTIL-ESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSDQIRICDFGNAVKFMPDEAQYCKYGTPEF 1822
Cdd:cd14121     83 SRFIRSRRTLpESTVRRFLQQLASALQFLREHNISHMDLKPQNLLLSSRYNPVLKLADFGFAQHLKPNDEAHSLRGSPLY 162

                          170       180       190
                   ....*....|....*....|....*....|....*
gi 1207186029 1823 VAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFA 1857
Cdd:cd14121    163 MAPEMILKKKYDARVDLWSVGVILYECLFGRAPFA 197

Catalytic domain of PRKX-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include human PRKX (X chromosome-encoded protein kinase), Drosophila DC2, and similar proteins. PRKX is present in many tissues including fetal and adult brain, kidney, and lung. The PRKX gene is located in the Xp22.3 subregion and has a homolog called PRKY on the Y chromosome. An abnormal interchange between PRKX aand PRKY leads to the sex reversal disorder of XX males and XY females. PRKX is implicated in granulocyte/macrophage lineage differentiation, renal cell epithelial migration, and tubular morphogenesis in the developing kidney. The PRKX-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270763 [Multi-domain] Cd Length: 292 Bit Score: 111.76 E-value: 2.75e-26

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1660 DYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFIS----ARAKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIIT 1735
Cdd:cd05612      1 DDFERIKTIGTGTFGRVHLVRDRISEHYYALKVMAipevIRLKQEQHVHNEKRVLKEVSHPFIIRLFWTEHDQRFLYMLM 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1736 E-LCHEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDFGNAVKFMPDEAQY 1814
Cdd:cd05612     81 EyVPGGELFSYLRNSGRFSNSTGLFYASEIVCALEYLHSKEIVYRDLKPENILL--DKEGHIKLTDFGFAKKLRDRTWTL 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1815 CkyGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMftDLchEAKGFVIKL 1894
Cdd:cd05612    159 C--GTPEYLAPEVIQSKGHNKAVDWWALGILIYEMLVGYPPFFDDNPFGIYEKILAGKLEFPRHL--DL--YAKDLIKKL 232

                          250       260
                   ....*....|....*....|....*....
gi 1207186029 1895 LVADRLR------PDANECLRHPWFKTLN 1917
Cdd:cd05612    233 LVVDRTRrlgnmkNGADDVKNHRWFKSVD 261

Catalytic domain of the Serine/Threonine kinase, Liver Kinase B1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LKB1, also called STK11, was first identified as a tumor suppressor responsible for Peutz-Jeghers syndrome, a disorder that leads to an increased risk of spontaneous epithelial cancer. It serves as a master upstream kinase that activates AMP-activated protein kinase (AMPK) and most AMPK-like kinases. LKB1 and AMPK are part of an energy-sensing pathway that links cell energy to metabolism and cell growth. They play critical roles in the establishment and maintenance of cell polarity, cell proliferation, cytoskeletal organization, as well as T-cell metabolism, including T-cell development, homeostasis, and effector function. To be activated, LKB1 requires the adaptor proteins STe20-Related ADaptor (STRAD) and mouse protein 25 (MO25). The LKB1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271021 [Multi-domain] Cd Length: 255 Bit Score: 110.81 E-value: 2.90e-26

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3309 GRFGVIRECRENATGNLYMAKIVPYE-----PESKQTVLQEYDILKSLHHEKIMALHEAYVTPR----YLVLisECCSG- 3378
Cdd:cd14119      4 GSYGKVKEVLDTETLCRRAVKILKKRklrriPNGEANVKREIQILRRLNHRNVIKLVDVLYNEEkqklYMVM--EYCVGg 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3379 -KELLHSLIDRfRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQtfnplFLKQFSP--- 3454
Cdd:cd14119     82 lQEMLDSAPDK-RLPIWQAHGYFVQLIDGLEYLHSQGIIHKDIKPGNLLLTTDGTLKISDFGVAE-----ALDLFAEddt 155

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3455 ---PIGTLDYMSPEMLKGDVV--GPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLSKlyqNVSQSASLFI 3529
Cdd:cd14119    156 cttSQGSPAFQPPEIANGQDSfsGFKVDIWSAGVTLYNMTTGKYPFEGDNIYKLFENIGKGEYTIPD---DVDPDLQDLL 232

                          250       260
                   ....*....|....*....|...
gi 1207186029 3530 KKILCSYPWARPTIKDCFTNSWL 3552
Cdd:cd14119    233 RGMLEKDPEKRFTIEQIRQHPWF 255

N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, in response to various stimuli such as growth factors, hormones, neurotransmitters, cellular stress, and pro-inflammatory cytokines. This triggers phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) in the C-terminal extension of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. MSKs are predominantly nuclear proteins. They are widely expressed in many tissues including heart, brain, lung, liver, kidney, and pancreas. There are two isoforms of MSK, called MSK1 and MSK2. The MSK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270735 [Multi-domain] Cd Length: 268 Bit Score: 110.95 E-value: 2.95e-26

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3307 ARGRFGVIRECRENATGNLYMAKIVpyepeSKQTVLQEYdilKSLHHEK--------------IMALHEAYVTPRYLVLI 3372
Cdd:cd05583      6 AYGKVFLVRKVGGHDAGKLYAMKVL-----KKATIVQKA---KTAEHTMterqvleavrqspfLVTLHYAFQTDAKLHLI 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3373 SECCSGKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLKQF 3452
Cdd:cd05583     78 LDYVNGGELFTHLYQREHFTESEVRIYIGEIVLALEHLHKLGIIYRDIKLENILLDSEGHVVLTDFGLSKEFLPGENDRA 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3453 SPPIGTLDYMSPEMLKGDVVG--PPADIWSIGILTYIMLSGRLPFT----ENDPAETEARIQAAKFDLSKlyqNVSQSAS 3526
Cdd:cd05583    158 YSFCGTIEYMAPEVVRGGSDGhdKAVDWWSLGVLTYELLTGASPFTvdgeRNSQSEISKRILKSHPPIPK---TFSAEAK 234

                          250
                   ....*....|....
gi 1207186029 3527 LFIKKILCSYPWAR 3540
Cdd:cd05583    235 DFILKLLEKDPKKR 248

Catalytic domain of the Protein Serine/Threonine Kinase, DMPK-related cell division control protein 42 binding kinase (MRCK) beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MRCK-beta is expressed ubiquitously in many tissues. MRCK is activated via interaction with the small GTPase Cdc42. MRCK/Cdc42 signaling mediates myosin-dependent cell motility. The MRCK-beta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. This alignment model includes the dimerization domain.

Pssm-ID: 270774 [Multi-domain] Cd Length: 409 Bit Score: 114.34 E-value: 3.40e-26

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1650 SILRKMRRLTDYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISA--RAKRKASAL--RELNILSHLDHERILYFHDAF 1725
Cdd:cd05624     62 QLVKEMQLHRDDFEIIKVIGRGAFGEVAVVKMKNTERIYAMKILNKweMLKRAETACfrEERNVLVNGDCQWITTLHYAF 141

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1726 EKKNAVIIITEL-CHEELLDRLTK-KSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDFGN 1803
Cdd:cd05624    142 QDENYLYLVMDYyVGGDLLTLLSKfEDKLPEDMARFYIGEMVLAIHSIHQLHYVHRDIKPDNVLL--DMNGHIRLADFGS 219

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1804 AVKFMPDEA--QYCKYGTPEFVAPEIVNQT-----PVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFE 1876
Cdd:cd05624    220 CLKMNDDGTvqSSVAVGTPDYISPEILQAMedgmgKYGPECDWWSLGVCMYEMLYGETPFYAESLVETYGKIMNHEERFQ 299

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*
gi 1207186029 1877 -ESMFTDLCHEAKGFVIKLLVADRLRPDAN---ECLRHPWFKTLN 1917
Cdd:cd05624    300 fPSHVTDVSEEAKDLIQRLICSRERRLGQNgieDFKKHAFFEGLN 344

Catalytic domain of Ste20-Like Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of the subfamily include SLK, STK10 (also called LOK for Lymphocyte-Oriented Kinase), SmSLK (Schistosoma mansoni SLK), and related proteins. SLK promotes apoptosis through apoptosis signal-regulating kinase 1 (ASK1) and the mitogen-activated protein kinase (MAPK) p38. It also plays a role in mediating actin reorganization. STK10 is responsible in regulating the CD28 responsive element in T cells, as well as leukocyte function associated antigen (LFA-1)-mediated lymphocyte adhesion. SmSLK is capable of activating the MAPK Jun N-terminal kinase (JNK) pathway in human embryonic kidney cells as well as in Xenopus oocytes. It may participate in regulating MAPK cascades during host-parasite interactions. The SLK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 132942 [Multi-domain] Cd Length: 280 Bit Score: 110.99 E-value: 4.49e-26

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1659 TDYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASA-LRELNILSHLDHERILYFHDAFEKKNAVIIITEL 1737
Cdd:cd06611      4 NDIWEIIGELGDGAFGKVYKAQHKETGLFAAAKIIQIESEEELEDfMVEIDILSECKHPNIVGLYEAYFYENKLWILIEF 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1738 CHEELLDRLTKK--STILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSsdQIRICDFGNAVKFM-PDEAQY 1814
Cdd:cd06611     84 CDGGALDSIMLEleRGLTEPQIRYVCRQMLEALNFLHSHKVIHRDLKAGNILLTLDG--DVKLADFGVSAKNKsTLQKRD 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1815 CKYGTPEFVAPEIVN-----QTPVSKATDIWPIGVlTYLCLTGVSPFAGENDRSSVLnirnYNVAFEESMFTDLCH---- 1885
Cdd:cd06611    162 TFIGTPYWMAPEVVAcetfkDNPYDYKADIWSLGI-TLIELAQMEPPHHELNPMRVL----LKILKSEPPTLDQPSkwss 236

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|
gi 1207186029 1886 EAKGFVIKLLVAD-RLRPDANECLRHPWFKTLNKGKSIST 1924
Cdd:cd06611    237 SFNDFLKSCLVKDpDDRPTAAELLKHPFVSDQSDNKAIKD 276

Catalytic subunit of the Serine/Threonine Kinase, cAMP-dependent protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The inactive PKA holoenzyme is a heterotetramer composed of two phosphorylated and active catalytic subunits with a dimer of regulatory (R) subunits. Activation is achieved through the binding of the important second messenger cAMP to the R subunits, which leads to the dissociation of PKA into the R dimer and two active subunits. PKA is present ubiquitously in cells and interacts with many different downstream targets. It plays a role in the regulation of diverse processes such as growth, development, memory, metabolism, gene expression, immunity, and lipolysis. The PKA subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271111 [Multi-domain] Cd Length: 290 Bit Score: 110.96 E-value: 5.17e-26

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1660 DYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFIS----ARAKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIIT 1735
Cdd:cd14209      1 DDFDRIKTLGTGSFGRVMLVRHKETGNYYAMKILDkqkvVKLKQVEHTLNEKRILQAINFPFLVKLEYSFKDNSNLYMVM 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1736 EL-CHEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMaDHSSdQIRICDFGNAVKFMPDEAQY 1814
Cdd:cd14209     81 EYvPGGEMFSHLRRIGRFSEPHARFYAAQIVLAFEYLHSLDLIYRDLKPENLLI-DQQG-YIKVTDFGFAKRVKGRTWTL 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1815 CkyGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDLcheaKGFVIKL 1894
Cdd:cd14209    159 C--GTPEYLAPEIILSKGYNKAVDWWALGVLIYEMAAGYPPFFADQPIQIYEKIVSGKVRFPSHFSSDL----KDLLRNL 232

                          250       260
                   ....*....|....*....|....*....
gi 1207186029 1895 LVAD------RLRPDANECLRHPWFKTLN 1917
Cdd:cd14209    233 LQVDltkrfgNLKNGVNDIKNHKWFATTD 261

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 104.26 E-value: 5.39e-26

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1123 PLFTRKLDVLEVIEGRNARFDCKVSGTPPPQVIWSHFDRPLEENEDIRILKEGGRHSLIISHVSNEDEGLYTVAARNSHG 1202
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVATNSAG 80

                           90
                   ....*....|
gi 1207186029 1203 EDECAAELYV 1212
Cdd:pfam07679   81 EAEASAELTV 90

Catalytic domain of the Serine/Threonine kinases, Mitogen-activated protein kinase-activated protein kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the MAPK-activated protein kinases MK2, MK3, MK5 (also called PRAK for p38-regulated/activated protein kinase), and related proteins. These proteins contain a catalytic kinase domain followed by a C-terminal autoinhibitory region that contains nuclear localization (NLS) and nuclear export (NES) signals with a p38 MAPK docking motif that overlaps the NLS. In addition, MK2 and MK3 contain an N-terminal proline-rich region that can bind to SH3 domains. MK2 and MK3 are bonafide substrates for the MAPK p38, while MK5 plays a functional role in the p38 MAPK pathway although their direct interaction has been difficult to detect. MK2 and MK3 are closely related and show, thus far, indistinguishable substrate specificity, while MK5 shows a distinct spectrum of substrates. MK2 and MK3 are mainly involved in the regulation of gene expression and they participate in diverse cellular processes such as endocytosis, cytokine production, cytoskeletal reorganization, cell migration, cell cycle control and chromatin remodeling. They are implicated in inflammation and cance and their substrates include mRNA-AU-rich-element (ARE)-binding proteins (TTP and hnRNP A0), Hsp proteins (Hsp27 and Hsp25) and RSK, among others. MK2/3 are both expressed ubiquitously but MK2 is expressed at significantly higher levels. MK5 is a ubiquitous protein that is implicated in neuronal morphogenesis, cell migration, and tumor angiogenesis. It interacts with PKA, which induces cytoplasmic translocation of MK5. Its substrates includes p53, ERK3/4, Hsp27, and cytosolic phospholipase A2 (cPLA2). The MAPKAPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270991 [Multi-domain] Cd Length: 263 Bit Score: 110.07 E-value: 6.04e-26

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3312 GVIRECRENATGNLYMAKIVPYEPESKQTVlqeydilkSLH-----HEKIMALHEAYVT----PRYLVLISECCSGKELL 3382
Cdd:cd14089     15 GKVLECFHKKTGEKFALKVLRDNPKARREV--------ELHwrasgCPHIVRIIDVYENtyqgRKCLLVVMECMEGGELF 86

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3383 HSLIDRFR--YSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMN---VVKIIDFGSA---QTFNPLFLKQFSP 3454
Cdd:cd14089     87 SRIQERADsaFTEREAAEIMRQIGSAVAHLHSMNIAHRDLKPENLLYSSKGpnaILKLTDFGFAketTTKKSLQTPCYTP 166

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3455 PigtldYMSPEmlkgdVVGP-----PADIWSIGILTYIMLSGRLPFTEND----PAETEARIQAAKFDL-SKLYQNVSQS 3524
Cdd:cd14089    167 Y-----YVAPE-----VLGPekydkSCDMWSLGVIMYILLCGYPPFYSNHglaiSPGMKKRIRNGQYEFpNPEWSNVSEE 236

                          250       260
                   ....*....|....*....|....*..
gi 1207186029 3525 ASLFIKKILCSYPWARPTIKDCFTNSW 3551
Cdd:cd14089    237 AKDLIRGLLKTDPSERLTIEEVMNHPW 263

Catalytic domain of the Protein Serine/Threonine Kinase, DMPK-related cell division control protein 42 binding kinase (MRCK) beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MRCK-beta is expressed ubiquitously in many tissues. MRCK is activated via interaction with the small GTPase Cdc42. MRCK/Cdc42 signaling mediates myosin-dependent cell motility. The MRCK-beta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. This alignment model includes the dimerization domain.

Pssm-ID: 270774 [Multi-domain] Cd Length: 409 Bit Score: 113.57 E-value: 6.68e-26

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKIVPYEPESKQT----VLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLh 3383
Cdd:cd05624     82 RGAFGEVAVVKMKNTERIYAMKILNKWEMLKRAetacFREERNVLVNGDCQWITTLHYAFQDENYLYLVMDYYVGGDLL- 160

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3384 SLIDRF--RYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLKQFSPPIGTLDY 3461
Cdd:cd05624    161 TLLSKFedKLPEDMARFYIGEMVLAIHSIHQLHYVHRDIKPDNVLLDMNGHIRLADFGSCLKMNDDGTVQSSVAVGTPDY 240

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3462 MSPEMLKG-----DVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARI--QAAKFDLSKLYQNVSQSASLFIKKILC 3534
Cdd:cd05624    241 ISPEILQAmedgmGKYGPECDWWSLGVCMYEMLYGETPFYAESLVETYGKImnHEERFQFPSHVTDVSEEAKDLIQRLIC 320


                   .
gi 1207186029 3535 S 3535
Cdd:cd05624    321 S 321

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK1 functions as a positive regulator of mitosis, meiosis, and cytokinesis. Its localization changes during mitotic progression; associating first with centrosomes in prophase, with kinetochores in prometaphase and metaphase, at the central spindle in anaphase, and in the midbody during telophase. It carries multiple functions throughout the cell cycle through interactions with differrent substrates at these specific subcellular locations. PLK1 is overexpressed in many human cancers and is associated with poor prognosis. The PLK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271089 [Multi-domain] Cd Length: 265 Bit Score: 110.02 E-value: 7.62e-26

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1653 RKMRRltdyYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFIS----ARAKRKASALRELNILSHLDHERILYFHDAFEKK 1728
Cdd:cd14187      4 RTRRR----YVRGRFLGKGGFAKCYEITDADTKEVFAGKIVPksllLKPHQKEKMSMEIAIHRSLAHQHVVGFHGFFEDN 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1729 NAVIIITELCHEE-LLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSsdQIRICDFGNAVKF 1807
Cdd:cd14187     80 DFVYVVLELCRRRsLLELHKRRKALTEPEARYYLRQIILGCQYLHRNRVIHRDLKLGNLFLNDDM--EVKIGDFGLATKV 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1808 MPD-EAQYCKYGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYnvafEESMFTDLCHE 1886
Cdd:cd14187    158 EYDgERKKTLCGTPNYIAPEVLSKKGHSFEVDIWSIGCIMYTLLVGKPPFETSCLKETYLRIKKN----EYSIPKHINPV 233

                          250       260       270
                   ....*....|....*....|....*....|
gi 1207186029 1887 AKGFVIKLLVAD-RLRPDANECLRHPWFKT 1915
Cdd:cd14187    234 AASLIQKMLQTDpTARPTINELLNDEFFTS 263

N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK1 plays a role in the regulation of translational control and transcriptional activation. It phosphorylates the transcription factors, CREB and NFkB. It also phosphorylates the nucleosomal proteins H3 and HMG-14. Increased phosphorylation of MSK1 is associated with the development of cerebral ischemic/hypoxic preconditioning. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. The MSK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270764 [Multi-domain] Cd Length: 290 Bit Score: 110.48 E-value: 8.61e-26

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQ----KAGKLeYAAKF-----ISARAKRKASALRELNILSHLDHERILY-FHDAFEKKNAV 1731
Cdd:cd05613      2 FELLKVLGTGAYGKVFLVRKvsghDAGKL-YAMKVlkkatIVQKAKTAEHTRTERQVLEHIRQSPFLVtLHYAFQTDTKL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1732 IIITELCHE-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDFGNAVKFMPD 1810
Cdd:cd05613     81 HLILDYINGgELFTHLSQRERFTENEVQIYIGEIVLALEHLHKLGIIYRDIKLENILL--DSSGHVVLTDFGLSKEFLLD 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1811 EAQ--YCKYGTPEFVAPEIVN--QTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDLCHE 1886
Cdd:cd05613    159 ENEraYSFCGTIEYMAPEIVRggDSGHDKAVDWWSLGVLMYELLTGASPFTVDGEKNSQAEISRRILKSEPPYPQEMSAL 238

                          250       260       270
                   ....*....|....*....|....*....|....*..
gi 1207186029 1887 AKGFVIKLLVAD---RL---RPDANECLRHPWFKTLN 1917
Cdd:cd05613    239 AKDIIQRLLMKDpkkRLgcgPNGADEIKKHPFFQKIN 275

Catalytic domain of the Serine/Threonine Kinase, cGMP-dependent protein kinase (cGK or PKG); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mammals have two cGK isoforms from different genes, cGKI and cGKII. cGKI exists as two splice variants, cGKI-alpha and cGKI-beta. cGK consists of an N-terminal regulatory domain containing a dimerization and an autoinhibitory pseudosubstrate region, two cGMP-binding domains, and a C-terminal catalytic domain. Binding of cGMP to both binding sites releases the inhibition of the catalytic center by the pseudosubstrate region, allowing autophosphorylation and activation of the kinase. cGKI is a soluble protein expressed in all smooth muscles, platelets, cerebellum, and kidney. It is also expressed at lower concentrations in other tissues. cGKII is a membrane-bound protein that is most abundantly expressed in the intestine. It is also present in the brain nuclei, adrenal cortex, kidney, lung, and prostate. cGKI is involved in the regulation of smooth muscle tone, smooth cell proliferation, and platelet activation. cGKII plays a role in the regulation of secretion, such as renin secretion by the kidney and aldosterone secretion by the adrenal. It also regulates bone growth and the circadian rhythm. The cGK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270724 [Multi-domain] Cd Length: 262 Bit Score: 109.24 E-value: 1.03e-25

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYVKRVIQKAGKLEYAAKFISARA----KRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITELCH-EEL 1742
Cdd:cd05572      1 LGVGGFGRVELVQLKSKGRTFALKCVKKRHivqtRQQEHIFSEKEILEECNSPFIVKLYRTFKDKKYLYMLMEYCLgGEL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1743 LDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMAdhSSDQIRICDFGNAVKFMPDEAQYCKYGTPEF 1822
Cdd:cd05572     81 WTILRDRGLFDEYTARFYTACVVLAFEYLHSRGIIYRDLKPENLLLD--SNGYVKLVDFGFAKKLGSGRKTWTFCGTPEY 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1823 VAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSsvlnIRNYNVAFEESMFTDLCH----EAKGFVIKLL--- 1895
Cdd:cd05572    159 VAPEIILNKGYDFSVDYWSLGILLYELLTGRPPFGGDDEDP----MKIYNIILKGIDKIEFPKyidkNAKNLIKQLLrrn 234

                          250       260
                   ....*....|....*....|.
gi 1207186029 1896 VADRL---RPDANECLRHPWF 1913
Cdd:cd05572    235 PEERLgylKGGIRDIKKHKWF 255

Catalytic domain of Cyclin-Dependent protein Kinase 9-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDK9 and CDK12 from higher eukaryotes, yeast BUR1, C-type plant CDKs (CdkC), and similar proteins. CDK9, BUR1, and CdkC are functionally equivalent. They act as a kinase for the C-terminal domain of RNA polymerase II and participate in regulating mutliple steps of gene expression including transcription elongation and RNA processing. CDK9 and CdkC associate with T-type cyclins while BUR1 associates with the cyclin BUR2. CDK12 is a unique CDK that contains an arginine/serine-rich (RS) domain, which is predominantly found in splicing factors. CDK12 interacts with cyclins L1 and L2, and participates in regulating transcription and alternative splicing. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK9-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270832 [Multi-domain] Cd Length: 291 Bit Score: 109.96 E-value: 1.04e-25

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3309 GRFGVIRECRENATGNLYMAKIVPYEPESK---QTVLQEYDILKSLHHEKIMALHEAYVTPR--------YLVLisECCS 3377
Cdd:cd07840     10 GTYGQVYKARNKKTGELVALKKIRMENEKEgfpITAIREIKLLQKLDHPNVVRLKEIVTSKGsakykgsiYMVF--EYMD 87

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3378 GKelLHSLIDR--FRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLKQFSPP 3455
Cdd:cd07840     88 HD--LTGLLDNpeVKFTESQIKCYMKQLLEGLQYLHSNGILHRDIKGSNILINNDGVLKLADFGLARPYTKENNADYTNR 165

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1207186029 3456 IGTLDYMSPEMLKGDV-VGPPADIWSIGILTYIMLSGRLPFtendPAETEAR 3506
Cdd:cd07840    166 VITLWYRPPELLLGATrYGPEVDMWSVGCILAELFTGKPIF----QGKTELE 213

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B beta (also called Akt2); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKB-beta is the predominant PKB isoform expressed in insulin-responsive tissues. It plays a critical role in the regulation of glucose homeostasis. It is also implicated in muscle cell differentiation. Mice deficient in PKB-beta display normal growth weights but exhibit severe insulin resistance and diabetes, accompanied by lipoatrophy and B-cell failure. PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain.The PKB-beta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173686 [Multi-domain] Cd Length: 323 Bit Score: 110.87 E-value: 1.16e-25

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKIVPYE-----PESKQTVlQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELL 3382
Cdd:cd05595      5 KGTFGKVILVREKATGRYYAMKILRKEviiakDEVAHTV-TESRVLQNTRHPFLTALKYAFQTHDRLCFVMEYANGGELF 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3383 HSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQ--TFNPLFLKQFSppiGTLD 3460
Cdd:cd05595     84 FHLSRERVFTEDRARFYGAEIVSALEYLHSRDVVYRDIKLENLMLDKDGHIKITDFGLCKegITDGATMKTFC---GTPE 160

                          170       180       190
                   ....*....|....*....|....*....|....*....
gi 1207186029 3461 YMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTEND 3499
Cdd:cd05595    161 YLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNQD 199

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK3, also called Prk or Fnk (FGF-inducible kinase), regulates angiogenesis and responses to DNA damage. Activated PLK3 mediates Chk2 phosphorylation by ATM and the resulting checkpoint activation. PLK3 phosphorylates DNA polymerase delta and may be involved in DNA repair. It also inhibits Cdc25c, thereby regulating the onset of mitosis. The PLK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271091 [Multi-domain] Cd Length: 255 Bit Score: 108.86 E-value: 1.19e-25

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYVKRVIQKAGKLEYAAKFIS----ARAKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITELCHEELL 1743
Cdd:cd14189      9 LGKGGFARCYEMTDLATNKTYAVKVIPhsrvAKPHQREKIVNEIELHRDLHHKHVVKFSHHFEDAENIYIFLELCSRKSL 88

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1744 DRLTK-KSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADhsSDQIRICDFGNAVKFMPDEAQ---YCkyGT 1819
Cdd:cd14189     89 AHIWKaRHTLLEPEVRYYLKQIISGLKYLHLKGILHRDLKLGNFFINE--NMELKVGDFGLAARLEPPEQRkktIC--GT 164

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1820 PEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVafeeSMFTDLCHEAKGFVIKLLVAD- 1898
Cdd:cd14189    165 PNYLAPEVLLRQGHGPESDVWSLGCVMYTLLCGNPPFETLDLKETYRCIKQVKY----TLPASLSLPARHLLAGILKRNp 240

                          250
                   ....*....|....*
gi 1207186029 1899 RLRPDANECLRHPWF 1913
Cdd:cd14189    241 GDRLTLDQILEHEFF 255

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase signal-integrating kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK signal-integrating kinases (Mnks) are MAPK-activated protein kinases and is comprised by a group of four proteins, produced by alternative splicing from two genes (Mnk1 and Mnk2). The isoforms of Mnk1 (1a/1b) and Mnk2 (2a/2b) differ at their C-termini, with the a-form having a longer C-terminus containing a MAPK-binding region. All Mnks contain a catalytic kinase domain and a polybasic region at the N-terminus which binds importin and the eukaryotic initiation factor eIF4G. The best characterized Mnk substrate is eIF4G, whose phosphorylation may promote the export of certain mRNAs from the nucleus. Mnk also phosphorylate substrates that bind to AU-rich elements that regulate mRNA stability and translation. Mnks have also been implicated in tyrosine kinase receptor signaling, inflammation, and cell prolieration or survival. The Mnk subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271076 [Multi-domain] Cd Length: 289 Bit Score: 109.73 E-value: 1.50e-25

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1655 MRRLTDyydvhKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKAS-ALRELNILSHLD-HERILYFHDAFEKKNAVI 1732
Cdd:cd14174      2 LYRLTD-----ELLGEGAYAKVQGCVSLQNGKEYAVKIIEKNAGHSRSrVFREVETLYQCQgNKNILELIEFFEDDTRFY 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1733 IITE-LCHEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMadHSSDQ---IRICDF--GNAVK 1806
Cdd:cd14174     77 LVFEkLRGGSILAHIQKRKHFNEREASRVVRDIASALDFLHTKGIAHRDLKPENILC--ESPDKvspVKICDFdlGSGVK 154

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1807 F--------MPDEAQYCkyGTPEFVAPEIV-----NQTPVSKATDIWPIGVLTYLCLTGVSPFAGEN------DRSSVL- 1866
Cdd:cd14174    155 LnsactpitTPELTTPC--GSAEYMAPEVVevftdEATFYDKRCDLWSLGVILYIMLSGYPPFVGHCgtdcgwDRGEVCr 232

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1207186029 1867 --------NIRNYNVAFEESMFTDLCHEAKGFVIKLLVAD-RLRPDANECLRHPWFK 1914
Cdd:cd14174    233 vcqnklfeSIQEGKYEFPDKDWSHISSEAKDLISKLLVRDaKERLSAAQVLQHPWVQ 289

Catalytic domain of the Serine/Threonine Kinase, Maternal Embryonic Leucine zipper Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MELK is a cell cycle dependent protein which functions in cytokinesis, cell cycle, apoptosis, cell proliferation, and mRNA processing. It is found upregulated in many types of cancer cells, playing an indispensable role in cancer cell survival. It makes an attractive target in the design of inhibitors for use in the treatment of a wide range of human cancer. The MELK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270980 [Multi-domain] Cd Length: 257 Bit Score: 108.24 E-value: 1.96e-25

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1658 LTDYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISA--------RAKRKASALRELNilshldHERILYFHDAFEKKN 1729
Cdd:cd14078      1 LLKYYELHETIGSGGFAKVKLATHILTGEKVAIKIMDKkalgddlpRVKTEIEALKNLS------HQHICRLYHVIETDN 74

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1730 AVIIITELCHE-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSsdQIRICDFGNAVK-- 1806
Cdd:cd14078     75 KIFMVLEYCPGgELFDYIVAKDRLSEDEARVFFRQIVSAVAYVHSQGYAHRDLKPENLLLDEDQ--NLKLIDFGLCAKpk 152

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1807 -FMPDEAQYCkYGTPEFVAPEIVNQTPV--SKAtDIWPIGVLTYLCLTGVSPFagENDRSSVLNIRNYNVAFEESMFtdL 1883
Cdd:cd14078    153 gGMDHHLETC-CGSPAYAAPELIQGKPYigSEA-DVWSMGVLLYALLCGFLPF--DDDNVMALYRKIQSGKYEEPEW--L 226

                          250       260       270
                   ....*....|....*....|....*....|
gi 1207186029 1884 CHEAKGFVIKLLVAD-RLRPDANECLRHPW 1912
Cdd:cd14078    227 SPSSKLLLDQMLQVDpKKRITVKELLNHPW 256

Catalytic domain of testis-specific serine/threonine kinase 6 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK6, also called SSTK, is expressed at the head of elongated sperm. It can phosphorylate histones and associate with heat shock protens HSP90 and HSC70. Male mice deficient in TSSK6 are infertile, showing spermatogenic impairment including reduced sperm counts, impaired DNA condensation, abnormal morphology and decreased motility rates. The TSSK6-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271066 [Multi-domain] Cd Length: 256 Bit Score: 108.02 E-value: 2.33e-25

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISaraKRKASA-------LRELNILSHLDHERILYFHDAFEKKNA-VII 1733
Cdd:cd14164      2 YTLGTTIGEGSFSKVKLATSQKYCCKVAIKIVD---RRRASPdfvqkflPRELSILRRVNHPNIVQMFECIEVANGrLYI 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1734 ITELCHEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADhSSDQIRICDFGNAvKFMPDEAQ 1813
Cdd:cd14164     79 VMEAAATDLLQKIQEVHHIPKDLARDMFAQMVGAVNYLHDMNIVHRDLKCENILLSA-DDRKIKIADFGFA-RFVEDYPE 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1814 ----YCkyGTPEFVAPEIVNQTPV-SKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIR--NY--NVAFEEsmftdlc 1884
Cdd:cd14164    157 lsttFC--GSRAYTPPEVILGTPYdPKKYDVWSLGVVLYVMVTGTMPFDETNVRRLRLQQRgvLYpsGVALEE------- 227

                          250       260
                   ....*....|....*....|....*....
gi 1207186029 1885 hEAKGFVIKLL-VADRLRPDANECLRHPW 1912
Cdd:cd14164    228 -PCRALIRTLLqFNPSTRPSIQQVAGNSW 255

Catalytic domain of cyclin G-Associated Kinase-like proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes cyclin G-Associated Kinase (GAK), Drosophila melanogaster Numb-Associated Kinase (NAK)-like proteins, and similar protein kinases. GAK plays regulatory roles in clathrin-mediated membrane trafficking, the maintenance of centrosome integrity and chromosome congression, neural patterning, survival of neurons, and immune responses. NAK plays a role in asymmetric cell division through its association with Numb. It also regulates the localization of Dlg, a protein essential for septate junction formation. The GAK-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270887 [Multi-domain] Cd Length: 272 Bit Score: 108.58 E-value: 2.42e-25

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3307 ARGRFGVIRECRENATGNLYMAKIVPY-EPESKQTVLQEYDILKSL-HHEKIMALHEA---YVTPRYLVLIS-ECCSGke 3380
Cdd:cd13985      9 GEGGFSYVYLAHDVNTGRRYALKRMYFnDEEQLRVAIKEIEIMKRLcGHPNIVQYYDSailSSEGRKEVLLLmEYCPG-- 86

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3381 llhSLIDRF------RYSEDDVVAYIVQILQGLDYLH--SRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLKQF 3452
Cdd:cd13985     87 ---SLVDILeksppsPLSEEEVLRIFYQICQAVGHLHsqSPPIIHRDIKIENILFSNTGRFKLCDFGSATTEHYPLERAE 163

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3453 SPPI--------GTLDYMSPEML---KGDVVGPPADIWSIGILTYIMLSGRLPFTENDPaeteARIQAAKFDLSKlyqNV 3521
Cdd:cd13985    164 EVNIieeeiqknTTPMYRAPEMIdlySKKPIGEKADIWALGCLLYKLCFFKLPFDESSK----LAIVAGKYSIPE---QP 236

                          250       260
                   ....*....|....*....|....
gi 1207186029 3522 SQSASL--FIKKILCSYPWARPTI 3543
Cdd:cd13985    237 RYSPELhdLIRHMLTPDPAERPDI 260

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK2 is ubiquitously expressed and is essential in autophagy induction. It displays partially redundant functions with ULK1 and is able to compensate for the loss of ULK1 in non-selective autophagy. It also displays neuron-specific functions and is important in axon development. The ULK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271103 [Multi-domain] Cd Length: 271 Bit Score: 108.17 E-value: 3.03e-25

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYV-KRVIQKAGKLEYAAKFISARAKRKASAL--RELNILSHLDHERILYFHDAFEKKNAVIIITELCHE-ELL 1743
Cdd:cd14201     14 VGHGAFAVVfKGRHRKKTDWEVAIKSINKKNLSKSQILlgKEIKILKELQHENIVALYDVQEMPNSVFLVMEYCNGgDLA 93

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1744 DRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILM-------ADHSSDQIRICDFGNAVKFMPDEAQYCK 1816
Cdd:cd14201     94 DYLQAKGTLSEDTIRVFLQQIAAAMRILHSKGIIHRDLKPQNILLsyasrkkSSVSGIRIKIADFGFARYLQSNMMAATL 173

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|
gi 1207186029 1817 YGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPF 1856
Cdd:cd14201    174 CGSPMYMAPEVIMSQHYDAKADLWSIGTVIYQCLVGKPPF 213

Catalytic domain of the yeast Serine/Threonine Kinase, Kin4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Kin4 is a central component of the spindle position checkpoint (SPOC), which monitors spindle position and regulates the mitotic exit network (MEN). Kin4 associates with spindle pole bodies in mother cells to inhibit MEN signaling and delay mitosis until the anaphase nucleus is properly positioned along the mother-bud axis. Kin4 activity is regulated by both the bud neck-associated kinase Elm1 and protein phosphatase 2A. The Kin4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270978 [Multi-domain] Cd Length: 270 Bit Score: 108.34 E-value: 3.07e-25

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3334 EPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLhSLIDRFRYSEDDVVAYI-VQILQGLDYLHS 3412
Cdd:cd14076     46 ENCQTSKIMREINILKGLTHPNIVRLLDVLKTKKYIGIVLEFVSGGELF-DYILARRRLKDSVACRLfAQLISGVAYLHK 124

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3413 RRILHLDIKPENIIV-TYMNVVkIIDFGSAQTFNPLFLKQFSPPIGTLDYMSPEMLKGDVV--GPPADIWSIGILTYIML 3489
Cdd:cd14076    125 KGVVHRDLKLENLLLdKNRNLV-ITDFGFANTFDHFNGDLMSTSCGSPCYAAPELVVSDSMyaGRKADIWSCGVILYAML 203

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1207186029 3490 SGRLPFtENDPAETEARiqaakfDLSKLYQNVSQSASLF-----------IKKILCSYPWARPTIKDCFTNSWL 3552
Cdd:cd14076    204 AGYLPF-DDDPHNPNGD------NVPRLYRYICNTPLIFpeyvtpkardlLRRILVPNPRKRIRLSAIMRHAWL 270

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase 1 (also called Doublecortin-like and CAM kinase-like 1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL1 (or DCAMKL1) belongs to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. In addition, DCKL1 contains a serine, threonine, and proline rich domain (SP) and a C-terminal kinase domain with similarity to CAMKs. DCKL1 interacts with tubulin, glucocorticoid receptor, dynein, JIP1/2, caspases (3 and 8), and calpain, among others. It plays roles in neurogenesis, neuronal migration, retrograde transport, and neuronal apoptosis. The DCKL1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271085 [Multi-domain] Cd Length: 268 Bit Score: 108.16 E-value: 3.08e-25

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3309 GRFGVIRECRENATGNLYMAKIVPYEP-ESKQTVLQ-EYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLHSLI 3386
Cdd:cd14183     17 GNFAVVKECVERSTGREYALKIINKSKcRGKEHMIQnEVSILRRVKHPNIVLLIEEMDMPTELYLVMELVKGGDLFDAIT 96

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3387 DRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMN----VVKIIDFGSAQTFN-PLFlkqfsPPIGTLDY 3461
Cdd:cd14183     97 STNKYTERDASGMLYNLASAIKYLHSLNIVHRDIKPENLLVYEHQdgskSLKLGDFGLATVVDgPLY-----TVCGTPTY 171

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3462 MSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPF--TENDPAETEARIQAAKFDL-SKLYQNVSQSASLFIKKILCSYPW 3538
Cdd:cd14183    172 VAPEIIAETGYGLKVDIWAAGVITYILLCGFPPFrgSGDDQEVLFDQILMGQVDFpSPYWDNVSDSAKELITMMLQVDVD 251

                          250
                   ....*....|....*.
gi 1207186029 3539 ARPTIKDCFTNSWLQD 3554
Cdd:cd14183    252 QRYSALQVLEHPWVND 267

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. There are three PKB isoforms from different genes, PKB-alpha (or Akt1), PKB-beta (or Akt2), and PKB-gamma (or Akt3). PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. It is activated downstream of phosphoinositide 3-kinase (PI3K) and plays important roles in diverse cellular functions including cell survival, growth, proliferation, angiogenesis, motility, and migration. PKB also has a central role in a variety of human cancers, having been implicated in tumor initiation, progression, and metastasis. The PKB subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and PI3K.

Pssm-ID: 270723 [Multi-domain] Cd Length: 322 Bit Score: 109.37 E-value: 3.25e-25

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKI----VPYEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLH 3383
Cdd:cd05571      5 KGTFGKVILCREKATGELYAIKIlkkeVIIAKDEVAHTLTENRVLQNTRHPFLTSLKYSFQTNDRLCFVMEYVNGGELFF 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3384 SLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFG----------SAQTFnplflkqfs 3453
Cdd:cd05571     85 HLSRERVFSEDRTRFYGAEIVLALGYLHSQGIVYRDLKLENLLLDKDGHIKITDFGlckeeisygaTTKTF--------- 155

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*.
gi 1207186029 3454 ppIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTEND 3499
Cdd:cd05571    156 --CGTPEYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNRD 199

Catalytic domain of testis-specific serine/threonine kinase 4 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK4, also called TSSK5, is expressed in testis from haploid round spermatids to mature spermatozoa. It phosphorylates Cre-Responsive Element Binding protein (CREB), facilitating the binding of CREB to the specific cis cAMP responsive element (CRE), which is important in activating genes related to germ cell differentiation. Mutations in the human TSSK4 gene is associated with infertile Chinese men with impaired spermatogenesis. The TSSK4-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271064 [Multi-domain] Cd Length: 259 Bit Score: 107.77 E-value: 3.31e-25

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVpyepeSKQ----TVLQ-----EYDILKSLHHEKIMALHEAYVTPRYLV 3370
Cdd:cd14162      2 YIVGKTLGHGSYAVVKKAYSTKHKCKVAIKIV-----SKKkapeDYLQkflprEIEVIKGLKHPNLICFYEAIETTSRVY 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3371 LISECCSGKELLhSLIDRFRY-SEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFG------SAQT 3443
Cdd:cd14162     77 IIMELAENGDLL-DYIRKNGAlPEPQARRWFRQLVAGVEYCHSKGVVHRDLKCENLLLDKNNNLKITDFGfargvmKTKD 155

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3444 FNPLFLKQFSppiGTLDYMSPEMLKGDVVGPP-ADIWSIGILTYIMLSGRLPFTENDPAETEARIQ-AAKFDLSKlyqNV 3521
Cdd:cd14162    156 GKPKLSETYC---GSYAYASPEILRGIPYDPFlSDIWSMGVVLYTMVYGRLPFDDSNLKVLLKQVQrRVVFPKNP---TV 229

                          250       260       270
                   ....*....|....*....|....*....|.
gi 1207186029 3522 SQSASLFIKKILCSYPwARPTIKDCFTNSWL 3552
Cdd:cd14162    230 SEECKDLILRMLSPVK-KRITIEEIKRDPWF 259

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 101.95 E-value: 3.38e-25

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  781 PVFEFPLQDTVASTGTEVLLKCIISGTPLPEVIWKKDNTEVKNSPTHVVKIEGERHSLLIKWTKPSDAGTYTVTAVNEVG 860
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVATNSAG 80

                           90
                   ....*....|
gi 1207186029  861 EVSSSATLFI 870
Cdd:pfam07679   81 EAEASAELTV 90

Catalytic domain of Myotonic Dystrophy protein kinase (DMPK)-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The DMPK-like subfamily is composed of DMPK and DMPK-related cell division control protein 42 (Cdc42) binding kinase (MRCK). DMPK is expressed in skeletal and cardiac muscles, and in central nervous tissues. The functional role of DMPK is not fully understood. It may play a role in the signal transduction and homeostasis of calcium. The DMPK gene is implicated in myotonic dystrophy 1 (DM1), an inherited multisystemic disorder with symptoms that include muscle hyperexcitability, progressive muscle weakness and wasting, cataract development, testicular atrophy, and cardiac conduction defects. The genetic basis for DM1 is the mutational expansion of a CTG repeat in the 3'-UTR of DMPK. MRCK is activated via interaction with the small GTPase Cdc42. MRCK/Cdc42 signaling mediates myosin-dependent cell motility. Three isoforms of MRCK are known, named alpha, beta and gamma. MRCKgamma is expressed in heart and skeletal muscles, unlike MRCKalpha and MRCKbeta, which are expressed ubiquitously. The DMPK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270748 [Multi-domain] Cd Length: 331 Bit Score: 109.74 E-value: 3.39e-25

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKIVpyepeSKQTVLQ---------EYDILKSLHHEKIMALHEAYVTPRYLVLISECCSG 3378
Cdd:cd05597     11 RGAFGEVAVVKLKSTEKVYAMKIL-----NKWEMLKraetacfreERDVLVNGDRRWITKLHYAFQDENYLYLVMDYYCG 85

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3379 KELLhSLIDRF--RYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLKQFSPPI 3456
Cdd:cd05597     86 GDLL-TLLSKFedRLPEEMARFYLAEMVLAIDSIHQLGYVHRDIKPDNVLLDRNGHIRLADFGSCLKLREDGTVQSSVAV 164

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3457 GTLDYMSPEMLKG-----DVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAK--FDLSKLYQNVSQSASLFI 3529
Cdd:cd05597    165 GTPDYISPEILQAmedgkGRYGPECDWWSLGVCMYEMLYGETPFYAESLVETYGKIMNHKehFSFPDDEDDVSEEAKDLI 244

                          250       260
                   ....*....|....*....|....
gi 1207186029 3530 KKILCS--YPWARPTIKDCFTNSW 3551
Cdd:cd05597    245 RRLICSreRRLGQNGIDDFKKHPF 268

Catalytic domain of Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed mainly of MAP3Ks and similar proteins, including TGF-beta Activated Kinase-1 (TAK1, also called MAP3K7), MAP3K12, MAP3K13, Mixed lineage kinase (MLK), MLK-Like mitogen-activated protein Triple Kinase (MLTK), and Raf (Rapidly Accelerated Fibrosarcoma) kinases. MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Also included in this subfamily is the pseudokinase Kinase Suppressor of Ras (KSR), which is a scaffold protein that functions downstream of Ras and upstream of Raf in the Extracellular signal-Regulated Kinase (ERK) pathway.

Pssm-ID: 270901 [Multi-domain] Cd Length: 245 Bit Score: 107.24 E-value: 3.41e-25

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYVKRVIQKaGKlEYAAKFISARAKRKASA---LRELNILSHLDHERILYFHDAFEKKNAVIIITELCHE-ELL 1743
Cdd:cd13999      1 IGSGSFGEVYKGKWR-GT-DVAIKKLKVEDDNDELLkefRREVSILSKLRHPNIVQFIGACLSPPPLCIVTEYMPGgSLY 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1744 DRLTKKSTILESEIRSSV-RQLLEGINYLHQLDILHLDIKPDNILMADHssDQIRICDFGNA-VKFMPDEAQYCKYGTPE 1821
Cdd:cd13999     79 DLLHKKKIPLSWSLRLKIaLDIARGMNYLHSPPIIHRDLKSLNILLDEN--FTVKIADFGLSrIKNSTTEKMTGVVGTPR 156

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*....
gi 1207186029 1822 FVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRN 1870
Cdd:cd13999    157 WMAPEVLRGEPYTEKADVYSFGIVLWELLTGEVPFKELSPIQIAAAVVQ 205

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 11; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek11 is involved, through direct phosphorylation, in regulating the degradation of Cdc25A (Cell Division Cycle 25 homolog A), which plays a role in cell cycle progression and in activating cyclin dependent kinases. Nek11 is activated by CHK1 (CHeckpoint Kinase 1) and may be involved in the G2/M checkpoint. Nek11 may also play a role in the S-phase checkpoint as well as in DNA replication and genotoxic stress responses. It is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270861 [Multi-domain] Cd Length: 260 Bit Score: 107.51 E-value: 4.09e-25

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISA------RAKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIIT 1735
Cdd:cd08222      2 YRVVRKLGSGNFGTVYLVSDLKATADEELKVLKEisvgelQPDETVDANREAKLLSKLDHPAIVKFHDSFVEKESFCIVT 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1736 ELCHEELLD---RLTKKS--TILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMadhSSDQIRICDFGNAVKFM-- 1808
Cdd:cd08222     82 EYCEGGDLDdkiSEYKKSgtTIDENQILDWFIQLLLAVQYMHERRILHRDLKAKNIFL---KNNVIKVGDFGISRILMgt 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1809 PDEAQYCKyGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIrnynVAFEESMFTDLCH-EA 1887
Cdd:cd08222    159 SDLATTFT-GTPYYMSPEVLKHEGYNSKSDIWSLGCILYEMCCLKHAFDGQNLLSVMYKI----VEGETPSLPDKYSkEL 233

                          250       260
                   ....*....|....*....|....*.
gi 1207186029 1888 KGFVIKLLVAD-RLRPDANECLRHPW 1912
Cdd:cd08222    234 NAIYSRMLNKDpALRPSAAEILKIPF 259

Catalytic domain of Fungal Pat1-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Schizosaccharomyces pombe Pat1 (also called Ran1), Saccharomyces cerevisiae VHS1 and KSP1, and similar fungal STKs. Pat1 blocks Mei2, an RNA-binding protein which is indispensable in the initiation of meiosis. Pat1 is inactivated and Mei2 activated, which initiates meiosis, under nutrient-deprived conditions through a signaling cascade involving Ste11. Meiosis induced by Pat1 inactivation may show different characteristics than normal meiosis including aberrant positioning of centromeres. VHS1 was identified in a screen for suppressors of cell cycle arrest at the G1/S transition, while KSP1 may be involved in regulating PRP20, which is required for mRNA export and maintenance of nuclear structure. The Pat1-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270895 [Multi-domain] Cd Length: 267 Bit Score: 107.82 E-value: 4.15e-25

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3309 GRFGVIRECRENATGNLYMAKIV--------PYEPESKQTVLQEYDILKSLH-HEKIMALHEAYVTPRYLVLISECCSGK 3379
Cdd:cd13993     11 GAYGVVYLAVDLRTGRKYAIKCLyksgpnskDGNDFQKLPQLREIDLHRRVSrHPNIITLHDVFETEVAIYIVLEYCPNG 90

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3380 ELLHSLIDRFRYSEDDVVA--YIVQILQGLDYLHSRRILHLDIKPENIIVTYM-NVVKIIDFGSAQTfnplflKQFSPP- 3455
Cdd:cd13993     91 DLFEAITENRIYVGKTELIknVFLQLIDAVKHCHSLGIYHRDIKPENILLSQDeGTVKLCDFGLATT------EKISMDf 164

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3456 -IGTLDYMSPEML--KGDVVGP----PADIWSIGILTYIMLSGRLPFTENDPAE-TEARIQAAKFDLSKLYQNVSQSASL 3527
Cdd:cd13993    165 gVGSEFYMAPECFdeVGRSLKGypcaAGDIWSLGIILLNLTFGRNPWKIASESDpIFYDYYLNSPNLFDVILPMSDDFYN 244

                          250
                   ....*....|....*...
gi 1207186029 3528 FIKKILCSYPWARPTIKD 3545
Cdd:cd13993    245 LLRQIFTVNPNNRILLPE 262

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein Kinase Kinase; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MAPKKs are dual-specificity PKs that phosphorylate their downstream targets, MAPKs, at specific threonine and tyrosine residues. The MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising the MAPK, which is phosphorylated and activated by a MAPK kinase (MAPKK or MKK or MAP2K), which itself is phosphorylated and activated by a MAPKK kinase (MAPKKK or MKKK or MAP3K). There are three MAPK subfamilies: extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38. In mammalian cells, there are seven MAPKKs (named MKK1-7) and 20 MAPKKKs. Each MAPK subfamily can be activated by at least two cognate MAPKKs and by multiple MAPKKKs. The MAPKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270782 [Multi-domain] Cd Length: 265 Bit Score: 107.43 E-value: 4.41e-25

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1666 KEIGRGAFSYVKRVIQKAGKLEYAAKFISA---RAKRKAsALRELNILSHLDHERILYFHDAFEKKNAVIIITELCHEEL 1742
Cdd:cd06605      7 GELGEGNGGVVSKVRHRPSGQIMAVKVIRLeidEALQKQ-ILRELDVLHKCNSPYIVGFYGAFYSEGDISICMEYMDGGS 85

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1743 LDRLTKKSTILESEIRSSV-RQLLEGINYLH-QLDILHLDIKPDNILMadHSSDQIRICDFGNAVKFMPDEAQyCKYGTP 1820
Cdd:cd06605     86 LDKILKEVGRIPERILGKIaVAVVKGLIYLHeKHKIIHRDVKPSNILV--NSRGQVKLCDFGVSGQLVDSLAK-TFVGTR 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1821 EFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGEN--DRSSVLNIRNYNV-----AFEESMFTDlchEAKGFVIK 1893
Cdd:cd06605    163 SYMAPERISGGKYTVKSDIWSLGLSLVELATGRFPYPPPNakPSMMIFELLSYIVdepppLLPSGKFSP---DFQDFVSQ 239

                          250       260
                   ....*....|....*....|..
gi 1207186029 1894 LLVAD-RLRPDANECLRHPWFK 1914
Cdd:cd06605    240 CLQKDpTERPSYKELMEHPFIK 261

Catalytic domain of the Serine/Threonine Kinase, Cell Cycle-Related Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CCRK was previously called p42. It is a Cyclin-Dependent Kinase (CDK)-Activating Kinase (CAK) which is essential for the activation of CDK2. It is indispensable for cell growth and has been implicated in the progression of glioblastoma multiforme. In the heart, a splice variant of CCRK with a different C-terminal half is expressed; this variant promotes cardiac cell growth and survival and is significantly down-regulated during the development of heart failure. The CCRK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270826 [Multi-domain] Cd Length: 287 Bit Score: 108.19 E-value: 4.51e-25

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKA---SALRELNILSHL-DHERILYFHDAFEKKNAVIIITEL 1737
Cdd:cd07832      2 YKILGRIGEGAHGIVFKAKDRETGETVALKKVALRKLEGGipnQALREIKALQACqGHPYVVKLRDVFPHGTGFVLVFEY 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1738 CHEELLDRLTKKSTIL-ESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHssDQIRICDFGNAVKFMPD-EAQYC 1815
Cdd:cd07832     82 MLSSLSEVLRDEERPLtEAQVKRYMRMLLKGVAYMHANRIMHRDLKPANLLISST--GVLKIADFGLARLFSEEdPRLYS 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1816 -KYGTPEFVAPEIVNQTP-VSKATDIWPIGVLTYLCLTGVSPFAGENDRS------SVLNIRN------------YN-VA 1874
Cdd:cd07832    160 hQVATRWYRAPELLYGSRkYDEGVDLWAVGCIFAELLNGSPLFPGENDIEqlaivlRTLGTPNektwpeltslpdYNkIT 239

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*..
gi 1207186029 1875 FEES-------MFTDLCHEAKGFVIKLLVAD-RLRPDANECLRHPWF 1913
Cdd:cd07832    240 FPESkgirleeIFPDCSPEAIDLLKGLLVYNpKKRLSAEEALRHPYF 286

Catalytic domain of an Uncharacterized subfamily of Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of uncharacterized proteins with similarity to MEKK3, MEKK2, and related proteins; they contain an N-terminal PB1 domain, which mediates oligomerization, and a C-terminal catalytic domain. MEKK2 and MEKK3 are MAPK kinase kinases (MAPKKKs or MKKKs), proteins that phosphorylate and activate MAPK kinases (MAPKKs or MKKs), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MEKK2 and MEKK3 activate MEK5 (also called MKK5), which activates ERK5. The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK3 plays an essential role in embryonic angiogenesis and early heart development. MEKK2 and MEKK3 can also activate the MAPKs, c-Jun N-terminal kinase (JNK) and p38, through their respective MAPKKs. The MEKK3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270819 [Multi-domain] Cd Length: 264 Bit Score: 107.42 E-value: 5.21e-25

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKIVPYEPESKQTVLQ------EYDILKSLHHEKIMALHEAYVTP--RYLVLISECCSGK 3379
Cdd:cd06653     12 RGAFGEVYLCYDADTGRELAVKQVPFDPDSQETSKEvnalecEIQLLKNLRHDRIVQYYGCLRDPeeKKLSIFVEYMPGG 91

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3380 ELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLK--QFSPPIG 3457
Cdd:cd06653     92 SVKDQLKAYGALTENVTRRYTRQILQGVSYLHSNMIVHRDIKGANILRDSAGNVKLGDFGASKRIQTICMSgtGIKSVTG 171

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3458 TLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFtendpAETEAriQAAKFDLS------KLYQNVSQSASLFIKK 3531
Cdd:cd06653    172 TPYWMSPEVISGEGYGRKADVWSVACTVVEMLTEKPPW-----AEYEA--MAAIFKIAtqptkpQLPDGVSDACRDFLRQ 244


                   ..
gi 1207186029 3532 IL 3533
Cdd:cd06653    245 IF 246

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK2 is ubiquitously expressed and is essential in autophagy induction. It displays partially redundant functions with ULK1 and is able to compensate for the loss of ULK1 in non-selective autophagy. It also displays neuron-specific functions and is important in axon development. The ULK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271103 [Multi-domain] Cd Length: 271 Bit Score: 107.40 E-value: 6.07e-25

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMA-KIVPYEPESKQTVL--QEYDILKSLHHEKIMALHEAYVTPRYLVLISECC 3376
Cdd:cd14201      8 YSRKDLVGHGAFAVVFKGRHRKKTDWEVAiKSINKKNLSKSQILlgKEIKILKELQHENIVALYDVQEMPNSVFLVMEYC 87

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3377 SGKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMN---------VVKIIDFGSAQTFNPL 3447
Cdd:cd14201     88 NGGDLADYLQAKGTLSEDTIRVFLQQIAAAMRILHSKGIIHRDLKPQNILLSYASrkkssvsgiRIKIADFGFARYLQSN 167

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1207186029 3448 FLKqfSPPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAE 3502
Cdd:cd14201    168 MMA--ATLCGSPMYMAPEVIMSQHYDAKADLWSIGTVIYQCLVGKPPFQANSPQD 220

Catalytic domain of the Serine/Threonine Kinases, Mammalian STe20-like protein kinase 1 and 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of MST1, MST2, and related proteins including Drosophila Hippo and Dictyostelium discoideum Krs1 (kinase responsive to stress 1). MST1/2 and Hippo are involved in a conserved pathway that governs cell contact inhibition, organ size control, and tumor development. MST1 activates the mitogen-activated protein kinases (MAPKs) p38 and c-Jun N-terminal kinase (JNK) through MKK7 and MEKK1 by acting as a MAPK kinase kinase kinase. Activation of JNK by MST1 leads to caspase activation and apoptosis. MST1 has also been implicated in cell proliferation and differentiation. Krs1 may regulate cell growth arrest and apoptosis in response to cellular stress. The MST1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 132943 [Multi-domain] Cd Length: 256 Bit Score: 106.97 E-value: 6.26e-25

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3296 PQKPYTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPESkQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISEC 3375
Cdd:cd06612      1 PEEVFDILEKLGEGSYGSVYKAIHKETGQVVAIKVVPVEEDL-QEIIKEISILKQCDSPYIVKYYGSYFKNTDLWIVMEY 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3376 CSGKellhSLID-----RFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFG-SAQTFNPLFL 3449
Cdd:cd06612     80 CGAG----SVSDimkitNKTLTEEEIAAILYQTLKGLEYLHSNKKIHRDIKAGNILLNEEGQAKLADFGvSGQLTDTMAK 155

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3450 KQfsPPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTE-----------NDPAETeariqaakfdLSKlY 3518
Cdd:cd06612    156 RN--TVIGTPFWMAPEVIQEIGYNNKADIWSLGITAIEMAEGKPPYSDihpmraifmipNKPPPT----------LSD-P 222

                          250       260
                   ....*....|....*....|....*..
gi 1207186029 3519 QNVSQSASLFIKKILCSYPWARPTIKD 3545
Cdd:cd06612    223 EKWSPEFNDFVKKCLVKDPEERPSAIQ 249

Catalytic domain of Mammalian Ste20-like protein kinase 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of MST3, MST4, STK25, Schizosaccharomyces pombe Nak1 and Sid1, Saccharomyces cerevisiae sporulation-specific protein 1 (SPS1), and related proteins. Nak1 is required by fission yeast for polarizing the tips of actin cytoskeleton and is involved in cell growth, cell separation, cell morphology and cell-cycle progression. Sid1 is a component in the septation initiation network (SIN) signaling pathway, and plays a role in cytokinesis. SPS1 plays a role in regulating proteins required for spore wall formation. MST4 plays a role in mitogen-activated protein kinase (MAPK) signaling during cytoskeletal rearrangement, morphogenesis, and apoptosis. MST3 phosphorylates the STK NDR and may play a role in cell cycle progression and cell morphology. STK25 may play a role in the regulation of cell migration and polarization. The MST3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270786 [Multi-domain] Cd Length: 274 Bit Score: 107.33 E-value: 6.96e-25

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPESKQ--TVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCS 3377
Cdd:cd06609      3 FTLLERIGKGSFGEVYKGIDKRTNQVVAIKVIDLEEAEDEieDIQQEIQFLSQCDSPYITKYYGSFLKGSKLWIIMEYCG 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3378 GKELLHsLIDRFRYSEDdVVAYIV-QILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFG-SAQ-TFNPLFLKQFsp 3454
Cdd:cd06609     83 GGSVLD-LLKPGPLDET-YIAFILrEVLLGLEYLHSEGKIHRDIKAANILLSEEGDVKLADFGvSGQlTSTMSKRNTF-- 158

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*.
gi 1207186029 3455 pIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDP 3500
Cdd:cd06609    159 -VGTPFWMAPEVIKQSGYDEKADIWSLGITAIELAKGEPPLSDLHP 203

C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK2 and MSK1 play nonredundant roles in activating histone H3 kinases, which play pivotal roles in compaction of the chromatin fiber. MSK2 is the required H3 kinase in response to stress stimuli and activation of the p38 MAPK pathway. MSK2 also plays a role in the pathogenesis of psoriasis. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family, similar to 90 kDa ribosomal protein S6 kinases (RSKs). MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. The MSK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271082 [Multi-domain] Cd Length: 309 Bit Score: 108.03 E-value: 7.44e-25

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYVKRVIQKAGKLEYAAKFISAR----AKRKASALRELNilshlDHERILYFHDAFEKKNAVIIITELCHE-EL 1742
Cdd:cd14180     14 LGEGSFSVCRKCRHRQSGQEYAVKIISRRmeanTQREVAALRLCQ-----SHPNIVALHEVLHDQYHTYLVMELLRGgEL 88

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1743 LDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSDQ-IRICDFGNAvKFMPDEAQYCKygTP- 1820
Cdd:cd14180     89 LDRIKKKARFSESEASQLMRSLVSAVSFMHEAGVVHRDLKPENILYADESDGAvLKVIDFGFA-RLRPQGSRPLQ--TPc 165

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1821 ---EFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSS-------VLNIRNYNVAFEESMFTDLCHEAKGF 1890
Cdd:cd14180    166 ftlQYAAPELFSNQGYDESCDLWSLGVILYTMLSGQVPFQSKRGKMFhnhaadiMHKIKEGDFSLEGEAWKGVSEEAKDL 245


                   ....*...
gi 1207186029 1891 VIKLLVAD 1898
Cdd:cd14180    246 VRGLLTVD 253

Catalytic domain of the Serine/Threonine kinase, With No Lysine (WNK) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNKs comprise a subfamily of STKs with an unusual placement of a catalytic lysine relative to all other protein kinases. They are critical in regulating ion balance and are thus, important components in the control of blood pressure. They are also involved in cell signaling, survival, proliferation, and organ development. WNKs are activated by hyperosmotic or low-chloride hypotonic stress and they function upstream of SPAK and OSR1 kinases, which regulate the activity of cation-chloride cotransporters through direct interaction and phosphorylation. There are four vertebrate WNKs which show varying expression patterns. WNK1 and WNK2 are widely expressed while WNK3 and WNK4 show a more restricted expression pattern. Because mutations in human WNK1 and WNK4 cause PseudoHypoAldosteronism type II (PHAII), characterized by hypertension (due to increased sodium reabsorption) and hyperkalemia (due to impaired renal potassium secretion), there are more studies conducted on these two proteins, compared to WNK2 and WNK3. The WNK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270885 [Multi-domain] Cd Length: 258 Bit Score: 106.54 E-value: 7.86e-25

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3329 KIVPYEPESKQTVLQEYDILKSLHHEKIMALHEAYVTP--RYLVLISECCSGKElLHSLIDRF-RYSEDDVVAYIVQILQ 3405
Cdd:cd13983     35 KLRKLPKAERQRFKQEIEILKSLKHPNIIKFYDSWESKskKEVIFITELMTSGT-LKQYLKRFkRLKLKVIKSWCRQILE 113

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3406 GLDYLHSRR--ILHLDIKPENIIVT-YMNVVKIIDFGSAQTFNPLFLKQFsppIGTLDYMSPEMLKGDvVGPPADIWSIG 3482
Cdd:cd13983    114 GLNYLHTRDppIIHRDLKCDNIFINgNTGEVKIGDLGLATLLRQSFAKSV---IGTPEFMAPEMYEEH-YDEKVDIYAFG 189

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1207186029 3483 ILTYIMLSGRLPFTE-NDPAETEARIQAAKFDLSkLYQNVSQSASLFIKKILCSyPWARPTIKDCFTNSWL 3552
Cdd:cd13983    190 MCLLEMATGEYPYSEcTNAAQIYKKVTSGIKPES-LSKVKDPELKDFIEKCLKP-PDERPSARELLEHPFF 258

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 8; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek8 contains an N-terminal kinase catalytic domain and a C-terminal RCC1 (regulator of chromosome condensation) domain. A double point mutation in Nek8 causes cystic kidney disease in mice that genetically resembles human autosomal recessive polycystic kidney disease (ARPKD). Nek8 is also associated with a rare form of juvenile renal cystic disease, nephronophthisis type 9. It has been suggested that a defect in the ciliary localization of Nek8 contributes to the development of cysts manifested by these diseases. Nek8 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270859 [Multi-domain] Cd Length: 256 Bit Score: 106.36 E-value: 9.11e-25

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKIVPYE---PESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLHS 3384
Cdd:cd08220     10 RGAYGTVYLCRRKDDNKLVIIKQIPVEqmtKEERQAALNEVKVLSMLHHPNIIEYYESFLEDKALMIVMEYAPGGTLFEY 89

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3385 LIDR--FRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVT-YMNVVKIIDFGSAQTFNPlfLKQFSPPIGTLDY 3461
Cdd:cd08220     90 IQQRkgSLLSEEEILHFFVQILLALHHVHSKQILHRDLKTQNILLNkKRTVVKIGDFGISKILSS--KSKAYTVVGTPCY 167

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3462 MSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPF-TENDPAETeARIQAAKFD-LSKLYqnvSQSASLFIKKILCSYPWA 3539
Cdd:cd08220    168 ISPELCEGKPYNQKSDIWALGCVLYELASLKRAFeAANLPALV-LKIMRGTFApISDRY---SEELRHLILSMLHLDPNK 243


                   ....*.
gi 1207186029 3540 RPTIKD 3545
Cdd:cd08220    244 RPTLSE 249

Catalytic domain of the Serine/Threonine kinases, Mitogen-activated protein kinase signal-integrating kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK signal-integrating kinases (Mnks) are MAPK-activated protein kinases and is comprised by a group of four proteins, produced by alternative splicing from two genes (Mnk1 and Mnk2). The isoforms of Mnk1 (1a/1b) and Mnk2 (2a/2b) differ at their C-termini, with the a-form having a longer C-terminus containing a MAPK-binding region. All Mnks contain a catalytic kinase domain and a polybasic region at the N-terminus which binds importin and the eukaryotic initiation factor eIF4G. The best characterized Mnk substrate is eIF4G, whose phosphorylation may promote the export of certain mRNAs from the nucleus. Mnk also phosphorylate substrates that bind to AU-rich elements that regulate mRNA stability and translation. Mnks have also been implicated in tyrosine kinase receptor signaling, inflammation, and cell prolieration or survival. The Mnk subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270992 [Multi-domain] Cd Length: 289 Bit Score: 107.12 E-value: 1.01e-24

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3309 GRFGVIRECRENATGNLYMAKIVPYEP-ESKQTVLQEYDILKSLH-HEKIMALHEAYVTPRYLVLISECCSGKELLHSLI 3386
Cdd:cd14090     13 GAYASVQTCINLYTGKEYAVKIIEKHPgHSRSRVFREVETLHQCQgHPNILQLIEYFEDDERFYLVFEKMRGGPLLSHIE 92

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3387 DRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNV---VKIIDFG-------SAQTFNPLFLKQFSPPI 3456
Cdd:cd14090     93 KRVHFTEQEASLVVRDIASALDFLHDKGIAHRDLKPENILCESMDKvspVKICDFDlgsgiklSSTSMTPVTTPELLTPV 172

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3457 GTLDYMSPEMLKGdVVGPP------ADIWSIGILTYIMLSGRLPFT------------ENDPAETE---ARIQAAKFDL- 3514
Cdd:cd14090    173 GSAEYMAPEVVDA-FVGEAlsydkrCDLWSLGVILYIMLCGYPPFYgrcgedcgwdrgEACQDCQEllfHSIQEGEYEFp 251

                          250       260       270
                   ....*....|....*....|....*....|....*..
gi 1207186029 3515 SKLYQNVSQSASLFIKKILCSYPWARPTIKDCFTNSW 3551
Cdd:cd14090    252 EKEWSHISAEAKDLISHLLVRDASQRYTAEQVLQHPW 288

Catalytic domain of the Alpha subunit of the Serine/Threonine Kinase, AMP-activated protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. AMPK, also called SNF1 (sucrose non-fermenting1) in yeasts and SnRK1 (SNF1-related kinase1) in plants, is a heterotrimeric enzyme composed of a catalytic alpha subunit and two regulatory subunits, beta and gamma. It is a stress-activated kinase that serves as master regulator of glucose and lipid metabolism by monitoring carbon and energy supplies, via sensing the cell's AMP:ATP ratio. In response to decreased ATP levels, it enhances energy-producing processes and inhibits energy-consuming pathways. Once activated, AMPK phosphorylates a broad range of downstream targets, with effects in carbohydrate metabolism and uptake, lipid and fatty acid biosynthesis, carbon energy storage, and inflammation, among others. Defects in energy homeostasis underlie many human diseases including Type 2 diabetes, obesity, heart disease, and cancer. As a result, AMPK has emerged as a therapeutic target in the treatment of these diseases. The AMPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270981 [Multi-domain] Cd Length: 256 Bit Score: 106.20 E-value: 1.07e-24

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISaRAKRKASAL-----RELNILSHLDHERILYFHDAFEKKNAVIIITE 1736
Cdd:cd14079      4 YILGKTLGVGSFGKVKLAEHELTGHKVAVKILN-RQKIKSLDMeekirREIQILKLFRHPHIIRLYEVIETPTDIFMVME 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1737 -LCHEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSsdQIRICDFGNAvKFMPDeAQYC 1815
Cdd:cd14079     83 yVSGGELFDYIVQKGRLSEDEARRFFQQIISGVEYCHRHMVVHRDLKPENLLLDSNM--NVKIADFGLS-NIMRD-GEFL 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1816 KY--GTPEFVAPEIVN-QTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNynvafeeSMFT---DLCHEAKG 1889
Cdd:cd14079    159 KTscGSPNYAAPEVISgKLYAGPEVDVWSCGVILYALLCGSLPFDDEHIPNLFKKIKS-------GIYTipsHLSPGARD 231

                          250       260
                   ....*....|....*....|....*
gi 1207186029 1890 FVIKLLVADRL-RPDANECLRHPWF 1913
Cdd:cd14079    232 LIKRMLVVDPLkRITIPEIRQHPWF 256

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK3 mRNA is up-regulated in fibroblasts after Ras-induced senescence, and its overexpression induces both autophagy and senescence in a fibroblast cell line. ULK3, through its kinase activity, positively regulates Gli proteins, mediators of the Sonic hedgehog (Shh) signaling pathway that is implicated in tissue homeostasis maintenance and neurogenesis. It is inhibited by binding to Suppressor of Fused (Sufu). The ULK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271023 [Multi-domain] Cd Length: 252 Bit Score: 106.22 E-value: 1.10e-24

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3337 SKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRIL 3416
Cdd:cd14121     38 STENLLTEIELLKKLKHPHIVELKDFQWDEEHIYLIMEYCSGGDLSRFIRSRRTLPESTVRRFLQQLASALQFLREHNIS 117

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3417 HLDIKPENIIVT--YMNVVKIIDFGSAQTfnpLFLKQFSPPI-GTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRL 3493
Cdd:cd14121    118 HMDLKPQNLLLSsrYNPVLKLADFGFAQH---LKPNDEAHSLrGSPLYMAPEMILKKKYDARVDLWSVGVILYECLFGRA 194

                          170
                   ....*....|....*...
gi 1207186029 3494 PFTENDPAETEARIQAAK 3511
Cdd:cd14121    195 PFASRSFEELEEKIRSSK 212

N-terminal catalytic domain of the Serine/Threonine Kinase, 90 kDa ribosomal protein S6 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. Mammals possess four RSK isoforms (RSK1-4) from distinct genes. RSK proteins are also referred to as MAP kinase-activated protein kinases (MAPKAPKs), p90-RSKs, or p90S6Ks. The RSK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270734 [Multi-domain] Cd Length: 317 Bit Score: 107.87 E-value: 1.20e-24

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1666 KEIGRGAFSYV----KRVIQKAGKLeYAAKFIsarakRKAS-----ALR---ELNILSHLDHERILYFHDAFEKKNAVII 1733
Cdd:cd05582      1 KVLGQGSFGKVflvrKITGPDAGTL-YAMKVL-----KKATlkvrdRVRtkmERDILADVNHPFIVKLHYAFQTEGKLYL 74

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1734 ITE-LCHEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSsdQIRICDFGNAVKFMPDEA 1812
Cdd:cd05582     75 ILDfLRGGDLFTRLSKEVMFTEEDVKFYLAELALALDHLHSLGIIYRDLKPENILLDEDG--HIKLTDFGLSKESIDHEK 152

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1813 Q-YCKYGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVafeeSMFTDLCHEAKGFV 1891
Cdd:cd05582    153 KaYSFCGTVEYMAPEVVNRRGHTQSADWWSFGVLMFEMLTGSLPFQGKDRKETMTMILKAKL----GMPQFLSPEAQSLL 228

                          250       260       270
                   ....*....|....*....|....*....|....*
gi 1207186029 1892 IKLL---VADRL--RPD-ANECLRHPWFKTLNKGK 1920
Cdd:cd05582    229 RALFkrnPANRLgaGPDgVEEIKRHPFFATIDWNK 263

Catalytic domain of the Serine/Threonine kinase, Aurora-B kinase and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Aurora kinases are key regulators of mitosis and are essential for the accurate and equal division of genomic material from parent to daughter cells. Vertebrates contain at least 2 Aurora kinases (A and B); mammals contains a third Aurora kinase gene (C). This subfamily includes Aurora-B and Aurora-C. Aurora-B is most active at the transition during metaphase to the end of mitosis. It associates with centromeres, relocates to the midzone of the central spindle, and concentrates at the midbody during cell division. It is critical for accurate chromosomal segregation, cytokinesis, protein localization to the centrosome and kinetochore, correct microtubule-kinetochore attachments, and regulation of the mitotic checkpoint. Aurora-C is mainly expressed in meiotically dividing cells; it was originally discovered in mice as a testis-specific STK called Aie1. Both Aurora-B and -C are chromosomal passenger proteins that can form complexes with INCENP and survivin, and they may have redundant cellular functions. INCENP participates in the activation of Aurora-B in a two-step process: first by binding to form an intermediate state of activation and the phosphorylation of its C-terminal TSS motif to generate the fully active kinase. The Aurora-B subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271019 [Multi-domain] Cd Length: 270 Bit Score: 106.49 E-value: 1.24e-24

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKIVPYEPESKQTV----LQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLH 3383
Cdd:cd14117     16 KGKFGNVYLAREKQSKFIVALKVLFKSQIEKEGVehqlRREIEIQSHLRHPNILRLYNYFHDRKRIYLILEYAPRGELYK 95

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3384 SLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLKQFSppiGTLDYMS 3463
Cdd:cd14117     96 ELQKHGRFDEQRTATFMEELADALHYCHEKKVIHRDIKPENLLMGYKGELKIADFGWSVHAPSLRRRTMC---GTLDYLP 172

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3464 PEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIqaAKFDLsKLYQNVSQSASLFIKKILCSYPWARPTI 3543
Cdd:cd14117    173 PEMIEGRTHDEKVDLWCIGVLCYELLVGMPPFESASHTETYRRI--VKVDL-KFPPFLSDGSRDLISKLLRYHPSERLPL 249

                          250
                   ....*....|
gi 1207186029 3544 KDCFTNSWLQ 3553
Cdd:cd14117    250 KGVMEHPWVK 259

Catalytic domain of the protein kinase, Dual-specificity tYrosine-phosphorylated and -Regulated Kinase; Protein Kinases (PKs), Dual-specificity tYrosine-phosphorylated and -Regulated Kinase (DYRK) subfamily, catalytic (c) domain. Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. The DYRK subfamily is part of a larger superfamily that includes the catalytic domains of other protein S/T PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K). DYRKs autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. They play important roles in cell proliferation, differentiation, survival, and development. Vertebrates contain multiple DYRKs (DYRK1-4) and mammals contain two types of DYRK1 proteins, DYRK1A and DYRK1B. DYRK1A is involved in neuronal differentiation and is implicated in the pathogenesis of DS (Down syndrome). DYRK1B plays a critical role in muscle differentiation by regulating transcription, cell motility, survival, and cell cycle progression. It is overexpressed in many solid tumors where it acts as a tumor survival factor. DYRK2 promotes apoptosis in response to DNA damage by phosphorylating the tumor suppressor p53, while DYRK3 promotes cell survival by phosphorylating SIRT1 and promoting p53 deacetylation. DYRK4 is a testis-specific kinase that may function during spermiogenesis.

Pssm-ID: 271112 [Multi-domain] Cd Length: 311 Bit Score: 107.25 E-value: 1.41e-24

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVI-QKAGKLeYAAKFISARAKRKASALRELNILSHL------DHERILYFHDAFEKKNAVIII 1734
Cdd:cd14210     15 YEVLSVLGKGSFGQVVKCLdHKTGQL-VAIKIIRNKKRFHQQALVEVKILKHLndndpdDKHNIVRYKDSFIFRGHLCIV 93

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1735 TELCHEELLDRLTKK-----STILeseIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSDQIRICDFGNAvkfmp 1809
Cdd:cd14210     94 FELLSINLYELLKSNnfqglSLSL---IRKFAKQILQALQFLHKLNIIHCDLKPENILLKQPSKSSIKVIDFGSS----- 165

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1810 deaqyCKYGTPEFV--------APEIVNQTPVSKATDIWPIGVLtyLC--LTGVSPFAGEN---------------DRSS 1864
Cdd:cd14210    166 -----CFEGEKVYTyiqsrfyrAPEVILGLPYDTAIDMWSLGCI--LAelYTGYPLFPGENeeeqlacimevlgvpPKSL 238

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1207186029 1865 VLNIRNYNVAFEESMFTDLCHEAKG-----------------------FVIKLLVAD-RLRPDANECLRHPWF 1913
Cdd:cd14210    239 IDKASRRKKFFDSNGKPRPTTNSKGkkrrpgskslaqvlkcddpsfldFLKKCLRWDpSERMTPEEALQHPWI 311

Immunoglobulin-like domain of human Aortic Preferentially Expressed Protein-1 (APEG-1) and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin I-set (IgI) domain of the Human Aortic Preferentially Expressed Protein-1 (APEG-1) and similar proteins. APEG-1 is a novel specific smooth muscle differentiation marker predicted to play a role in the growth and differentiation of arterial smooth muscle cells (SMCs). The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the human APEG-1 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409567 Cd Length: 91 Bit Score: 100.24 E-value: 1.48e-24

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  928 PAFLAVIGDQSVIEGQEVTMSVLVTGQPKPMLYWLRDRVTIKTGTRHIVQETEEGNFEMIIKSAQRSDTGVYTCKIINEY 1007
Cdd:cd20975      1 PTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEAEGGLCRLRILAAERGDAGFYTCKAVNEY 80

                           90
                   ....*....|.
gi 1207186029 1008 GTKQCEGKLEV 1018
Cdd:cd20975     81 GARQCEARLEV 91

Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ROCK is also referred to as Rho-associated kinase or simply as Rho kinase. It contains an N-terminal extension, a catalytic kinase domain, and a long C-terminal extension, which contains a coiled-coil region encompassing a Rho-binding domain (RBD) and a pleckstrin homology (PH) domain. ROCK is auto-inhibited by the RBD and PH domain interacting with the catalytic domain. It is activated via interaction with Rho GTPases and is involved in many cellular functions including contraction, adhesion, migration, motility, proliferation, and apoptosis. The ROCK subfamily consists of two isoforms, ROCK1 and ROCK2, which may be functionally redundant in some systems, but exhibit different tissue distributions. Both isoforms are ubiquitously expressed in most tissues, but ROCK2 is more prominent in brain and skeletal muscle while ROCK1 is more pronounced in the liver, testes, and kidney. Studies in knockout mice result in different phenotypes, suggesting that the two isoforms do not compensate for each other during embryonic development. The ROCK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270747 [Multi-domain] Cd Length: 352 Bit Score: 108.23 E-value: 1.58e-24

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKIVpyepeSKQTVL---------QEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSG 3378
Cdd:cd05596     36 RGAFGEVQLVRHKSTKKVYAMKLL-----SKFEMIkrsdsaffwEERDIMAHANSEWIVQLHYAFQDDKYLYMVMDYMPG 110

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3379 KELLhSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLKQFSPPIGT 3458
Cdd:cd05596    111 GDLV-NLMSNYDVPEKWARFYTAEVVLALDAIHSMGFVHRDVKPDNMLLDASGHLKLADFGTCMKMDKDGLVRSDTAVGT 189

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|.
gi 1207186029 3459 LDYMSPEMLK---GD-VVGPPADIWSIGILTYIMLSGRLPF 3495
Cdd:cd05596    190 PDYISPEVLKsqgGDgVYGRECDWWSVGVFLYEMLVGDTPF 230

Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 2 and 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKL2, also called p56 KKIAMRE, is expressed in testis, kidney, lung, and brain. It functions mainly in mature neurons and plays an important role in learning and memory. Inactivation of CDKL3, also called NKIAMRE (NKIATRE in rat), by translocation is associated with mild mental retardation. It has been reported that CDKL3 is lost in leukemic cells having a chromosome arm 5q deletion, and may contribute to the transformed phenotype. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL2/3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270836 [Multi-domain] Cd Length: 286 Bit Score: 105.97 E-value: 2.50e-24

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3309 GRFGVIRECRENATGNLYMAKIVPYEPES---KQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECcsgkeLLHSL 3385
Cdd:cd07846     12 GSYGMVMKCRHKETGQIVAIKKFLESEDDkmvKKIAMREIKMLKQLRHENLVNLIEVFRRKKRWYLVFEF-----VDHTV 86

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3386 IDRFRY-----SEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFlKQFSPPIGTLD 3460
Cdd:cd07846     87 LDDLEKypnglDESRVRKYLFQILRGIDFCHSHNIIHRDIKPENILVSQSGVVKLCDFGFARTLAAPG-EVYTDYVATRW 165

                          170       180       190
                   ....*....|....*....|....*....|..
gi 1207186029 3461 YMSPEMLKGDV-VGPPADIWSIGILTYIMLSG 3491
Cdd:cd07846    166 YRAPELLVGDTkYGKAVDVWAVGCLVTEMLTG 197

Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PIM gene locus was discovered as a result of the cloning of retroviral intergration sites in murine Moloney leukemia virus, leading to the identification of PIM kinases. They are constitutively active STKs with a broad range of cellular targets and are overexpressed in many haematopoietic malignancies and solid cancers. Vertebrates contain three distinct PIM kinase genes (PIM1-3); each gene may result in mutliple protein isoforms. There are two PIM1 and three PIM2 isoforms as a result of alternative translation initiation sites, while there is only one PIM3 protein. Compound knockout mice deficient of all three PIM kinases that survive the perinatal period show a profound reduction in body size, indicating that PIMs are important for body growth. The PIM subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270907 [Multi-domain] Cd Length: 255 Bit Score: 105.01 E-value: 2.51e-24

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3350 SLHHEKIMALHEAYVTPRYLVLISECCSG-KELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVT 3428
Cdd:cd14005     62 KPGVPGVIRLLDWYERPDGFLLIMERPEPcQDLFDFITERGALSENLARIIFRQVVEAVRHCHQRGVLHRDIKDENLLIN 141

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3429 yMNV--VKIIDFGSAQtfnplFLKQ--FSPPIGTLDYMSPE-MLKGDVVGPPADIWSIGILTYIMLSGRLPFtENDPAET 3503
Cdd:cd14005    142 -LRTgeVKLIDFGCGA-----LLKDsvYTDFDGTRVYSPPEwIRHGRYHGRPATVWSLGILLYDMLCGDIPF-ENDEQIL 214

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*....
gi 1207186029 3504 EARIQaakfdlskLYQNVSQSASLFIKKILCSYPWARPTIKDCFTNSWL 3552
Cdd:cd14005    215 RGNVL--------FRPRLSKECCDLISRCLQFDPSKRPSLEQILSHPWF 255

Catalytic domain of fungal Rim15-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include Saccharomyces cerevisiae Rim15, Schizosaccharomyces pombe cek1, and similar fungal proteins. They contain a central catalytic domain, which contains an insert relative to MAST kinases. In addition, Rim15 contains a C-terminal signal receiver (REC) domain while cek1 contains an N-terminal PAS domain. Rim15 (or Rim15p) functions as a regulator of meiosis. It acts as a downstream effector of PKA and regulates entry into stationary phase (G0). Thus, it plays a crucial role in regulating yeast proliferation, differentiation, and aging. Cek1 may facilitate progression of mitotic anaphase. The Rim15-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270762 [Multi-domain] Cd Length: 263 Bit Score: 105.26 E-value: 2.57e-24

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1666 KEIGRGAFSYVKRVIQKAGKLEYAAKFIsarakrKASALRELNILSHLDHERI-------------LYFhdAFEKKNAVI 1732
Cdd:cd05611      2 KPISKGAFGSVYLAKKRSTGDYFAIKVL------KKSDMIAKNQVTNVKAERAimmiqgespyvakLYY--SFQSKDYLY 73

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1733 IITELCHEELLDRLTKKSTIL-ESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADhsSDQIRICDFGnaVKFMPDE 1811
Cdd:cd05611     74 LVMEYLNGGDCASLIKTLGGLpEDWAKQYIAEVVLGVEDLHQRGIIHRDIKPENLLIDQ--TGHLKLTDFG--LSRNGLE 149

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1812 AQYCK--YGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDLCHEAKG 1889
Cdd:cd05611    150 KRHNKkfVGTPDYLAPETILGVGDDKMSDWWSLGCVIFEFLFGYPPFHAETPDAVFDNILSRRINWPEEVKEFCSPEAVD 229

                          250       260       270
                   ....*....|....*....|....*....|..
gi 1207186029 1890 FVIKLLVAD-RLRPDAN---ECLRHPWFKTLN 1917
Cdd:cd05611    230 LINRLLCMDpAKRLGANgyqEIKSHPFFKSIN 261

Catalytic domain of the Serine/Threonine Kinase, 70 kDa ribosomal protein S6 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p70S6K (or S6K) contains only one catalytic kinase domain, unlike p90 ribosomal S6 kinases (RSKs). It acts as a downstream effector of the STK mTOR (mammalian Target of Rapamycin) and plays a role in the regulation of the translation machinery during protein synthesis. p70S6K also plays a pivotal role in regulating cell size and glucose homeostasis. Its targets include S6, the translation initiation factor eIF3, and the insulin receptor substrate IRS-1, among others. Mammals contain two isoforms of p70S6K, named S6K1 and S6K2 (or S6K-beta). The p70S6K subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270736 [Multi-domain] Cd Length: 323 Bit Score: 106.72 E-value: 3.12e-24

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3325 LYMAKIVPYEPESKQTVlQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLHSLIDRFRYSEDDVVAYIVQIL 3404
Cdd:cd05584     32 LKKASIVRNQKDTAHTK-AERNILEAVKHPFIVDLHYAFQTGGKLYLILEYLSGGELFMHLEREGIFMEDTACFYLAEIT 110

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3405 QGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFG----------SAQTFnplflkqfsppIGTLDYMSPEMLKGDVVGP 3474
Cdd:cd05584    111 LALGHLHSLGIIYRDLKPENILLDAQGHVKLTDFGlckesihdgtVTHTF-----------CGTIEYMAPEILTRSGHGK 179

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1207186029 3475 PADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLSKLyqnVSQSASLFIKKILCSYPWAR 3540
Cdd:cd05584    180 AVDWWSLGALMYDMLTGAPPFTAENRKKTIDKILKGKLNLPPY---LTNEARDLLKKLLKRNVSSR 242

Catalytic domain of the Serine/Threonine kinase, Aurora-A kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Aurora kinases are key regulators of mitosis and are essential for the accurate and equal division of genomic material from parent to daughter cells. Vertebrates contain at least 2 Aurora kinases (A and B); mammals contains a third Aurora kinase gene (C). Aurora-A regulates cell cycle events from the late S-phase through the M-phase including centrosome maturation, mitotic entry, centrosome separation, spindle assembly, chromosome alignment, cytokinesis, and mitotic exit. Aurora-A activation depends on its autophosphorylation and binding to the microtubule-associated protein TPX2, which also localizes the kinase to spindle microtubules. Aurora-A is overexpressed in many cancer types such as prostate, ovarian, breast, bladder, gastric, and pancreatic. The Aurora subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271018 [Multi-domain] Cd Length: 258 Bit Score: 105.04 E-value: 3.19e-24

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1660 DYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASA----LRELNILSHLDHERIL----YFHDAFEkknaV 1731
Cdd:cd14116      5 EDFEIGRPLGKGKFGNVYLAREKQSKFILALKVLFKAQLEKAGVehqlRREVEIQSHLRHPNILrlygYFHDATR----V 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1732 IIITELCHE-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMAdhSSDQIRICDFGNAVKfMPD 1810
Cdd:cd14116     81 YLILEYAPLgTVYRELQKLSKFDEQRTATYITELANALSYCHSKRVIHRDIKPENLLLG--SAGELKIADFGWSVH-APS 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1811 EAQYCKYGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRnyNVAFEESMFtdLCHEAKGF 1890
Cdd:cd14116    158 SRRTTLCGTLDYLPPEMIEGRMHDEKVDLWSLGVLCYEFLVGKPPFEANTYQETYKRIS--RVEFTFPDF--VTEGARDL 233

                          250       260
                   ....*....|....*....|...
gi 1207186029 1891 VIKLLVADRL-RPDANECLRHPW 1912
Cdd:cd14116    234 ISRLLKHNPSqRPMLREVLEHPW 256

Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMP-activated protein kinase (AMPK). Vertebrates contain two CaMKKs, CaMKK1 (or alpha) and CaMKK2 (or beta). CaMKK1 is involved in the regulation of glucose uptake in skeletal muscles. CaMKK2 is involved in regulating energy balance, glucose metabolism, adiposity, hematopoiesis, inflammation, and cancer. The CaMKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271020 [Multi-domain] Cd Length: 275 Bit Score: 105.13 E-value: 3.96e-24

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1667 EIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASAL------------------------RELNILSHLDHERIL--- 1719
Cdd:cd14118      1 EIGKGSYGIVKLAYNEEDNTLYAMKILSKKKLLKQAGFfrrppprrkpgalgkpldpldrvyREIAILKKLDHPNVVklv 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1720 ---------YFHDAFE--KKNAVI-IITElcheelldrltkkSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNIL 1787
Cdd:cd14118     81 evlddpnedNLYMVFElvDKGAVMeVPTD-------------NPLSEETARSYFRDIVLGIEYLHYQKIIHRDIKPSNLL 147

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1788 MADhsSDQIRICDFGNAVKFMPDEAQYCK-YGTPEFVAPEIVNQTPVS---KATDIWPIGVLTYLCLTGVSPFAGENDRS 1863
Cdd:cd14118    148 LGD--DGHVKIADFGVSNEFEGDDALLSStAGTPAFMAPEALSESRKKfsgKALDIWAMGVTLYCFVFGRCPFEDDHILG 225

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1864 SVLNIRNYNVAFEESmfTDLCHEAKGFVIKLLVAD-RLRPDANECLRHPW 1912
Cdd:cd14118    226 LHEKIKTDPVVFPDD--PVVSEQLKDLILRMLDKNpSERITLPEIKEHPW 273

Catalytic domain of Ste20-Like Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of the subfamily include SLK, STK10 (also called LOK for Lymphocyte-Oriented Kinase), SmSLK (Schistosoma mansoni SLK), and related proteins. SLK promotes apoptosis through apoptosis signal-regulating kinase 1 (ASK1) and the mitogen-activated protein kinase (MAPK) p38. It also plays a role in mediating actin reorganization. STK10 is responsible in regulating the CD28 responsive element in T cells, as well as leukocyte function associated antigen (LFA-1)-mediated lymphocyte adhesion. SmSLK is capable of activating the MAPK Jun N-terminal kinase (JNK) pathway in human embryonic kidney cells as well as in Xenopus oocytes. It may participate in regulating MAPK cascades during host-parasite interactions. The SLK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 132942 [Multi-domain] Cd Length: 280 Bit Score: 104.82 E-value: 5.07e-24

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3309 GRFGVIRECRENATGNLYMAKIVPYEPESK-QTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELlHSLID 3387
Cdd:cd06611     16 GAFGKVYKAQHKETGLFAAAKIIQIESEEElEDFMVEIDILSECKHPNIVGLYEAYFYENKLWILIEFCDGGAL-DSIML 94

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3388 RFR--YSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFG-SAQtfNPLFLKQFSPPIGTLDYMSP 3464
Cdd:cd06611     95 ELErgLTEPQIRYVCRQMLEALNFLHSHKVIHRDLKAGNILLTLDGDVKLADFGvSAK--NKSTLQKRDTFIGTPYWMAP 172

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3465 EML-----KGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQaaKFDLSKLYQNVSQSASL--FIKKILCSYP 3537
Cdd:cd06611    173 EVVacetfKDNPYDYKADIWSLGITLIELAQMEPPHHELNPMRVLLKIL--KSEPPTLDQPSKWSSSFndFLKSCLVKDP 250

                          250
                   ....*....|....*...
gi 1207186029 3538 WARPTIKDCFTNSWLQDA 3555
Cdd:cd06611    251 DDRPTAAELLKHPFVSDQ 268

Catalytic domain of PRKX-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include human PRKX (X chromosome-encoded protein kinase), Drosophila DC2, and similar proteins. PRKX is present in many tissues including fetal and adult brain, kidney, and lung. The PRKX gene is located in the Xp22.3 subregion and has a homolog called PRKY on the Y chromosome. An abnormal interchange between PRKX aand PRKY leads to the sex reversal disorder of XX males and XY females. PRKX is implicated in granulocyte/macrophage lineage differentiation, renal cell epithelial migration, and tubular morphogenesis in the developing kidney. The PRKX-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270763 [Multi-domain] Cd Length: 292 Bit Score: 105.21 E-value: 5.22e-24

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3309 GRFGVIRECRENATGNLYMAKI--VPYEPESKQT--VLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLHS 3384
Cdd:cd05612     12 GTFGRVHLVRDRISEHYYALKVmaIPEVIRLKQEqhVHNEKRVLKEVSHPFIIRLFWTEHDQRFLYMLMEYVPGGELFSY 91

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3385 LIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGsaqtfnplFLKQFSPPI----GTLD 3460
Cdd:cd05612     92 LRNSGRFSNSTGLFYASEIVCALEYLHSKEIVYRDLKPENILLDKEGHIKLTDFG--------FAKKLRDRTwtlcGTPE 163

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1207186029 3461 YMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLSKlyqNVSQSASLFIKKIL 3533
Cdd:cd05612    164 YLAPEVIQSKGHNKAVDWWALGILIYEMLVGYPPFFDDNPFGIYEKILAGKLEFPR---HLDLYAKDLIKKLL 233

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Neks are involved in the regulation of downstream processes following the activation of Cdc2, and many of their functions are cell cycle-related. They play critical roles in microtubule dynamics during ciliogenesis and mitosis. The specific function of Nek5 is unknown. Nek5 is one in a family of 11 different Neks (Nek1-11). The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173765 [Multi-domain] Cd Length: 257 Bit Score: 104.27 E-value: 5.47e-24

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3310 RFGVIRECRENATGNLYMAKIvpyEPESKQTVLQEYD-----------------ILKSLHHEKIMALHEAYVTPRYLVLI 3372
Cdd:cd08225      1 RYEIIKKIGEGSFGKIYLAKA---KSDSEHCVIKEIDltkmpvkekeaskkeviLLAKMKHPNIVTFFASFQENGRLFIV 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3373 SECCSGKELLHSlIDRFR---YSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVV-KIIDFGSAQTFN-PL 3447
Cdd:cd08225     78 MEYCDGGDLMKR-INRQRgvlFSEDQILSWFVQISLGLKHIHDRKILHRDIKSQNIFLSKNGMVaKLGDFGIARQLNdSM 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3448 FLKQFSppIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFdlSKLYQNVSQSASL 3527
Cdd:cd08225    157 ELAYTC--VGTPYYLSPEICQNRPYNNKTDIWSLGCVLYELCTLKHPFEGNNLHQLVLKICQGYF--APISPNFSRDLRS 232

                          250       260       270
                   ....*....|....*....|....*....|
gi 1207186029 3528 FIKKILCSYPWARPTIkdcftNSWLQDAYL 3557
Cdd:cd08225    233 LISQLFKVSPRDRPSI-----TSILKRPFL 257

Catalytic domain of the Serine/Threonine kinase, Protein Kinase D; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKDs are important regulators of many intracellular signaling pathways such as ERK and JNK, and cellular processes including the organization of the trans-Golgi network, membrane trafficking, cell proliferation, migration, and apoptosis. They contain N-terminal cysteine-rich zinc binding C1 (PKC conserved region 1), central PH (Pleckstrin Homology), and C-terminal catalytic kinase domains. Mammals harbor three types of PKDs: PKD1 (or PKCmu), PKD2, and PKD3 (or PKCnu). PKDs are activated in a PKC-dependent manner by many agents including diacylglycerol (DAG), PDGF, neuropeptides, oxidative stress, and tumor-promoting phorbol esters, among others. The PKD subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270984 [Multi-domain] Cd Length: 260 Bit Score: 104.42 E-value: 5.50e-24

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3309 GRFGVIRECRENATGNLYMAKIVPYE--PESKQTVLQ-EYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKEL---L 3382
Cdd:cd14082     14 GQFGIVYGGKHRKTGRDVAIKVIDKLrfPTKQESQLRnEVAILQQLSHPGVVNLECMFETPERVFVVMEKLHGDMLemiL 93

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3383 HSliDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMN---VVKIIDFGSAQTFNPlflKQFSPPI-GT 3458
Cdd:cd14082     94 SS--EKGRLPERITKFLVTQILVALRYLHSKNIVHCDLKPENVLLASAEpfpQVKLCDFGFARIIGE---KSFRRSVvGT 168

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3459 LDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDpaETEARIQAAKFDL-SKLYQNVSQSASLFIKKILCSYP 3537
Cdd:cd14082    169 PAYLAPEVLRNKGYNRSLDMWSVGVIIYVSLSGTFPFNEDE--DINDQIQNAAFMYpPNPWKEISPDAIDLINNLLQVKM 246

                          250
                   ....*....|....
gi 1207186029 3538 WARPTIKDCFTNSW 3551
Cdd:cd14082    247 RKRYSVDKSLSHPW 260

The catalytic domain of the Serine/Threonine Kinase, Glycogen Synthase Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GSK3 is a mutifunctional kinase involved in many cellular processes including cell division, proliferation, differentiation, adhesion, and apoptosis. In plants, GSK3 plays a role in the response to osmotic stress. In Caenorhabditis elegans, it plays a role in regulating normal oocyte-to-embryo transition and response to oxidative stress. In Chlamydomonas reinhardtii, GSK3 regulates flagellar length and assembly. In mammals, there are two isoforms, GSK3alpha and GSK3beta, which show both distinct and redundant functions. The two isoforms differ mainly in their N-termini. They are both involved in axon formation and in Wnt signaling.They play distinct roles in cardiogenesis, with GSKalpha being essential in cardiomyocyte survival, and GSKbeta regulating heart positioning and left-right symmetry. GSK3beta was first identified as a regulator of glycogen synthesis, but has since been determined to play other roles. It regulates the degradation of beta-catenin and IkB. Beta-catenin is the main effector of Wnt, which is involved in normal haematopoiesis and stem cell function. IkB is a central inhibitor of NF-kB, which is critical in maintaining leukemic cell growth. GSK3beta is enriched in the brain and is involved in regulating neuronal signaling pathways. It is implicated in the pathogenesis of many diseases including Type II diabetes, obesity, mood disorders, Alzheimer's disease, osteoporosis, and some types of cancer, among others. The GSK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271039 [Multi-domain] Cd Length: 293 Bit Score: 105.28 E-value: 5.50e-24

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVI-QKAGKLeYAAK--FISARAKRkasalRELNILSHLDHERILYFHDAF----EKKNAVI-- 1732
Cdd:cd14137      6 YTIEKVIGSGSFGVVYQAKlLETGEV-VAIKkvLQDKRYKN-----RELQIMRRLKHPNIVKLKYFFyssgEKKDEVYln 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1733 IITE-----LcHEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMaDHSSDQIRICDFGNAvKF 1807
Cdd:cd14137     80 LVMEympetL-YRVIRHYSKNKQTIPIIYVKLYSYQLFRGLAYLHSLGICHRDIKPQNLLV-DPETGVLKLCDFGSA-KR 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1808 M-PDEAQyckygTPEFV-----APE-IVNQTPVSKATDIWPIG-VLTYLcLTGVSPFAGENDRS------SVL------N 1867
Cdd:cd14137    157 LvPGEPN-----VSYICsryyrAPElIFGATDYTTAIDIWSAGcVLAEL-LLGQPLFPGESSVDqlveiiKVLgtptreQ 230

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1207186029 1868 IRNYNVAFEESMFTDL-------------CHEAKGFVIKLLVAD-RLRPDANECLRHPWFKTL 1916
Cdd:cd14137    231 IKAMNPNYTEFKFPQIkphpwekvfpkrtPPDAIDLLSKILVYNpSKRLTALEALAHPFFDEL 293

Catalytic domain of the Serine/Threonine Kinase, DMPK-related cell division control protein 42 binding kinase (MRCK) alpha; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MRCK-alpha is expressed ubiquitously in many tissues. It plays a role in the regulation of peripheral actin reorganization and neurite outgrowth. It may also play a role in the transferrin iron uptake pathway. MRCK is activated via interaction with the small GTPase Cdc42. MRCK/Cdc42 signaling mediates myosin-dependent cell motility. The MRCK-alpha subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. This alignment model includes the dimerization domain.

Pssm-ID: 270773 [Multi-domain] Cd Length: 409 Bit Score: 107.79 E-value: 6.03e-24

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1649 ASILRKMRRLTDYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISA--RAKRKASAL--RELNILSHLDHERILYFHDA 1724
Cdd:cd05623     61 TSKVKQMRLHKEDFEILKVIGRGAFGEVAVVKLKNADKVFAMKILNKweMLKRAETACfrEERDVLVNGDSQWITTLHYA 140

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1725 FEKKNAVIIITEL-CHEELLDRLTKKSTILESEI-RSSVRQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDFG 1802
Cdd:cd05623    141 FQDDNNLYLVMDYyVGGDLLTLLSKFEDRLPEDMaRFYLAEMVLAIDSVHQLHYVHRDIKPDNILM--DMNGHIRLADFG 218

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1803 NAVKFMPDEA--QYCKYGTPEFVAPEIVNQTPVSKAT-----DIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAF 1875
Cdd:cd05623    219 SCLKLMEDGTvqSSVAVGTPDYISPEILQAMEDGKGKygpecDWWSLGVCMYEMLYGETPFYAESLVETYGKIMNHKERF 298

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|..
gi 1207186029 1876 E-ESMFTDLCHEAKGFVIKLLVADRLRPDAN---ECLRHPWF 1913
Cdd:cd05623    299 QfPTQVTDVSENAKDLIRRLICSREHRLGQNgieDFKNHPFF 340

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Neks are involved in the regulation of downstream processes following the activation of Cdc2, and many of their functions are cell cycle-related. They play critical roles in microtubule dynamics during ciliogenesis and mitosis. The specific function of Nek5 is unknown. Nek5 is one in a family of 11 different Neks (Nek1-11). The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173765 [Multi-domain] Cd Length: 257 Bit Score: 103.88 E-value: 6.19e-24

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFIS---ARAKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITELC 1738
Cdd:cd08225      2 YEIIKKIGEGSFGKIYLAKAKSDSEHCVIKEIDltkMPVKEKEASKKEVILLAKMKHPNIVTFFASFQENGRLFIVMEYC 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1739 HE-ELLDRLTKKSTIL--ESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSdQIRICDFGNAvKFMPDE---A 1812
Cdd:cd08225     82 DGgDLMKRINRQRGVLfsEDQILSWFVQISLGLKHIHDRKILHRDIKSQNIFLSKNGM-VAKLGDFGIA-RQLNDSmelA 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1813 QYCkYGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTdlcHEAKGFVI 1892
Cdd:cd08225    160 YTC-VGTPYYLSPEICQNRPYNNKTDIWSLGCVLYELCTLKHPFEGNNLHQLVLKICQGYFAPISPNFS---RDLRSLIS 235

                          250       260
                   ....*....|....*....|..
gi 1207186029 1893 KLL-VADRLRPDANECLRHPWF 1913
Cdd:cd08225    236 QLFkVSPRDRPSITSILKRPFL 257

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ULK4 is a functionally uncharacterized kinase that shows similarity to ATG1/ULKs. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. The ULK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270912 [Multi-domain] Cd Length: 269 Bit Score: 104.30 E-value: 6.35e-24

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNlYMAkIVPYEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGK 3379
Cdd:cd14010      2 YVLYDEIGRGKHSVVYKGRRKGTIE-FVA-IKCVDKSKRPEVLNEVRLTHELKHPNVLKFYEWYETSNHLWLVVEYCTGG 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3380 ELLhSLI--DRfRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTF---NPLFLKQFS- 3453
Cdd:cd14010     80 DLE-TLLrqDG-NLPESSVRKFGRDLVRGLHYIHSKGIIYCDLKPSNILLDGNGTLKLSDFGLARREgeiLKELFGQFSd 157

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3454 -----------PPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAE 3502
Cdd:cd14010    158 egnvnkvskkqAKRGTPYYMAPELFQGGVHSFASDLWALGCVLYEMFTGKPPFVAESFTE 217

Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein kinase subfamily 2, group 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The SnRKs form three different subfamilies designated SnRK1-3. SnRK2 is represented in this cd. SnRK2s are involved in plant response to abiotic stresses and abscisic acid (ABA)-dependent plant development. The SnRK2s subfamily is in turn classed into three subgroups, all 3 of which are represented in this CD. Group 1 comprises kinases not activated by ABA, group 2 - kinases not activated or activated very weakly by ABA (depending on plant species), and group 3 - kinases strongly activated by ABA. The SnRKs belong to a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271135 [Multi-domain] Cd Length: 257 Bit Score: 103.91 E-value: 7.00e-24

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASALRElnILSH--LDHERILYFHDAFEKKNAVIIITELCH 1739
Cdd:cd14665      2 YELVKDIGSGNFGVARLMRDKQTKELVAVKYIERGEKIDENVQRE--IINHrsLRHPNIVRFKEVILTPTHLAIVMEYAA 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1740 E-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSDQIRICDFGNAVKFMPDEAQYCKYG 1818
Cdd:cd14665     80 GgELFERICNAGRFSEDEARFFFQQLISGVSYCHSMQICHRDLKLENTLLDGSPAPRLKICDFGYSKSSVLHSQPKSTVG 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1819 TPEFVAPEIVNQTPVS-KATDIWPIGVLTYLCLTGVSPFAGEND----RSSVLNIRNYNVAFEEsmFTDLCHEAKGFVIK 1893
Cdd:cd14665    160 TPAYIAPEVLLKKEYDgKIADVWSCGVTLYVMLVGAYPFEDPEEprnfRKTIQRILSVQYSIPD--YVHISPECRHLISR 237

                          250       260
                   ....*....|....*....|
gi 1207186029 1894 LLVAD-RLRPDANECLRHPW 1912
Cdd:cd14665    238 IFVADpATRITIPEIRNHEW 257

Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein kinase subfamily 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The SnRKs form three different subfamilies designated SnRK1-3. SnRK2 is represented in this cd. SnRK2s are involved in plant response to abiotic stresses and abscisic acid (ABA)-dependent plant development. The SnRK2s subfamily is in turn classed into three subgroups, all 3 of which are represented in this CD. Group 1 comprises kinases not activated by ABA, group 2 - kinases not activated or activated very weakly by ABA (depending on plant species), and group 3 - kinases strongly activated by ABA. The SnRKs belong to a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271132 [Multi-domain] Cd Length: 257 Bit Score: 103.70 E-value: 7.32e-24

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASALRElnILSH--LDHERILYFHDAFEKKNAVIIITELCH 1739
Cdd:cd14662      2 YELVKDIGSGNFGVARLMRNKETKELVAVKYIERGLKIDENVQRE--IINHrsLRHPNIIRFKEVVLTPTHLAIVMEYAA 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1740 E-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSDQIRICDFGNAVKFMPDEAQYCKYG 1818
Cdd:cd14662     80 GgELFERICNAGRFSEDEARYFFQQLISGVSYCHSMQICHRDLKLENTLLDGSPAPRLKICDFGYSKSSVLHSQPKSTVG 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1819 TPEFVAPEIVNQTPVS-KATDIWPIGVLTYLCLTGVSPFAGEND----RSSVLNIRNYNVAFEEsmFTDLCHEAKGFVIK 1893
Cdd:cd14662    160 TPAYIAPEVLSRKEYDgKVADVWSCGVTLYVMLVGAYPFEDPDDpknfRKTIQRIMSVQYKIPD--YVRVSQDCRHLLSR 237

                          250       260
                   ....*....|....*....|
gi 1207186029 1894 LLVADRL-RPDANECLRHPW 1912
Cdd:cd14662    238 IFVANPAkRITIPEIKNHPW 257

N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK1 plays a role in the regulation of translational control and transcriptional activation. It phosphorylates the transcription factors, CREB and NFkB. It also phosphorylates the nucleosomal proteins H3 and HMG-14. Increased phosphorylation of MSK1 is associated with the development of cerebral ischemic/hypoxic preconditioning. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. The MSK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270764 [Multi-domain] Cd Length: 290 Bit Score: 104.31 E-value: 1.16e-23

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3307 ARGRFGVIRECRENATGNLYMAKIVpyepeSKQTVLQ----------EYDILKSLHHEK-IMALHEAYVTPRYLVLISEC 3375
Cdd:cd05613     12 AYGKVFLVRKVSGHDAGKLYAMKVL-----KKATIVQkaktaehtrtERQVLEHIRQSPfLVTLHYAFQTDTKLHLILDY 86

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3376 CSGKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLKQFSPP 3455
Cdd:cd05613     87 INGGELFTHLSQRERFTENEVQIYIGEIVLALEHLHKLGIIYRDIKLENILLDSSGHVVLTDFGLSKEFLLDENERAYSF 166

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3456 IGTLDYMSPEMLKGDVVG--PPADIWSIGILTYIMLSGRLPFT----ENDPAETEARIQAAKfdlSKLYQNVSQSASLFI 3529
Cdd:cd05613    167 CGTIEYMAPEIVRGGDSGhdKAVDWWSLGVLMYELLTGASPFTvdgeKNSQAEISRRILKSE---PPYPQEMSALAKDII 243

                          250
                   ....*....|.
gi 1207186029 3530 KKILCSYPWAR 3540
Cdd:cd05613    244 QRLLMKDPKKR 254

Catalytic domain of the Serine/Threonine Kinases, fungal Byr2-like Mitogen-Activated Protein Kinase Kinase Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include the MAPKKKs Schizosaccharomyces pombe Byr2, Saccharomyces cerevisiae and Cryptococcus neoformans Ste11, and related proteins. They contain an N-terminal SAM (sterile alpha-motif) domain, which mediates protein-protein interaction, and a C-terminal catalytic domain. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Fission yeast Byr2 is regulated by Ras1. It responds to pheromone signaling and controls mating through the MAPK pathway. Budding yeast Ste11 functions in MAPK cascades that regulate mating, high osmolarity glycerol, and filamentous growth responses. The Byr2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270798 [Multi-domain] Cd Length: 267 Bit Score: 103.38 E-value: 1.16e-23

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1676 VKRVIQKAGKLEYAAkfisaRAKRKASAL-RELNILSHLDHERILYFHDAFEKKNAVIIITELC-HEELLDRLTKKSTIL 1753
Cdd:cd06628     30 VKQVELPSVSAENKD-----RKKSMLDALqREIALLRELQHENIVQYLGSSSDANHLNIFLEYVpGGSVATLLNNYGAFE 104

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1754 ESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSdqIRICDFG-------NAVKFMPDEAQYCKYGTPEFVAPE 1826
Cdd:cd06628    105 ESLVRNFVRQILKGLNYLHNRGIIHRDIKGANILVDNKGG--IKISDFGiskkleaNSLSTKNNGARPSLQGSVFWMAPE 182

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1827 IVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAfeeSMFTDLCHEAKGFVIKLLVAD-RLRPDAN 1905
Cdd:cd06628    183 VVKQTSYTRKADIWSLGCLVVEMLTGTHPFPDCTQMQAIFKIGENASP---TIPSNISSEARDFLEKTFEIDhNKRPTAD 259


                   ....*..
gi 1207186029 1906 ECLRHPW 1912
Cdd:cd06628    260 ELLKHPF 266

Catalytic domain of the Serine/Threonine Kinases, Never In Mitosis gene A (NIMA)-related kinase 6 and 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek6 and Nek7 are the shortest Neks, consisting only of the catalytic domain and a very short N-terminal extension. They show distinct expression patterns and both appear to be downstream substrates of Nek9. They are required for mitotic spindle formation and cytokinesis. They may also be regulators of the p70 ribosomal S6 kinase. Nek6/7 is part of a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270863 [Multi-domain] Cd Length: 262 Bit Score: 103.12 E-value: 1.31e-23

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAK----FISARAKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITEL 1737
Cdd:cd08224      2 YEIEKKIGKGQFSVVYRARCLLDGRLVALKkvqiFEMMDAKARQDCLKEIDLLQQLNHPNIIKYLASFIENNELNIVLEL 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1738 CHEELLDRLTK-----KSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMAdhSSDQIRICDFGNAvKFMPDE- 1811
Cdd:cd08224     82 ADAGDLSRLIKhfkkqKRLIPERTIWKYFVQLCSALEHMHSKRIMHRDIKPANVFIT--ANGVVKLGDLGLG-RFFSSKt 158

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1812 -AQYCKYGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGEN 1860
Cdd:cd08224    159 tAAHSLVGTPYYMSPERIREQGYDFKSDIWSLGCLLYEMAALQSPFYGEK 208

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase signal-integrating kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK signal-integrating kinases (Mnks) are MAPK-activated protein kinases and is comprised by a group of four proteins, produced by alternative splicing from two genes (Mnk1 and Mnk2). The isoforms of Mnk1 (1a/1b) and Mnk2 (2a/2b) differ at their C-termini, with the a-form having a longer C-terminus containing a MAPK-binding region. All Mnks contain a catalytic kinase domain and a polybasic region at the N-terminus which binds importin and the eukaryotic initiation factor eIF4G. The best characterized Mnk substrate is eIF4G, whose phosphorylation may promote the export of certain mRNAs from the nucleus. Mnk also phosphorylate substrates that bind to AU-rich elements that regulate mRNA stability and translation. Mnks have also been implicated in tyrosine kinase receptor signaling, inflammation, and cell prolieration or survival. The Mnk subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271076 [Multi-domain] Cd Length: 289 Bit Score: 103.96 E-value: 1.37e-23

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEK-ARGRFGVIRECRENATGNLYMAKIVPYEP-ESKQTVLQEYDILKSLHHEK-IMALHEAYVTPRYLVLISECC 3376
Cdd:cd14174      3 YRLTDELlGEGAYAKVQGCVSLQNGKEYAVKIIEKNAgHSRSRVFREVETLYQCQGNKnILELIEFFEDDTRFYLVFEKL 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3377 SGKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTY---MNVVKIIDF--GSAQTFN----PL 3447
Cdd:cd14174     83 RGGSILAHIQKRKHFNEREASRVVRDIASALDFLHTKGIAHRDLKPENILCESpdkVSPVKICDFdlGSGVKLNsactPI 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3448 FLKQFSPPIGTLDYMSPEML-----KGDVVGPPADIWSIGILTYIMLSGRLPFTEN-------DPAET--------EARI 3507
Cdd:cd14174    163 TTPELTTPCGSAEYMAPEVVevftdEATFYDKRCDLWSLGVILYIMLSGYPPFVGHcgtdcgwDRGEVcrvcqnklFESI 242

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*..
gi 1207186029 3508 QAAKFDLS-KLYQNVSQSASLFIKKILCSYPWARPTIKDCFTNSWLQ 3553
Cdd:cd14174    243 QEGKYEFPdKDWSHISSEAKDLISKLLVRDAKERLSAAQVLQHPWVQ 289

Catalytic domain of the Serine/Threonine Kinase, Citron Rho-interacting kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CRIK (also called citron kinase) is an effector of the small GTPase Rho. It plays an important function during cytokinesis and affects its contractile process. CRIK-deficient mice show severe ataxia and epilepsy as a result of abnormal cytokinesis and massive apoptosis in neuronal precursors. A Down syndrome critical region protein TTC3 interacts with CRIK and inhibits CRIK-dependent neuronal differentiation and neurite extension. CRIK contains a catalytic domain, a central coiled-coil domain, and a C-terminal region containing a Rho-binding domain (RBD), a zinc finger, and a pleckstrin homology (PH) domain, in addition to other motifs. The CRIK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270752 [Multi-domain] Cd Length: 328 Bit Score: 104.70 E-value: 1.48e-23

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFIsarakRKASAL---------RELNILSHLDHERILYFHDAFEKKNAVI 1732
Cdd:cd05601      3 FEVKNVIGRGHFGEVQVVKEKATGDIYAMKVL-----KKSETLaqeevsffeEERDIMAKANSPWITKLQYAFQDSENLY 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1733 IITELcHE--ELLDRLTKKSTIL-ESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDFGNAVKFMP 1809
Cdd:cd05601     78 LVMEY-HPggDLLSLLSRYDDIFeESMARFYLAELVLAIHSLHSMGYVHRDIKPENILI--DRTGHIKLADFGSAAKLSS 154

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1810 DEAQYCKY--GTPEFVAPEI---VNQTPVSK---ATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNY--NVAFEESM 1879
Cdd:cd05601    155 DKTVTSKMpvGTPDYIAPEVltsMNGGSKGTygvECDWWSLGIVAYEMLYGKTPFTEDTVIKTYSNIMNFkkFLKFPEDP 234

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|
gi 1207186029 1880 ftDLCHEAKGFVIKLLV--ADRLRPDANEClrHPWFKTLN 1917
Cdd:cd05601    235 --KVSESAVDLIKGLLTdaKERLGYEGLCC--HPFFSGID 270

Catalytic domain of the Serine/Threonine kinases, Unc-51-like kinases 1 and 2, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK1 is required for efficient amino acid starvation-induced autophagy and mitochondrial clearance. ULK2 is ubiquitously expressed and is essential in autophagy induction. ULK1 and ULK2 have unique and cell-type specific roles, but also display partially redundant roles in starvation-induced autophagy. They both display neuron-specific functions: ULK1 is involved in non-clathrin-coated endocytosis in growth cones, filopodia extension, and axon branching; ULK2 plays a role in axon development. The ULK1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271022 [Multi-domain] Cd Length: 256 Bit Score: 102.83 E-value: 1.49e-23

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3309 GRFGVIRECRENATGNLYMA-KIVPYEPESK-QTVL-QEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLHSL 3385
Cdd:cd14120      4 GAFAVVFKGRHRKKPDLPVAiKCITKKNLSKsQNLLgKEIKILKELSHENVVALLDCQETSSSVYLVMEYCNGGDLADYL 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3386 IDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMN---------VVKIIDFGSAQtfnplFLkQFSPPI 3456
Cdd:cd14120     84 QAKGTLSEDTIRVFLQQIAAAMKALHSKGIVHRDLKPQNILLSHNSgrkpspndiRLKIADFGFAR-----FL-QDGMMA 157

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3457 GTL----DYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAE 3502
Cdd:cd14120    158 ATLcgspMYMAPEVIMSLQYDAKADLWSIGTIVYQCLTGKAPFQAQTPQE 207

Catalytic domain of testis-specific serine/threonine kinase 3 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK3 has been reported to be expressed in the interstitial Leydig cells of adult testis. Its mRNA levels is low at birth, increases at puberty, and remains high throughout adulthood. The TSSK3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271065 [Multi-domain] Cd Length: 257 Bit Score: 102.76 E-value: 1.60e-23

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASAL----RELNILSHLDHERILYFHDAFEKKNAVI-IITE 1736
Cdd:cd14163      2 YQLGKTIGEGTYSKVKEAFSKKHQRKVAIKIIDKSGGPEEFIQrflpRELQIVERLDHKNIIHVYEMLESADGKIyLVME 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1737 LCHE-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSsdqIRICDFGNAvKFMPDEAQ-- 1813
Cdd:cd14163     82 LAEDgDVFDCVLHGGPLPEHRAKALFRQLVEAIRYCHGCGVAHRDLKCENALLQGFT---LKLTDFGFA-KQLPKGGRel 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1814 ---YCkyGTPEFVAPEIVNQTPV-SKATDIWPIGVLTYLCLTGVSPFaGENDRSSVLNIRNYNVAFEESMftDLCHEAKG 1889
Cdd:cd14163    158 sqtFC--GSTAYAAPEVLQGVPHdSRKGDIWSMGVVLYVMLCAQLPF-DDTDIPKMLCQQQKGVSLPGHL--GVSRTCQD 232

                          250       260
                   ....*....|....*....|....*
gi 1207186029 1890 FVIKLLVADR-LRPDANECLRHPWF 1913
Cdd:cd14163    233 LLKRLLEPDMvLRPSIEEVSWHPWL 257

Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TLKs play important functions during the cell cycle and are implicated in chromatin remodeling, DNA replication and repair, and mitosis. They phosphorylate and regulate Anti-silencing function 1 protein (Asf1), a histone H3/H4 chaperone that helps facilitate the assembly of chromatin following DNA replication during S phase. TLKs also phosphorylate the H3 histone tail and are essential in transcription. Vertebrates contain two subfamily members, TLK1 and TLK2. The TLK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270892 [Multi-domain] Cd Length: 279 Bit Score: 103.55 E-value: 1.64e-23

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYVKRVIQKAGKLEYAAKF----ISARAKRKAS----ALRELNILSHLDHERILYFHDAFE-KKNAVIIITELC 1738
Cdd:cd13990      8 LGKGGFSEVYKAFDLVEQRYVACKIhqlnKDWSEEKKQNyikhALREYEIHKSLDHPRIVKLYDVFEiDTDSFCTVLEYC 87

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1739 HEELLD-RLTKKSTILESEIRSSVRQLLEGINYLHQLD--ILHLDIKPDNILMAD-HSSDQIRICDFGNAvKFMPDEAQY 1814
Cdd:cd13990     88 DGNDLDfYLKQHKSIPEREARSIIMQVVSALKYLNEIKppIIHYDLKPGNILLHSgNVSGEIKITDFGLS-KIMDDESYN 166

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1815 CK--------YGTPEFVAPEI--VNQTP--VSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLN----IRNYNVAFEES 1878
Cdd:cd13990    167 SDgmeltsqgAGTYWYLPPECfvVGKTPpkISSKVDVWSVGVIFYQMLYGRKPFGHNQSQEAILEentiLKATEVEFPSK 246

                          250       260       270
                   ....*....|....*....|....*....|....*
gi 1207186029 1879 mfTDLCHEAKGFVIKLLVAD-RLRPDANECLRHPW 1912
Cdd:cd13990    247 --PVVSSEAKDFIRRCLTYRkEDRPDVLQLANDPY 279

Catalytic domain of the Wee1-like Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. This subfamily is composed of the dual-specificity kinase Myt1, the protein tyrosine kinase Wee1, and similar proteins. These proteins are cell cycle checkpoint kinases that are involved in the regulation of cyclin-dependent kinase CDK1, the master engine for mitosis. CDK1 is kept inactivated through phosphorylation of N-terminal thr (T14 by Myt1) and tyr (Y15 by Myt1 and Wee1) residues. Mitosis progression is ensured through activation of CDK1 by dephoshorylation and inactivation of Myt1/Wee1. The Wee1-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270899 [Multi-domain] Cd Length: 252 Bit Score: 102.46 E-value: 1.79e-23

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3309 GRFGVIRECRENATGNLYMAK--IVP-YEPESKQTVLQEYDILKSL-HHEKIMALHEAYVTPRYLVLISECCSG---KEL 3381
Cdd:cd13997     11 GSFSEVFKVRSKVDGCLYAVKksKKPfRGPKERARALREVEAHAALgQHPNIVRYYSSWEEGGHLYIQMELCENgslQDA 90

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3382 LHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPlflkqfSPPI--GTL 3459
Cdd:cd13997     91 LEELSPISKLSEAEVWDLLLQVALGLAFIHSKGIVHLDIKPDNIFISNKGTCKIGDFGLATRLET------SGDVeeGDS 164

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3460 DYMSPEMLKGDVV-GPPADIWSIGILTYIMLSGrLPFTENDPAETEARIQAAKFDLSKLYqnvSQSASLFIKKILCSYPW 3538
Cdd:cd13997    165 RYLAPELLNENYThLPKADIFSLGVTVYEAATG-EPLPRNGQQWQQLRQGKLPLPPGLVL---SQELTRLLKVMLDPDPT 240


                   ....*
gi 1207186029 3539 ARPTI 3543
Cdd:cd13997    241 RRPTA 245

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors, which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. GRKs play important roles in the cardiovascular, immune, respiratory, skeletal, and nervous systems. They contain a central catalytic domain, flanked by N- and C-terminal extensions. The N-terminus contains an RGS (regulator of G protein signaling) homology (RH) domain and several motifs. The C-terminus diverges among different groups of GRKs. There are seven types of GRKs, named GRK1 to GRK7, which are subdivided into three main groups: visual (GRK1/7); beta-adrenergic receptor kinases (GRK2/3); and GRK4-like (GRK4/5/6). Expression of GRK2/3/5/6 is widespread while GRK1/4/7 show a limited tissue distribution. The substrate spectrum of the widely expressed GRKs partially overlaps. The GRK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270729 [Multi-domain] Cd Length: 278 Bit Score: 103.38 E-value: 1.82e-23

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKIVPYEPESK----QTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLH 3383
Cdd:cd05577      3 RGGFGEVCACQVKATGKMYACKKLDKKRIKKkkgeTMALNEKIILEKVSSPFIVSLAYAFETKDKLCLVLTLMNGGDLKY 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3384 SL--IDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPlfLKQFSPPIGTLDY 3461
Cdd:cd05577     83 HIynVGTRGFSEARAIFYAAEIICGLEHLHNRFIVYRDLKPENILLDDHGHVRISDLGLAVEFKG--GKKIKGRVGTHGY 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3462 MSPEMLKGDVV-GPPADIWSIGILTYIMLSGRLPFTE-NDPAETEARIQAAKFDLSKLYQNVSQSASLFIKKILCSYPWA 3539
Cdd:cd05577    161 MAPEVLQKEVAyDFSVDWFALGCMLYEMIAGRSPFRQrKEKVDKEELKRRTLEMAVEYPDSFSPEARSLCEGLLQKDPER 240


                   .
gi 1207186029 3540 R 3540
Cdd:cd05577    241 R 241

Catalytic domain of the Serine/Threonine kinase, Oocyte maturation factor Mos; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mos (or c-Mos) is a germ-cell specific kinase that plays roles in both the release of primary arrest and the induction of secondary arrest in oocytes. It is expressed towards the end of meiosis I and is quickly degraded upon fertilization. It is a component of the cytostatic factor (CSF), which is responsible for metaphase II arrest. In addition, Mos activates a phoshorylation cascade that leads to the activation of the p34 subunit of MPF (mitosis-promoting factor or maturation promoting factor), a cyclin-dependent kinase that is responsible for the release of primary arrest in meiosis I. The Mos subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270881 [Multi-domain] Cd Length: 265 Bit Score: 102.85 E-value: 1.93e-23

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1667 EIGRGAFSYVKRVIQKAGKLeyAAKFISARAKRKAS--ALR-ELNILsHLDHE---RILYFHDAFEKKNAVIIITELCH- 1739
Cdd:cd13979     10 PLGSGGFGSVYKATYKGETV--AVKIVRRRRKNRASrqSFWaELNAA-RLRHEnivRVLAAETGTDFASLGLIIMEYCGn 86

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1740 ---EELLDRLTKkstILESEIRssVRQLLE---GINYLHQLDILHLDIKPDNILMADHssDQIRICDFGNAVK-FMPDEA 1812
Cdd:cd13979     87 gtlQQLIYEGSE---PLPLAHR--ILISLDiarALRFCHSHGIVHLDVKPANILISEQ--GVCKLCDFGCSVKlGEGNEV 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1813 QYCK---YGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGenDRSSVL------NIRNYNVAFEESMFTDL 1883
Cdd:cd13979    160 GTPRshiGGTYTYRAPELLKGERVTPKADIYSFGITLWQMLTRELPYAG--LRQHVLyavvakDLRPDLSGLEDSEFGQR 237

                          250       260
                   ....*....|....*....|....*.
gi 1207186029 1884 CheaKGFVIKLLVAD-RLRPDANECL 1908
Cdd:cd13979    238 L---RSLISRCWSAQpAERPNADESL 260

Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ROCK1 is preferentially expressed in the liver, lung, spleen, testes, and kidney. It mediates signaling from Rho to the actin cytoskeleton. It is implicated in the development of cardiac fibrosis, cardiomyocyte apoptosis, and hyperglycemia. Mice deficient with ROCK1 display eyelids open at birth (EOB) and omphalocele phenotypes due to the disorganization of actin filaments in the eyelids and the umbilical ring. ROCK contains an N-terminal extension, a catalytic kinase domain, and a C-terminal extension, which contains a coiled-coil region encompassing a Rho-binding domain (RBD) and a pleckstrin homology (PH) domain. ROCK is auto-inhibited by the RBD and PH domain interacting with the catalytic domain, and is activated via interaction with Rho GTPases. The ROCK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270772 [Multi-domain] Cd Length: 405 Bit Score: 106.24 E-value: 2.01e-23

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1646 EDEASILRKMRRLTDYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISA--RAKRKASAL--RELNILSHLDHERILYF 1721
Cdd:cd05622     59 KDTINKIRDLRMKAEDYEVVKVIGRGAFGEVQLVRHKSTRKVYAMKLLSKfeMIKRSDSAFfwEERDIMAFANSPWVVQL 138

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1722 HDAFEKKNAVIIITELCHEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDF 1801
Cdd:cd05622    139 FYAFQDDRYLYMVMEYMPGGDLVNLMSNYDVPEKWARFYTAEVVLALDAIHSMGFIHRDVKPDNMLL--DKSGHLKLADF 216

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1802 GNAVKFMPDEAQYCK--YGTPEFVAPEIVNQTP----VSKATDIWPIGVLTYLCLTGVSPFAGEN---DRSSVLNIRNyN 1872
Cdd:cd05622    217 GTCMKMNKEGMVRCDtaVGTPDYISPEVLKSQGgdgyYGRECDWWSVGVFLYEMLVGDTPFYADSlvgTYSKIMNHKN-S 295

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*
gi 1207186029 1873 VAFEESmfTDLCHEAKGFVIKLLVADRLRPDAN---ECLRHPWFK 1914
Cdd:cd05622    296 LTFPDD--NDISKEAKNLICAFLTDREVRLGRNgveEIKRHLFFK 338

Catalytic domain of the Serine/Threonine kinase, SH3 Binding Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SBK1, also called BSK146, is predominantly expressed in the brain. Its expression is increased in the developing brain during the late embryonic stage, coinciding with dramatic neuronal proliferation, migration, and maturation. SBK1 may play an important role in regulating brain development. The SBK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270889 [Multi-domain] Cd Length: 259 Bit Score: 102.40 E-value: 2.01e-23

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASALRELNILSHL-DHERIL-YFHDAFEKKNAVIIITELC-HEELLD 1744
Cdd:cd13987      1 LGEGTYGKVLLAVHKGSGTKMALKFVPKPSTKLKDFLREYNISLELsVHPHIIkTYDVAFETEDYYVFAQEYApYGDLFS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1745 RLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSDQIRICDFG------NAVKFMPDEAQYCkyg 1818
Cdd:cd13987     81 IIPPQVGLPEERVKRCAAQLASALDFMHSKNLVHRDIKPENVLLFDKDCRRVKLCDFGltrrvgSTVKRVSGTIPYT--- 157

                          170       180       190
                   ....*....|....*....|....*....|....*...
gi 1207186029 1819 TPEfVAPEIVNQT-PVSKATDIWPIGVLTYLCLTGVSP 1855
Cdd:cd13987    158 APE-VCEAKKNEGfVVDPSIDVWAFGVLLFCCLTGNFP 194

Catalytic domain of Mammalian Ste20-like protein kinase 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of MST3, MST4, STK25, Schizosaccharomyces pombe Nak1 and Sid1, Saccharomyces cerevisiae sporulation-specific protein 1 (SPS1), and related proteins. Nak1 is required by fission yeast for polarizing the tips of actin cytoskeleton and is involved in cell growth, cell separation, cell morphology and cell-cycle progression. Sid1 is a component in the septation initiation network (SIN) signaling pathway, and plays a role in cytokinesis. SPS1 plays a role in regulating proteins required for spore wall formation. MST4 plays a role in mitogen-activated protein kinase (MAPK) signaling during cytoskeletal rearrangement, morphogenesis, and apoptosis. MST3 phosphorylates the STK NDR and may play a role in cell cycle progression and cell morphology. STK25 may play a role in the regulation of cell migration and polarization. The MST3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270786 [Multi-domain] Cd Length: 274 Bit Score: 103.09 E-value: 2.14e-23

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRK--ASALRELNILSHLDHERILYFHDAFEKKNAVIIITELCH 1739
Cdd:cd06609      3 FTLLERIGKGSFGEVYKGIDKRTNQVVAIKVIDLEEAEDeiEDIQQEIQFLSQCDSPYITKYYGSFLKGSKLWIIMEYCG 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1740 E-ELLDrLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSsdQIRICDFGNAVKFmpdEAQYCK-- 1816
Cdd:cd06609     83 GgSVLD-LLKPGPLDETYIAFILREVLLGLEYLHSEGKIHRDIKAANILLSEEG--DVKLADFGVSGQL---TSTMSKrn 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1817 --YGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNI-RNYNVAFEESMFTDlchEAKGFVIK 1893
Cdd:cd06609    157 tfVGTPFWMAPEVIKQSGYDEKADIWSLGITAIELAKGEPPLSDLHPMRVLFLIpKNNPPSLEGNKFSK---PFKDFVEL 233

                          250       260       270
                   ....*....|....*....|....*....|...
gi 1207186029 1894 LLVAD-RLRPDANECLRHPWFKTlNKGKSISTE 1925
Cdd:cd06609    234 CLNKDpKERPSAKELLKHKFIKK-AKKTSYLTL 265

Catalytic domain of the Serine/Threonine Kinase, Ste20-Like Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SLK promotes apoptosis through apoptosis signal-regulating kinase 1 (ASK1) and the mitogen-activated protein kinase (MAPK) p38. It acts as a MAPK kinase kinase by phosphorylating ASK1, resulting in the phosphorylation of p38. SLK also plays a role in mediating actin reorganization. It is part of a microtubule-associated complex that is targeted at adhesion sites, and is required in focal adhesion turnover and in regulating cell migration. The SLK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270811 [Multi-domain] Cd Length: 283 Bit Score: 103.18 E-value: 2.40e-23

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1660 DYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRK-ASALRELNILSHLDHERILYFHDAFEKKNAVIIITELC 1738
Cdd:cd06643      5 DFWEIVGELGDGAFGKVYKAQNKETGILAAAKVIDTKSEEElEDYMVEIDILASCDHPNIVKLLDAFYYENNLWILIEFC 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1739 HEELLD--RLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMAdhSSDQIRICDFGNAVKFMPDEAQYCK 1816
Cdd:cd06643     85 AGGAVDavMLELERPLTEPQIRVVCKQTLEALVYLHENKIIHRDLKAGNILFT--LDGDIKLADFGVSAKNTRTLQRRDS 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1817 Y-GTPEFVAPEIV-----NQTPVSKATDIWPIGVlTYLCLTGVSPFAGENDRSSVLnirnYNVAFEE----SMFTDLCHE 1886
Cdd:cd06643    163 FiGTPYWMAPEVVmcetsKDRPYDYKADVWSLGV-TLIEMAQIEPPHHELNPMRVL----LKIAKSEpptlAQPSRWSPE 237

                          250       260       270
                   ....*....|....*....|....*....|....*..
gi 1207186029 1887 AKGFVIKLLVAD-RLRPDANECLRHPWFKTLNKGKSI 1922
Cdd:cd06643    238 FKDFLRKCLEKNvDARWTTSQLLQHPFVSVLVSNKPL 274

Catalytic domain of Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of MEKK3, MEKK2, and related proteins; all contain an N-terminal PB1 domain, which mediates oligomerization, and a C-terminal catalytic domain. MEKK2 and MEKK3 are MAPK kinase kinases (MAPKKKs or MKKK) that activate MEK5 (also called MKK5), which activates ERK5. The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK3 plays an essential role in embryonic angiogenesis and early heart development. MEKK2 and MEKK3 can also activate the MAPKs, c-Jun N-terminal kinase (JNK) and p38, through their respective MAPKKs. The MEKK3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270795 [Multi-domain] Cd Length: 260 Bit Score: 102.43 E-value: 2.43e-23

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1666 KEIGRGAFSYVKRVIQKAGKLEYAAKFI-----SARAKRKASAL-RELNILSHLDHERILYFHDAFEKKNAVIIITE-LC 1738
Cdd:cd06625      6 KLLGQGAFGQVYLCYDADTGRELAVKQVeidpiNTEASKEVKALeCEIQLLKNLQHERIVQYYGCLQDEKSLSIFMEyMP 85

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1739 HEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDFGNAVKFMP-DEAQYCK- 1816
Cdd:cd06625     86 GGSVKDEIKAYGALTENVTRKYTRQILEGLAYLHSNMIVHRDIKGANILR--DSNGNVKLGDFGASKRLQTiCSSTGMKs 163

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1817 -YGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEesMFTDLCHEAKGFVIKLL 1895
Cdd:cd06625    164 vTGTPYWMSPEVINGEGYGRKADIWSVGCTVVEMLTTKPPWAEFEPMAAIFKIATQPTNPQ--LPPHVSEDARDFLSLIF 241

                          250
                   ....*....|....*....
gi 1207186029 1896 VAD-RLRPDANECLRHPWF 1913
Cdd:cd06625    242 VRNkKQRPSAEELLSHSFV 260

Catalytic domain of the Serine/Threonine Kinase, NIM1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NIM1 is a widely-expressed kinase belonging to the AMP-activated protein kinase (AMPK) subfamily. Although present in most tissues, NIM1 kinase activity is only observed in the brain and testis. NIM1 is capable of autophosphorylating and activating itself, but may be present in other tissues in the inactive form. The physiological function of NIM1 has yet to be elucidated. The NIM1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270977 [Multi-domain] Cd Length: 255 Bit Score: 102.03 E-value: 2.81e-23

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1661 YYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFIS-ARAKRKASAL--RELNILSHLDHERILYFHDAFEKKNAVIIITE- 1736
Cdd:cd14075      3 FYRIRGELGSGNFSQVKLGIHQLTKEKVAIKILDkTKLDQKTQRLlsREISSMEKLHHPNIIRLYEVVETLSKLHLVMEy 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1737 LCHEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMAdhSSDQIRICDFGNAVKFMPDEA--QY 1814
Cdd:cd14075     83 ASGGELYTKISTEGKLSESEAKPLFAQIVSAVKHMHENNIIHRDLKAENVFYA--SNNCVKVGDFGFSTHAKRGETlnTF 160

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1207186029 1815 CkyGTPEFVAPEIVNQT-----PVskatDIWPIGVLTYLCLTGVSPFAGEN 1860
Cdd:cd14075    161 C--GSPPYAAPELFKDEhyigiYV----DIWALGVLLYFMVTGVMPFRAET 205

N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK2 and MSK1 play nonredundant roles in activating histone H3 kinases, which play pivotal roles in compaction of the chromatin fiber. MSK2 is the required H3 kinase in response to stress stimuli and activation of the p38 MAPK pathway. MSK2 also plays a role in the pathogenesis of psoriasis. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family, similar to 90 kDa ribosomal protein S6 kinases (RSKs). MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. The MSK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270765 [Multi-domain] Cd Length: 332 Bit Score: 103.85 E-value: 3.04e-23

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYV----KRVIQKAGKLeYAAKF-----ISARAKRKASALRELNILSHLDHERILY-FHDAFEKKNAV 1731
Cdd:cd05614      2 FELLKVLGTGAYGKVflvrKVSGHDANKL-YAMKVlrkaaLVQKAKTVEHTRTERNVLEHVRQSPFLVtLHYAFQTDAKL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1732 -IIITELCHEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDFGNAVKFMPD 1810
Cdd:cd05614     81 hLILDYVSGGELFTHLYQRDHFSEDEVRFYSGEIILALEHLHKLGIVYRDIKLENILL--DSEGHVVLTDFGLSKEFLTE 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1811 EAQ--YCKYGTPEFVAPEIV-NQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDLCHEA 1887
Cdd:cd05614    159 EKErtYSFCGTIEYMAPEIIrGKSGHGKAVDWWSLGILMFELLTGASPFTLEGEKNTQSEVSRRILKCDPPFPSFIGPVA 238

                          250       260       270
                   ....*....|....*....|....*....|....*.
gi 1207186029 1888 KGFVIKLLVAD---RL---RPDANECLRHPWFKTLN 1917
Cdd:cd05614    239 RDLLQKLLCKDpkkRLgagPQGAQEIKEHPFFKGLD 274

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B gamma (also called Akt3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKB-gamma is predominantly expressed in neuronal tissues. Mice deficient in PKB-gamma show a reduction in brain weight due to the decreases in cell size and cell number. PKB-gamma has also been shown to be upregulated in estrogen-deficient breast cancer cells, androgen-independent prostate cancer cells, and primary ovarian tumors. It acts as a key mediator in the genesis of ovarian cancer. PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. The PKB-gamma subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270745 [Multi-domain] Cd Length: 348 Bit Score: 104.39 E-value: 3.15e-23

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVPYE----PESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISEC 3375
Cdd:cd05593     17 FDYLKLLGKGTFGKVILVREKASGKYYAMKILKKEviiaKDEVAHTLTESRVLKNTRHPFLTSLKYSFQTKDRLCFVMEY 96

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3376 CSGKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQ--TFNPLFLKQFS 3453
Cdd:cd05593     97 VNGGELFFHLSRERVFSEDRTRFYGAEIVSALDYLHSGKIVYRDLKLENLMLDKDGHIKITDFGLCKegITDAATMKTFC 176

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*.
gi 1207186029 3454 ppiGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTEND 3499
Cdd:cd05593    177 ---GTPEYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNQD 219

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK4, also called SAK or STK18, is structurally different from other PLKs in that it contains only one polo box that can form two adjacent polo boxes and a functional PDB by homodimerization. It is required for late mitotic progression, cell survival, and embryonic development. It localizes to centrosomes and is required for centriole duplication and chromosomal stability. Overexpression of PLK4 may be associated with colon tumors. The PLK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271088 [Multi-domain] Cd Length: 256 Bit Score: 101.86 E-value: 3.39e-23

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3339 QTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLHSLIDRFR-YSEDDVVAYIVQILQGLDYLHSRRILH 3417
Cdd:cd14186     46 QRVRNEVEIHCQLKHPSILELYNYFEDSNYVYLVLEMCHNGEMSRYLKNRKKpFTEDEARHFMHQIVTGMLYLHSHGILH 125

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3418 LDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLKQFSpPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTE 3497
Cdd:cd14186    126 RDLTLSNLLLTRNMNIKIADFGLATQLKMPHEKHFT-MCGTPNYISPEIATRSAHGLESDVWSLGCMFYTLLVGRPPFDT 204

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*.
gi 1207186029 3498 NDPAETEARIQAAKFDLSklyQNVSQSASLFIKKILCSYPWARPTI 3543
Cdd:cd14186    205 DTVKNTLNKVVLADYEMP---AFLSREAQDLIHQLLRKNPADRLSL 247

Catalytic domain of the Serine/Threonine kinases, Mitogen-activated protein kinase-activated protein kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the MAPK-activated protein kinases MK2, MK3, MK5 (also called PRAK for p38-regulated/activated protein kinase), and related proteins. These proteins contain a catalytic kinase domain followed by a C-terminal autoinhibitory region that contains nuclear localization (NLS) and nuclear export (NES) signals with a p38 MAPK docking motif that overlaps the NLS. In addition, MK2 and MK3 contain an N-terminal proline-rich region that can bind to SH3 domains. MK2 and MK3 are bonafide substrates for the MAPK p38, while MK5 plays a functional role in the p38 MAPK pathway although their direct interaction has been difficult to detect. MK2 and MK3 are closely related and show, thus far, indistinguishable substrate specificity, while MK5 shows a distinct spectrum of substrates. MK2 and MK3 are mainly involved in the regulation of gene expression and they participate in diverse cellular processes such as endocytosis, cytokine production, cytoskeletal reorganization, cell migration, cell cycle control and chromatin remodeling. They are implicated in inflammation and cance and their substrates include mRNA-AU-rich-element (ARE)-binding proteins (TTP and hnRNP A0), Hsp proteins (Hsp27 and Hsp25) and RSK, among others. MK2/3 are both expressed ubiquitously but MK2 is expressed at significantly higher levels. MK5 is a ubiquitous protein that is implicated in neuronal morphogenesis, cell migration, and tumor angiogenesis. It interacts with PKA, which induces cytoplasmic translocation of MK5. Its substrates includes p53, ERK3/4, Hsp27, and cytosolic phospholipase A2 (cPLA2). The MAPKAPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270991 [Multi-domain] Cd Length: 263 Bit Score: 101.98 E-value: 3.45e-23

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1660 DYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKrkasALRELNIlsHL---DHERILYFHDAFE----KKNAVI 1732
Cdd:cd14089      1 DYTISKQVLGLGINGKVLECFHKKTGEKFALKVLRDNPK----ARREVEL--HWrasGCPHIVRIIDVYEntyqGRKCLL 74

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1733 IITElCHE--ELLDRLTKK--STILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSDQI-RICDFGNAVKF 1807
Cdd:cd14089     75 VVME-CMEggELFSRIQERadSAFTEREAAEIMRQIGSAVAHLHSMNIAHRDLKPENLLYSSKGPNAIlKLTDFGFAKET 153

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1808 MPDEA----QYckygTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPF---------AGENDRssvlnIRNYNVA 1874
Cdd:cd14089    154 TTKKSlqtpCY----TPYYVAPEVLGPEKYDKSCDMWSLGVIMYILLCGYPPFysnhglaisPGMKKR-----IRNGQYE 224

                          250       260       270
                   ....*....|....*....|....*....|....*....
gi 1207186029 1875 FEESMFTDLCHEAKGFVIKLLVAD-RLRPDANECLRHPW 1912
Cdd:cd14089    225 FPNPEWSNVSEEAKDLIRGLLKTDpSERLTIEEVMNHPW 263

protein kinase A catalytic subunit; Provisional

Pssm-ID: 140289 [Multi-domain] Cd Length: 329 Bit Score: 103.74 E-value: 3.65e-23

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3309 GRFGVIRECRENATGNLYMAKIVPYEP----ESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLHS 3384
Cdd:PTZ00263    29 GSFGRVRIAKHKGTGEYYAIKCLKKREilkmKQVQHVAQEKSILMELSHPFIVNMMCSFQDENRVYFLLEFVVGGELFTH 108

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3385 LIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQ-----TFNplflkqfspPIGTL 3459
Cdd:PTZ00263   109 LRKAGRFPNDVAKFYHAELVLAFEYLHSKDIIYRDLKPENLLLDNKGHVKVTDFGFAKkvpdrTFT---------LCGTP 179

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3460 DYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLSKLyqnVSQSASLFIKKILCSYPWA 3539
Cdd:PTZ00263   180 EYLAPEVIQSKGHGKAVDWWTMGVLLYEFIAGYPPFFDDTPFRIYEKILAGRLKFPNW---FDGRARDLVKGLLQTDHTK 256


                   .
gi 1207186029 3540 R 3540
Cdd:PTZ00263   257 R 257

Catalytic domain of the Serine/Threonine kinase, With No Lysine (WNK) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNKs comprise a subfamily of STKs with an unusual placement of a catalytic lysine relative to all other protein kinases. They are critical in regulating ion balance and are thus, important components in the control of blood pressure. They are also involved in cell signaling, survival, proliferation, and organ development. WNKs are activated by hyperosmotic or low-chloride hypotonic stress and they function upstream of SPAK and OSR1 kinases, which regulate the activity of cation-chloride cotransporters through direct interaction and phosphorylation. There are four vertebrate WNKs which show varying expression patterns. WNK1 and WNK2 are widely expressed while WNK3 and WNK4 show a more restricted expression pattern. Because mutations in human WNK1 and WNK4 cause PseudoHypoAldosteronism type II (PHAII), characterized by hypertension (due to increased sodium reabsorption) and hyperkalemia (due to impaired renal potassium secretion), there are more studies conducted on these two proteins, compared to WNK2 and WNK3. The WNK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270885 [Multi-domain] Cd Length: 258 Bit Score: 101.53 E-value: 3.90e-23

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1667 EIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASALR---ELNILSHLDHERILYFHDAFE--KKNAVIIITELCHEE 1741
Cdd:cd13983      8 VLGRGSFKTVYRAFDTEEGIEVAWNEIKLRKLPKAERQRfkqEIEILKSLKHPNIIKFYDSWEskSKKEVIFITELMTSG 87

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1742 LLDRLTKKSTIL-ESEIRSSVRQLLEGINYLHQLD--ILHLDIKPDNILMaDHSSDQIRICDFGNAVKFMPDEAQYCkYG 1818
Cdd:cd13983     88 TLKQYLKRFKRLkLKVIKSWCRQILEGLNYLHTRDppIIHRDLKCDNIFI-NGNTGEVKIGDLGLATLLRQSFAKSV-IG 165

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1819 TPEFVAPEIVNQTPVSKAtDIWPIGvltyLCL----TGVSPF-----AGENDRSSVLNIRnynvafEESMFTDLCHEAKG 1889
Cdd:cd13983    166 TPEFMAPEMYEEHYDEKV-DIYAFG----MCLlemaTGEYPYsectnAAQIYKKVTSGIK------PESLSKVKDPELKD 234

                          250       260
                   ....*....|....*....|....
gi 1207186029 1890 FVIKLLVADRLRPDANECLRHPWF 1913
Cdd:cd13983    235 FIEKCLKPPDERPSARELLEHPFF 258

Catalytic domain of the Serine/Threonine kinase, SH3 Binding Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SBK1, also called BSK146, is predominantly expressed in the brain. Its expression is increased in the developing brain during the late embryonic stage, coinciding with dramatic neuronal proliferation, migration, and maturation. SBK1 may play an important role in regulating brain development. The SBK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270889 [Multi-domain] Cd Length: 259 Bit Score: 101.63 E-value: 4.17e-23

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3307 ARGRFGVIRECRENATGNLYMAKIVPYEPESKQTVLQEYDILKSL--HHEKIMALHEAYVTPRYLVLISECCSGKELLHS 3384
Cdd:cd13987      2 GEGTYGKVLLAVHKGSGTKMALKFVPKPSTKLKDFLREYNISLELsvHPHIIKTYDVAFETEDYYVFAQEYAPYGDLFSI 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3385 LIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMN--VVKIIDFGSAQTFNpLFLKQFSppiGTLDYM 3462
Cdd:cd13987     82 IPPQVGLPEERVKRCAAQLASALDFMHSKNLVHRDIKPENVLLFDKDcrRVKLCDFGLTRRVG-STVKRVS---GTIPYT 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3463 SPEML-----KGDVVGPPADIWSIGILTYIMLSGRLPFTENDP-----AETEARIQAAKFDLSKLYQNVSQSASLFIKKI 3532
Cdd:cd13987    158 APEVCeakknEGFVVDPSIDVWAFGVLLFCCLTGNFPWEKADSddqfyEEFVRWQKRKNTAVPSQWRRFTPKALRMFKKL 237

                          250
                   ....*....|....*
gi 1207186029 3533 LCSYPWARPTIKDCF 3547
Cdd:cd13987    238 LAPEPERRCSIKEVF 252

Catalytic domain of Phototropin-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phototropins are blue-light receptors that control responses such as phototropism, stromatal opening, and chloroplast movement in order to optimize the photosynthetic efficiency of plants. They are light-activated STKs that contain an N-terminal photosensory domain and a C-terminal catalytic domain. The N-terminal domain contains two LOV (Light, Oxygen or Voltage) domains that binds FMN. Photoexcitation of the LOV domains results in autophosphorylation at multiple sites and activation of the catalytic domain. In addition to plant phototropins, included in this subfamily are predominantly uncharacterized fungal STKs whose catalytic domains resemble the phototropin kinase domain. One protein from Neurospora crassa is called nrc-2, which plays a role in growth and development by controlling entry into the conidiation program. The phototropin-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270726 [Multi-domain] Cd Length: 316 Bit Score: 103.09 E-value: 4.76e-23

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKIVPYE---PESKQT-VLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELlH 3383
Cdd:cd05574     11 KGDVGRVYLVRLKGTGKLFAMKVLDKEemiKRNKVKrVLTEREILATLDHPFLPTLYASFQTSTHLCFVMDYCPGGEL-F 89

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3384 SLIDR---FRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFG---SAQTFNPLFLKQFSPP-- 3455
Cdd:cd05574     90 RLLQKqpgKRLPEEVARFYAAEVLLALEYLHLLGFVYRDLKPENILLHESGHIMLTDFDlskQSSVTPPPVRKSLRKGsr 169

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3456 -----------------------IGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKF 3512
Cdd:cd05574    170 rssvksieketfvaepsarsnsfVGTEEYIAPEVIKGDGHGSAVDWWTLGILLYEMLYGTTPFKGSNRDETFSNILKKEL 249

                          250       260
                   ....*....|....*....|.
gi 1207186029 3513 DLSKlYQNVSQSASLFIKKIL 3533
Cdd:cd05574    250 TFPE-SPPVSSEAKDLIRKLL 269

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein Kinase Kinase; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MAPKKs are dual-specificity PKs that phosphorylate their downstream targets, MAPKs, at specific threonine and tyrosine residues. The MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising the MAPK, which is phosphorylated and activated by a MAPK kinase (MAPKK or MKK or MAP2K), which itself is phosphorylated and activated by a MAPKK kinase (MAPKKK or MKKK or MAP3K). There are three MAPK subfamilies: extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38. In mammalian cells, there are seven MAPKKs (named MKK1-7) and 20 MAPKKKs. Each MAPK subfamily can be activated by at least two cognate MAPKKs and by multiple MAPKKKs. The MAPKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270782 [Multi-domain] Cd Length: 265 Bit Score: 101.27 E-value: 5.69e-23

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3302 FMDEKARGRFGVIRECRENATGNLYMAKIV---PYEPESKQtVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSG 3378
Cdd:cd06605      5 YLGELGEGNGGVVSKVRHRPSGQIMAVKVIrleIDEALQKQ-ILRELDVLHKCNSPYIVGFYGAFYSEGDISICMEYMDG 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3379 KELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRR-ILHLDIKPENIIVTYMNVVKIIDFG-SAQTFNPLfLKQFsppI 3456
Cdd:cd06605     84 GSLDKILKEVGRIPERILGKIAVAVVKGLIYLHEKHkIIHRDVKPSNILVNSRGQVKLCDFGvSGQLVDSL-AKTF---V 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3457 GTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAakfdLSKLYQ---------NVSQSASL 3527
Cdd:cd06605    160 GTRSYMAPERISGGKYTVKSDIWSLGLSLVELATGRFPYPPPNAKPSMMIFEL----LSYIVDepppllpsgKFSPDFQD 235

                          250       260
                   ....*....|....*....|....*.
gi 1207186029 3528 FIKKILCSYPWARPTIKDCFTNSWLQ 3553
Cdd:cd06605    236 FVSQCLQKDPTERPSYKELMEHPFIK 261

Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-3 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-3 shows a restricted pattern of expression and is present in brain, kidney, and intestine. It is elevated in Alzheimer's disease (AD) and has been shown to associate with paired helical filaments (PHFs) and stimulate Tau phosphorylation. As AD progresses, phosphorylated Tau aggregates and forms PHFs, which leads to the formation of neurofibrillary tangles. In human glioma cells, PCTAIRE-3 induces cell cycle arrest and cell death. PCTAIRE-3 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PCTAIRE-3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270853 [Multi-domain] Cd Length: 288 Bit Score: 102.01 E-value: 6.07e-23

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPESKQ--TVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCS 3377
Cdd:cd07871      7 YVKLDKLGEGTYATVFKGRSKLTENLVALKEIRLEHEEGApcTAIREVSLLKNLKHANIVTLHDIIHTERCLTLVFEYLD 86

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3378 GKelLHSLIDRF--RYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTfNPLFLKQFSPP 3455
Cdd:cd07871     87 SD--LKQYLDNCgnLMSMHNVKIFMFQLLRGLSYCHKRKILHRDLKPQNLLINEKGELKLADFGLARA-KSVPTKTYSNE 163

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|.
gi 1207186029 3456 IGTLDYMSPEMLKGDV-VGPPADIWSIGILTYIMLSGRLPF 3495
Cdd:cd07871    164 VVTLWYRPPDVLLGSTeYSTPIDMWGVGCILYEMATGRPMF 204

Catalytic domain of the yeast Serine/Threonine Kinase, Kin4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Kin4 is a central component of the spindle position checkpoint (SPOC), which monitors spindle position and regulates the mitotic exit network (MEN). Kin4 associates with spindle pole bodies in mother cells to inhibit MEN signaling and delay mitosis until the anaphase nucleus is properly positioned along the mother-bud axis. Kin4 activity is regulated by both the bud neck-associated kinase Elm1 and protein phosphatase 2A. The Kin4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270978 [Multi-domain] Cd Length: 270 Bit Score: 101.02 E-value: 9.09e-23

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKA-----GKLEYAAKFIS----ARAKRKASALRELNILSHLDHERILYFHDAFEKKNAVI 1732
Cdd:cd14076      3 YILGRTLGEGEFGKVKLGWPLPkanhrSGVQVAIKLIRrdtqQENCQTSKIMREINILKGLTHPNIVRLLDVLKTKKYIG 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1733 IITELCHE-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSdqIRICDFGNAVKFMPDE 1811
Cdd:cd14076     83 IVLEFVSGgELFDYILARRRLKDSVACRLFAQLISGVAYLHKKGVVHRDLKLENLLLDKNRN--LVITDFGFANTFDHFN 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1812 AQYCKY--GTPEFVAPEIVNQTPVSKAT--DIWPIGVLTYLCLTGVSPFAGENDRSSVLN-------IRNYNVAFEEsMF 1880
Cdd:cd14076    161 GDLMSTscGSPCYAAPELVVSDSMYAGRkaDIWSCGVILYAMLAGYLPFDDDPHNPNGDNvprlyryICNTPLIFPE-YV 239

                          250       260       270
                   ....*....|....*....|....*....|...
gi 1207186029 1881 TDLcheAKGFVIKLLVAD-RLRPDANECLRHPW 1912
Cdd:cd14076    240 TPK---ARDLLRRILVPNpRKRIRLSAIMRHAW 269

Catalytic subunit of the Serine/Threonine Kinase, cAMP-dependent protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The inactive PKA holoenzyme is a heterotetramer composed of two phosphorylated and active catalytic subunits with a dimer of regulatory (R) subunits. Activation is achieved through the binding of the important second messenger cAMP to the R subunits, which leads to the dissociation of PKA into the R dimer and two active subunits. PKA is present ubiquitously in cells and interacts with many different downstream targets. It plays a role in the regulation of diverse processes such as growth, development, memory, metabolism, gene expression, immunity, and lipolysis. The PKA subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271111 [Multi-domain] Cd Length: 290 Bit Score: 101.33 E-value: 1.19e-22

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3309 GRFGVIRECRENATGNLYMAKIVPYEP--ESKQT--VLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLHS 3384
Cdd:cd14209     12 GSFGRVMLVRHKETGNYYAMKILDKQKvvKLKQVehTLNEKRILQAINFPFLVKLEYSFKDNSNLYMVMEYVPGGEMFSH 91

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3385 LIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGsaqtFNPLFLKQFSPPIGTLDYMSP 3464
Cdd:cd14209     92 LRRIGRFSEPHARFYAAQIVLAFEYLHSLDLIYRDLKPENLLIDQQGYIKVTDFG----FAKRVKGRTWTLCGTPEYLAP 167

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1207186029 3465 EMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKF--------DLSKLYQNVSQ 3523
Cdd:cd14209    168 EIILSKGYNKAVDWWALGVLIYEMAAGYPPFFADQPIQIYEKIVSGKVrfpshfssDLKDLLRNLLQ 234

Catalytic domain of the Serine/Threonine Kinases, fungal Byr2-like Mitogen-Activated Protein Kinase Kinase Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include the MAPKKKs Schizosaccharomyces pombe Byr2, Saccharomyces cerevisiae and Cryptococcus neoformans Ste11, and related proteins. They contain an N-terminal SAM (sterile alpha-motif) domain, which mediates protein-protein interaction, and a C-terminal catalytic domain. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Fission yeast Byr2 is regulated by Ras1. It responds to pheromone signaling and controls mating through the MAPK pathway. Budding yeast Ste11 functions in MAPK cascades that regulate mating, high osmolarity glycerol, and filamentous growth responses. The Byr2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270798 [Multi-domain] Cd Length: 267 Bit Score: 100.30 E-value: 1.30e-22

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3309 GRFGVIRECRENATGNLYMAKIVPYEPESKQT---------VLQ-EYDILKSLHHEKIMALHEAYVTPRYLVLISECCSG 3378
Cdd:cd06628     11 GSFGSVYLGMNASSGELMAVKQVELPSVSAENkdrkksmldALQrEIALLRELQHENIVQYLGSSSDANHLNIFLEYVPG 90

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3379 KELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTF--NPLFLKQFS--P 3454
Cdd:cd06628     91 GSVATLLNNYGAFEESLVRNFVRQILKGLNYLHNRGIIHRDIKGANILVDNKGGIKISDFGISKKLeaNSLSTKNNGarP 170

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3455 PI-GTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDpaETEARIQAAKFDLSKLYQNVSQSASLFIKKIL 3533
Cdd:cd06628    171 SLqGSVFWMAPEVVKQTSYTRKADIWSLGCLVVEMLTGTHPFPDCT--QMQAIFKIGENASPTIPSNISSEARDFLEKTF 248

                          250
                   ....*....|....*....
gi 1207186029 3534 CSYPWARPTIKDCFTNSWL 3552
Cdd:cd06628    249 EIDHNKRPTADELLKHPFL 267

Catalytic domain of the Serine/Threonine Kinases, Mammalian STe20-like protein kinase 1 and 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of MST1, MST2, and related proteins including Drosophila Hippo and Dictyostelium discoideum Krs1 (kinase responsive to stress 1). MST1/2 and Hippo are involved in a conserved pathway that governs cell contact inhibition, organ size control, and tumor development. MST1 activates the mitogen-activated protein kinases (MAPKs) p38 and c-Jun N-terminal kinase (JNK) through MKK7 and MEKK1 by acting as a MAPK kinase kinase kinase. Activation of JNK by MST1 leads to caspase activation and apoptosis. MST1 has also been implicated in cell proliferation and differentiation. Krs1 may regulate cell growth arrest and apoptosis in response to cellular stress. The MST1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 132943 [Multi-domain] Cd Length: 256 Bit Score: 100.03 E-value: 1.33e-22

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKaSALRELNILSHLDHERILYFHDAFEKKNAVIIITELCHE- 1740
Cdd:cd06612      5 FDILEKLGEGSYGSVYKAIHKETGQVVAIKVVPVEEDLQ-EIIKEISILKQCDSPYIVKYYGSYFKNTDLWIVMEYCGAg 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1741 ELLD--RLTKKsTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSsdQIRICDFGNAVKFMPDEAQYCKY- 1817
Cdd:cd06612     84 SVSDimKITNK-TLTEEEIAAILYQTLKGLEYLHSNKKIHRDIKAGNILLNEEG--QAKLADFGVSGQLTDTMAKRNTVi 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1818 GTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNV-AFEESmfTDLCHEAKGFVIKLLV 1896
Cdd:cd06612    161 GTPFWMAPEVIQEIGYNNKADIWSLGITAIEMAEGKPPYSDIHPMRAIFMIPNKPPpTLSDP--EKWSPEFNDFVKKCLV 238

                          250
                   ....*....|....*...
gi 1207186029 1897 AD-RLRPDANECLRHPWF 1913
Cdd:cd06612    239 KDpEERPSAIQLLQHPFI 256

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK2 is a MAPK kinase kinase (MAPKKK or MKKK), that phosphorylates and activates the MAPK kinase MEK5 (or MKK5), which in turn phosphorylates and activates ERK5. The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK2 also activates ERK1/2, c-Jun N-terminal kinase (JNK) and p38 through their respective MAPKKs MEK1/2, JNK-activating kinase 2 (JNKK2), and MKK3/6. MEKK2 plays roles in T cell receptor signaling, immune synapse formation, cytokine gene expression, as well as in EGF and FGF receptor signaling. The MEKK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270818 [Multi-domain] Cd Length: 264 Bit Score: 100.50 E-value: 1.36e-22

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3307 ARGRFGVIRECRENATGNLYMAKIVPYEPESKQTVLQ------EYDILKSLHHEKIMALHEAYVTP--RYLVLISECCSG 3378
Cdd:cd06652     11 GQGAFGRVYLCYDADTGRELAVKQVQFDPESPETSKEvnalecEIQLLKNLLHERIVQYYGCLRDPqeRTLSIFMEYMPG 90

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3379 KELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLK--QFSPPI 3456
Cdd:cd06652     91 GSIKDQLKSYGALTENVTRKYTRQILEGVHYLHSNMIVHRDIKGANILRDSVGNVKLGDFGASKRLQTICLSgtGMKSVT 170

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3457 GTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFtendpAETEAriQAAKFDLS------KLYQNVSQSASLFIK 3530
Cdd:cd06652    171 GTPYWMSPEVISGEGYGRKADIWSVGCTVVEMLTEKPPW-----AEFEA--MAAIFKIAtqptnpQLPAHVSDHCRDFLK 243


                   ...
gi 1207186029 3531 KIL 3533
Cdd:cd06652    244 RIF 246

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase C; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. PKCs undergo three phosphorylations in order to take mature forms. In addition, classical PKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. Novel PKCs are calcium-independent, but require DAG and PS for activity, while atypical PKCs only require PS. PKCs phosphorylate and modify the activities of a wide variety of cellular proteins including receptors, enzymes, cytoskeletal proteins, transcription factors, and other kinases. They play a central role in signal transduction pathways that regulate cell migration and polarity, proliferation, differentiation, and apoptosis. Also included in this subfamily are the PKC-like proteins, called PKNs. The PKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270722 [Multi-domain] Cd Length: 318 Bit Score: 101.52 E-value: 1.46e-22

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKIVpyepeSKQTVLQEYDI----------LKSLHHEKIMALHEAYVTPRYLVLISECCS 3377
Cdd:cd05570      5 KGSFGKVMLAERKKTDELYAIKVL-----KKEVIIEDDDVectmtekrvlALANRHPFLTGLHACFQTEDRLYFVMEYVN 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3378 GKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFG----------SAQTFnpl 3447
Cdd:cd05570     80 GGDLMFHIQRARRFTEERARFYAAEICLALQFLHERGIIYRDLKLDNVLLDAEGHIKIADFGmckegiwggnTTSTF--- 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3448 flkqfsppIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFtendPAETEARI-QAAKFDLSKLYQNVSQSAS 3526
Cdd:cd05570    157 --------CGTPDYIAPEILREQDYGFSVDWWALGVLLYEMLAGQSPF----EGDDEDELfEAILNDEVLYPRWLSREAV 224

                          250
                   ....*....|....
gi 1207186029 3527 LFIKKILCSYPWAR 3540
Cdd:cd05570    225 SILKGLLTKDPARR 238

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated protein kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK-activated protein kinase 5 (MAPKAP5 or MK5) is also called PRAK (p38-regulated/activated protein kinase). It contains a catalytic kinase domain followed by a C-terminal autoinhibitory region that contains nuclear localization (NLS) and nuclear export (NES) signals with a p38 MAPK docking motif that overlaps the NLS. MK5 is a ubiquitous protein that is implicated in neuronal morphogenesis, cell migration, and tumor angiogenesis. It interacts with PKA, which induces cytoplasmic translocation of MK5. Its substrates includes p53, ERK3/4, Hsp27, and cytosolic phospholipase A2 (cPLA2). The MAPKAPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271073 [Multi-domain] Cd Length: 289 Bit Score: 101.00 E-value: 1.52e-22

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3312 GVIRECRENATGNLYMAKIVPYEPESKQTVL------------QEYDILKSlhheKIMALHEAYVTPRyLVLISECCSGK 3379
Cdd:cd14171     20 GPVRVCVKKSTGERFALKILLDRPKARTEVRlhmmcsghpnivQIYDVYAN----SVQFPGESSPRAR-LLIVMELMEGG 94

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3380 ELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIV---TYMNVVKIIDFGSAQTFN-PLFLKQFSPP 3455
Cdd:cd14171     95 ELFDRISQHRHFTEKQAAQYTKQIALAVQHCHSLNIAHRDLKPENLLLkdnSEDAPIKLCDFGFAKVDQgDLMTPQFTPY 174

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3456 igtldYMSPEML---------KGDVVGPPA--------DIWSIGILTYIMLSGRLPFTENDPAET-----EARIQAAKFD 3513
Cdd:cd14171    175 -----YVAPQVLeaqrrhrkeRSGIPTSPTpytydkscDMWSLGVIIYIMLCGYPPFYSEHPSRTitkdmKRKIMTGSYE 249

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|
gi 1207186029 3514 L-SKLYQNVSQSASLFIKKILCSYPWARPTIKDCFTNSWL 3552
Cdd:cd14171    250 FpEEEWSQISEMAKDIVRKLLCVDPEERMTIEEVLHHPWL 289

Catalytic domain of the Serine/Threonine Kinase, Cell Division Cycle 2-like 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDC2L1, also called PITSLRE, exists in different isoforms which are named using the alias CDK11(p). The CDC2L1 gene produces two protein products, CDK11(p110) and CDK11(p58). CDC2L1 is also represented by the caspase-processed CDK11(p46). CDK11(p110), the major isoform, associates with cyclin L and is expressed throughout the cell cycle. It is involved in RNA processing and the regulation of transcription. CDK11(p58) associates with cyclin D3 and is expressed during the G2/M phase of the cell cycle. It plays roles in spindle morphogenesis, centrosome maturation, sister chromatid cohesion, and the completion of mitosis. CDK11(p46) is formed from the larger isoforms by caspases during TNFalpha- and Fas-induced apoptosis. It functions as a downstream effector kinase in apoptotic signaling pathways and interacts with eukaryotic initiation factor 3f (eIF3f), p21-activated kinase (PAK1), and Ran-binding protein (RanBPM). CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDC2L1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173741 [Multi-domain] Cd Length: 293 Bit Score: 100.76 E-value: 1.60e-22

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3309 GRFGVIRECRENATGNLYMAKIVPYEPESKQ---TVLQEYDILKSLHHEKIMALHEAYVTPR----YLVLisECCSG--K 3379
Cdd:cd07843     16 GTYGVVYRARDKKTGEIVALKKLKMEKEKEGfpiTSLREINILLKLQHPNIVTVKEVVVGSNldkiYMVM--EYVEHdlK 93

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3380 ELLHSLIDRFRYSEddVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTF-NPlfLKQFSPPIGT 3458
Cdd:cd07843     94 SLMETMKQPFLQSE--VKCLMLQLLSGVAHLHDNWILHRDLKTSNLLLNNRGILKICDFGLAREYgSP--LKPYTQLVVT 169

                          170       180
                   ....*....|....*....|....*
gi 1207186029 3459 LDYMSPEMLKG-DVVGPPADIWSIG 3482
Cdd:cd07843    170 LWYRAPELLLGaKEYSTAIDMWSVG 194

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK1 is required for efficient amino acid starvation-induced autophagy and mitochondrial clearance. It associates with three autophagy-related proteins (Atg13, FIP200 amd Atg101) to form the ULK1 complex. All fours proteins are essential for autophagosome formation. ULK1 is regulated by both mammalian target-of rapamycin complex 1 (mTORC1) and AMP-activated protein kinase (AMPK). mTORC1 negatively regulates the ULK1 complex in a nutrient-dependent manner while AMPK stimulates autophagy by inhibiting mTORC1. ULK1 also plays neuron-specific roles and is involved in non-clathrin-coated endocytosis in growth cones, filopodia extension, neurite extension, and axon branching. The ULK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271104 [Multi-domain] Cd Length: 267 Bit Score: 100.09 E-value: 1.89e-22

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3309 GRFGVIRECRENATGNLYMA-KIVPYEPESK-QTVL-QEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLHSL 3385
Cdd:cd14202     13 GAFAVVFKGRHKEKHDLEVAvKCINKKNLAKsQTLLgKEIKILKELKHENIVALYDFQEIANSVYLVMEYCNGGDLADYL 92

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3386 IDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYM--------NV-VKIIDFGSAQTFNPLFLKqfSPPI 3456
Cdd:cd14202     93 HTMRTLSEDTIRLFLQQIAGAMKMLHSKGIIHRDLKPQNILLSYSggrksnpnNIrIKIADFGFARYLQNNMMA--ATLC 170

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*.
gi 1207186029 3457 GTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAE 3502
Cdd:cd14202    171 GSPMYMAPEVIMSQHYDAKADLWSIGTIIYQCLTGKAPFQASSPQD 216

Catalytic domain of the Serine/Threonine Kinase, Hormonally up-regulated Neu-associated kinase (also called MAK-V); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HUNK/MAK-V was identified from a mammary tumor in an MMTV-neu transgenic mouse. It is required for the metastasis of c-myc-induced mammary tumors, but is not necessary for c-myc-induced primary tumor formation or normal development. It is required for HER2/neu-induced tumor formation and maintenance of the cells' tumorigenic phenotype. It is over-expressed in aggressive subsets of ovary, colon, and breast carcinomas. HUNK interacts with synaptopodin, and may also play a role in synaptic plasticity. The HUNK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270972 [Multi-domain] Cd Length: 262 Bit Score: 99.89 E-value: 2.03e-22

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASAL-----RELNILSHLDHERILYFHDAFEKKNAVIIITE 1736
Cdd:cd14070      4 YLIGRKLGEGSFAKVREGLHAVTGEKVAIKVIDKKKAKKDSYVtknlrREGRIQQMIRHPNITQLLDILETENSYYLVME 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1737 LCHE-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADhsSDQIRICDFG--NAVKFMP-DEA 1812
Cdd:cd14070     84 LCPGgNLMHRIYDKKRLEEREARRYIRQLVSAVEHLHRAGVVHRDLKIENLLLDE--NDNIKLIDFGlsNCAGILGySDP 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1813 QYCKYGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENdrssvLNIRnynvAFEESMFT--------DLC 1884
Cdd:cd14070    162 FSTQCGSPAYAAPELLARKKYGPKVDVWSIGVNMYAMLTGTLPFTVEP-----FSLR----ALHQKMVDkemnplptDLS 232

                          250       260
                   ....*....|....*....|....*....
gi 1207186029 1885 HEAKGFVIKLLVADRL-RPDANECLRHPW 1912
Cdd:cd14070    233 PGAISFLRSLLEPDPLkRPNIKQALANRW 261

Catalytic domain of fungal Byr1-like dual-specificity Mitogen-activated protein Kinase Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include the MAPKKs Byr1 from Schizosaccharomyces pombe, FUZ7 from Ustilago maydis, and related proteins. Byr1 phosphorylates its downstream target, the MAPK Spk1, and is regulated by the MAPKK kinase Byr2. The Spk1 cascade is pheromone-responsive and is essential for sporulation and sexual differentiation in fission yeast. FUZ7 phosphorylates and activates its target, the MAPK Crk1, which is required in mating and virulence in U. maydis. MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The Byr-1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270792 [Multi-domain] Cd Length: 286 Bit Score: 100.21 E-value: 2.46e-22

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3324 NLYMA-KIVPYEPESK--QTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLI----SECCSgkelLHSLIDRFRYSEDDV 3396
Cdd:cd06620     30 GTIMAkKVIHIDAKSSvrKQILRELQILHECHSPYIVSFYGAFLNENNNIIIcmeyMDCGS----LDKILKKKGPFPEEV 105

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3397 VAYI-VQILQGLDYLHSR-RILHLDIKPENIIVTYMNVVKIIDFGS--------AQTFnplflkqfsppIGTLDYMSPEM 3466
Cdd:cd06620    106 LGKIaVAVLEGLTYLYNVhRIIHRDIKPSNILVNSKGQIKLCDFGVsgelinsiADTF-----------VGTSTYMSPER 174

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3467 LKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLskLYQNV-------------SQSASLFIKKIL 3533
Cdd:cd06620    175 IQGGKYSVKSDVWSLGLSIIELALGEFPFAGSNDDDDGYNGPMGILDL--LQRIVneppprlpkdrifPKDLRDFVDRCL 252

                          250       260
                   ....*....|....*....|..
gi 1207186029 3534 CSYPWARPTIKDCFTNSWLQDA 3555
Cdd:cd06620    253 LKDPRERPSPQLLLDHDPFIQA 274

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK7 plays essential roles in the cell cycle and in transcription. It associates with cyclin H and MAT1 and acts as a CDK-Activating Kinase (CAK) by phosphorylating and activating cell cycle CDKs (CDK1/2/4/6). In the brain, it activates CDK5. CDK7 is also a component of the general transcription factor TFIIH, which phosphorylates the C-terminal domain (CTD) of RNA polymerase II when it is bound with unphosphorylated DNA, as present in the pre-initiation complex. Following phosphorylation, the CTD dissociates from the DNA which allows transcription initiation. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK7 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270833 [Multi-domain] Cd Length: 298 Bit Score: 100.34 E-value: 2.51e-22

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKA------SALRELNILSHLDHERILYFHDAFEKKNAVIIIT 1735
Cdd:cd07841      2 YEKGKKLGEGTYAVVYKARDKETGRIVAIKKIKLGERKEAkdginfTALREIKLLQELKHPNIIGLLDVFGHKSNINLVF 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1736 ELCHEELLDRLTKKSTIL-ESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSsdQIRICDFGNAVKF-MPDEAQ 1813
Cdd:cd07841     82 EFMETDLEKVIKDKSIVLtPADIKSYMLMTLRGLEYLHSNWILHRDLKPNNLLIASDG--VLKLADFGLARSFgSPNRKM 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1814 YCKYGTPEFVAPEIV-NQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRN-----------------YNVAF 1875
Cdd:cd07841    160 THQVVTRWYRAPELLfGARHYGVGVDMWSVGCIFAELLLRVPFLPGDSDIDQLGKIFEalgtpteenwpgvtslpDYVEF 239

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*....
gi 1207186029 1876 EES-------MFTDLCHEAKGFVIKLLVAD-RLRPDANECLRHPWFKTL 1916
Cdd:cd07841    240 KPFpptplkqIFPAASDDALDLLQRLLTLNpNKRITARQALEHPYFSND 288

Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TLKs play important functions during the cell cycle and are implicated in chromatin remodeling, DNA replication and repair, and mitosis. They phosphorylate and regulate Anti-silencing function 1 protein (Asf1), a histone H3/H4 chaperone that helps facilitate the assembly of chromatin following DNA replication during S phase. TLKs also phosphorylate the H3 histone tail and are essential in transcription. Vertebrates contain two subfamily members, TLK1 and TLK2. The TLK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270892 [Multi-domain] Cd Length: 279 Bit Score: 99.70 E-value: 2.98e-22

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3341 VLQEYDILKSLHHEKIMALHEAY-VTPRYLVLISECCSGKELLHSLIDRFRYSEDDVVAYIVQILQGLDYL--HSRRILH 3417
Cdd:cd13990     51 ALREYEIHKSLDHPRIVKLYDVFeIDTDSFCTVLEYCDGNDLDFYLKQHKSIPEREARSIIMQVVSALKYLneIKPPIIH 130

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3418 LDIKPENIIV---TYMNVVKIIDFGSAQTF-----NPLFLKQFSPPIGTLDYMSPEMLkgdVVG--PP-----ADIWSIG 3482
Cdd:cd13990    131 YDLKPGNILLhsgNVSGEIKITDFGLSKIMddesyNSDGMELTSQGAGTYWYLPPECF---VVGktPPkisskVDVWSVG 207

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1207186029 3483 ILTYIMLSGRLPFTENDPAETEAR---IQAAKFDLSKLYQNVSQSASLFIKKILCSYPWARPtikDCFTNSwlQDAY 3556
Cdd:cd13990    208 VIFYQMLYGRKPFGHNQSQEAILEentILKATEVEFPSKPVVSSEAKDFIRRCLTYRKEDRP---DVLQLA--NDPY 279

Catalytic domain of fungal Byr1-like dual-specificity Mitogen-activated protein Kinase Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include the MAPKKs Byr1 from Schizosaccharomyces pombe, FUZ7 from Ustilago maydis, and related proteins. Byr1 phosphorylates its downstream target, the MAPK Spk1, and is regulated by the MAPKK kinase Byr2. The Spk1 cascade is pheromone-responsive and is essential for sporulation and sexual differentiation in fission yeast. FUZ7 phosphorylates and activates its target, the MAPK Crk1, which is required in mating and virulence in U. maydis. MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The Byr-1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270792 [Multi-domain] Cd Length: 286 Bit Score: 99.82 E-value: 3.17e-22

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1666 KEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASA--LRELNILSHLDHERILYFHDAF-EKKNAVIIITELCHEEL 1742
Cdd:cd06620     11 KDLGAGNGGSVSKVLHIPTGTIMAKKVIHIDAKSSVRKqiLRELQILHECHSPYIVSFYGAFlNENNNIIICMEYMDCGS 90

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1743 LDRLTKKSTILESEIRSSVR-QLLEGINYLH-QLDILHLDIKPDNILMadHSSDQIRICDFGNAVKFMPDEAQyCKYGTP 1820
Cdd:cd06620     91 LDKILKKKGPFPEEVLGKIAvAVLEGLTYLYnVHRIIHRDIKPSNILV--NSKGQIKLCDFGVSGELINSIAD-TFVGTS 167

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1821 EFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRS-------SVLNIRNYNV-----------AFEESM--F 1880
Cdd:cd06620    168 TYMSPERIQGGKYSVKSDVWSLGLSIIELALGEFPFAGSNDDDdgyngpmGILDLLQRIVneppprlpkdrIFPKDLrdF 247

                          250       260       270
                   ....*....|....*....|....*....|....
gi 1207186029 1881 TDLCheakgfvikLLVADRLRPDANECLRHPWFK 1914
Cdd:cd06620    248 VDRC---------LLKDPRERPSPQLLLDHDPFI 272

Catalytic domain of the Serine/Threonine Kinase, Cell Cycle-Related Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CCRK was previously called p42. It is a Cyclin-Dependent Kinase (CDK)-Activating Kinase (CAK) which is essential for the activation of CDK2. It is indispensable for cell growth and has been implicated in the progression of glioblastoma multiforme. In the heart, a splice variant of CCRK with a different C-terminal half is expressed; this variant promotes cardiac cell growth and survival and is significantly down-regulated during the development of heart failure. The CCRK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270826 [Multi-domain] Cd Length: 287 Bit Score: 99.71 E-value: 3.21e-22

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVP---YEPESKQTVLQEYDILKSL-HHEKIMALHEAYVTPRYLVLISEC 3375
Cdd:cd07832      2 YKILGRIGEGAHGIVFKAKDRETGETVALKKVAlrkLEGGIPNQALREIKALQACqGHPYVVKLRDVFPHGTGFVLVFEY 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3376 csgkeLLHSLIDRFRYSED-----DVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLK 3450
Cdd:cd07832     82 -----MLSSLSEVLRDEERplteaQVKRYMRMLLKGVAYMHANRIMHRDLKPANLLISSTGVLKIADFGLARLFSEEDPR 156

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1207186029 3451 QFSPPIGTLDYMSPEMLKG-DVVGPPADIWSIGILTYIMLSGRLPFT-END 3499
Cdd:cd07832    157 LYSHQVATRWYRAPELLYGsRKYDEGVDLWAVGCIFAELLNGSPLFPgEND 207

Catalytic domain, repeat 2, of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or General Control Non-derepressible-2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GCN2 (or EIF2AK4) is activated by amino acid or serum starvation and UV irradiation. It induces GCN4, a transcriptional activator of amino acid biosynthetic genes, leading to increased production of amino acids under amino acid-deficient conditions. In serum-starved cells, GCN2 activation induces translation of the stress-responsive transcription factor ATF4, while under UV stress, GCN2 triggers transcriptional rescue via NF-kB signaling. GCN2 contains an N-terminal RWD, a degenerate kinase-like (repeat 1), the catalytic kinase (repeat 2), a histidyl-tRNA synthetase (HisRS)-like, and a C-terminal ribosome-binding and dimerization (RB/DD) domains. Its kinase domain is activated via conformational changes as a result of the binding of uncharged tRNA to the HisRS-like domain. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the overall downregulation of protein synthesis. The GCN2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270948 [Multi-domain] Cd Length: 278 Bit Score: 99.75 E-value: 3.31e-22

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKIVPYEPESK--QTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSgKELLHSL 3385
Cdd:cd14046     16 KGAFGQVVKVRNKLDGRYYAIKKIKLRSESKnnSRILREVMLLSRLNHQHVVRYYQAWIERANLYIQMEYCE-KSTLRDL 94

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3386 IDRFRYSEDDVV-AYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAqTFNPLFLKQFSPPI-------- 3456
Cdd:cd14046     95 IDSGLFQDTDRLwRLFRQILEGLAYIHSQGIIHRDLKPVNIFLDSNGNVKIGDFGLA-TSNKLNVELATQDInkstsaal 173

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....
gi 1207186029 3457 ----------GTLDYMSPEMLKGD--VVGPPADIWSIGILTYIM 3488
Cdd:cd14046    174 gssgdltgnvGTALYVAPEVQSGTksTYNEKVDMYSLGIIFFEM 217

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated protein kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK-activated protein kinase 3 (MAPKAP3 or MK3) contains an N-terminal proline-rich region that can bind to SH3 domains, a catalytic kinase domain followed by a C-terminal autoinhibitory region that contains nuclear localization (NLS) and nuclear export (NES) signals with a p38 MAPK docking motif that overlaps the NLS. MK3 is a bonafide substrate for the MAPK p38. It is closely related to MK2 and thus far, MK2/3 show indistinguishable substrate specificity. They are mainly involved in the regulation of gene expression and they participate in diverse cellular processes such as endocytosis, cytokine production, cytoskeletal reorganization, cell migration, cell cycle control and chromatin remodeling. They are implicated in inflammation and cance and their substrates include mRNA-AU-rich-element (ARE)-binding proteins (TTP and hnRNP A0), Hsp proteins (Hsp27 and Hsp25) and RSK, among others. MK2/3 are both expressed ubiquitously but MK2 is expressed at significantly higher levels. MK3 activity is only significant when MK2 is absent. The MK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271074 [Multi-domain] Cd Length: 267 Bit Score: 99.29 E-value: 3.62e-22

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3312 GVIRECRENATGNLYMAKIVPYEPESKQTVLQEYDILKSLHHEKIMALHE-AYVTPRYLVLISECCSGKELLHSLIDRF- 3389
Cdd:cd14172     18 GKVLECFHRRTGQKCALKLLYDSPKARREVEHHWRASGGPHIVHILDVYEnMHHGKRCLLIIMECMEGGELFSRIQERGd 97

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3390 -RYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMN---VVKIIDFGSAQ---TFNPLflkqfSPPIGTLDYM 3462
Cdd:cd14172     98 qAFTEREASEIMRDIGTAIQYLHSMNIAHRDVKPENLLYTSKEkdaVLKLTDFGFAKettVQNAL-----QTPCYTPYYV 172

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3463 SPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTEN-----DPAeTEARIQAAKFDL-SKLYQNVSQSASLFIKKILCSY 3536
Cdd:cd14172    173 APEVLGPEKYDKSCDMWSLGVIMYILLCGFPPFYSNtgqaiSPG-MKRRIRMGQYGFpNPEWAEVSEEAKQLIRHLLKTD 251

                          250
                   ....*....|....*.
gi 1207186029 3537 PWARPTIKDCFTNSWL 3552
Cdd:cd14172    252 PTERMTITQFMNHPWI 267

Catalytic domain of Myotonic Dystrophy protein kinase (DMPK)-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The DMPK-like subfamily is composed of DMPK and DMPK-related cell division control protein 42 (Cdc42) binding kinase (MRCK). DMPK is expressed in skeletal and cardiac muscles, and in central nervous tissues. The functional role of DMPK is not fully understood. It may play a role in the signal transduction and homeostasis of calcium. The DMPK gene is implicated in myotonic dystrophy 1 (DM1), an inherited multisystemic disorder with symptoms that include muscle hyperexcitability, progressive muscle weakness and wasting, cataract development, testicular atrophy, and cardiac conduction defects. The genetic basis for DM1 is the mutational expansion of a CTG repeat in the 3'-UTR of DMPK. MRCK is activated via interaction with the small GTPase Cdc42. MRCK/Cdc42 signaling mediates myosin-dependent cell motility. Three isoforms of MRCK are known, named alpha, beta and gamma. MRCKgamma is expressed in heart and skeletal muscles, unlike MRCKalpha and MRCKbeta, which are expressed ubiquitously. The DMPK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270748 [Multi-domain] Cd Length: 331 Bit Score: 100.50 E-value: 4.04e-22

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1660 DYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISA-----RAKRkASALRELNILSHLDHERILYFHDAFEKKNAVIII 1734
Cdd:cd05597      1 DDFEILKVIGRGAFGEVAVVKLKSTEKVYAMKILNKwemlkRAET-ACFREERDVLVNGDRRWITKLHYAFQDENYLYLV 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1735 TEL-CHEELLDRLTKKSTILESEI-RSSVRQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDFGNAVKFMPDEA 1812
Cdd:cd05597     80 MDYyCGGDLLTLLSKFEDRLPEEMaRFYLAEMVLAIDSIHQLGYVHRDIKPDNVLL--DRNGHIRLADFGSCLKLREDGT 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1813 QYCK--YGTPEFVAPEIVNQTPVSKAT-----DIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFE-ESMFTDLC 1884
Cdd:cd05597    158 VQSSvaVGTPDYISPEILQAMEDGKGRygpecDWWSLGVCMYEMLYGETPFYAESLVETYGKIMNHKEHFSfPDDEDDVS 237

                          250       260       270
                   ....*....|....*....|....*....|....*.
gi 1207186029 1885 HEAKGFVIKLLVA--DRL-RPDANECLRHPWFKTLN 1917
Cdd:cd05597    238 EEAKDLIRRLICSreRRLgQNGIDDFKKHPFFEGID 273

Catalytic domain of the Dual-specificity protein kinase, Myt1; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. Myt1 is a cytoplasmic cell cycle checkpoint kinase that can keep the cyclin-dependent kinase CDK1 in an inactive state through phosphorylation of N-terminal thr (T14) and tyr (Y15) residues, leading to the delay of meiosis I entry. Meiotic progression is ensured by a two-step inhibition and downregulation of Myt1 by CDK1/XRINGO and p90Rsk during oocyte maturation. In addition, Myt1 targets cyclin B1/B2 and is essential for Golgi and ER assembly during telophase. In Drosophila, Myt1 may be a downstream target of Notch during eye development. The Myt1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270952 [Multi-domain] Cd Length: 249 Bit Score: 98.53 E-value: 4.18e-22

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISAR---AKRKASALRELNILSHL-DHERILYFHDAFEKKNAVIIITEL 1737
Cdd:cd14050      3 FTILSKLGEGSFGEVFKVRSREDGKLYAVKRSRSRfrgEKDRKRKLEEVERHEKLgEHPNCVRFIKAWEEKGILYIQTEL 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1738 CHEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMadhSSDQI-RICDFGNAVKFMPDEAQYCK 1816
Cdd:cd14050     83 CDTSLQQYCEETHSLPESEVWNILLDLLKGLKHLHDHGLIHLDIKPANIFL---SKDGVcKLGDFGLVVELDKEDIHDAQ 159

                          170       180
                   ....*....|....*....|....*...
gi 1207186029 1817 YGTPEFVAPEIVNQTPvSKATDIWPIGV 1844
Cdd:cd14050    160 EGDPRYMAPELLQGSF-TKAADIFSLGI 186

Catalytic domain of Cyclin-Dependent protein Kinase 1-like Serine/Threonine Kinases and of Plant B-type Cyclin-Dependent protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDK, CDK2, and CDK3. CDK1 is also called Cell division control protein 2 (Cdc2) or p34 protein kinase, and is regulated by cyclins A, B, and E. The CDK1/cyclin A complex controls G2 phase entry and progression while the CDK1/cyclin B complex is critical for G2 to M phase transition. CDK2 is regulated by cyclin E or cyclin A. Upon activation by cyclin E, it phosphorylates the retinoblastoma (pRb) protein which activates E2F mediated transcription and allows cells to move into S phase. The CDK2/cyclin A complex plays a role in regulating DNA replication. Studies in knockout mice revealed that CDK1 can compensate for the loss of the cdk2 gene as it can also bind cyclin E and drive G1 to S phase transition. CDK3 is regulated by cyclin C and it phosphorylates pRB specifically during the G0/G1 transition. This phosphorylation is required for cells to exit G0 efficiently and enter the G1 phase. The plant-specific B-type CDKs are expressed from the late S to the M phase of the cell cycle. They are characterized by the cyclin binding motif PPT[A/T]LRE. They play a role in controlling mitosis and integrating developmental pathways, such as stomata and leaf development. CdkB has been shown to associate with both cyclin B, which controls G2/M transition, and cyclin D, which acts as a mediator in linking extracellular signals to the cell cycle. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270829 [Multi-domain] Cd Length: 283 Bit Score: 99.29 E-value: 4.82e-22

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3309 GRFGVIRECRENATGNLYMAKIVPYEPESK---QTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSG--KELLH 3383
Cdd:cd07835     10 GTYGVVYKARDKLTGEIVALKKIRLETEDEgvpSTAIREISLLKELNHPNIVRLLDVVHSENKLYLVFEFLDLdlKKYMD 89

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3384 SlIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNpLFLKQFSPPIGTLDYMS 3463
Cdd:cd07835     90 S-SPLTGLDPPLIKSYLYQLLQGIAFCHSHRVLHRDLKPQNLLIDTEGALKLADFGLARAFG-VPVRTYTHEVVTLWYRA 167

                          170       180
                   ....*....|....*....|
gi 1207186029 3464 PEMLKGD-VVGPPADIWSIG 3482
Cdd:cd07835    168 PEILLGSkHYSTPVDIWSVG 187

Catalytic domain of the Serine/Threonine Kinase, Pre-mRNA-Processing factor 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PRP4 phosphorylates a number of factors involved in the formation of active spliceosomes, which catalyze pre-mRNA splicing. It phosphorylates PRP6 and PRP31, components of the U4/U6-U5 tri-small nuclear ribonucleoprotein (snRNP), during spliceosomal complex formation. In fission yeast, PRP4 phosphorylates the splicing factor PRP1 (U5-102 kD in mammals). Thus, PRP4 plays a key role in regulating spliceosome assembly and pre-mRNA splicing. It also plays an important role in mitosis by acting as a spindle assembly checkpoint kinase that is required for chromosome alignment and the recruitment of the checkpoint proteins MPS1, MAD1, and MAD2 at kinetochores. The PRP4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271037 [Multi-domain] Cd Length: 318 Bit Score: 99.99 E-value: 5.07e-22

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1661 YYDVHKEIGRGAFSYVKRVIQ-KAGKLEYAAKFISARAKRKASALRELNILSHL------DHERILYFHDAFEKKNAVII 1733
Cdd:cd14135      1 RYRVYGYLGKGVFSNVVRARDlARGNQEVAIKIIRNNELMHKAGLKELEILKKLndadpdDKKHCIRLLRHFEHKNHLCL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1734 ITELCH---EELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILM-ADHSSdqIRICDFGNAVKFMP 1809
Cdd:cd14135     81 VFESLSmnlREVLKKYGKNVGLNIKAVRSYAQQLFLALKHLKKCNILHADIKPDNILVnEKKNT--LKLCDFGSASDIGE 158

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1207186029 1810 DEAqyckygTPEFV-----APEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGEN 1860
Cdd:cd14135    159 NEI------TPYLVsrfyrAPEIILGLPYDYPIDMWSVGCTLYELYTGKILFPGKT 208

Catalytic domain of fungal Pek1-like dual-specificity Mitogen-Activated Protein Kinase Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include the MAPKKs Pek1/Skh1 from Schizosaccharomyces pombe and MKK2 from Saccharomyces cerevisiae, and related proteins. Both fission yeast Pek1 and baker's yeast MKK2 are components of the cell integrity MAPK pathway. In fission yeast, Pek1 phosphorylates and activates Pmk1/Spm1 and is regulated by the MAPKK kinase Mkh1. In baker's yeast, the pathway involves the MAPK Slt2, the MAPKKs MKK1 and MKK2, and the MAPKK kinase Bck1. The cell integrity MAPK cascade is activated by multiple stress conditions, and is essential in cell wall construction, morphogenesis, cytokinesis, and ion homeostasis. MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The MAPKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270793 [Multi-domain] Cd Length: 287 Bit Score: 99.03 E-value: 5.30e-22

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3309 GRFGVIRECRENATGNLYMAKIVPYE--PESKQTVLQEYDILKSLHHEKIMALHEAYVTPR--YLVLISECCSGKELlHS 3384
Cdd:cd06621     12 GAGGSVTKCRLRNTKTIFALKTITTDpnPDVQKQILRELEINKSCASPYIVKYYGAFLDEQdsSIGIAMEYCEGGSL-DS 90

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3385 LIDRF-----RYSEDdVVAYIVQ-ILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLKQFsppIGT 3458
Cdd:cd06621     91 IYKKVkkkggRIGEK-VLGKIAEsVLKGLSYLHSRKIIHRDIKPSNILLTRKGQVKLCDFGVSGELVNSLAGTF---TGT 166

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*....
gi 1207186029 3459 LDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFtendPAETEARI 3507
Cdd:cd06621    167 SYYMAPERIQGGPYSITSDVWSLGLTLLEVAQNRFPF----PPEGEPPL 211

Catalytic domain of the Serine/Threonine Kinase, Yeast Sps1/Ste20-related Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. YSK4 is a putative MAPKKK, whose mammalian gene has been isolated. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The YSK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270801 [Multi-domain] Cd Length: 266 Bit Score: 98.66 E-value: 5.48e-22

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIReCRENATGNLYMAKIVPYEPESKQTVLQEY-------DILKSLHHEKIMALHEAYVTPRYLVLISECCSGKE 3380
Cdd:cd06631     11 KGAYGTVY-CGLTSTGQLIAVKQVELDTSDKEKAEKEYeklqeevDLLKTLKHVNIVGYLGTCLEDNVVSIFMEFVPGGS 89

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3381 LlHSLIDRFRYSEDDVVA-YIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLKQFSPPI--- 3456
Cdd:cd06631     90 I-ASILARFGALEEPVFCrYTKQILEGVAYLHNNNVIHRDIKGNNIMLMPNGVIKLIDFGCAKRLCINLSSGSQSQLlks 168

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3457 --GTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLSKLYQNVSQSASLFIKKILC 3534
Cdd:cd06631    169 mrGTPYWMAPEVINETGHGRKSDIWSIGCTVFEMATGKPPWADMNPMAAIFAIGSGRKPVPRLPDKFSPEARDFVHACLT 248


                   ....*...
gi 1207186029 3535 SYPWARPT 3542
Cdd:cd06631    249 RDQDERPS 256

Catalytic domain of fungal Rim15-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include Saccharomyces cerevisiae Rim15, Schizosaccharomyces pombe cek1, and similar fungal proteins. They contain a central catalytic domain, which contains an insert relative to MAST kinases. In addition, Rim15 contains a C-terminal signal receiver (REC) domain while cek1 contains an N-terminal PAS domain. Rim15 (or Rim15p) functions as a regulator of meiosis. It acts as a downstream effector of PKA and regulates entry into stationary phase (G0). Thus, it plays a crucial role in regulating yeast proliferation, differentiation, and aging. Cek1 may facilitate progression of mitotic anaphase. The Rim15-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270762 [Multi-domain] Cd Length: 263 Bit Score: 98.32 E-value: 6.25e-22

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKIVP-YEPESKQ---TVLQEYDILKSLHHEKIMA-LHEAYVTPRYLVLISECCSGKELl 3382
Cdd:cd05611      6 KGAFGSVYLAKKRSTGDYFAIKVLKkSDMIAKNqvtNVKAERAIMMIQGESPYVAkLYYSFQSKDYLYLVMEYLNGGDC- 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3383 HSLIDRFRY-SEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQtfNPLFLKQFSPPIGTLDY 3461
Cdd:cd05611     85 ASLIKTLGGlPEDWAKQYIAEVVLGVEDLHQRGIIHRDIKPENLLIDQTGHLKLTDFGLSR--NGLEKRHNKKFVGTPDY 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3462 MSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLSK-LYQNVSQSASLFIKKILCSYPWAR 3540
Cdd:cd05611    163 LAPETILGVGDDKMSDWWSLGCVIFEFLFGYPPFHAETPDAVFDNILSRRINWPEeVKEFCSPEAVDLINRLLCMDPAKR 242

Catalytic domain of the Serine/Threonine Kinases, MAP/microtubule affinity-regulating kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MARKs, also called Partitioning-defective 1 (Par1) proteins, function as regulators of diverse cellular processes in nematodes, Drosophila, yeast, and vertebrates. They are involved in embryogenesis, epithelial cell polarization, cell signaling, and neuronal differentiation. MARKs phosphorylate tau and related microtubule-associated proteins (MAPs), and regulates microtubule-based intracellular transport. Vertebrates contain four isoforms, namely MARK1 (or Par1c), MARK2 (or Par1b), MARK3 (Par1a), and MARK4 (or MARKL1). Known substrates of MARKs include the cell cycle-regulating phosphatase Cdc25, tyrosine phosphatase PTPH1, MAPK scaffolding protein KSR1, class IIa histone deacetylases, and plakophilin 2. The MARK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270974 [Multi-domain] Cd Length: 253 Bit Score: 97.98 E-value: 6.68e-22

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKAS---ALRELNILSHLDHERILYFHDAFEKKNAVIIITELC 1738
Cdd:cd14072      2 YRLLKTIGKGNFAKVKLARHVLTGREVAIKIIDKTQLNPSSlqkLFREVRIMKILNHPNIVKLFEVIETEKTLYLVMEYA 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1739 HE-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDFGNAVKFMPDEA--QYC 1815
Cdd:cd14072     82 SGgEVFDYLVAHGRMKEKEARAKFRQIVSAVQYCHQKRIVHRDLKAENLLL--DADMNIKIADFGFSNEFTPGNKldTFC 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1816 kyGTPEFVAPEIVNQTPVS-KATDIWPIGVLTYLCLTGVSPFAGEN---DRSSVLNIRnYNVAFeeSMFTDLCHEAKGFV 1891
Cdd:cd14072    160 --GSPPYAAPELFQGKKYDgPEVDVWSLGVILYTLVSGSLPFDGQNlkeLRERVLRGK-YRIPF--YMSTDCENLLKKFL 234


                   .
gi 1207186029 1892 I 1892
Cdd:cd14072    235 V 235

Catalytic domain of the Serine/Threonine Kinase, STK10 (also called Lymphocyte-Oriented Kinase or LOK); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK10/LOK is also called polo-like kinase kinase 1 in Xenopus (xPlkk1). It is highly expressed in lymphocytes and is responsible in regulating leukocyte function associated antigen (LFA-1)-mediated lymphocyte adhesion. It plays a role in regulating the CD28 responsive element in T cells, and may also function as a regulator of polo-like kinase 1 (Plk1), a protein which is overexpressed in multiple tumor types. The STK10 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 132975 [Multi-domain] Cd Length: 292 Bit Score: 98.95 E-value: 7.26e-22

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1660 DYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRK-ASALRELNILSHLDHERILYFHDAFEKKNAVIIITELC 1738
Cdd:cd06644     12 EVWEIIGELGDGAFGKVYKAKNKETGALAAAKVIETKSEEElEDYMVEIEILATCNHPYIVKLLGAFYWDGKLWIMIEFC 91

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1739 HEELLD--RLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMAdhSSDQIRICDFGNAVKFMPDEAQYCK 1816
Cdd:cd06644     92 PGGAVDaiMLELDRGLTEPQIQVICRQMLEALQYLHSMKIIHRDLKAGNVLLT--LDGDIKLADFGVSAKNVKTLQRRDS 169

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1817 Y-GTPEFVAPEIV-----NQTPVSKATDIWPIGVlTYLCLTGVSPFAGENDRSSVLnirnYNVAFEE----SMFTDLCHE 1886
Cdd:cd06644    170 FiGTPYWMAPEVVmcetmKDTPYDYKADIWSLGI-TLIEMAQIEPPHHELNPMRVL----LKIAKSEpptlSQPSKWSME 244

                          250       260       270
                   ....*....|....*....|....*....|....*....
gi 1207186029 1887 AKGFVIKLLvaDR---LRPDANECLRHPWFKTLNKGKSI 1922
Cdd:cd06644    245 FRDFLKTAL--DKhpeTRPSAAQLLEHPFVSSVTSNRPL 281

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C eta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-eta is predominantly expressed in squamous epithelia, where it plays a crucial role in the signaling of cell-type specific differentiation. It is also expressed in pro-B cells and early-stage thymocytes, and acts as a key regulator in early B-cell development. PKC-eta increases glioblastoma multiforme (GBM) proliferation and resistance to radiation, and is being developed as a therapeutic target for the management of GBM. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC-eta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270742 [Multi-domain] Cd Length: 323 Bit Score: 99.60 E-value: 7.92e-22

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKIVpyepeSKQTVLQEYDILKSLHHEKIMALHE----------AYVTPRYLVLISECCS 3377
Cdd:cd05590      5 KGSFGKVMLARLKESGRLYAVKVL-----KKDVILQDDDVECTMTEKRILSLARnhpfltqlycCFQTPDRLFFVMEFVN 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3378 GKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQ--TFNPLFLKQFSpp 3455
Cdd:cd05590     80 GGDLMFHIQKSRRFDEARARFYAAEITSALMFLHDKGIIYRDLKLDNVLLDHEGHCKLADFGMCKegIFNGKTTSTFC-- 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3456 iGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTendpAETEARIQAAKFDLSKLYQN-VSQSASLFIKKILC 3534
Cdd:cd05590    158 -GTPDYIAPEILQEMLYGPSVDWWAMGVLLYEMLCGHAPFE----AENEDDLFEAILNDEVVYPTwLSQDAVDILKAFMT 232


                   ....*.
gi 1207186029 3535 SYPWAR 3540
Cdd:cd05590    233 KNPTMR 238

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 10; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. No function has yet been ascribed to Nek10. The gene encoding Nek10 is a putative causative gene for breast cancer; it is located within a breast cancer susceptibility loci on chromosome 3p24. Nek10 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270867 [Multi-domain] Cd Length: 270 Bit Score: 97.96 E-value: 9.88e-22

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFG-VIRECRENATGNLYMAKIVPY--------EPESKQTV---LQEYDILK-SLHHEKIMALHEAYVTP 3366
Cdd:cd08528      2 YAVLELLGSGAFGcVYKVRKKSNGQTLLALKEINMtnpafgrtEQERDKSVgdiISEVNIIKeQLRHPNIVRYYKTFLEN 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3367 RYLVLISECCSG---KELLHSLIDR-FRYSEDDVVAYIVQILQGLDYLH-SRRILHLDIKPENIIVTYMNVVKIIDFGSA 3441
Cdd:cd08528     82 DRLYIVMELIEGaplGEHFSSLKEKnEHFTEDRIWNIFVQMVLALRYLHkEKQIVHRDLKPNNIMLGEDDKVTITDFGLA 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3442 QTFNPLFLKQFSPpIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDL--SKLYq 3519
Cdd:cd08528    162 KQKGPESSKMTSV-VGTILYSCPEIVQNEPYGEKADIWALGCILYQMCTLQPPFYSTNMLTLATKIVEAEYEPlpEGMY- 239

                          250       260
                   ....*....|....*....|....*.
gi 1207186029 3520 nvSQSASLFIKKILCSYPWARPTIKD 3545
Cdd:cd08528    240 --SDDITFVIRSCLTPDPEARPDIVE 263

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase C; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. PKCs undergo three phosphorylations in order to take mature forms. In addition, classical PKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. Novel PKCs are calcium-independent, but require DAG and PS for activity, while atypical PKCs only require PS. PKCs phosphorylate and modify the activities of a wide variety of cellular proteins including receptors, enzymes, cytoskeletal proteins, transcription factors, and other kinases. They play a central role in signal transduction pathways that regulate cell migration and polarity, proliferation, differentiation, and apoptosis. Also included in this subfamily are the PKC-like proteins, called PKNs. The PKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270722 [Multi-domain] Cd Length: 318 Bit Score: 99.21 E-value: 1.06e-21

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1767 GINYLHQLDILHLDIKPDNILMAdhSSDQIRICDFGnavkfMPDE--------AQYCkyGTPEFVAPEIVNQTPVSKATD 1838
Cdd:cd05570    108 ALQFLHERGIIYRDLKLDNVLLD--AEGHIKIADFG-----MCKEgiwggnttSTFC--GTPDYIAPEILREQDYGFSVD 178

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1839 IWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTdlchEAKGFVIKLLVAD---RL--RP-DANECLRHPW 1912
Cdd:cd05570    179 WWALGVLLYEMLAGQSPFEGDDEDELFEAILNDEVLYPRWLSR----EAVSILKGLLTKDparRLgcGPkGEADIKAHPF 254


                   ....*
gi 1207186029 1913 FKTLN 1917
Cdd:cd05570    255 FRNID 259

Catalytic domain of Fungal Nak1-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Schizosaccharomyces pombe Nak1, Saccharomyces cerevisiae Kic1p (kinase that interacts with Cdc31p) and related proteins. Nak1 (also called N-rich kinase 1), is required by fission yeast for polarizing the tips of actin cytoskeleton and is involved in cell growth, cell separation, cell morphology and cell-cycle progression. Kic1p is required by budding yeast for cell integrity and morphogenesis. Kic1p interacts with Cdc31p, the yeast homologue of centrin, and phosphorylates substrates in a Cdc31p-dependent manner. The Nak1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270822 [Multi-domain] Cd Length: 277 Bit Score: 97.93 E-value: 1.11e-21

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYVKRVIQKAGKLEYAAKFISARAKRK--ASALRELNILSHLDH---ERILYFHDAFEKKNAVIIITELCHEEL 1742
Cdd:cd06917      9 VGRGSYGAVYRGYHVKTGRVVALKVLNLDTDDDdvSDIQKEVALLSQLKLgqpKNIIKYYGSYLKGPSLWIIMDYCEGGS 88

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1743 LDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMAdhSSDQIRICDFGNAVKFMPDEAQYCKY-GTPE 1821
Cdd:cd06917     89 IRTLMRAGPIAERYIAVIMREVLVALKFIHKDGIIHRDIKAANILVT--NTGNVKLCDFGVAASLNQNSSKRSTFvGTPY 166

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1822 FVAPEIV--NQTPVSKAtDIWPIGVLTYLCLTGVSPFAGEND-RSSVLNIRNYNVAFEESMFTDLCHEakgFVIKLLVAD 1898
Cdd:cd06917    167 WMAPEVIteGKYYDTKA-DIWSLGITTYEMATGNPPYSDVDAlRAVMLIPKSKPPRLEGNGYSPLLKE---FVAACLDEE 242

                          250       260       270
                   ....*....|....*....|....*....|....*.
gi 1207186029 1899 -RLRPDANECLRHPWFKTLNKgksISTESLKKFLSR 1933
Cdd:cd06917    243 pKDRLSADELLKSKWIKQHSK---TPTSVLKELISR 275

Stk1 family PASTA domain-containing Ser/Thr kinase;

Pssm-ID: 468045 [Multi-domain] Cd Length: 563 Bit Score: 102.57 E-value: 1.18e-21

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3379 KELLHsliDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLKQFSPPIGT 3458
Cdd:NF033483    95 KDYIR---EHGPLSPEEAVEIMIQILSALEHAHRNGIVHRDIKPQNILITKDGRVKVTDFGIARALSSTTMTQTNSVLGT 171

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 1207186029 3459 LDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFT 3496
Cdd:NF033483   172 VHYLSPEQARGGTVDARSDIYSLGIVLYEMLTGRPPFD 209

Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PKC beta isoforms (I and II), generated by alternative splicing of a single gene, are preferentially activated by hyperglycemia-induced DAG (1,2-diacylglycerol) in retinal tissues. This is implicated in diabetic microangiopathy such as ischemia, neovascularization, and abnormal vasodilator function. PKC-beta also plays an important role in VEGF signaling. In addition, glucose regulates proliferation in retinal endothelial cells via PKC-betaI. PKC-beta is also being explored as a therapeutic target in cancer. It contributes to tumor formation and is involved in the tumor host mechanisms of inflammation and angiogenesis. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. PKCs undergo three phosphorylations in order to take mature forms. In addition, cPKCs depend on calcium, DAG, and in most cases, phosphatidylserine (PS) for activation. The cPKC-beta subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270767 [Multi-domain] Cd Length: 323 Bit Score: 98.92 E-value: 1.30e-21

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVpyepeSKQTVLQEYDILKSLHHEKIMAL----------HEAYVTPRYL 3369
Cdd:cd05616      2 FNFLMVLGKGSFGKVMLAERKGTDELYAVKIL-----KKDVVIQDDDVECTMVEKRVLALsgkppfltqlHSCFQTMDRL 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3370 VLISECCSGKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQ--TFNPL 3447
Cdd:cd05616     77 YFVMEYVNGGDLMYHIQQVGRFKEPHAVFYAAEIAIGLFFLQSKGIIYRDLKLDNVMLDSEGHIKIADFGMCKenIWDGV 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3448 FLKQFSppiGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLSKlyqNVSQSASL 3527
Cdd:cd05616    157 TTKTFC---GTPDYIAPEIIAYQPYGKSVDWWAFGVLLYEMLAGQAPFEGEDEDELFQSIMEHNVAYPK---SMSKEAVA 230

                          250
                   ....*....|...
gi 1207186029 3528 FIKKILCSYPWAR 3540
Cdd:cd05616    231 ICKGLMTKHPGKR 243

Catalytic domain of the Serine/Threonine Kinase, DMPK-related cell division control protein 42 binding kinase (MRCK) alpha; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MRCK-alpha is expressed ubiquitously in many tissues. It plays a role in the regulation of peripheral actin reorganization and neurite outgrowth. It may also play a role in the transferrin iron uptake pathway. MRCK is activated via interaction with the small GTPase Cdc42. MRCK/Cdc42 signaling mediates myosin-dependent cell motility. The MRCK-alpha subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. This alignment model includes the dimerization domain.

Pssm-ID: 270773 [Multi-domain] Cd Length: 409 Bit Score: 100.47 E-value: 1.48e-21

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3284 GKPGDSTLRQ-GVPQKPYTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPESKQT----VLQEYDILKSLHHEKIMA 3358
Cdd:cd05623     57 AKPFTSKVKQmRLHKEDFEILKVIGRGAFGEVAVVKLKNADKVFAMKILNKWEMLKRAetacFREERDVLVNGDSQWITT 136

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3359 LHEAYVTPRYLVLISECCSGKELLhSLIDRF--RYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKII 3436
Cdd:cd05623    137 LHYAFQDDNNLYLVMDYYVGGDLL-TLLSKFedRLPEDMARFYLAEMVLAIDSVHQLHYVHRDIKPDNILMDMNGHIRLA 215

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3437 DFGSAQTFNPLFLKQFSPPIGTLDYMSPEML------KGDvVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAA 3510
Cdd:cd05623    216 DFGSCLKLMEDGTVQSSVAVGTPDYISPEILqamedgKGK-YGPECDWWSLGVCMYEMLYGETPFYAESLVETYGKIMNH 294

                          250       260
                   ....*....|....*....|....*..
gi 1207186029 3511 K--FDLSKLYQNVSQSASLFIKKILCS 3535
Cdd:cd05623    295 KerFQFPTQVTDVSENAKDLIRRLICS 321

Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMP-activated protein kinase (AMPK). Vertebrates contain two CaMKKs, CaMKK1 (or alpha) and CaMKK2 (or beta). CaMKK1 is involved in the regulation of glucose uptake in skeletal muscles. CaMKK2 is involved in regulating energy balance, glucose metabolism, adiposity, hematopoiesis, inflammation, and cancer. The CaMKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271020 [Multi-domain] Cd Length: 275 Bit Score: 97.43 E-value: 1.49e-21

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3339 QTVLQEYDILKSLHHEKIMALHEAYVTPR--YLVLISECCSGKELLHSLIDRfRYSEDDVVAYIVQILQGLDYLHSRRIL 3416
Cdd:cd14118     59 DRVYREIAILKKLDHPNVVKLVEVLDDPNedNLYMVFELVDKGAVMEVPTDN-PLSEETARSYFRDIVLGIEYLHYQKII 137

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3417 HLDIKPENIIVTYMNVVKIIDFGSAQTF--NPLFLkqfSPPIGTLDYMSPEMLKGD---VVGPPADIWSIGILTYIMLSG 3491
Cdd:cd14118    138 HRDIKPSNLLLGDDGHVKIADFGVSNEFegDDALL---SSTAGTPAFMAPEALSESrkkFSGKALDIWAMGVTLYCFVFG 214

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1207186029 3492 RLPFTENDPAETEARIqaaKFDLSKLYQNVSQSASL--FIKKILCSYPWARPTIKDCFTNSW 3551
Cdd:cd14118    215 RCPFEDDHILGLHEKI---KTDPVVFPDDPVVSEQLkdLILRMLDKNPSERITLPEIKEHPW 273

Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 1 and 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKL1, also called p42 KKIALRE, is a glial protein that is upregulated in gliosis. It is present in neuroblastoma and A431 human carcinoma cells, and may be implicated in neoplastic transformation. The function of CDKL4 is unknown. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL1/4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270837 [Multi-domain] Cd Length: 286 Bit Score: 97.83 E-value: 1.55e-21

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1660 DYYDVHKEIGRGAFSYV-KRVIQKAGKLEYAAKFISARAKR--KASALRELNILSHLDHERILYFHDAFEKKNAVIIITE 1736
Cdd:cd07847      1 EKYEKLSKIGEGSYGVVfKCRNRETGQIVAIKKFVESEDDPviKKIALREIRMLKQLKHPNLVNLIEVFRRKRKLHLVFE 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1737 LCHEELLDRLTKKSTIL-ESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHssDQIRICDFGNAVKFMPDEAQYC 1815
Cdd:cd07847     81 YCDHTVLNELEKNPRGVpEHLIKKIIWQTLQAVNFCHKHNCIHRDVKPENILITKQ--GQIKLCDFGFARILTGPGDDYT 158

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*...
gi 1207186029 1816 KY-GTPEFVAPE-IVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGEND 1861
Cdd:cd07847    159 DYvATRWYRAPElLVGDTQYGPPVDVWAIGCVFAELLTGQPLWPGKSD 206

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase signal-integrating kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK signal-integrating kinases (Mnks) are MAPK-activated protein kinases and is comprised by a group of four proteins, produced by alternative splicing from two genes (Mnk1 and Mnk2). The isoforms of Mnk1 (1a/1b) and Mnk2 (2a/2b) differ at their C-termini, with the a-form having a longer C-terminus containing a MAPK-binding region. All Mnks contain a catalytic kinase domain and a polybasic region at the N-terminus which binds importin and the eukaryotic initiation factor eIF4G. The best characterized Mnk substrate is eIF4G, whose phosphorylation may promote the export of certain mRNAs from the nucleus. Mnk also phosphorylate substrates that bind to AU-rich elements that regulate mRNA stability and translation. Mnks have also been implicated in tyrosine kinase receptor signaling, inflammation, and cell prolieration or survival. The Mnk subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271075 [Multi-domain] Cd Length: 288 Bit Score: 97.79 E-value: 1.56e-21

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3309 GRFGVIRECRENATGNLYMAKIVPYEP-ESKQTVLQEYDILKSLH-HEKIMALHEAYVTPRYLVLISECCSGKELLHSLI 3386
Cdd:cd14173     13 GAYARVQTCINLITNKEYAVKIIEKRPgHSRSRVFREVEMLYQCQgHRNVLELIEFFEEEDKFYLVFEKMRGGSILSHIH 92

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3387 DRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNV---VKIIDF--GSAQTFN----PLFLKQFSPPIG 3457
Cdd:cd14173     93 RRRHFNELEASVVVQDIASALDFLHNKGIAHRDLKPENILCEHPNQvspVKICDFdlGSGIKLNsdcsPISTPELLTPCG 172

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3458 TLDYMSPEML-----KGDVVGPPADIWSIGILTYIMLSGRLPFT------------ENDPAETE---ARIQAAKFDL-SK 3516
Cdd:cd14173    173 SAEYMAPEVVeafneEASIYDKRCDLWSLGVILYIMLSGYPPFVgrcgsdcgwdrgEACPACQNmlfESIQEGKYEFpEK 252

                          250       260       270
                   ....*....|....*....|....*....|....*.
gi 1207186029 3517 LYQNVSQSASLFIKKILCSYPWARPTIKDCFTNSWL 3552
Cdd:cd14173    253 DWAHISCAAKDLISKLLVRDAKQRLSAAQVLQHPWV 288

Catalytic domain of the Serine/Threonine Kinase, Group I p21-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Group I PAKs, also called conventional PAKs, include PAK1, PAK2, and PAK3. Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). They interact with the SH3 domain containing proteins Nck, Grb2 and PIX. Binding of group I PAKs to activated GTPases leads to conformational changes that destabilize the AID, allowing autophosphorylation and full activation of the kinase domain. Known group I PAK substrates include MLCK, Bad, Raf, MEK1, LIMK, Merlin, Vimentin, Myc, Stat5a, and Aurora A, among others. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs are implicated in the regulation of many cellular processes including growth factor receptor-mediated proliferation, cell polarity, cell motility, cell death and survival, and actin cytoskeleton organization. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270814 [Multi-domain] Cd Length: 261 Bit Score: 96.92 E-value: 1.73e-21

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3294 GVPQKPYTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPE-SKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLI 3372
Cdd:cd06647      3 GDPKKKYTRFEKIGQGASGTVYTAIDVATGQEVAIKQMNLQQQpKKELIINEILVMRENKNPNIVNYLDSYLVGDELWVV 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3373 SECCSGKELLhSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLKQf 3452
Cdd:cd06647     83 MEYLAGGSLT-DVVTETCMDEGQIAAVCRECLQALEFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFCAQITPEQSKR- 160

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*...
gi 1207186029 3453 SPPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDP 3500
Cdd:cd06647    161 STMVGTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPYLNENP 208

Catalytic domain of the Serine/Threonine Kinase, Group II p21-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Group II PAKs, also called non-conventional PAKs, include PAK4, PAK5, and PAK6. Group II PAKs contain PBD (p21-binding domain) and catalytic domains, but lack other motifs found in group I PAKs, such as an AID (autoinhibitory domain) and SH3 binding sites. Since group II PAKs do not contain an obvious AID, they may be regulated differently from group I PAKs. While group I PAKs interact with the SH3 containing proteins Nck, Grb2 and PIX, no such binding has been demonstrated for group II PAKs. Some known substrates of group II PAKs are also substrates of group I PAKs such as Raf, BAD, LIMK and GEFH1. Unique group II substrates include MARK/Par-1 and PDZ-RhoGEF. Group II PAKs play important roles in filopodia formation, neuron extension, cytoskeletal organization, and cell survival. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270815 [Multi-domain] Cd Length: 261 Bit Score: 96.74 E-value: 1.88e-21

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3307 ARGRFGVIRECRENATGNLYMAKIVPYEPESKQTVL-QEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLhSL 3385
Cdd:cd06648     16 GEGSTGIVCIATDKSTGRQVAVKKMDLRKQQRRELLfNEVVIMRDYQHPNIVEMYSSYLVGDELWVVMEFLEGGALT-DI 94

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3386 IDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGsaqtfnplFLKQFSPPI-------GT 3458
Cdd:cd06648     95 VTHTRMNEEQIATVCRAVLKALSFLHSQGVIHRDIKSDSILLTSDGRVKLSDFG--------FCAQVSKEVprrkslvGT 166

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3459 LDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLSKLYQNVSQSASLFIKKILCSYPW 3538
Cdd:cd06648    167 PYWMAPEVISRLPYGTEVDIWSLGIMVIEMVDGEPPYFNEPPLQAMKRIRDNEPPKLKNLHKVSPRLRSFLDRMLVRDPA 246


                   ....*..
gi 1207186029 3539 ARPTIKD 3545
Cdd:cd06648    247 QRATAAE 253

Catalytic domain of the Serine/Threonine Kinase, STK10 (also called Lymphocyte-Oriented Kinase or LOK); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK10/LOK is also called polo-like kinase kinase 1 in Xenopus (xPlkk1). It is highly expressed in lymphocytes and is responsible in regulating leukocyte function associated antigen (LFA-1)-mediated lymphocyte adhesion. It plays a role in regulating the CD28 responsive element in T cells, and may also function as a regulator of polo-like kinase 1 (Plk1), a protein which is overexpressed in multiple tumor types. The STK10 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 132975 [Multi-domain] Cd Length: 292 Bit Score: 97.79 E-value: 2.03e-21

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3296 PQKPYTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPESK-QTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISE 3374
Cdd:cd06644     10 PNEVWEIIGELGDGAFGKVYKAKNKETGALAAAKVIETKSEEElEDYMVEIEILATCNHPYIVKLLGAFYWDGKLWIMIE 89

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3375 CCSGKELLHSLIDRFR-YSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFG-SAQtfNPLFLKQF 3452
Cdd:cd06644     90 FCPGGAVDAIMLELDRgLTEPQIQVICRQMLEALQYLHSMKIIHRDLKAGNVLLTLDGDIKLADFGvSAK--NVKTLQRR 167

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3453 SPPIGTLDYMSPEM-----LKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIqaAKFDLSKLYQNVSQSASL 3527
Cdd:cd06644    168 DSFIGTPYWMAPEVvmcetMKDTPYDYKADIWSLGITLIEMAQIEPPHHELNPMRVLLKI--AKSEPPTLSQPSKWSMEF 245

                          250
                   ....*....|....*..
gi 1207186029 3528 --FIKKILCSYPWARPT 3542
Cdd:cd06644    246 rdFLKTALDKHPETRPS 262

Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ROCK2 was the first identified target of activated RhoA, and was found to play a role in stress fiber and focal adhesion formation. It is prominently expressed in the brain, heart, and skeletal muscles. It is implicated in vascular and neurological disorders, such as hypertension and vasospasm of the coronary and cerebral arteries. ROCK2 is also activated by caspase-2 cleavage, resulting in thrombin-induced microparticle generation in response to cell activation. Mice deficient in ROCK2 show intrauterine growth retardation and embryonic lethality because of placental dysfunction. ROCK contains an N-terminal extension, a catalytic kinase domain, and a C-terminal extension, which contains a coiled-coil region encompassing a Rho-binding domain (RBD) and a pleckstrin homology (PH) domain. ROCK is auto-inhibited by the RBD and PH domain interacting with the catalytic domain, and is activated via interaction with Rho GTPases. The ROCK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270771 [Multi-domain] Cd Length: 379 Bit Score: 99.69 E-value: 2.05e-21

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1651 ILRKMRRL---TDYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISA--RAKRKASAL--RELNILSHLDHERILYFHD 1723
Cdd:cd05621     40 IVNKIRELqmkAEDYDVVKVIGRGAFGEVQLVRHKASQKVYAMKLLSKfeMIKRSDSAFfwEERDIMAFANSPWVVQLFC 119

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1724 AFEKKNAVIIITELCHEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSsdQIRICDFGN 1803
Cdd:cd05621    120 AFQDDKYLYMVMEYMPGGDLVNLMSNYDVPEKWAKFYTAEVVLALDAIHSMGLIHRDVKPDNMLLDKYG--HLKLADFGT 197

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1804 AVKFMPDEAQYCK--YGTPEFVAPEIVNQTP----VSKATDIWPIGVLTYLCLTGVSPFAGEN---DRSSVLNIRNyNVA 1874
Cdd:cd05621    198 CMKMDETGMVHCDtaVGTPDYISPEVLKSQGgdgyYGRECDWWSVGVFLFEMLVGDTPFYADSlvgTYSKIMDHKN-SLN 276

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|...
gi 1207186029 1875 FEESMftDLCHEAKGFVIKLLVADRLRPDAN---ECLRHPWFK 1914
Cdd:cd05621    277 FPDDV--EISKHAKNLICAFLTDREVRLGRNgveEIKQHPFFR 317

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 11; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek11 is involved, through direct phosphorylation, in regulating the degradation of Cdc25A (Cell Division Cycle 25 homolog A), which plays a role in cell cycle progression and in activating cyclin dependent kinases. Nek11 is activated by CHK1 (CHeckpoint Kinase 1) and may be involved in the G2/M checkpoint. Nek11 may also play a role in the S-phase checkpoint as well as in DNA replication and genotoxic stress responses. It is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270861 [Multi-domain] Cd Length: 260 Bit Score: 96.72 E-value: 2.32e-21

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3309 GRFGV---IRECRENATGNLYMAKIVP---YEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELl 3382
Cdd:cd08222     11 GNFGTvylVSDLKATADEELKVLKEISvgeLQPDETVDANREAKLLSKLDHPAIVKFHDSFVEKESFCIVTEYCEGGDL- 89

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3383 HSLIDRFRYS-----EDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTyMNVVKIIDFG----------SAQTFNpl 3447
Cdd:cd08222     90 DDKISEYKKSgttidENQILDWFIQLLLAVQYMHERRILHRDLKAKNIFLK-NNVIKVGDFGisrilmgtsdLATTFT-- 166

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|.
gi 1207186029 3448 flkqfsppiGTLDYMSPEMLKGDVVGPPADIWSIGILTYIM 3488
Cdd:cd08222    167 ---------GTPYYMSPEVLKHEGYNSKSDIWSLGCILYEM 198

Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 2 subunit; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phosphorylase kinase (PhK) catalyzes the phosphorylation of inactive phosphorylase b to form the active phosphorylase a. It coordinates hormonal, metabolic, and neuronal signals to initiate the breakdown of glycogen stores, which enables the maintenance of blood-glucose homeostasis during fasting, and is also used as a source of energy for muscle contraction. PhK is one of the largest and most complex protein kinases, composed of a heterotetramer containing four molecules each of four subunit types: one catalytic (gamma) and three regulatory (alpha, beta, and delta). The gamma 2 subunit (PhKG2) is also referred to as the testis/liver gamma isoform. Mutations in its gene cause autosomal-recessive glycogenosis of the liver. The gamma subunit, when isolated, is constitutively active and does not require phosphorylation of the A-loop for activity. The regulatory subunits restrain this kinase activity until signals are received to relieve this inhibition. For example, the kinase is activated in response to hormonal stimulation, after autophosphorylation or phosphorylation by cAMP-dependent kinase of the alpha and beta subunits. The high-affinity binding of ADP to the beta subunit also stimulates kinase activity, whereas calcium relieves inhibition by binding to the delta (calmodulin) subunit. The PhKG2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271083 [Multi-domain] Cd Length: 279 Bit Score: 96.96 E-value: 2.34e-21

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKIVPYEPES---------KQTVLQEYDILKSLH-HEKIMALHEAYVTPRYLVLISECCS 3377
Cdd:cd14181     20 RGVSSVVRRCVHRHTGQEFAVKIIEVTAERlspeqleevRSSTLKEIHILRQVSgHPSIITLIDSYESSTFIFLVFDLMR 99

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3378 GKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPlfLKQFSPPIG 3457
Cdd:cd14181    100 RGELFDYLTEKVTLSEKETRSIMRSLLEAVSYLHANNIVHRDLKPENILLDDQLHIKLSDFGFSCHLEP--GEKLRELCG 177

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3458 TLDYMSPEMLKGDV------VGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDL-SKLYQNVSQSASLFIK 3530
Cdd:cd14181    178 TPGYLAPEILKCSMdethpgYGKEVDLWACGVILFTLLAGSPPFWHRRQMLMLRMIMEGRYQFsSPEWDDRSSTVKDLIS 257

                          250       260
                   ....*....|....*....|..
gi 1207186029 3531 KILCSYPWARPTIKDCFTNSWL 3552
Cdd:cd14181    258 RLLVVDPEIRLTAEQALQHPFF 279

Catalytic domain of the Dual-specificity protein kinases, CDC-like kinases; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. CLKs are involved in the phosphorylation and regulation of serine/arginine-rich (SR) proteins, which play a crucial role in pre-mRNA splicing by directing splice site selection. SR proteins are phosphorylated first by SR protein kinases (SRPKs) at the N-terminus, which leads to its assembly into nuclear speckles where splicing factors are stored. CLKs phosphorylate the C-terminal part of SR proteins, causing the nuclear speckles to dissolve and splicing factors to be recruited at sites of active transcription. Based on a conserved "EHLAMMERILG" signature motif which may be crucial for substrate specificity, CLKs are also referred to as LAMMER kinases. CLKs autophosphorylate at tyrosine residues and phosphorylate their substrates exclusively on S/T residues. In Drosophila, the CLK homolog DOA (Darkener of apricot) is essential for embryogenesis and its mutation leads to defects in sexual differentiation, eye formation, and neuronal development. In fission yeast, the CLK homolog Lkh1 is a negative regulator of filamentous growth and asexual flocculation, and is also involved in oxidative stress response. Vertebrates contain mutliple CLK proteins and mammals have four (CLK1-4). The CLK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271036 [Multi-domain] Cd Length: 332 Bit Score: 98.02 E-value: 2.69e-21

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1658 LTDYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASALRELNILSHLDHE------RILYFHDAFEKKNAV 1731
Cdd:cd14134     10 LTNRYKILRLLGEGTFGKVLECWDRKRKRYVAVKIIRNVEKYREAAKIEIDVLETLAEKdpngksHCVQLRDWFDYRGHM 89

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1732 IIITELCHEELLDRLTKKS----TIleSEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHS--------------- 1792
Cdd:cd14134     90 CIVFELLGPSLYDFLKKNNygpfPL--EHVQHIAKQLLEAVAFLHDLKLTHTDLKPENILLVDSDyvkvynpkkkrqirv 167

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1793 --SDQIRICDFGNAVkfmpDEAQYCKY--GTPEFVAPEIVNQTPVSKATDIWPIG-VLTYLClTGVSPF----------- 1856
Cdd:cd14134    168 pkSTDIKLIDFGSAT----FDDEYHSSivSTRHYRAPEVILGLGWSYPCDVWSIGcILVELY-TGELLFqthdnlehlam 242

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1857 ---------------------------------AGENDRSSVLNIRNYNVAFEES------MFTDLCHeakgfviKLLVA 1897
Cdd:cd14134    243 merilgplpkrmirrakkgakyfyfyhgrldwpEGSSSGRSIKRVCKPLKRLMLLvdpehrLLFDLIR-------KMLEY 315

                          330
                   ....*....|....*..
gi 1207186029 1898 DR-LRPDANECLRHPWF 1913
Cdd:cd14134    316 DPsKRITAKEALKHPFF 332

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B beta (also called Akt2); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKB-beta is the predominant PKB isoform expressed in insulin-responsive tissues. It plays a critical role in the regulation of glucose homeostasis. It is also implicated in muscle cell differentiation. Mice deficient in PKB-beta display normal growth weights but exhibit severe insulin resistance and diabetes, accompanied by lipoatrophy and B-cell failure. PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain.The PKB-beta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173686 [Multi-domain] Cd Length: 323 Bit Score: 97.38 E-value: 4.09e-21

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1666 KEIGRGAFSYVKRVIQKAGKLEYAAKFISAR---AKRK-ASALRELNILSHLDHERILYFHDAFEKKNAVIIITELCHE- 1740
Cdd:cd05595      1 KLLGKGTFGKVILVREKATGRYYAMKILRKEviiAKDEvAHTVTESRVLQNTRHPFLTALKYAFQTHDRLCFVMEYANGg 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1741 ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNiLMADHSSdQIRICDFGNAVKFMPDEAQ---YCky 1817
Cdd:cd05595     81 ELFFHLSRERVFTEDRARFYGAEIVSALEYLHSRDVVYRDIKLEN-LMLDKDG-HIKITDFGLCKEGITDGATmktFC-- 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1818 GTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGEnDRSSVLNIrnynVAFEESMFT-DLCHEAKGFVIKLLV 1896
Cdd:cd05595    157 GTPEYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNQ-DHERLFEL----ILMEEIRFPrTLSPEAKSLLAGLLK 231

                          250       260
                   ....*....|....*....|....*..
gi 1207186029 1897 AD---RL---RPDANECLRHPWFKTLN 1917
Cdd:cd05595    232 KDpkqRLgggPSDAKEVMEHRFFLSIN 258

Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase 2 and 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK2 is regulated by cyclin E or cyclin A. Upon activation by cyclin E, it phosphorylates the retinoblastoma (pRb) protein which activates E2F mediated transcription and allows cells to move into S phase. The CDK2/cyclin A complex plays a role in regulating DNA replication. CDK2, together with CDK4, also regulates embryonic cell proliferation. Despite these important roles, mice deleted for the cdk2 gene are viable and normal except for being sterile. This may be due to compensation provided by CDK1 (also called Cdc2), which can also bind cyclin E and drive the G1 to S phase transition. CDK3 is regulated by cyclin C and it phosphorylates pRB specifically during the G0/G1 transition. This phosphorylation is required for cells to exit G0 efficiently and enter the G1 phase. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK2/3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270844 [Multi-domain] Cd Length: 284 Bit Score: 96.42 E-value: 4.25e-21

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3309 GRFGVIRECRENATGNLYMAKIVPYEPESK---QTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISE----------- 3374
Cdd:cd07860     11 GTYGVVYKARNKLTGEVVALKKIRLDTETEgvpSTAIREISLLKELNHPNIVKLLDVIHTENKLYLVFEflhqdlkkfmd 90

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3375 CCSGKELLHSLIDrfryseddvvAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNpLFLKQFSP 3454
Cdd:cd07860     91 ASALTGIPLPLIK----------SYLFQLLQGLAFCHSHRVLHRDLKPQNLLINTEGAIKLADFGLARAFG-VPVRTYTH 159

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1207186029 3455 PIGTLDYMSPEMLKG-DVVGPPADIWSIGILTYIMLSGRLPFtendPAETE 3504
Cdd:cd07860    160 EVVTLWYRAPEILLGcKYYSTAVDIWSLGCIFAEMVTRRALF----PGDSE 206

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B gamma (also called Akt3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKB-gamma is predominantly expressed in neuronal tissues. Mice deficient in PKB-gamma show a reduction in brain weight due to the decreases in cell size and cell number. PKB-gamma has also been shown to be upregulated in estrogen-deficient breast cancer cells, androgen-independent prostate cancer cells, and primary ovarian tumors. It acts as a key mediator in the genesis of ovarian cancer. PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. The PKB-gamma subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270745 [Multi-domain] Cd Length: 348 Bit Score: 97.84 E-value: 4.28e-21

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1646 EDEASILRKMRRLTDYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISAR---AKRK-ASALRELNILSHLDHERILYF 1721
Cdd:cd05593      1 EMDASTTHHKRKTMNDFDYLKLLGKGTFGKVILVREKASGKYYAMKILKKEviiAKDEvAHTLTESRVLKNTRHPFLTSL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1722 HDAFEKKNAVIIITELCHE-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICD 1800
Cdd:cd05593     81 KYSFQTKDRLCFVMEYVNGgELFFHLSRERVFSEDRTRFYGAEIVSALDYLHSGKIVYRDLKLENLML--DKDGHIKITD 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1801 FGNAVKFMPDEAQYCKY-GTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESM 1879
Cdd:cd05593    159 FGLCKEGITDAATMKTFcGTPEYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNQDHEKLFELILMEDIKFPRTL 238

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....
gi 1207186029 1880 FTDlcheAKGFVIKLLVAD---RL---RPDANECLRHPWFKTLN 1917
Cdd:cd05593    239 SAD----AKSLLSGLLIKDpnkRLgggPDDAKEIMRHSFFTGVN 278

Catalytic domain of Fungal Pat1-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Schizosaccharomyces pombe Pat1 (also called Ran1), Saccharomyces cerevisiae VHS1 and KSP1, and similar fungal STKs. Pat1 blocks Mei2, an RNA-binding protein which is indispensable in the initiation of meiosis. Pat1 is inactivated and Mei2 activated, which initiates meiosis, under nutrient-deprived conditions through a signaling cascade involving Ste11. Meiosis induced by Pat1 inactivation may show different characteristics than normal meiosis including aberrant positioning of centromeres. VHS1 was identified in a screen for suppressors of cell cycle arrest at the G1/S transition, while KSP1 may be involved in regulating PRP20, which is required for mRNA export and maintenance of nuclear structure. The Pat1-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270895 [Multi-domain] Cd Length: 267 Bit Score: 95.88 E-value: 4.78e-21

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1661 YYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFIS--------ARAKRKASALRELNILSHL-DHERILYFHDAFEKKNAV 1731
Cdd:cd13993      1 RYQLISPIGEGAYGVVYLAVDLRTGRKYAIKCLYksgpnskdGNDFQKLPQLREIDLHRRVsRHPNIITLHDVFETEVAI 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1732 IIITELCHE-ELLDRLT-KKSTILESE-IRSSVRQLLEGINYLHQLDILHLDIKPDNILMADhSSDQIRICDFGNAVkfm 1808
Cdd:cd13993     81 YIVLEYCPNgDLFEAITeNRIYVGKTElIKNVFLQLIDAVKHCHSLGIYHRDIKPENILLSQ-DEGTVKLCDFGLAT--- 156

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1207186029 1809 pDEAQYCKY--GTPEFVAPEIVNQTPVSKAT------DIWPIGVLTYLCLTGVSPF--AGENDRS 1863
Cdd:cd13993    157 -TEKISMDFgvGSEFYMAPECFDEVGRSLKGypcaagDIWSLGIILLNLTFGRNPWkiASESDPI 220

N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK2 and MSK1 play nonredundant roles in activating histone H3 kinases, which play pivotal roles in compaction of the chromatin fiber. MSK2 is the required H3 kinase in response to stress stimuli and activation of the p38 MAPK pathway. MSK2 also plays a role in the pathogenesis of psoriasis. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family, similar to 90 kDa ribosomal protein S6 kinases (RSKs). MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. The MSK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270765 [Multi-domain] Cd Length: 332 Bit Score: 97.30 E-value: 5.88e-21

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3307 ARGRFGVIRECRENATGNLYMAKIVPYEPESKQTVLQEY-----DILKSLHHEK-IMALHEAYVTPRYLVLISECCSGKE 3380
Cdd:cd05614     12 AYGKVFLVRKVSGHDANKLYAMKVLRKAALVQKAKTVEHtrterNVLEHVRQSPfLVTLHYAFQTDAKLHLILDYVSGGE 91

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3381 LLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLKQFSPPIGTLD 3460
Cdd:cd05614     92 LFTHLYQRDHFSEDEVRFYSGEIILALEHLHKLGIVYRDIKLENILLDSEGHVVLTDFGLSKEFLTEEKERTYSFCGTIE 171

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3461 YMSPEMLKGDV-VGPPADIWSIGILTYIMLSGRLPFT----ENDPAETEARIQAAKFDLSKLYQNVSQSaslFIKKILCS 3535
Cdd:cd05614    172 YMAPEIIRGKSgHGKAVDWWSLGILMFELLTGASPFTlegeKNTQSEVSRRILKCDPPFPSFIGPVARD---LLQKLLCK 248


                   ....*
gi 1207186029 3536 YPWAR 3540
Cdd:cd05614    249 DPKKR 253

Catalytic domain of the Serine/Threonine Kinase, Serine-aRginine Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SRPKs phosphorylate and regulate splicing factors from the SR protein family by specifically phosphorylating multiple serine residues residing in SR/RS dipeptide motifs (also known as RS domains). Phosphorylation of the RS domains enhances interaction with transportin SR and facilitates entry of the SR proteins into the nucleus. SRPKs contain a nonconserved insert domain, within the well-conserved catalytic kinase domain, that regulates their subcellular localization. They play important roles in mediating pre-mRNA processing and mRNA maturation, as well as other cellular functions such as chromatin reorganization, cell cycle and p53 regulation, and metabolic signaling. Vertebrates contain three distinct SRPKs, called SRPK1-3. The SRPK homolog in budding yeast, Sky1p, recognizes and phosphorylates its substrate Npl3p, which lacks a classic RS domain but contains a single RS dipeptide at the C-terminus of its RGG domain. Npl3p is a shuttling heterogeneous nuclear ribonucleoprotein (hnRNP) that exports a distinct class of mRNA from the nucleus to the cytoplasm. The SRPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271038 [Multi-domain] Cd Length: 320 Bit Score: 96.88 E-value: 6.53e-21

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3378 GKELLHsLIDRFRYSE---DDVVAYIVQILQGLDYLHSR-RILHLDIKPENIIVTYMNV-VKIIDFGSAQTFNplflKQF 3452
Cdd:cd14136    101 GPNLLK-LIKRYNYRGiplPLVKKIARQVLQGLDYLHTKcGIIHTDIKPENVLLCISKIeVKIADLGNACWTD----KHF 175

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 1207186029 3453 SPPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPF 3495
Cdd:cd14136    176 TEDIQTRQYRSPEVILGAGYGTPADIWSTACMAFELATGDYLF 218

The catalytic domain of the Serine/Threonine Kinase, Glycogen Synthase Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GSK3 is a mutifunctional kinase involved in many cellular processes including cell division, proliferation, differentiation, adhesion, and apoptosis. In plants, GSK3 plays a role in the response to osmotic stress. In Caenorhabditis elegans, it plays a role in regulating normal oocyte-to-embryo transition and response to oxidative stress. In Chlamydomonas reinhardtii, GSK3 regulates flagellar length and assembly. In mammals, there are two isoforms, GSK3alpha and GSK3beta, which show both distinct and redundant functions. The two isoforms differ mainly in their N-termini. They are both involved in axon formation and in Wnt signaling.They play distinct roles in cardiogenesis, with GSKalpha being essential in cardiomyocyte survival, and GSKbeta regulating heart positioning and left-right symmetry. GSK3beta was first identified as a regulator of glycogen synthesis, but has since been determined to play other roles. It regulates the degradation of beta-catenin and IkB. Beta-catenin is the main effector of Wnt, which is involved in normal haematopoiesis and stem cell function. IkB is a central inhibitor of NF-kB, which is critical in maintaining leukemic cell growth. GSK3beta is enriched in the brain and is involved in regulating neuronal signaling pathways. It is implicated in the pathogenesis of many diseases including Type II diabetes, obesity, mood disorders, Alzheimer's disease, osteoporosis, and some types of cancer, among others. The GSK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271039 [Multi-domain] Cd Length: 293 Bit Score: 96.03 E-value: 6.69e-21

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3297 QKPYTFMDEK--ARGRFGVIRECRENATGNLYMAKIVPYEPESKQtvlQEYDILKSLHHEKIMALHEAYVTP------RY 3368
Cdd:cd14137      1 PVEISYTIEKviGSGSFGVVYQAKLLETGEVVAIKKVLQDKRYKN---RELQIMRRLKHPNIVKLKYFFYSSgekkdeVY 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3369 LVLISECCSgkELLHSLIDRFRYSED-----DVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMN-VVKIIDFGSAQ 3442
Cdd:cd14137     78 LNLVMEYMP--ETLYRVIRHYSKNKQtipiiYVKLYSYQLFRGLAYLHSLGICHRDIKPQNLLVDPETgVLKLCDFGSAK 155

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....
gi 1207186029 3443 tfnplFLKQFSPP---IGTLDYMSPEMLKGDVV-GPPADIWSIG 3482
Cdd:cd14137    156 -----RLVPGEPNvsyICSRYYRAPELIFGATDyTTAIDIWSAG 194

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase Like 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mutations in the gene encoding CDKL5, previously called STK9, are associated with early onset epilepsy and severe mental retardation [X-linked infantile spasm syndrome (ISSX) or West syndrome]. In addition, CDKL5 mutations also sometimes cause a phenotype similar to Rett syndrome (RTT), a progressive neurodevelopmental disorder. These pathogenic mutations are located in the N-terminal portion of the protein within the kinase domain. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270838 [Multi-domain] Cd Length: 287 Bit Score: 95.83 E-value: 6.79e-21

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGK-LEYAAKFISARAKR--KASALRELNILSHLDHERILYFHDAFEKKNAVIIITELC 1738
Cdd:cd07848      3 FEVLGVVGEGAYGVVLKCRHKETKeIVAIKKFKDSEENEevKETTLRELKMLRTLKQENIVELKEAFRRRGKLYLVFEYV 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1739 HEELLDRLTKKST-ILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMAdhSSDQIRICDFGNAVKFMP-DEAQYCK 1816
Cdd:cd07848     83 EKNMLELLEEMPNgVPPEKVRSYIYQLIKAIHWCHKNDIVHRDIKPENLLIS--HNDVLKLCDFGFARNLSEgSNANYTE 160

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1207186029 1817 Y-GTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIR 1869
Cdd:cd07848    161 YvATRWYRSPELLLGAPYGKAVDMWSVGCILGELSDGQPLFPGESEIDQLFTIQ 214

Catalytic domain of the Serine/Threonine Kinases, Oxidative stress response kinase and Ste20-related proline alanine-rich kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SPAK is also referred to as STK39 or PASK (proline-alanine-rich STE20-related kinase). OSR1 and SPAK regulate the activity of cation-chloride cotransporters through direct interaction and phosphorylation. They are also implicated in cytoskeletal rearrangement, cell differentiation, transformation and proliferation. OSR1 and SPAK contain a conserved C-terminal (CCT) domain, which recognizes a unique motif ([RK]FX[VI]) present in their activating kinases (WNK1/WNK4) and their substrates. The OSR1 and SPAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270787 [Multi-domain] Cd Length: 267 Bit Score: 95.50 E-value: 7.42e-21

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1660 DYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARaKRKAS---ALRELNILSHLDHERILYFHDAFEKKNAVIIITE 1736
Cdd:cd06610      1 DDYELIEVIGSGATAVVYAAYCLPKKEKVAIKRIDLE-KCQTSmdeLRKEIQAMSQCNHPNVVSYYTSFVVGDELWLVMP 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1737 LCHE----ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSdqIRICDFGNAVKF----- 1807
Cdd:cd06610     80 LLSGgsllDIMKSSYPRGGLDEAIIATVLKEVLKGLEYLHSNGQIHRDVKAGNILLGEDGS--VKIADFGVSASLatggd 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1808 MPDEAQYCKYGTPEFVAPEIVNQTP--VSKAtDIWPIGVLTYLCLTGVSPFAGEND-RSSVLNIRNYNVAFEESMFTDLC 1884
Cdd:cd06610    158 RTRKVRKTFVGTPCWMAPEVMEQVRgyDFKA-DIWSFGITAIELATGAAPYSKYPPmKVLMLTLQNDPPSLETGADYKKY 236

                          250       260       270
                   ....*....|....*....|....*....|.
gi 1207186029 1885 -HEAKGFVIKLLVADRL-RPDANECLRHPWF 1913
Cdd:cd06610    237 sKSFRKMISLCLQKDPSkRPTAEELLKHKFF 267

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek1 is associated with centrosomes throughout the cell cycle. It is involved in the formation of primary cilium and in the maintenance of centrosomes. It cycles through the nucleus and may be capable of relaying signals between the cilium and the nucleus. Nek1 is implicated in the development of polycystic kidney disease, which is characterized by benign polycystic tumors formed by abnormal overgrowth of renal epithelial cells. It appears also to be involved in DNA damage response, and may be important for both correct DNA damage checkpoint activation and DNA repair. Nek1 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270858 [Multi-domain] Cd Length: 256 Bit Score: 94.88 E-value: 7.47e-21

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFIS---ARAKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITELC 1738
Cdd:cd08218      2 YVRIKKIGEGSFGKALLVKSKEDGKQYVIKEINiskMSPKEREESRKEVAVLSKMKHPNIVQYQESFEENGNLYIVMDYC 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1739 HE-ELLDRLTKKSTIL--ESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSdqIRICDFGNA--VKFMPDEAQ 1813
Cdd:cd08218     82 DGgDLYKRINAQRGVLfpEDQILDWFVQLCLALKHVHDRKILHRDIKSQNIFLTKDGI--IKLGDFGIArvLNSTVELAR 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1814 YCkYGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTdlcHEAKGFVIK 1893
Cdd:cd08218    160 TC-IGTPYYLSPEICENKPYNNKSDIWALGCVLYEMCTLKHAFEAGNMKNLVLKIIRGSYPPVPSRYS---YDLRSLVSQ 235

                          250
                   ....*....|....*....
gi 1207186029 1894 LLVAD-RLRPDANECLRHP 1911
Cdd:cd08218    236 LFKRNpRDRPSINSILEKP 254

Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase kinase kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP4K5, also called germinal center kinase-related enzyme (GCKR), has been shown to activate the MAPK c-Jun N-terminal kinase (JNK). MAP4K5 also facilitates Wnt signaling in B cells, and may therefore be implicated in the control of cell fate, proliferation, and polarity. MAP4Ks are involved in some MAPK signaling pathways by activating a MAPK kinase kinase. Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Members of this subfamily contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. The MAP4K5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270813 [Multi-domain] Cd Length: 268 Bit Score: 95.48 E-value: 7.90e-21

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3296 PQKPYTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPESKQTVLQ-EYDILKSLHHEKIMALHEAYVTPRYLVLISE 3374
Cdd:cd06646      7 PQHDYELIQRVGSGTYGDVYKARNLHTGELAAVKIIKLEPGDDFSLIQqEIFMVKECKHCNIVAYFGSYLSREKLWICME 86

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3375 CCSGKellhSLIDRFRYS---EDDVVAYIV-QILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLK 3450
Cdd:cd06646     87 YCGGG----SLQDIYHVTgplSELQIAYVCrETLQGLAYLHSKGKMHRDIKGANILLTDNGDVKLADFGVAAKITATIAK 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3451 QFSpPIGTLDYMSPEML---KGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLSKLYQNVSQSASL 3527
Cdd:cd06646    163 RKS-FIGTPYWMAPEVAaveKNGGYNQLCDIWAVGITAIELAELQPPMFDLHPMRALFLMSKSNFQPPKLKDKTKWSSTF 241

                          250       260
                   ....*....|....*....|....*..
gi 1207186029 3528 --FIKKILCSYPWARPTIKDCFTNSWL 3552
Cdd:cd06646    242 hnFVKISLTKNPKKRPTAERLLTHLFV 268

Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase Kinases 12 and 13; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP3K12 is also called MAPK upstream kinase (MUK), dual leucine zipper-bearing kinase (DLK) or leucine-zipper protein kinase (ZPK). It is involved in the c-Jun N-terminal kinase (JNK) pathway that directly regulates axonal regulation through the phosphorylation of microtubule-associated protein 1B (MAP1B). It also regulates the differentiation of many cell types including adipocytes and may play a role in adipogenesis. MAP3K13, also called leucine zipper-bearing kinase (LZK), directly phosphorylates and activates MKK7, which in turn activates the JNK pathway. It also activates NF-kB through IKK activation and this activity is enhanced by antioxidant protein-1 (AOP-1). MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAP2Ks (MAPKKs or MKKs), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The MAP3K12/13 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270961 [Multi-domain] Cd Length: 237 Bit Score: 94.48 E-value: 7.99e-21

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3342 LQEYDI--LKSLHHEKIMALHEAYVT-PRYLVLISECCSGK--ELLHsliDRFRYSEDDVVAYIVQILQGLDYLHSRRIL 3416
Cdd:cd14059     27 EKETDIkhLRKLNHPNIIKFKGVCTQaPCYCILMEYCPYGQlyEVLR---AGREITPSLLVDWSKQIASGMNYLHLHKII 103

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3417 HLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLK-QFSppiGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPF 3495
Cdd:cd14059    104 HRDLKSPNVLVTYNDVLKISDFGTSKELSEKSTKmSFA---GTVAWMAPEVIRNEPCSEKVDIWSFGVVLWELLTGEIPY 180


                   ....*.
gi 1207186029 3496 TENDPA 3501
Cdd:cd14059    181 KDVDSS 186

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase Like 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mutations in the gene encoding CDKL5, previously called STK9, are associated with early onset epilepsy and severe mental retardation [X-linked infantile spasm syndrome (ISSX) or West syndrome]. In addition, CDKL5 mutations also sometimes cause a phenotype similar to Rett syndrome (RTT), a progressive neurodevelopmental disorder. These pathogenic mutations are located in the N-terminal portion of the protein within the kinase domain. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270838 [Multi-domain] Cd Length: 287 Bit Score: 95.45 E-value: 9.27e-21

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3309 GRFGVIRECRENATGNLYMAKIVPYEPES---KQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGK--ELLH 3383
Cdd:cd07848     12 GAYGVVLKCRHKETKEIVAIKKFKDSEENeevKETTLRELKMLRTLKQENIVELKEAFRRRGKLYLVFEYVEKNmlELLE 91

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3384 SLIDRfrYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLKQFSPPIGTLDYMS 3463
Cdd:cd07848     92 EMPNG--VPPEKVRSYIYQLIKAIHWCHKNDIVHRDIKPENLLISHNDVLKLCDFGFARNLSEGSNANYTEYVATRWYRS 169

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|.
gi 1207186029 3464 PEMLKGDVVGPPADIWSIGILTYIMLSGRLPFtendPAETE 3504
Cdd:cd07848    170 PELLLGAPYGKAVDMWSVGCILGELSDGQPLF----PGESE 206

Catalytic domain of Suppressor of loss of cAMP-dependent protein kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Schizosaccharomyces pombe Sck1 and similar fungal proteins. Sck1 plays a role in trehalase activation triggered by glucose and a nitrogen source. Trehalase catalyzes the cleavage of the disaccharide trehalose to glucose. Trehalose, as a carbohydrate reserve and stress metabolite, plays an important role in the response of yeast to environmental changes. The Sck1-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270738 [Multi-domain] Cd Length: 330 Bit Score: 96.49 E-value: 9.33e-21

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYVKRVIQKAGKLEYAAKFIS----ARAKRKASALRELNIL---SHLDHERILYFHDAFEKKNAVIIITE-LCH 1739
Cdd:cd05586      1 IGKGTFGQVYQVRKKDTRRIYAMKVLSkkviVAKKEVAHTIGERNILvrtALDESPFIVGLKFSFQTPTDLYLVTDyMSG 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1740 EELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDFGNAVKFMPDEAQ---YCk 1816
Cdd:cd05586     81 GELFWHLQKEGRFSEDRAKFYIAELVLALEHLHKNDIVYRDLKPENILL--DANGHIALCDFGLSKADLTDNKTtntFC- 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1817 yGTPEFVAPEI-VNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDlchEAKGFVIKLL 1895
Cdd:cd05586    158 -GTTEYLAPEVlLDEKGYTKMVDFWSLGVLVFEMCCGWSPFYAEDTQQMYRNIAFGKVRFPKDVLSD---EGRSFVKGLL 233

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1896 VAD---RL--RPDANECLRHPWFktlnkgKSISTESLKKFLSRRKWQRSLISYKSkmVMRSVPELLDDSSSHISIaVPRH 1970
Cdd:cd05586    234 NRNpkhRLgaHDDAVELKEHPFF------ADIDWDLLSKKKITPPFKPIVDSDTD--VSNFDPEFTNASLLNANI-VPWA 304


                   ....*.
gi 1207186029 1971 LKKGSP 1976
Cdd:cd05586    305 QRPGLP 310

Catalytic domain of Dual-specificity tYrosine-phosphorylated and -Regulated Kinase-like protein kinases; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. This subfamily is composed of the dual-specificity DYRKs and YAK1, as well as the S/T kinases (STKs), HIPKs. DYRKs and YAK1 autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. Proteins in this subfamily play important roles in cell proliferation, differentiation, survival, growth, and development. The DYRK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271035 [Multi-domain] Cd Length: 262 Bit Score: 94.64 E-value: 9.90e-21

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKIVPYEPESKQTVLQEYDILKSLH------HEKIMALHEAYVTPRYLVLISECCSGKel 3381
Cdd:cd14133      9 KGTFGQVVKCYDLLTGEEVALKIIKNNKDYLDQSLDEIRLLELLNkkdkadKYHIVRLKDVFYFKNHLCIVFELLSQN-- 86

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3382 LHSLI--DRFRYSEDDVVAYIV-QILQGLDYLHSRRILHLDIKPENIIVTYMN--VVKIIDFGSAqtfnpLFLKQ-FSPP 3455
Cdd:cd14133     87 LYEFLkqNKFQYLSLPRIRKIAqQILEALVFLHSLGLIHCDLKPENILLASYSrcQIKIIDFGSS-----CFLTQrLYSY 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3456 IGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQA--AKFDLSKLYQNVSQSASL--FIKK 3531
Cdd:cd14133    162 IQSRYYRAPEVILGLPYDEKIDMWSLGCILAELYTGEPLFPGASEVDQLARIIGtiGIPPAHMLDQGKADDELFvdFLKK 241

                          250       260
                   ....*....|....*....|.
gi 1207186029 3532 ILCSYPWARPTIKDCFTNSWL 3552
Cdd:cd14133    242 LLEIDPKERPTASQALSHPWL 262

Catalytic domain of the Serine/Threonine kinase, Aurora-B kinase and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Aurora kinases are key regulators of mitosis and are essential for the accurate and equal division of genomic material from parent to daughter cells. Vertebrates contain at least 2 Aurora kinases (A and B); mammals contains a third Aurora kinase gene (C). This subfamily includes Aurora-B and Aurora-C. Aurora-B is most active at the transition during metaphase to the end of mitosis. It associates with centromeres, relocates to the midzone of the central spindle, and concentrates at the midbody during cell division. It is critical for accurate chromosomal segregation, cytokinesis, protein localization to the centrosome and kinetochore, correct microtubule-kinetochore attachments, and regulation of the mitotic checkpoint. Aurora-C is mainly expressed in meiotically dividing cells; it was originally discovered in mice as a testis-specific STK called Aie1. Both Aurora-B and -C are chromosomal passenger proteins that can form complexes with INCENP and survivin, and they may have redundant cellular functions. INCENP participates in the activation of Aurora-B in a two-step process: first by binding to form an intermediate state of activation and the phosphorylation of its C-terminal TSS motif to generate the fully active kinase. The Aurora-B subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271019 [Multi-domain] Cd Length: 270 Bit Score: 94.93 E-value: 1.03e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1656 RRLT-DYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAK--FISARAKR--KASALRELNILSHLDHERILYFHDAFEKKNA 1730
Cdd:cd14117      1 RKFTiDDFDIGRPLGKGKFGNVYLAREKQSKFIVALKvlFKSQIEKEgvEHQLRREIEIQSHLRHPNILRLYNYFHDRKR 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1731 VIIITELCHE-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMAdhSSDQIRICDFGNAVKfMP 1809
Cdd:cd14117     81 IYLILEYAPRgELYKELQKHGRFDEQRTATFMEELADALHYCHEKKVIHRDIKPENLLMG--YKGELKIADFGWSVH-AP 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1810 DEAQYCKYGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDlcheAKG 1889
Cdd:cd14117    158 SLRRRTMCGTLDYLPPEMIEGRTHDEKVDLWCIGVLCYELLVGMPPFESASHTETYRRIVKVDLKFPPFLSDG----SRD 233

                          250       260
                   ....*....|....*....|....*....
gi 1207186029 1890 FVIKLLvadRLRPDANECLR----HPWFK 1914
Cdd:cd14117    234 LISKLL---RYHPSERLPLKgvmeHPWVK 259

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B alpha (also called Akt1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKB-alpha is predominantly expressed in endothelial cells. It is critical for the regulation of angiogenesis and the maintenance of vascular integrity. It also plays a role in adipocyte differentiation. Mice deficient in PKB-alpha exhibit perinatal morbidity, growth retardation, reduction in body weight accompanied by reduced sizes of multiple organs, and enhanced apoptosis in some cell types. PKB-alpha activity has been reported to be frequently elevated in breast and prostate cancers. In some cancer cells, PKB-alpha may act as a suppressor of metastasis. PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. The PKB-alpha subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270746 [Multi-domain] Cd Length: 356 Bit Score: 97.02 E-value: 1.09e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3289 STLRQGVPQKPYTFMDEKARGRFGVIRECRENATGNLYMAKIVPYE----PESKQTVLQEYDILKSLHHEKIMALHEAYV 3364
Cdd:cd05594     16 TKPKHKVTMNDFEYLKLLGKGTFGKVILVKEKATGRYYAMKILKKEvivaKDEVAHTLTENRVLQNSRHPFLTALKYSFQ 95

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3365 TPRYLVLISECCSGKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRR-ILHLDIKPENIIVTYMNVVKIIDFGSAQ- 3442
Cdd:cd05594     96 THDRLCFVMEYANGGELFFHLSRERVFSEDRARFYGAEIVSALDYLHSEKnVVYRDLKLENLMLDKDGHIKITDFGLCKe 175

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1207186029 3443 -TFNPLFLKQFSppiGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTEND 3499
Cdd:cd05594    176 gIKDGATMKTFC---GTPEYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNQD 230

Catalytic domain of Cyclin-Dependent protein Kinase 4 and 6-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK4 and CDK6 partner with D-type cyclins to regulate the early G1 phase of the cell cycle. They are the first kinases activated by mitogenic signals to release cells from the G0 arrested state. CDK4 and CDK6 are both expressed ubiquitously, associate with all three D cyclins (D1, D2 and D3), and phosphorylate the retinoblastoma (pRb) protein. They are also regulated by the INK4 family of inhibitors which associate with either the CDK alone or the CDK/cyclin complex. CDK4 and CDK6 show differences in subcellular localization, sensitivity to some inhibitors, timing in activation, tumor selectivity, and possibly substrate profiles. Although CDK4 and CDK6 seem to show some redundancy, they also have discrete, nonoverlapping functions. CDK6 plays an important role in cell differentiation. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK4/6-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270831 [Multi-domain] Cd Length: 287 Bit Score: 95.42 E-value: 1.13e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLY-MAKI-VPYEPES-KQTVLQEYDILKSL---HHEKIMALHEAYVTPRYlvlis 3373
Cdd:cd07838      1 YEEVAEIGEGAYGTVYKARDLQDGRFVaLKKVrVPLSEEGiPLSTIREIALLKQLesfEHPNVVRLLDVCHGPRT----- 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3374 eccsGKELLHSLIdrFRYSEDDVVAYI-----------------VQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKII 3436
Cdd:cd07838     76 ----DRELKLTLV--FEHVDQDLATYLdkcpkpglppetikdlmRQLLRGLDFLHSHRIVHRDLKPQNILVTSDGQVKLA 149

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3437 DFGSAQTFNplFLKQFSPPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPF---TEND-----------PAE 3502
Cdd:cd07838    150 DFGLARIYS--FEMALTSVVVTLWYRAPEVLLQSSYATPVDMWSVGCIFAELFNRRPLFrgsSEADqlgkifdviglPSE 227

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3503 TE-------ARI---QAAKFDLSKLYQNVSQSASLFIKKILCSYPWARPTIKDCFTNSWL 3552
Cdd:cd07838    228 EEwprnsalPRSsfpSYTPRPFKSFVPEIDEEGLDLLKKMLTFNPHKRISAFEALQHPYF 287

Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMP-activated protein kinase (AMPK). CaMKK1, also called CaMKK alpha, is involved in the regulation of glucose uptake in skeletal muscles, independently of AMPK and PKB activation. It also play roles in learning and memory. Studies on CaMKK1 knockout mice reveal deficits in fear conditioning. The CaMKK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271102 [Multi-domain] Cd Length: 284 Bit Score: 95.02 E-value: 1.17e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISA---------------RAKRKASA------------LRELNILSHLD 1714
Cdd:cd14200      2 YKLQSEIGKGSYGVVKLAYNESDDKYYAMKVLSKkkllkqygfprrpppRGSKAAQGeqakplaplervYQEIAILKKLD 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1715 HERILYFHDAFEK--KNAVIIITELCHEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHS 1792
Cdd:cd14200     82 HVNIVKLIEVLDDpaEDNLYMVFDLLRKGPVMEVPSDKPFSEDQARLYFRDIVLGIEYLHYQKIVHRDIKPSNLLLGDDG 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1793 sdQIRICDFGNAVKFMPDEAQYCKY-GTPEFVAPEIVNQTPVS---KATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNI 1868
Cdd:cd14200    162 --HVKIADFGVSNQFEGNDALLSSTaGTPAFMAPETLSDSGQSfsgKALDVWAMGVTLYCFVYGKCPFIDEFILALHNKI 239

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*
gi 1207186029 1869 RNYNVAFEESmfTDLCHEAKGFVIKLLVAD-RLRPDANECLRHPW 1912
Cdd:cd14200    240 KNKPVEFPEE--PEISEELKDLILKMLDKNpETRITVPEIKVHPW 282

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated protein kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK-activated protein kinase 2 (MAPKAP2 or MK2) contains an N-terminal proline-rich region that can bind to SH3 domains, a catalytic kinase domain followed by a C-terminal autoinhibitory region that contains nuclear localization (NLS) and nuclear export (NES) signals with a p38 MAPK docking motif that overlaps the NLS. MK2 is a bonafide substrate for the MAPK p38. It is closely related to MK3 and thus far, MK2/3 show indistinguishable substrate specificity. They are mainly involved in the regulation of gene expression and they participate in diverse cellular processes such as endocytosis, cytokine production, cytoskeletal reorganization, cell migration, cell cycle control and chromatin remodeling. They are implicated in inflammation and cance and their substrates include mRNA-AU-rich-element (ARE)-binding proteins (TTP and hnRNP A0), Hsp proteins (Hsp27 and Hsp25) and RSK, among others. MK2/3 are both expressed ubiquitously but MK2 is expressed at significantly higher levels. The MK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271072 [Multi-domain] Cd Length: 303 Bit Score: 95.49 E-value: 1.26e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3312 GVIRECRENATGNLYMAKIVPYEPESKQTVLQEYDILKSLHHEKIMALHE-AYVTPRYLVLISECCSGKELLHSLIDRF- 3389
Cdd:cd14170     16 GKVLQIFNKRTQEKFALKMLQDCPKARREVELHWRASQCPHIVRIVDVYEnLYAGRKCLLIVMECLDGGELFSRIQDRGd 95

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3390 -RYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMN---VVKIIDFGSAQ---TFNPLflkqfSPPIGTLDYM 3462
Cdd:cd14170     96 qAFTEREASEIMKSIGEAIQYLHSINIAHRDVKPENLLYTSKRpnaILKLTDFGFAKettSHNSL-----TTPCYTPYYV 170

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3463 SPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTEN-----DPAeTEARIQAAKFDL-SKLYQNVSQSASLFIKKILCSY 3536
Cdd:cd14170    171 APEVLGPEKYDKSCDMWSLGVIMYILLCGYPPFYSNhglaiSPG-MKTRIRMGQYEFpNPEWSEVSEEVKMLIRNLLKTE 249

                          250       260       270
                   ....*....|....*....|....*....|....*...
gi 1207186029 3537 PWARPTIKDCFTNSWLQDAYLMrlrRQTLTFTTTRLKE 3574
Cdd:cd14170    250 PTQRMTITEFMNHPWIMQSTKV---PQTPLHTSRVLKE 284

Catalytic domain of fungal Pek1-like dual-specificity Mitogen-Activated Protein Kinase Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include the MAPKKs Pek1/Skh1 from Schizosaccharomyces pombe and MKK2 from Saccharomyces cerevisiae, and related proteins. Both fission yeast Pek1 and baker's yeast MKK2 are components of the cell integrity MAPK pathway. In fission yeast, Pek1 phosphorylates and activates Pmk1/Spm1 and is regulated by the MAPKK kinase Mkh1. In baker's yeast, the pathway involves the MAPK Slt2, the MAPKKs MKK1 and MKK2, and the MAPKK kinase Bck1. The cell integrity MAPK cascade is activated by multiple stress conditions, and is essential in cell wall construction, morphogenesis, cytokinesis, and ion homeostasis. MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The MAPKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270793 [Multi-domain] Cd Length: 287 Bit Score: 95.18 E-value: 1.31e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYVKRVIQKAGKLEYAAKFISARAKR--KASALRELNILSHLDHERILYFHDAF--EKKNAVIIITELCHEELL 1743
Cdd:cd06621      9 LGEGAGGSVTKCRLRNTKTIFALKTITTDPNPdvQKQILRELEINKSCASPYIVKYYGAFldEQDSSIGIAMEYCEGGSL 88

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1744 DRLTKKstILESEIRSSVRQL-------LEGINYLHQLDILHLDIKPDNILMAdhSSDQIRICDFGNAVKFMPDEAQYCK 1816
Cdd:cd06621     89 DSIYKK--VKKKGGRIGEKVLgkiaesvLKGLSYLHSRKIIHRDIKPSNILLT--RKGQVKLCDFGVSGELVNSLAGTFT 164

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1817 yGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDR--------SSVLNIRNYNVAFEESMFTDLCHEAK 1888
Cdd:cd06621    165 -GTSYYMAPERIQGGPYSITSDVWSLGLTLLEVAQNRFPFPPEGEPplgpiellSYIVNMPNPELKDEPENGIKWSESFK 243

                          250       260       270
                   ....*....|....*....|....*....|...
gi 1207186029 1889 GFVIKLLVADRL-RPDANECLRHPWFKTLNKGK 1920
Cdd:cd06621    244 DFIEKCLEKDGTrRPGPWQMLAHPWIKAQEKKK 276

Catalytic domain of the Protein Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGK1 is ubiquitously expressed and is under transcriptional control of numerous stimuli including cell stress (cell shrinkage), serum, hormones (gluco- and mineralocorticoids), gonadotropins, growth factors, interleukin-6, and other cytokines. It plays roles in sodium retention and potassium elimination in the kidney, nutrient transport, salt sensitivity, memory consolidation, and cardiac repolarization. A common SGK1 variant is associated with increased blood pressure and body weight. SGK1 may also contribute to tumor growth, neurodegeneration, fibrosing disease, and ischemia. The SGK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270753 [Multi-domain] Cd Length: 339 Bit Score: 96.24 E-value: 1.32e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARA----KRKASALRELNIL-SHLDHERILYFHDAFEKKNAVIIITE 1736
Cdd:cd05602      9 FHFLKVIGKGSFGKVLLARHKSDEKFYAVKVLQKKAilkkKEEKHIMSERNVLlKNVKHPFLVGLHFSFQTTDKLYFVLD 88

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1737 LCHE-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDFG---NAVKFMPDEA 1812
Cdd:cd05602     89 YINGgELFYHLQRERCFLEPRARFYAAEIASALGYLHSLNIVYRDLKPENILL--DSQGHIVLTDFGlckENIEPNGTTS 166

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1813 QYCkyGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEesmfTDLCHEAKGFVI 1892
Cdd:cd05602    167 TFC--GTPEYLAPEVLHKQPYDRTVDWWCLGAVLYEMLYGLPPFYSRNTAEMYDNILNKPLQLK----PNITNSARHLLE 240

                          250       260       270
                   ....*....|....*....|....*....|
gi 1207186029 1893 KLLVADRLR-----PDANECLRHPWFKTLN 1917
Cdd:cd05602    241 GLLQKDRTKrlgakDDFTEIKNHIFFSPIN 270

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 1 from higher eukaryotes; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK1 is also called Cell division control protein 2 (Cdc2) or p34 protein kinase, and is regulated by cyclins A, B, and E. The CDK1/cyclin A complex controls G2 phase entry and progression. CDK1/cyclin A2 has also been implicated as an important regulator of S phase events. The CDK1/cyclin B complex is critical for G2 to M phase transition. It induces mitosis by activating nuclear enzymes that regulate chromatin condensation, nuclear membrane degradation, mitosis-specific microtubule and cytoskeletal reorganization. CDK1 also associates with cyclin E and plays a role in the entry into S phase. CDK1 transcription is stable throughout the cell cycle but is modulated in some pathological conditions. It may play a role in regulating apoptosis under these conditions. In breast cancer cells, HER2 can mediate apoptosis by inactivating CDK1. Activation of CDK1 may contribute to HIV-1 induced apoptosis as well as neuronal apoptosis in neurodegenerative diseases. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270845 [Multi-domain] Cd Length: 285 Bit Score: 94.79 E-value: 1.54e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPESK---QTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISE-- 3374
Cdd:cd07861      2 YTKIEKIGEGTYGVVYKGRNKKTGQIVAMKKIRLESEEEgvpSTAIREISLLKELQHPNIVCLEDVLMQENRLYLVFEfl 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3375 CCSGKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNpLFLKQFSP 3454
Cdd:cd07861     82 SMDLKKYLDSLPKGKYMDAELVKSYLYQILQGILFCHSRRVLHRDLKPQNLLIDNKGVIKLADFGLARAFG-IPVRVYTH 160

                          170       180
                   ....*....|....*....|....*....
gi 1207186029 3455 PIGTLDYMSPEMLKGDV-VGPPADIWSIG 3482
Cdd:cd07861    161 EVVTLWYRAPEVLLGSPrYSTPVDIWSIG 189

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek6 is required for the transition from metaphase to anaphase. It also plays important roles in mitotic spindle formation and cytokinesis. Activated by Nek9 during mitosis, Nek6 phosphorylates Eg5, a kinesin that is important for spindle bipolarity. Nek6 localizes to spindle microtubules during metaphase and anaphase, and to the midbody during cytokinesis. It is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270865 [Multi-domain] Cd Length: 268 Bit Score: 94.32 E-value: 1.62e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3334 EPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELlHSLIDRFRYS-----EDDVVAYIVQILQGLD 3408
Cdd:cd08228     42 DAKARQDCVKEIDLLKQLNHPNVIKYLDSFIEDNELNIVLELADAGDL-SQMIKYFKKQkrlipERTVWKYFVQLCSAVE 120

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3409 YLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLKQFSpPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIM 3488
Cdd:cd08228    121 HMHSRRVMHRDIKPANVFITATGVVKLGDLGLGRFFSSKTTAAHS-LVGTPYYMSPERIHENGYNFKSDIWSLGCLLYEM 199

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*....
gi 1207186029 3489 LSGRLPFTENdpaeteariqaaKFDLSKLYQNVSQsaslfikkilCSYP 3537
Cdd:cd08228    200 AALQSPFYGD------------KMNLFSLCQKIEQ----------CDYP 226

Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Activated Kinase-1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAK1 is also known as mitogen-activated protein kinase kinase kinase 7 (MAPKKK7 or MAP3K7), TAK, or MEKK7. As a MAPKKK, it is an important mediator of cellular responses to extracellular signals. It regulates both the c-Jun N-terminal kinase and p38 MAPK cascades by activating the MAPK kinases, MKK4 and MKK3/6. In addition, TAK1 plays diverse roles in immunity and development, in different biological contexts, through many signaling pathways including TGFbeta/BMP, Wnt/Fz, and NF-kB. It is also implicated in the activation of the tumor suppressor kinase, LKB1. The TAK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270960 [Multi-domain] Cd Length: 253 Bit Score: 94.04 E-value: 1.66e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENatGNLYMAKIVPYEPEsKQTVLQEYDILKSLHHEKIMALHEA--YVTPRYLVL-ISECCSGKELLHS 3384
Cdd:cd14058      3 RGSFGVVCKARWR--NQIVAVKIIESESE-KKAFEVEVRQLSRVDHPNIIKLYGAcsNQKPVCLVMeYAEGGSLYNVLHG 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3385 LIDRFRYSEDDVVAYIVQILQGLDYLHS---RRILHLDIKPENIIVTYM-NVVKIIDFGSAQTFNplflKQFSPPIGTLD 3460
Cdd:cd14058     80 KEPKPIYTAAHAMSWALQCAKGVAYLHSmkpKALIHRDLKPPNLLLTNGgTVLKICDFGTACDIS----THMTNNKGSAA 155

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*....
gi 1207186029 3461 YMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFtenDPAETEARIQA 3509
Cdd:cd14058    156 WMAPEVFEGSKYSEKCDVFSWGIILWEVITRRKPF---DHIGGPAFRIM 201

Catalytic domain of the Serine/Threonine Kinase, MAPK/MAK/MRK Overlapping Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MOK, also called Renal tumor antigen 1 (RAGE-1), is widely expressed and is enriched in testis, kidney, lung, and brain. It is expressed in approximately 50% of renal cell carcinomas (RCC) and is a potential target for immunotherapy. MOK is stabilized by its association with the HSP90 molecular chaperone. It is induced by the transcription factor Cdx2 and may be involved in regulating intestinal epithelial development and differentiation. The MOK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270825 [Multi-domain] Cd Length: 282 Bit Score: 94.65 E-value: 1.73e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPESKQTV--LQEYDILKSL-HHEKIMALHEAYV--TPRYLVLISE 3374
Cdd:cd07831      1 YKILGKIGEGTFSEVLKAQSRKTGKYYAIKCMKKHFKSLEQVnnLREIQALRRLsPHPNILRLIEVLFdrKTGRLALVFE 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3375 CCSGKelLHSLI-DRFRY-SEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYmNVVKIIDFGSAQTfnpLFLKQ- 3451
Cdd:cd07831     81 LMDMN--LYELIkGRKRPlPEKRVKNYMYQLLKSLDHMHRNGIFHRDIKPENILIKD-DILKLADFGSCRG---IYSKPp 154

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|
gi 1207186029 3452 FSPPIGTLDYMSPE-MLKGDVVGPPADIWSIGILTYIMLS 3490
Cdd:cd07831    155 YTEYISTRWYRAPEcLLTDGYYGPKMDIWAVGCVFFEILS 194

Catalytic domain of the Serine/Threonine Kinase, Large Tumor Suppressor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LATS was originally identified in Drosophila using a screen for genes whose inactivation led to overproliferation of cells. In tetrapods, there are two LATS isoforms, LATS1 and LATS2. Inactivation of LATS1 in mice results in the development of various tumors, including sarcomas and ovarian cancer. LATS functions as a tumor suppressor and is implicated in cell cycle regulation. The LATS subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270749 [Multi-domain] Cd Length: 333 Bit Score: 95.85 E-value: 1.86e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1660 DYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFIsarakRKASALR---------ELNILSHLDHERI--LYFhdAFEKK 1728
Cdd:cd05598      1 SMFEKIKTIGVGAFGEVSLVRKKDTNALYAMKTL-----RKKDVLKrnqvahvkaERDILAEADNEWVvkLYY--SFQDK 73

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1729 NAVIIITE-LCHEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSsdQIRICDFG--NAV 1805
Cdd:cd05598     74 ENLYFVMDyIPGGDLMSLLIKKGIFEEDLARFYIAELVCAIESVHKMGFIHRDIKPDNILIDRDG--HIKLTDFGlcTGF 151

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1806 KFMPDEAQYCKY---GTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTD 1882
Cdd:cd05598    152 RWTHDSKYYLAHslvGTPNYIAPEVLLRTGYTQLCDWWSVGVILYEMLVGQPPFLAQTPAETQLKVINWRTTLKIPHEAN 231

                          250       260       270
                   ....*....|....*....|....*....|....*...
gi 1207186029 1883 LCHEAKGFVIKLL--VADRL-RPDANECLRHPWFKTLN 1917
Cdd:cd05598    232 LSPEAKDLILRLCcdAEDRLgRNGADEIKAHPFFAGID 269

Catalytic domain of the Wee1-like Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. This subfamily is composed of the dual-specificity kinase Myt1, the protein tyrosine kinase Wee1, and similar proteins. These proteins are cell cycle checkpoint kinases that are involved in the regulation of cyclin-dependent kinase CDK1, the master engine for mitosis. CDK1 is kept inactivated through phosphorylation of N-terminal thr (T14 by Myt1) and tyr (Y15 by Myt1 and Wee1) residues. Mitosis progression is ensured through activation of CDK1 by dephoshorylation and inactivation of Myt1/Wee1. The Wee1-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270899 [Multi-domain] Cd Length: 252 Bit Score: 93.60 E-value: 1.89e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKfisaRAKRK-------ASALRELNILSHL-DHERILYFHDAFEKKNAVII 1733
Cdd:cd13997      2 FHELEQIGSGSFSEVFKVRSKVDGCLYAVK----KSKKPfrgpkerARALREVEAHAALgQHPNIVRYYSSWEEGGHLYI 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1734 ITELCH----EELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMAdhSSDQIRICDFGNAVK--- 1806
Cdd:cd13997     78 QMELCEngslQDALEELSPISKLSEAEVWDLLLQVALGLAFIHSKGIVHLDIKPDNIFIS--NKGTCKIGDFGLATRlet 155

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1807 FMPDEAqyckyGTPEFVAPEIVNQTPV-SKATDIWPIGVlTYLCLTGVSPFAgeNDRSSVLNIRNYNVAFEESMftDLCH 1885
Cdd:cd13997    156 SGDVEE-----GDSRYLAPELLNENYThLPKADIFSLGV-TVYEAATGEPLP--RNGQQWQQLRQGKLPLPPGL--VLSQ 225

                          250       260
                   ....*....|....*....|....*..
gi 1207186029 1886 EAKGFVIKLLVAD-RLRPDANECLRHP 1911
Cdd:cd13997    226 ELTRLLKVMLDPDpTRRPTADQLLAHD 252

Catalytic domain of the Serine/Threonine Kinases, Novel Protein Kinase C theta, delta, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-theta is selectively expressed in T-cells and plays an important and non-redundant role in several aspects of T-cell biology. PKC-delta plays a role in cell cycle regulation and programmed cell death in many cell types. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. There are four nPKC isoforms, delta, epsilon, eta, and theta. The nPKC-theta-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270744 [Multi-domain] Cd Length: 320 Bit Score: 95.14 E-value: 2.07e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3352 HHEKIMALHEAYVTPRYLVLISECCSGKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMN 3431
Cdd:cd05592     54 QHPFLTHLFCTFQTESHLFFVMEYLNGGDLMFHIQQSGRFDEDRARFYGAEIICGLQFLHSRGIIYRDLKLDNVLLDREG 133

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1207186029 3432 VVKIIDFGSAQTfNPLFLKQFSPPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTEND 3499
Cdd:cd05592    134 HIKIADFGMCKE-NIYGENKASTFCGTPDYIAPEILKGQKYNQSVDWWSFGVLLYEMLIGQSPFHGED 200

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek1 is associated with centrosomes throughout the cell cycle. It is involved in the formation of primary cilium and in the maintenance of centrosomes. It cycles through the nucleus and may be capable of relaying signals between the cilium and the nucleus. Nek1 is implicated in the development of polycystic kidney disease, which is characterized by benign polycystic tumors formed by abnormal overgrowth of renal epithelial cells. It appears also to be involved in DNA damage response, and may be important for both correct DNA damage checkpoint activation and DNA repair. Nek1 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270858 [Multi-domain] Cd Length: 256 Bit Score: 93.72 E-value: 2.12e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3309 GRFGVIRECRENATGNLYMAK---IVPYEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELlHSL 3385
Cdd:cd08218     11 GSFGKALLVKSKEDGKQYVIKeinISKMSPKEREESRKEVAVLSKMKHPNIVQYQESFEENGNLYIVMDYCDGGDL-YKR 89

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3386 IDRFR---YSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLfLKQFSPPIGTLDYM 3462
Cdd:cd08218     90 INAQRgvlFPEDQILDWFVQLCLALKHVHDRKILHRDIKSQNIFLTKDGIIKLGDFGIARVLNST-VELARTCIGTPYYL 168

                          170       180       190
                   ....*....|....*....|....*....|...
gi 1207186029 3463 SPEMLKGDVVGPPADIWSIGILTYIMLSGRLPF 3495
Cdd:cd08218    169 SPEICENKPYNNKSDIWALGCVLYEMCTLKHAF 201

Catalytic domain, repeat 2, of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or General Control Non-derepressible-2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GCN2 (or EIF2AK4) is activated by amino acid or serum starvation and UV irradiation. It induces GCN4, a transcriptional activator of amino acid biosynthetic genes, leading to increased production of amino acids under amino acid-deficient conditions. In serum-starved cells, GCN2 activation induces translation of the stress-responsive transcription factor ATF4, while under UV stress, GCN2 triggers transcriptional rescue via NF-kB signaling. GCN2 contains an N-terminal RWD, a degenerate kinase-like (repeat 1), the catalytic kinase (repeat 2), a histidyl-tRNA synthetase (HisRS)-like, and a C-terminal ribosome-binding and dimerization (RB/DD) domains. Its kinase domain is activated via conformational changes as a result of the binding of uncharged tRNA to the HisRS-like domain. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the overall downregulation of protein synthesis. The GCN2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270948 [Multi-domain] Cd Length: 278 Bit Score: 94.36 E-value: 2.18e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1656 RRLTDYYDVhKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASA--LRELNILSHLDHERILYFHDAFEKKNAVII 1733
Cdd:cd14046      3 RYLTDFEEL-QVLGKGAFGQVVKVRNKLDGRYYAIKKIKLRSESKNNSriLREVMLLSRLNHQHVVRYYQAWIERANLYI 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1734 ITELCHEELLDRLTKKSTILE-SEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDFGNA-------- 1804
Cdd:cd14046     82 QMEYCEKSTLRDLIDSGLFQDtDRLWRLFRQILEGLAYIHSQGIIHRDLKPVNIFL--DSNGNVKIGDFGLAtsnklnve 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1805 -----------VKFMPDEAQYCKYGTPEFVAPEIVNQTPVS---KAtDIWPIGVLTY-LCLtgvsPFAGENDRSSVL-NI 1868
Cdd:cd14046    160 latqdinkstsAALGSSGDLTGNVGTALYVAPEVQSGTKSTyneKV-DMYSLGIIFFeMCY----PFSTGMERVQILtAL 234

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....
gi 1207186029 1869 RNYNVAFeESMFTDLCHEAKGFVIKLLV--ADRLRPDANECLRH 1910
Cdd:cd14046    235 RSVSIEF-PPDFDDNKHSKQAKLIRWLLnhDPAKRPSAQELLKS 277

Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK1 is a MAPK kinase kinase (MAPKKK or MKKK) that phosphorylates and activates activates the ERK1/2 and c-Jun N-terminal kinase (JNK) pathways by activating their respective MAPKKs, MEK1/2 and MKK4/MKK7, respectively. MEKK1 is important in regulating cell survival and apoptosis. MEKK1 also plays a role in cell migration, tissue maintenance and homeostasis, and wound healing. The MEKK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270800 [Multi-domain] Cd Length: 268 Bit Score: 94.03 E-value: 2.40e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3309 GRFGVIRECRENATGNLYMAKIVPYEPESK-------QTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKEL 3381
Cdd:cd06630     11 GAFSSCYQARDVKTGTLMAVKQVSFCRNSSseqeevvEAIREEIRMMARLNHPNIVRMLGATQHKSHFNIFVEWMAGGSV 90

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3382 LHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIV-TYMNVVKIIDFGSAQTFNP------LFLKQFsp 3454
Cdd:cd06630     91 ASLLSKYGAFSENVIINYTLQILRGLAYLHDNQIIHRDLKGANLLVdSTGQRLRIADFGAAARLASkgtgagEFQGQL-- 168

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*
gi 1207186029 3455 pIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTEND 3499
Cdd:cd06630    169 -LGTIAFMAPEVLRGEQYGRSCDVWSVGCVIIEMATAKPPWNAEK 212

Catalytic domain of Yeast Protein Kinase 1-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of fungal proteins with similarity to the AGC STKs, Saccharomyces cerevisiae YPK1 and Schizosaccharomyces pombe Gad8p. YPK1 is required for cell growth and acts as a downstream kinase in the sphingolipid-mediated signaling pathway of yeast. It also plays a role in efficient endocytosis and in the maintenance of cell wall integrity. Gad8p is a downstream target of Tor1p, the fission yeast homolog of mTOR. It plays a role in cell growth and sexual development. The YPK1-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270737 [Multi-domain] Cd Length: 313 Bit Score: 94.95 E-value: 2.48e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYVKRVIQKAGKLEYAAKFIsarakRKA---------SALRELNILSHLDHERILYFHDAFEKKNAVIIITELC 1738
Cdd:cd05585      2 IGKGSFGKVMQVRKKDTSRIYALKTI-----RKAhivsrsevtHTLAERTVLAQVDCPFIVPLKFSFQSPEKLYLVLAFI 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1739 HE-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMaDHSSdQIRICDFGNAVKFMPDEAQ---Y 1814
Cdd:cd05585     77 NGgELFHHLQREGRFDLSRARFYTAELLCALECLHKFNVIYRDLKPENILL-DYTG-HIALCDFGLCKLNMKDDDKtntF 154

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1815 CkyGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDlcheAKGFVIKL 1894
Cdd:cd05585    155 C--GTPEYLAPELLLGHGYTKAVDWWTLGVLLYEMLTGLPPFYDENTNEMYRKILQEPLRFPDGFDRD----AKDLLIGL 228

                          250       260
                   ....*....|....*....|....*..
gi 1207186029 1895 LVAD---RLRPD-ANECLRHPWFKTLN 1917
Cdd:cd05585    229 LNRDptkRLGYNgAQEIKNHPFFDQID 255

Catalytic domain of an Uncharacterized subfamily of Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of uncharacterized proteins with similarity to MEKK3, MEKK2, and related proteins; they contain an N-terminal PB1 domain, which mediates oligomerization, and a C-terminal catalytic domain. MEKK2 and MEKK3 are MAPK kinase kinases (MAPKKKs or MKKKs), proteins that phosphorylate and activate MAPK kinases (MAPKKs or MKKs), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MEKK2 and MEKK3 activate MEK5 (also called MKK5), which activates ERK5. The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK3 plays an essential role in embryonic angiogenesis and early heart development. MEKK2 and MEKK3 can also activate the MAPKs, c-Jun N-terminal kinase (JNK) and p38, through their respective MAPKKs. The MEKK3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270819 [Multi-domain] Cd Length: 264 Bit Score: 93.55 E-value: 2.64e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1666 KEIGRGAFSYVKRVIQKAGKLEYAAKFI-----SARAKRKASALR-ELNILSHLDHERILYFHDAF---EKKNAVIIITE 1736
Cdd:cd06653      8 KLLGRGAFGEVYLCYDADTGRELAVKQVpfdpdSQETSKEVNALEcEIQLLKNLRHDRIVQYYGCLrdpEEKKLSIFVEY 87

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1737 LCHEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDFGNAVK----FMPDEA 1812
Cdd:cd06653     88 MPGGSVKDQLKAYGALTENVTRRYTRQILQGVSYLHSNMIVHRDIKGANILR--DSAGNVKLGDFGASKRiqtiCMSGTG 165

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1813 QYCKYGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNI--RNYNVAFEESMfTDLCheaKGF 1890
Cdd:cd06653    166 IKSVTGTPYWMSPEVISGEGYGRKADVWSVACTVVEMLTEKPPWAEYEAMAAIFKIatQPTKPQLPDGV-SDAC---RDF 241

                          250       260
                   ....*....|....*....|..
gi 1207186029 1891 VIKLLVADRLRPDANECLRHPW 1912
Cdd:cd06653    242 LRQIFVEEKRRPTAEFLLRHPF 263

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek3 is primarily localized in the cytoplasm and shows no cell cycle-dependent changes in its activity. It is present in the axons of neurons and affects morphogenesis and polarity through its regulation of microtubule acetylation. Nek3 modulates the signaling of the prolactin receptor through its activation of Vav2 and contributes to prolactin-mediated motility of breast cancer cells. It is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173759 [Multi-domain] Cd Length: 255 Bit Score: 93.11 E-value: 2.92e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFG-VIRECRENATGNLYMAKI-VPYEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCS 3377
Cdd:cd08219      2 YNVLRVVGEGSFGrALLVQHVNSDQKYAMKEIrLPKSSSAVEDSRKEAVLLAKMKHPNIVAFKESFEADGHLYIVMEYCD 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3378 GKELLHSLID-RFR-YSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTF-NPLFLKqfSP 3454
Cdd:cd08219     82 GGDLMQKIKLqRGKlFPEDTILQWFVQMCLGVQHIHEKRVLHRDIKSKNIFLTQNGKVKLGDFGSARLLtSPGAYA--CT 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3455 PIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENdpAETEARIQAAKFDLSKLYQNVSQSASLFIKKILC 3534
Cdd:cd08219    160 YVGTPYYVPPEIWENMPYNNKSDIWSLGCILYELCTLKHPFQAN--SWKNLILKVCQGSYKPLPSHYSYELRSLIKQMFK 237


                   ....*...
gi 1207186029 3535 SYPWARPT 3542
Cdd:cd08219    238 RNPRSRPS 245

Catalytic domain of testis-specific serine/threonine kinase 6 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK6, also called SSTK, is expressed at the head of elongated sperm. It can phosphorylate histones and associate with heat shock protens HSP90 and HSC70. Male mice deficient in TSSK6 are infertile, showing spermatogenic impairment including reduced sperm counts, impaired DNA condensation, abnormal morphology and decreased motility rates. The TSSK6-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271066 [Multi-domain] Cd Length: 256 Bit Score: 93.00 E-value: 3.36e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3341 VLQEYDILKSLHHEKIMALHEAY-VTPRYLVLISECcSGKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLD 3419
Cdd:cd14164     47 LPRELSILRRVNHPNIVQMFECIeVANGRLYIVMEA-AATDLLQKIQEVHHIPKDLARDMFAQMVGAVNYLHDMNIVHRD 125

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3420 IKPENIIVTYMN-VVKIIDFGsaqtfnplFLKQFSPP-------IGTLDYMSPEMLKGDVVGPPA-DIWSIGILTYIMLS 3490
Cdd:cd14164    126 LKCENILLSADDrKIKIADFG--------FARFVEDYpelsttfCGSRAYTPPEVILGTPYDPKKyDVWSLGVVLYVMVT 197

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1207186029 3491 GRLPFTEnDPAETEARIQAAKFDLSKLyqNVSQSASLFIKKILCSYPWARPTIKDCFTNSWL 3552
Cdd:cd14164    198 GTMPFDE-TNVRRLRLQQRGVLYPSGV--ALEEPCRALIRTLLQFNPSTRPSIQQVAGNSWL 256

Catalytic domain of Nuclear Dbf2-Related kinase-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NDR kinases regulate mitosis, cell growth, embryonic development, and neurological processes. They are also required for proper centrosome duplication. Higher eukaryotes contain two NDR isoforms, NDR1 and NDR2. This subfamily also contains fungal NDR-like kinases. NDR kinase contains an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Like many other AGC kinases, NDR kinase requires phosphorylation at two sites, the activation loop (A-loop) and the hydrophobic motif (HM), for activity. The NDR kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270750 [Multi-domain] Cd Length: 324 Bit Score: 94.60 E-value: 3.46e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKIVPYEP--ESKQT--VLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLH 3383
Cdd:cd05599     11 RGAFGEVRLVRKKDTGHVYAMKKLRKSEmlEKEQVahVRAERDILAEADNPWVVKLYYSFQDEENLYLIMEFLPGGDMMT 90

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3384 SLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLKqFSpPIGTLDYMS 3463
Cdd:cd05599     91 LLMKKDTLTEEETRFYIAETVLAIESIHKLGYIHRDIKPDNLLLDARGHIKLSDFGLCTGLKKSHLA-YS-TVGTPDYIA 168

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|
gi 1207186029 3464 PEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAET 3503
Cdd:cd05599    169 PEVFLQKGYGKECDWWSLGVIMYEMLIGYPPFCSDDPQET 208

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 10; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK10, also called PISSLRE, is essential for cell growth and proliferation, and acts through the G2/M phase of the cell cycle. CDK10 has also been identified as an important factor in endocrine therapy resistance in breast cancer. CDK10 silencing increases the transcription of c-RAF and the activation of the p42/p44 MAPK pathway, which leads to antiestrogen resistance. Patients who express low levels of CDK10 relapse early on tamoxifen. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK10 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173742 [Multi-domain] Cd Length: 309 Bit Score: 94.36 E-value: 3.73e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3309 GRFGVIRECRENATGNLYMAKIVPYEPESKQ---TVLQEYDILKSLHHEKIMALHEAYVTPRY--LVLISECCsgKELLH 3383
Cdd:cd07845     18 GTYGIVYRARDTTSGEIVALKKVRMDNERDGipiSSLREITLLLNLRHPNIVELKEVVVGKHLdsIFLVMEYC--EQDLA 95

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3384 SLIDRFR--YSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLfLKQFSPPIGTLDY 3461
Cdd:cd07845     96 SLLDNMPtpFSESQVKCLMLQLLRGLQYLHENFIIHRDLKVSNLLLTDKGCLKIADFGLARTYGLP-AKPMTPKVVTLWY 174

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3462 MSPEMLKGDVVGPPA-DIWSIGILTYIMLSGRLPFtendPAETEAR-----IQ------------------AAKFDLSKL 3517
Cdd:cd07845    175 RAPELLLGCTTYTTAiDMWAVGCILAELLAHKPLL----PGKSEIEqldliIQllgtpnesiwpgfsdlplVGKFTLPKQ 250

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*.
gi 1207186029 3518 -YQNVSQ------SASLFIKKILCSY-PWARPTIKDCFTNSWLQDA 3555
Cdd:cd07845    251 pYNNLKHkfpwlsEAGLRLLNFLLMYdPKKRATAEEALESSYFKEK 296

Catalytic domain of the Serine/Threonine Kinases, fungal Bck1-like Mitogen-Activated Protein Kinase Kinase Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include the MAPKKKs Saccharomyces cerevisiae Bck1 and Schizosaccharomyces pombe Mkh1, and related proteins. Budding yeast Bck1 is part of the cell integrity MAPK pathway, which is activated by stresses and aggressions to the cell wall. The MAPKKK Bck1, MAPKKs Mkk1 and Mkk2, and the MAPK Slt2 make up the cascade that is important in the maintenance of cell wall homeostasis. Fission yeast Mkh1 is involved in MAPK cascades regulating cell morphology, cell wall integrity, salt resistance, and filamentous growth in response to stress. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The Bck1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270799 [Multi-domain] Cd Length: 270 Bit Score: 93.22 E-value: 3.80e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3343 QEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLhSLIDRFRYSEDDVVAYIV-QILQGLDYLHSRRILHLDIK 3421
Cdd:cd06629     57 SEIDTLKDLDHPNIVQYLGFEETEDYFSIFLEYVPGGSIG-SCLRKYGKFEEDLVRFFTrQILDGLAYLHSKGILHRDLK 135

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3422 PENIIVTYMNVVKIIDFG-SAQTFNPLFLKQFSPPIGTLDYMSPEMLKGDVVGPPA--DIWSIGILTYIMLSGRLPFTEN 3498
Cdd:cd06629    136 ADNILVDLEGICKISDFGiSKKSDDIYGNNGATSMQGSVFWMAPEVIHSQGQGYSAkvDIWSLGCVVLEMLAGRRPWSDD 215

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1207186029 3499 DpaetearIQAAKFDLSKLYQ--------NVSQSASLFIKKILCSYPWARPTIKDCFTNSWL 3552
Cdd:cd06629    216 E-------AIAAMFKLGNKRSappvpedvNLSPEALDFLNACFAIDPRDRPTAAELLSHPFL 270

Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase (IKK); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The IKK complex functions as a master regulator of Nuclear Factor-KappaB (NF-kB) proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. It is composed of two kinases, IKKalpha and IKKbeta, and the regulatory subunit IKKgamma or NEMO (NF-kB Essential MOdulator). IKKs facilitate the release of NF-kB dimers from an inactive state, allowing them to migrate to the nucleus where they regulate gene transcription. There are two IKK pathways that regulate NF-kB signaling, called the classical (involving IKKbeta and NEMO) and non-canonical (involving IKKalpha) pathways. The classical pathway regulates the majority of genes activated by NF-kB. The IKK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).

Pssm-ID: 270891 [Multi-domain] Cd Length: 289 Bit Score: 93.67 E-value: 3.83e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3344 EYDILKSLHHEKIMAL-----HEAYVTPRYLVLIS-ECCSGKELLHSLiDRFRYS----EDDVVAYIVQILQGLDYLHSR 3413
Cdd:cd13989     43 EVQIMKKLNHPNVVSArdvppELEKLSPNDLPLLAmEYCSGGDLRKVL-NQPENCcglkESEVRTLLSDISSAISYLHEN 121

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3414 RILHLDIKPENIIVTYMN---VVKIIDFGSAQTfnplfLKQFS---PPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYI 3487
Cdd:cd13989    122 RIIHRDLKPENIVLQQGGgrvIYKLIDLGYAKE-----LDQGSlctSFVGTLQYLAPELFESKKYTCTVDYWSFGTLAFE 196

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1207186029 3488 MLSGRLPFTEN-DPAETEARIQAAKFDLSKLYQ----NVSQSASLFIKKILCSypwarpTIKDCFtNSWLQ 3553
Cdd:cd13989    197 CITGYRPFLPNwQPVQWHGKVKQKKPEHICAYEdltgEVKFSSELPSPNHLSS------ILKEYL-ESWLQ 260

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek3 is primarily localized in the cytoplasm and shows no cell cycle-dependent changes in its activity. It is present in the axons of neurons and affects morphogenesis and polarity through its regulation of microtubule acetylation. Nek3 modulates the signaling of the prolactin receptor through its activation of Vav2 and contributes to prolactin-mediated motility of breast cancer cells. It is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173759 [Multi-domain] Cd Length: 255 Bit Score: 93.11 E-value: 3.85e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFIsaRAKRKASAL----RELNILSHLDHERILYFHDAFEKKNAVIIITEL 1737
Cdd:cd08219      2 YNVLRVVGEGSFGRALLVQHVNSDQKYAMKEI--RLPKSSSAVedsrKEAVLLAKMKHPNIVAFKESFEADGHLYIVMEY 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1738 CHE-ELLDRLTKKSTIL--ESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSsdQIRICDFGNAVKFMPDEAQY 1814
Cdd:cd08219     80 CDGgDLMQKIKLQRGKLfpEDTILQWFVQMCLGVQHIHEKRVLHRDIKSKNIFLTQNG--KVKLGDFGSARLLTSPGAYA 157

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1207186029 1815 CKY-GTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNI 1868
Cdd:cd08219    158 CTYvGTPYYVPPEIWENMPYNNKSDIWSLGCILYELCTLKHPFQANSWKNLILKV 212

Catalytic domain of Phototropin-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phototropins are blue-light receptors that control responses such as phototropism, stromatal opening, and chloroplast movement in order to optimize the photosynthetic efficiency of plants. They are light-activated STKs that contain an N-terminal photosensory domain and a C-terminal catalytic domain. The N-terminal domain contains two LOV (Light, Oxygen or Voltage) domains that binds FMN. Photoexcitation of the LOV domains results in autophosphorylation at multiple sites and activation of the catalytic domain. In addition to plant phototropins, included in this subfamily are predominantly uncharacterized fungal STKs whose catalytic domains resemble the phototropin kinase domain. One protein from Neurospora crassa is called nrc-2, which plays a role in growth and development by controlling entry into the conidiation program. The phototropin-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270726 [Multi-domain] Cd Length: 316 Bit Score: 94.23 E-value: 4.05e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1666 KEIGRGAFSYVKRVIQKAGKLEYAAKFIS-----ARAKRKaSALRELNILSHLDHERILYFHDAFEKKNAVIIITELCH- 1739
Cdd:cd05574      7 KLLGKGDVGRVYLVRLKGTGKLFAMKVLDkeemiKRNKVK-RVLTEREILATLDHPFLPTLYASFQTSTHLCFVMDYCPg 85

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1740 EELLDRLTKKST--ILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDF---------------- 1801
Cdd:cd05574     86 GELFRLLQKQPGkrLPEEVARFYAAEVLLALEYLHLLGFVYRDLKPENILL--HESGHIMLTDFdlskqssvtpppvrks 163

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1802 GNAVKFMPDEAQYCKY--------------GTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLN 1867
Cdd:cd05574    164 LRKGSRRSSVKSIEKEtfvaepsarsnsfvGTEEYIAPEVIKGDGHGSAVDWWTLGILLYEMLYGTTPFKGSNRDETFSN 243

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1207186029 1868 IRNYNVAFEESMftDLCHEAKGFVIKLLVAD---RL--RPDANECLRHPWFKTLN 1917
Cdd:cd05574    244 ILKKELTFPESP--PVSSEAKDLIRKLLVKDpskRLgsKRGASEIKRHPFFRGVN 296

cyclin-dependent protein kinase; Provisional

Pssm-ID: 240233 [Multi-domain] Cd Length: 335 Bit Score: 94.83 E-value: 4.15e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3340 TVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKelLHSLID-RFRYSEDDVVAYIVQILQGLDYLHSRRILHL 3418
Cdd:PTZ00024    66 TTLRELKIMNEIKHENIMGLVDVYVEGDFINLVMDIMASD--LKKVVDrKIRLTESQVKCILLQILNGLNVLHKWYFMHR 143

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3419 DIKPENIIVTYMNVVKIIDFGSAQTF-NPLFLKQFS------------PPIGTLDYMSPEMLKG-DVVGPPADIWSIGIL 3484
Cdd:PTZ00024   144 DLSPANIFINSKGICKIADFGLARRYgYPPYSDTLSkdetmqrreemtSKVVTLWYRAPELLMGaEKYHFAVDMWSVGCI 223

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3485 TYIMLSGRLPFtendPAETEARiqaakfDLSKLYQ--------NVSQSASLfikKILCSYPWARPT-IKDCFTNSwlqDA 3555
Cdd:PTZ00024   224 FAELLTGKPLF----PGENEID------QLGRIFEllgtpnedNWPQAKKL---PLYTEFTPRKPKdLKTIFPNA---SD 287

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1207186029 3556 YLMRLRRQTLTftttrlkefLEQQQHIRAQEATKHKVllrsYQSNPqTPSTP 3607
Cdd:PTZ00024   288 DAIDLLQSLLK---------LNPLERISAKEALKHEY----FKSDP-LPCDP 325

Catalytic domain of Extracellular signal-Regulated Kinase 1 and 2-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the mitogen-activated protein kinases (MAPKs) ERK1, ERK2, baker's yeast Fus3, and similar proteins. MAPK pathways are important mediators of cellular responses to extracellular signals. ERK1/2 activation is preferentially by mitogenic factors, differentiation stimuli, and cytokines, through a kinase cascade involving the MAPK kinases MEK1/2 and a MAPK kinase kinase from the Raf family. ERK1/2 have numerous substrates, many of which are nuclear and participate in transcriptional regulation of many cellular processes. They regulate cell growth, cell proliferation, and cell cycle progression from G1 to S phase. Although the distinct roles of ERK1 and ERK2 have not been fully determined, it is known that ERK2 can maintain most functions in the absence of ERK1, and that the deletion of ERK2 is embryonically lethal. The MAPK, Fus3, regulates yeast mating processes including mating-specific gene expression, G1 arrest, mating projection, and cell fusion. This ERK1/2-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270839 [Multi-domain] Cd Length: 336 Bit Score: 94.68 E-value: 4.19e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3329 KIVPYEpesKQTV----LQEYDILKSLHHEKIMALHEAyVTPR--------YLVliseccsgKEL----LHSLIDRFRYS 3392
Cdd:cd07849     37 KISPFE---HQTYclrtLREIKILLRFKHENIIGILDI-QRPPtfesfkdvYIV--------QELmetdLYKLIKTQHLS 104

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3393 EDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSA-----QTFNPLFLKQFsppIGTLDYMSPE-M 3466
Cdd:cd07849    105 NDHIQYFLYQILRGLKYIHSANVLHRDLKPSNLLLNTNCDLKICDFGLAriadpEHDHTGFLTEY---VATRWYRAPEiM 181

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3467 LKGDVVGPPADIWSIGILTYIMLSGRLPFTEND--------------PAETE--------AR--IQA----AKFDLSKLY 3518
Cdd:cd07849    182 LNSKGYTKAIDIWSVGCILAEMLSNRPLFPGKDylhqlnlilgilgtPSQEDlnciislkARnyIKSlpfkPKVPWNKLF 261

                          250       260       270
                   ....*....|....*....|....*....|....*...
gi 1207186029 3519 QNVSQSASLFIKKILCSYPWARPTIKDCFTNSWLQDAY 3556
Cdd:cd07849    262 PNADPKALDLLDKMLTFNPHKRITVEEALAHPYLEQYH 299

Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-1 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-1 is expressed ubiquitously and is localized in the cytoplasm. Its kinase activity is cell cycle dependent and peaks at the S and G2 phases. PCTAIRE-1 is highly expressed in the brain and may play a role in regulating neurite outgrowth. It can also associate with Trap (Tudor repeat associator with PCTAIRE-2), a physiological partner of PCTAIRE-2; with p11, a small dimeric protein with similarity to S100; and with 14-3-3 proteins, mediators of phosphorylation-dependent interactions in many different proteins. PCTAIRE-1 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PCTAIRE-1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270854 [Multi-domain] Cd Length: 297 Bit Score: 93.53 E-value: 5.36e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPESKQ--TVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCS 3377
Cdd:cd07873      4 YIKLDKLGEGTYATVYKGRSKLTDNLVALKEIRLEHEEGApcTAIREVSLLKDLKHANIVTLHDIIHTEKSLTLVFEYLD 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3378 gKELLHSLIDRFRY-SEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTfNPLFLKQFSPPI 3456
Cdd:cd07873     84 -KDLKQYLDDCGNSiNMHNVKLFLFQLLRGLAYCHRRKVLHRDLKPQNLLINERGELKLADFGLARA-KSIPTKTYSNEV 161

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|
gi 1207186029 3457 GTLDYMSPEMLKGDV-VGPPADIWSIGILTYIMLSGRLPF 3495
Cdd:cd07873    162 VTLWYRPPDILLGSTdYSTQIDMWGVGCIFYEMSTGRPLF 201

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK6 may play a role in stress responses through its activation by the mitogen-activated protein kinase (MAPK) p38 and MAPK kinase 6 (MKK6) pathway. PAK6 is highly expressed in the brain. It is not required for viability, but together with PAK5, it is required for normal levels of locomotion and activity, and for learning and memory. Increased expression of PAK6 is found in primary and metastatic prostate cancer. PAK6 may play a role in the regulation of motility. PAK6 belongs to the group II PAKs, which contain a PBD (p21-binding domain) and a C-terminal catalytic domain, but do not harbor an AID (autoinhibitory domain) or SH3 binding sites. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270821 [Multi-domain] Cd Length: 297 Bit Score: 93.51 E-value: 5.84e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3289 STLRQGVPQ-KPYTFMDEKAR---GRFGVIRECRENATGNLYMAKIVPYEPESKQTVL-QEYDILKSLHHEKIMALHEAY 3363
Cdd:cd06659      8 AALRMVVDQgDPRQLLENYVKigeGSTGVVCIAREKHSGRQVAVKMMDLRKQQRRELLfNEVVIMRDYQHPNVVEMYKSY 87

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3364 VTPRYLVLISECCSGKELLhSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQT 3443
Cdd:cd06659     88 LVGEELWVLMEYLQGGALT-DIVSQTRLNEEQIATVCEAVLQALAYLHSQGVIHRDIKSDSILLTLDGRVKLSDFGFCAQ 166

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3444 FNPLFLKQFSpPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLSKLYQNVSQ 3523
Cdd:cd06659    167 ISKDVPKRKS-LVGTPYWMAPEVISRCPYGTEVDIWSLGIMVIEMVDGEPPYFSDSPVQAMKRLRDSPPPKLKNSHKASP 245

                          250       260
                   ....*....|....*....|....*....
gi 1207186029 3524 SASLFIKKILCSYPWARPTIKDCFTNSWL 3552
Cdd:cd06659    246 VLRDFLERMLVRDPQERATAQELLDHPFL 274

Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ROCK1 is preferentially expressed in the liver, lung, spleen, testes, and kidney. It mediates signaling from Rho to the actin cytoskeleton. It is implicated in the development of cardiac fibrosis, cardiomyocyte apoptosis, and hyperglycemia. Mice deficient with ROCK1 display eyelids open at birth (EOB) and omphalocele phenotypes due to the disorganization of actin filaments in the eyelids and the umbilical ring. ROCK contains an N-terminal extension, a catalytic kinase domain, and a C-terminal extension, which contains a coiled-coil region encompassing a Rho-binding domain (RBD) and a pleckstrin homology (PH) domain. ROCK is auto-inhibited by the RBD and PH domain interacting with the catalytic domain, and is activated via interaction with Rho GTPases. The ROCK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270772 [Multi-domain] Cd Length: 405 Bit Score: 95.46 E-value: 5.85e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3307 ARGRFGVIRECRENATGNLYMAKIVPYEPESKQT----VLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELL 3382
Cdd:cd05622     82 GRGAFGEVQLVRHKSTRKVYAMKLLSKFEMIKRSdsafFWEERDIMAFANSPWVVQLFYAFQDDRYLYMVMEYMPGGDLV 161

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3383 hSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLKQFSPPIGTLDYM 3462
Cdd:cd05622    162 -NLMSNYDVPEKWARFYTAEVVLALDAIHSMGFIHRDVKPDNMLLDKSGHLKLADFGTCMKMNKEGMVRCDTAVGTPDYI 240

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1207186029 3463 SPEMLK---GD-VVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLSKLYQN-VSQSAslfiKKILCSY 3536
Cdd:cd05622    241 SPEVLKsqgGDgYYGRECDWWSVGVFLYEMLVGDTPFYADSLVGTYSKIMNHKNSLTFPDDNdISKEA----KNLICAF 315

Catalytic domain of the Serine/Threonine Kinase, SNF1-related kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SNRK is a kinase highly expressed in testis and brain that is found inactive in cells that lack the LKB1 tumour suppressor protein kinase. The regulatory subunits STRAD and MO25 are required for LKB1 to activate SNRK. The SNRK mRNA is increased 3-fold when granule neurons are cultured in low potassium, and may thus play a role in the survival responses in these cells. In some vertebrates, a second SNRK gene (snrkb or snrk-1) has been sequenced and/or identified. Snrk-1 is expressed specifically in embryonic zebrafish vasculature; it plays an essential role in angioblast differentiation, maintenance, and migration. The SNRK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270976 [Multi-domain] Cd Length: 258 Bit Score: 92.48 E-value: 6.62e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVK-------------RVIQKAgKLEYAAKfisarakrkASALRELNILSHLDHERILYFHDAFEKK 1728
Cdd:cd14074      5 YDLEETLGRGHFAVVKlarhvftgekvavKVIDKT-KLDDVSK---------AHLFQEVRCMKLVQHPNVVRLYEVIDTQ 74

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1729 NAVIIITELCHE-ELLDRLTKKSTILESEI-RSSVRQLLEGINYLHQLDILHLDIKPDNILMADhSSDQIRICDFGNAVK 1806
Cdd:cd14074     75 TKLYLILELGDGgDMYDYIMKHENGLNEDLaRKYFRQIVSAISYCHKLHVVHRDLKPENVVFFE-KQGLVKLTDFGFSNK 153

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1807 FMPDEAQYCKYGTPEFVAPEI-VNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRN--YNVAfeeSMFTDL 1883
Cdd:cd14074    154 FQPGEKLETSCGSLAYSAPEIlLGDEYDAPAVDIWSLGVILYMLVCGQPPFQEANDSETLTMIMDckYTVP---AHVSPE 230

                          250       260       270
                   ....*....|....*....|....*....|
gi 1207186029 1884 CheaKGFVIKLLVAD-RLRPDANECLRHPW 1912
Cdd:cd14074    231 C---KDLIRRMLIRDpKKRASLEEIENHPW 257

Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MST4 is sometimes referred to as MASK (MST3 and SOK1-related kinase). It plays a role in mitogen-activated protein kinase (MAPK) signaling during cytoskeletal rearrangement, morphogenesis, and apoptosis. It influences cell growth and transformation by modulating the extracellular signal-regulated kinase (ERK) pathway. MST4 may also play a role in tumor formation and progression. It localizes in the Golgi apparatus by interacting with the Golgi matrix protein GM130 and may play a role in cell migration. The MST4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 132971 [Multi-domain] Cd Length: 277 Bit Score: 92.81 E-value: 6.65e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3296 PQKPYTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEP--ESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLIS 3373
Cdd:cd06640      2 PEELFTKLERIGKGSFGEVFKGIDNRTQQVVAIKIIDLEEaeDEIEDIQQEITVLSQCDSPYVTKYYGSYLKGTKLWIIM 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3374 ECCSGKELLhSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLKQfS 3453
Cdd:cd06640     82 EYLGGGSAL-DLLRAGPFDEFQIATMLKEILKGLDYLHSEKKIHRDIKAANVLLSEQGDVKLADFGVAGQLTDTQIKR-N 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3454 PPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIqaAKFDLSKLYQNVSQSASLFIKKIL 3533
Cdd:cd06640    160 TFVGTPFWMAPEVIQQSAYDSKADIWSLGITAIELAKGEPPNSDMHPMRVLFLI--PKNNPPTLVGDFSKPFKEFIDACL 237

                          250
                   ....*....|....*....
gi 1207186029 3534 CSYPWARPTIKDCFTNSWL 3552
Cdd:cd06640    238 NKDPSFRPTAKELLKHKFI 256

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek4 is highly abundant in the testis. Its specific function is unknown. Neks are involved in the regulation of downstream processes following the activation of Cdc2, and many of their functions are cell cycle-related. They play critical roles in microtubule dynamics during ciliogenesis and mitosis. Nek4 is one in a family of 11 different Neks (Nek1-11). The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270862 [Multi-domain] Cd Length: 257 Bit Score: 92.11 E-value: 7.07e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPESK---QTVLQEYDILKSLHHEKIMALHEAYVTPR-YLVLISEC 3375
Cdd:cd08223      2 YQFLRVIGKGSYGEVWLVRHKRDRKQYVIKKLNLKNASKrerKAAEQEAKLLSKLKHPNIVSYKESFEGEDgFLYIVMGF 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3376 CSGKELLHSLIDR--FRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFlKQFS 3453
Cdd:cd08223     82 CEGGDLYTRLKEQkgVLLEERQVVEWFVQIAMALQYMHERNILHRDLKTQNIFLTKSNIIKVGDLGIARVLESSS-DMAT 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3454 PPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKF-DLSKLYqnvSQSASLFIKKI 3532
Cdd:cd08223    161 TLIGTPYYMSPELFSNKPYNHKSDVWALGCCVYEMATLKHAFNAKDMNSLVYKILEGKLpPMPKQY---SPELGELIKAM 237

                          250       260
                   ....*....|....*....|
gi 1207186029 3533 LCSYPWARPTIKDCFTNSWL 3552
Cdd:cd08223    238 LHQDPEKRPSVKRILRQPYI 257

Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase Pho85; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Pho85 is a multifunctional CDK in yeast. It is regulated by 10 different cyclins (Pcls) and plays a role in G1 progression, cell polarity, phosphate and glycogen metabolism, gene expression, and in signaling changes in the environment. It is not essential for yeast viability and is the functional homolog of mammalian CDK5, which plays a role in central nervous system development. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The Pho85 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143341 [Multi-domain] Cd Length: 284 Bit Score: 92.93 E-value: 7.09e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3309 GRFGVIRECRENATGNLYMAKIVPYEPE--SKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSG--KELLHS 3384
Cdd:cd07836     11 GTYATVYKGRNRTTGEIVALKEIHLDAEegTPSTAIREISLMKELKHENIVRLHDVIHTENKLMLVFEYMDKdlKKYMDT 90

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3385 LIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNpLFLKQFSPPIGTLDYMSP 3464
Cdd:cd07836     91 HGVRGALDPNTVKSFTYQLLKGIAFCHENRVLHRDLKPQNLLINKRGELKLADFGLARAFG-IPVNTFSNEVVTLWYRAP 169

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....
gi 1207186029 3465 EMLKGD-VVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARI 3507
Cdd:cd07836    170 DVLLGSrTYSTSIDIWSVGCIMAEMITGRPLFPGTNNEDQLLKI 213

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 12; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK12 is also called Cdc2-related protein kinase 7 (CRK7) or Cdc2-related kinase arginine/serine-rich (CrkRS). It is a unique CDK that contains an RS domain, which is predominantly found in splicing factors. CDK12 is widely expressed in tissues. It interacts with cyclins L1 and L2, and plays roles in regulating transcription and alternative splicing. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK12 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270847 [Multi-domain] Cd Length: 302 Bit Score: 93.33 E-value: 7.26e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPESKQ---TVLQEYDILKSLHHEKIMALHEAyVTPR--------- 3367
Cdd:cd07864      9 FDIIGIIGEGTYGQVYKAKDKDTGELVALKKVRLDNEKEGfpiTAIREIKILRQLNHRSVVNLKEI-VTDKqdaldfkkd 87

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3368 ----YLVLISECCSGKELLHS-LIDrfrYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQ 3442
Cdd:cd07864     88 kgafYLVFEYMDHDLMGLLESgLVH---FSEDHIKSFMKQLLEGLNYCHKKNFLHRDIKCSNILLNNKGQIKLADFGLAR 164

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|.
gi 1207186029 3443 TFNPLFLKQFSPPIGTLDYMSPEMLKGD-VVGPPADIWSIG 3482
Cdd:cd07864    165 LYNSEESRPYTNKVITLWYRPPELLLGEeRYGPAIDVWSCG 205

Catalytic domain of the Serine/Threonine Kinases, Oxidative stress response kinase and Ste20-related proline alanine-rich kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SPAK is also referred to as STK39 or PASK (proline-alanine-rich STE20-related kinase). OSR1 and SPAK regulate the activity of cation-chloride cotransporters through direct interaction and phosphorylation. They are also implicated in cytoskeletal rearrangement, cell differentiation, transformation and proliferation. OSR1 and SPAK contain a conserved C-terminal (CCT) domain, which recognizes a unique motif ([RK]FX[VI]) present in their activating kinases (WNK1/WNK4) and their substrates. The OSR1 and SPAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270787 [Multi-domain] Cd Length: 267 Bit Score: 92.42 E-value: 7.39e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVPYE--PESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCS 3377
Cdd:cd06610      3 YELIEVIGSGATAVVYAAYCLPKKEKVAIKRIDLEkcQTSMDELRKEIQAMSQCNHPNVVSYYTSFVVGDELWLVMPLLS 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3378 GKELLHslIDRFRYSED----DVVAYIV-QILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFG-SAQTFNP----- 3446
Cdd:cd06610     83 GGSLLD--IMKSSYPRGgldeAIIATVLkEVLKGLEYLHSNGQIHRDVKAGNILLGEDGSVKIADFGvSASLATGgdrtr 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3447 LFLKQFsppIGTLDYMSPEMLKGDV-VGPPADIWSIGILTYIMLSGRLPFT------------ENDPAETEARIQAAKFd 3513
Cdd:cd06610    161 KVRKTF---VGTPCWMAPEVMEQVRgYDFKADIWSFGITAIELATGAAPYSkyppmkvlmltlQNDPPSLETGADYKKY- 236

                          250       260
                   ....*....|....*....|....*....
gi 1207186029 3514 lSKLYQNvsqsaslFIKKILCSYPWARPT 3542
Cdd:cd06610    237 -SKSFRK-------MISLCLQKDPSKRPT 257

Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma 1 subunit; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phosphorylase kinase (PhK) catalyzes the phosphorylation of inactive phosphorylase b to form the active phosphorylase a. It coordinates hormonal, metabolic, and neuronal signals to initiate the breakdown of glycogen stores, which enables the maintenance of blood-glucose homeostasis during fasting, and is also used as a source of energy for muscle contraction. PhK is one of the largest and most complex protein kinases, composed of a heterotetramer containing four molecules each of four subunit types: one catalytic (gamma) and three regulatory (alpha, beta, and delta). The gamma 1 subunit (PhKG1) is also referred to as the muscle gamma isoform. The gamma subunit, when isolated, is constitutively active and does not require phosphorylation of the A-loop for activity. The regulatory subunits restrain this kinase activity until signals are received to relieve this inhibition. For example, the kinase is activated in response to hormonal stimulation, after autophosphorylation or phosphorylation by cAMP-dependent kinase of the alpha and beta subunits. The high-affinity binding of ADP to the beta subunit also stimulates kinase activity, whereas calcium relieves inhibition by binding to the delta (calmodulin) subunit. The PhKG1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271084 [Multi-domain] Cd Length: 276 Bit Score: 92.67 E-value: 7.52e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKIVPYEP----------ESKQTVLQEYDILKSLH-HEKIMALHEAYVTPRYLVLISECC 3376
Cdd:cd14182     13 RGVSSVVRRCIHKPTRQEYAVKIIDITGggsfspeevqELREATLKEIDILRKVSgHPNIIQLKDTYETNTFFFLVFDLM 92

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3377 SGKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPlfLKQFSPPI 3456
Cdd:cd14182     93 KKGELFDYLTEKVTLSEKETRKIMRALLEVICALHKLNIVHRDLKPENILLDDDMNIKLTDFGFSCQLDP--GEKLREVC 170

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3457 GTLDYMSPEMLKGDV------VGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDL-SKLYQNVSQSASLFI 3529
Cdd:cd14182    171 GTPGYLAPEIIECSMddnhpgYGKEVDMWSTGVIMYTLLAGSPPFWHRKQMLMLRMIMSGNYQFgSPEWDDRSDTVKDLI 250

                          250       260
                   ....*....|....*....|....
gi 1207186029 3530 KKILCSYPWARPTIKDCFTNSWLQ 3553
Cdd:cd14182    251 SRFLVVQPQKRYTAEEALAHPFFQ 274

serine/threonine-protein kinase 1; Provisional

Pssm-ID: 223069 [Multi-domain] Cd Length: 267 Bit Score: 92.23 E-value: 7.77e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3309 GRFGVIRECRENATGNLYMAKIVpyepESKQtvlqeYDILKSLHHEkIMA-------LHEAYVTPRYLVLISECCSGKEL 3381
Cdd:PHA03390    27 GKFGKVSVLKHKPTQKLFVQKII----KAKN-----FNAIEPMVHQ-LMKdnpnfikLYYSVTTLKGHVLIMDYIKDGDL 96

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3382 LHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVT-YMNVVKIIDFGSAQTFNplflkqfSPPI--GT 3458
Cdd:PHA03390    97 FDLLKKEGKLSEAEVKKIIRQLVEALNDLHKHNIIHNDIKLENVLYDrAKDRIYLCDYGLCKIIG-------TPSCydGT 169

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3459 LDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTEN-----DPAETEARIQaakFDLSKLYqNVSQSASLFIKKIL 3533
Cdd:PHA03390   170 LDYFSPEKIKGHNYDVSFDWWAVGVLTYELLTGKHPFKEDedeelDLESLLKRQQ---KKLPFIK-NVSKNANDFVQSML 245


                   .
gi 1207186029 3534 C 3534
Cdd:PHA03390   246 K 246

Catalytic domain of the Serine/Threonine kinase, Inositol-requiring protein 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRE1, also called Endoplasmic reticulum (ER)-to-nucleus signaling protein (or ERN), is an ER-localized type I transmembrane protein with kinase and endoribonuclease domains in the cytoplasmic side. It acts as an ER stress sensor and is the oldest and most conserved component of the unfolded protein response (UPR) in eukaryotes. The UPR is activated when protein misfolding is detected in the ER in order to decrease the synthesis of new proteins and increase the capacity of the ER to cope with the stress. During ER stress, IRE1 dimerizes and forms oligomers, allowing the kinase domain to undergo trans-autophosphorylation. This leads to a conformational change that stimulates its endoribonuclease activity and results in the cleavage of its mRNA substrate, HAC1 in yeast and XBP1 in metazoans, promoting a splicing event that enables translation into a transcription factor which activates the UPR. Mammals contain two IRE1 proteins, IRE1alpha (or ERN1) and IRE1beta (or ERN2). The Ire1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270884 [Multi-domain] Cd Length: 269 Bit Score: 92.34 E-value: 7.79e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1703 ALRELNILSHLD-HERILYFHDAFEKKNAVIIITELCHEELLD-----RLTKKSTILESEIRSSVRQLLEGINYLHQLDI 1776
Cdd:cd13982     41 ADREVQLLRESDeHPNVIRYFCTEKDRQFLYIALELCAASLQDlvespRESKLFLRPGLEPVRLLRQIASGLAHLHSLNI 120

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1777 LHLDIKPDNILMA-DHSSDQIR--ICDFGNAVKFMPDEAQY-CKY---GTPEFVAPEIVNQTP---VSKATDIWPIGVLT 1846
Cdd:cd13982    121 VHRDLKPQNILIStPNAHGNVRamISDFGLCKKLDVGRSSFsRRSgvaGTSGWIAPEMLSGSTkrrQTRAVDIFSLGCVF 200

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1207186029 1847 YLCLT-GVSPFAGENDRSSvlNI--RNYNVAFEESMFTDLcHEAKGFVIKLLVAD-RLRPDANECLRHPWF 1913
Cdd:cd13982    201 YYVLSgGSHPFGDKLEREA--NIlkGKYSLDKLLSLGEHG-PEAQDLIERMIDFDpEKRPSAEEVLNHPFF 268

Catalytic domain of the Protein Serine/Threonine Kinase, p21-activated kinase 3; Serine/threonine kinases (STKs), p21-activated kinase (PAK) 3, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs from higher eukaryotes are classified into two groups (I and II), according to their biochemical and structural features. PAK3 belongs to group I. Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). PAK3 is highly expressed in the brain. It is implicated in neuronal plasticity, synapse formation, dendritic spine morphogenesis, cell cycle progression, neuronal migration, and apoptosis. Inactivating mutations in the PAK3 gene cause X-linked non-syndromic mental retardation, the severity of which depends on the site of the mutation.

Pssm-ID: 132987 [Multi-domain] Cd Length: 297 Bit Score: 92.86 E-value: 8.59e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3289 STLRQGVPQKPYTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPE-SKQTVLQEYDILKSLHHEKIMALHEAYVTPR 3367
Cdd:cd06656     10 SIVSVGDPKKKYTRFEKIGQGASGTVYTAIDIATGQEVAIKQMNLQQQpKKELIINEILVMRENKNPNIVNYLDSYLVGD 89

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3368 YLVLISECCSGKELLhSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPL 3447
Cdd:cd06656     90 ELWVVMEYLAGGSLT-DVVTETCMDEGQIAAVCRECLQALDFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFCAQITPE 168

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1207186029 3448 FLKQfSPPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDP 3500
Cdd:cd06656    169 QSKR-STMVGTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPYLNENP 220

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK2 is a MAPK kinase kinase (MAPKKK or MKKK), that phosphorylates and activates the MAPK kinase MEK5 (or MKK5), which in turn phosphorylates and activates ERK5. The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK2 also activates ERK1/2, c-Jun N-terminal kinase (JNK) and p38 through their respective MAPKKs MEK1/2, JNK-activating kinase 2 (JNKK2), and MKK3/6. MEKK2 plays roles in T cell receptor signaling, immune synapse formation, cytokine gene expression, as well as in EGF and FGF receptor signaling. The MEKK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270818 [Multi-domain] Cd Length: 264 Bit Score: 92.03 E-value: 9.08e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1666 KEIGRGAFSYVKRVIQKAGKLEYAAKFI-----SARAKRKASALR-ELNILSHLDHERILYFHDAF---EKKNAVIIITE 1736
Cdd:cd06652      8 KLLGQGAFGRVYLCYDADTGRELAVKQVqfdpeSPETSKEVNALEcEIQLLKNLLHERIVQYYGCLrdpQERTLSIFMEY 87

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1737 LCHEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDFGNAVKF----MPDEA 1812
Cdd:cd06652     88 MPGGSIKDQLKSYGALTENVTRKYTRQILEGVHYLHSNMIVHRDIKGANILR--DSVGNVKLGDFGASKRLqticLSGTG 165

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1813 QYCKYGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVafEESMFTDLCHEAKGFVI 1892
Cdd:cd06652    166 MKSVTGTPYWMSPEVISGEGYGRKADIWSVGCTVVEMLTEKPPWAEFEAMAAIFKIATQPT--NPQLPAHVSDHCRDFLK 243

                          250
                   ....*....|....*...
gi 1207186029 1893 KLLVADRLRPDANECLRH 1910
Cdd:cd06652    244 RIFVEAKLRPSADELLRH 261

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK2 plays a role in pro-apoptotic signaling. It is cleaved and activated by caspases leading to morphological changes during apoptosis. PAK2 is also activated in response to a variety of stresses including DNA damage, hyperosmolarity, serum starvation, and contact inhibition, and may play a role in coordinating the stress response. PAK2 also contributes to cancer cell invasion through a mechanism distinct from that of PAK1. It belongs to the group I PAKs, which contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 132986 [Multi-domain] Cd Length: 296 Bit Score: 92.86 E-value: 9.33e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3294 GVPQKPYTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPE-SKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLI 3372
Cdd:cd06655     15 GDPKKKYTRYEKIGQGASGTVFTAIDVATGQEVAIKQINLQKQpKKELIINEILVMKELKNPNIVNFLDSFLVGDELFVV 94

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3373 SECCSGKELLhSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLKQf 3452
Cdd:cd06655     95 MEYLAGGSLT-DVVTETCMDEAQIAAVCRECLQALEFLHANQVIHRDIKSDNVLLGMDGSVKLTDFGFCAQITPEQSKR- 172

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*...
gi 1207186029 3453 SPPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDP 3500
Cdd:cd06655    173 STMVGTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPYLNENP 220

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 9; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK9, together with a cyclin partner (cyclin T1, T2a, T2b, or K), is the main component of distinct positive transcription elongation factors (P-TEFb), which function as Ser2 C-terminal domain kinases of RNA polymerase II. P-TEFb participates in multiple steps of gene expression including transcription elongation, mRNA synthesis, processing, export, and translation. It also plays a role in mediating cytokine induced transcription networks such as IL6-induced STAT3 signaling. In addition, the CDK9/cyclin T2a complex promotes muscle differentiation and enhances the function of some myogenic regulatory factors. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK9 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270848 [Multi-domain] Cd Length: 310 Bit Score: 93.20 E-value: 9.66e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3309 GRFGVIRECRENATGNLYMAKIVPYEPESKQ---TVLQEYDILKSLHHEKIMALHEAYVTPR----------YLVLisEC 3375
Cdd:cd07865     23 GTFGEVFKARHRKTGQIVALKKVLMENEKEGfpiTALREIKILQLLKHENVVNLIEICRTKAtpynrykgsiYLVF--EF 100

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3376 C----SGkeLLHSLIDRFRYSEddVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNplfLKQ 3451
Cdd:cd07865    101 CehdlAG--LLSNKNVKFTLSE--IKKVMKMLLNGLYYIHRNKILHRDMKAANILITKDGVLKLADFGLARAFS---LAK 173

                          170       180       190
                   ....*....|....*....|....*....|....*...
gi 1207186029 3452 FSPP------IGTLDYMSPEMLKGDV-VGPPADIWSIG 3482
Cdd:cd07865    174 NSQPnrytnrVVTLWYRPPELLLGERdYGPPIDMWGAG 211

Catalytic domain of Kin1, Kin2, and simlar Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of yeast Kin1, Kin2, and similar proteins. Fission yeast Kin1 is a membrane-associated kinase that is involved in regulating cell surface cohesiveness during interphase. It also plays a role during mitosis, linking actomyosin ring assembly with septum synthesis and membrane closure to ensure separation of daughter cells. Budding yeast Kin1 and Kin2 act downstream of the Rab-GTPase Sec4 and are associated with the exocytic apparatus; they play roles in the secretory pathway. The Kin1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270979 [Multi-domain] Cd Length: 267 Bit Score: 92.13 E-value: 9.95e-20

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAK----------------RKASALRELNILSHLDHERILYFHDAF 1725
Cdd:cd14077      3 WEFVKTIGAGSMGKVKLAKHIRTGEKCAIKIIPRASNaglkkerekrlekeisRDIRTIREAALSSLLNHPHICRLRDFL 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1726 EKKNAVIIITELCH-EELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADhsSDQIRICDFGNA 1804
Cdd:cd14077     83 RTPNHYYMLFEYVDgGQLLDYIISHGKLKEKQARKFARQIASALDYLHRNSIVHRDLKIENILISK--SGNIKIIDFGLS 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1805 VKFMPDE--AQYCkyGTPEFVAPEIVNQTP-VSKATDIWPIGVLTYLCLTGVSPFAGENdrSSVLN--IRNYNVAFEESm 1879
Cdd:cd14077    161 NLYDPRRllRTFC--GSLYFAAPELLQAQPyTGPEVDVWSFGVVLYVLVCGKVPFDDEN--MPALHakIKKGKVEYPSY- 235

                          250       260       270
                   ....*....|....*....|....*....|....
gi 1207186029 1880 ftdLCHEAKGFVIKLLVAD-RLRPDANECLRHPW 1912
Cdd:cd14077    236 ---LSSECKSLISRMLVVDpKKRATLEQVLNHPW 266

Catalytic domain of Male germ cell-Associated Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of human MAK and MAK-related kinase (MRK), Saccharomyces cerevisiae Ime2p, Schizosaccharomyces pombe Mei4-dependent protein 3 (Mde3) and Pit1, Caenorhabditis elegans dyf-5, Arabidopsis thaliana MHK, and similar proteins. These proteins play important roles during meiosis. MAK is highly expressed in testicular cells specifically in the meiotic phase, but is not essential for spermatogenesis and fertility. It functions as a coactivator of the androgen receptor in prostate cells. MRK, also called Intestinal Cell Kinase (ICK), is expressed ubiquitously, with highest expression in the ovary and uterus. A missense mutation in MRK causes endocrine-cerebro-osteodysplasia, suggesting that this protein plays an important role in the development of many organs. MAK and MRK may be involved in regulating cell cycle and cell fate. Ime2p is a meiosis-specific kinase that is important during meiotic initiation and during the later stages of meiosis. Mde3 functions downstream of the transcription factor Mei-4 which is essential for meiotic prophase I. The MAK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270824 [Multi-domain] Cd Length: 283 Bit Score: 92.21 E-value: 1.08e-19

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYV-KRVIQKAGKLeYAAKfisaRAKRKASA------LRELNILSHL-DHERILYFHDAFEKKNAVII 1733
Cdd:cd07830      1 YKVIKQLGDGTFGSVyLARNKETGEL-VAIK----KMKKKFYSweecmnLREVKSLRKLnEHPNIVKLKEVFRENDELYF 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1734 ITELCHEELLD--RLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMAdhSSDQIRICDFGNA--VKFMP 1809
Cdd:cd07830     76 VFEYMEGNLYQlmKDRKGKPFSESVIRSIIYQILQGLAHIHKHGFFHRDLKPENLLVS--GPEVVKIADFGLAreIRSRP 153

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1810 DeaqYCKY-GTPEFVAPEIVNQTPV-SKATDIWPIGVLTYLCLTGVSPFAGENDR------------------------S 1863
Cdd:cd07830    154 P---YTDYvSTRWYRAPEILLRSTSySSPVDIWALGCIMAELYTLRPLFPGSSEIdqlykicsvlgtptkqdwpegyklA 230

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1207186029 1864 SVLNIR--NYNVAFEESMFTDLCHEAKGFVIKLLVAD-RLRPDANECLRHPWF 1913
Cdd:cd07830    231 SKLGFRfpQFAPTSLHQLIPNASPEAIDLIKDMLRWDpKKRPTASQALQHPYF 283

Catalytic domain of the Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGK2 shows a more restricted distribution than SGK1 and is most abundantly expressed in epithelial tissues including kidney, liver, pancreas, and the choroid plexus of the brain. In vitro cellular assays show that SGK2 can stimulate the activity of ion channels, the glutamate transporter EEAT4, and the glutamate receptors, GluR6 and GLUR1. The SGK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270754 [Multi-domain] Cd Length: 321 Bit Score: 93.11 E-value: 1.27e-19

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKIVpyepeSKQTVLQEYD----------ILKSLHHEKIMALHEAYVTPRYLVLISECCS 3377
Cdd:cd05603      5 KGSFGKVLLAKRKCDGKFYAVKVL-----QKKTILKKKEqnhimaernvLLKNLKHPFLVGLHYSFQTSEKLYFVLDYVN 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3378 GKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFG----------SAQTFnpl 3447
Cdd:cd05603     80 GGELFFHLQRERCFLEPRARFYAAEVASAIGYLHSLNIIYRDLKPENILLDCQGHVVLTDFGlckegmepeeTTSTF--- 156

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1207186029 3448 flkqfsppIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAE 3502
Cdd:cd05603    157 --------CGTPEYLAPEVLRKEPYDRTVDWWCLGAVLYEMLYGLPPFYSRDVSQ 203

Catalytic domain of the Serine/Threonine Kinase, Serine-aRginine Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SRPKs phosphorylate and regulate splicing factors from the SR protein family by specifically phosphorylating multiple serine residues residing in SR/RS dipeptide motifs (also known as RS domains). Phosphorylation of the RS domains enhances interaction with transportin SR and facilitates entry of the SR proteins into the nucleus. SRPKs contain a nonconserved insert domain, within the well-conserved catalytic kinase domain, that regulates their subcellular localization. They play important roles in mediating pre-mRNA processing and mRNA maturation, as well as other cellular functions such as chromatin reorganization, cell cycle and p53 regulation, and metabolic signaling. Vertebrates contain three distinct SRPKs, called SRPK1-3. The SRPK homolog in budding yeast, Sky1p, recognizes and phosphorylates its substrate Npl3p, which lacks a classic RS domain but contains a single RS dipeptide at the C-terminus of its RGG domain. Npl3p is a shuttling heterogeneous nuclear ribonucleoprotein (hnRNP) that exports a distinct class of mRNA from the nucleus to the cytoplasm. The SRPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271038 [Multi-domain] Cd Length: 320 Bit Score: 92.64 E-value: 1.42e-19

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASALRELNIL--------SHLDHERILYFHDAFEKK----N 1729
Cdd:cd14136     12 YHVVRKLGWGHFSTVWLCWDLQNKRFVALKVVKSAQHYTEAALDEIKLLkcvreadpKDPGREHVVQLLDDFKHTgpngT 91

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1730 AVIIITELCHEELLDrLTKKST---ILESEIRSSVRQLLEGINYLH-QLDILHLDIKPDNILMAdHSSDQIRICDFGNAV 1805
Cdd:cd14136     92 HVCMVFEVLGPNLLK-LIKRYNyrgIPLPLVKKIARQVLQGLDYLHtKCGIIHTDIKPENVLLC-ISKIEVKIADLGNAC 169

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1806 ---KFMPDEAQyckygTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGV---SPFAGE-------------------- 1859
Cdd:cd14136    170 wtdKHFTEDIQ-----TRQYRSPEVILGAGYGTPADIWSTACMAFELATGDylfDPHSGEdysrdedhlaliiellgrip 244

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1207186029 1860 --------------NDRSSVLNIRN------YNVAFEESMFTDlcHEAKGFVIKLL----VADRLRPDANECLRHPWF 1913
Cdd:cd14136    245 rsiilsgkysreffNRKGELRHISKlkpwplEDVLVEKYKWSK--EEAKEFASFLLpmleYDPEKRATAAQCLQHPWL 320

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK6 is widely expressed in many tissues and is expressed as multiple splice variants with different domain architectures. It is post-translationally palmitoylated and localized in the membrane. GRK6 plays important roles in the regulation of dopamine, M3 muscarinic, opioid, and chemokine receptor signaling. It also plays maladaptive roles in addiction and Parkinson's disease. GRK6-deficient mice exhibit altered dopamine receptor regulation, decreased lymphocyte chemotaxis, and increased acute inflammation and neutrophil chemotaxis. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270779 [Multi-domain] Cd Length: 285 Bit Score: 92.01 E-value: 1.46e-19

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3307 ARGRFGVIRECRENATGNLYMAKIVPYEPESKQT----VLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELL 3382
Cdd:cd05630      9 GKGGFGEVCACQVRATGKMYACKKLEKKRIKKRKgeamALNEKQILEKVNSRFVVSLAYAYETKDALCLVLTLMNGGDLK 88

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3383 HSL--IDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSA------QTFNplflkqfsP 3454
Cdd:cd05630     89 FHIyhMGQAGFPEARAVFYAAEICCGLEDLHRERIVYRDLKPENILLDDHGHIRISDLGLAvhvpegQTIK--------G 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3455 PIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPA----ETEARIQAAKFDLSKLYqnvSQSASLFIK 3530
Cdd:cd05630    161 RVGTVGYMAPEVVKNERYTFSPDWWALGCLLYEMIAGQSPFQQRKKKikreEVERLVKEVPEEYSEKF---SPQARSLCS 237

                          250
                   ....*....|
gi 1207186029 3531 KILCSYPWAR 3540
Cdd:cd05630    238 MLLCKDPAER 247

Catalytic domain of the Serine/Threonine Kinase, Plant Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of plant MAPK kinase kinases (MAPKKKs) including Arabidopsis thaliana MEKK1 and MAPKKK3. Arabidopsis thaliana MEKK1 activates MPK4, a MAPK that regulates systemic acquired resistance. MEKK1 also participates in the regulation of temperature-sensitive and tissue-specific cell death. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The plant MEKK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270802 [Multi-domain] Cd Length: 259 Bit Score: 91.31 E-value: 1.61e-19

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1705 RELNILSHLDHERILYFHDAFEKKNAVIIITELCHEELLDRLTKKSTIL-ESEIRSSVRQLLEGINYLHQLDILHLDIKP 1783
Cdd:cd06632     51 QEIALLSKLRHPNIVQYYGTEREEDNLYIFLEYVPGGSIHKLLQRYGAFeEPVIRLYTRQILSGLAYLHSRNTVHRDIKG 130

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1784 DNILMadHSSDQIRICDFGNAVKFM-PDEAQYCKyGTPEFVAPEIVNQ--TPVSKATDIWPIGVLTYLCLTGVSPFAGEN 1860
Cdd:cd06632    131 ANILV--DTNGVVKLADFGMAKHVEaFSFAKSFK-GSPYWMAPEVIMQknSGYGLAVDIWSLGCTVLEMATGKPPWSQYE 207

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1207186029 1861 DRSSVLNIRNYNVAFEesMFTDLCHEAKGFVIKLLVAD-RLRPDANECLRHP 1911
Cdd:cd06632    208 GVAAIFKIGNSGELPP--IPDHLSPDAKDFIRLCLQRDpEDRPTASQLLEHP 257

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK5 is widely expressed in many tissues. It associates with the membrane though an N-terminal PIP2 binding domain and also binds phospholipids via its C-terminus. GRK5 deficiency is associated with early Alzheimer's disease in humans and mouse models. GRK5 also plays a crucial role in the pathogenesis of sporadic Parkinson's disease. It participates in the regulation and desensitization of PDGFRbeta, a receptor tyrosine kinase involved in a variety of downstream cellular effects including cell growth, chemotaxis, apoptosis, and angiogenesis. GRK5 also regulates Toll-like receptor 4, which is involved in innate and adaptive immunity. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270780 [Multi-domain] Cd Length: 313 Bit Score: 92.34 E-value: 1.64e-19

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1660 DYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISAR--AKRKAS--ALRELNILSHLDHERILYFHDAFEKKNAV-III 1734
Cdd:cd05632      2 NTFRQYRVLGKGGFGEVCACQVRATGKMYACKRLEKKriKKRKGEsmALNEKQILEKVNSQFVVNLAYAYETKDALcLVL 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1735 TELCHEELLDRLTKKST--ILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSsdQIRICDFGNAVKFMPDEA 1812
Cdd:cd05632     82 TIMNGGDLKFHIYNMGNpgFEEERALFYAAEILCGLEDLHRENTVYRDLKPENILLDDYG--HIRISDLGLAVKIPEGES 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1813 QYCKYGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDLCHEAKGFVI 1892
Cdd:cd05632    160 IRGRVGTVGYMAPEVLNNQRYTLSPDYWGLGCLIYEMIEGQSPFRGRKEKVKREEVDRRVLETEEVYSAKFSEEAKSICK 239

                          250       260       270
                   ....*....|....*....|....*....|.
gi 1207186029 1893 KLLVAD---RL---RPDANECLRHPWFKTLN 1917
Cdd:cd05632    240 MLLTKDpkqRLgcqEEGAGEVKRHPFFRNMN 270

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK4 regulates cell morphology and cytoskeletal organization. It is essential for embryonic viability and proper neural development. Mice lacking PAK4 die due to defects in the fetal heart. In addition, their spinal cord motor neurons showed failure to differentiate and migrate. PAK4 also plays a role in cell survival and tumorigenesis. It is overexpressed in many primary tumors including colon, esophageal, and mammary tumors. PAK4 has also been implicated in viral and bacterial infection pathways. PAK4 belongs to the group II PAKs, which contain a PBD (p21-binding domain) and a C-terminal catalytic domain, but do not harbor an AID (autoinhibitory domain) or SH3 binding sites. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 132988 [Multi-domain] Cd Length: 292 Bit Score: 92.01 E-value: 1.65e-19

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3296 PQKPYTFMD---EKARGRFGVIRECRENATGNLYMAKIVPYEPESKQTVL-QEYDILKSLHHEKIMALHEAYVTPRYLVL 3371
Cdd:cd06657     15 PGDPRTYLDnfiKIGEGSTGIVCIATVKSSGKLVAVKKMDLRKQQRRELLfNEVVIMRDYQHENVVEMYNSYLVGDELWV 94

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3372 ISECCSGKELLhSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLKQ 3451
Cdd:cd06657     95 VMEFLEGGALT-DIVTHTRMNEEQIAAVCLAVLKALSVLHAQGVIHRDIKSDSILLTHDGRVKLSDFGFCAQVSKEVPRR 173

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3452 FSpPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLSKLYQNVSQSASLFIKK 3531
Cdd:cd06657    174 KS-LVGTPYWMAPELISRLPYGPEVDIWSLGIMVIEMVDGEPPYFNEPPLKAMKMIRDNLPPKLKNLHKVSPSLKGFLDR 252

                          250       260
                   ....*....|....*....|....
gi 1207186029 3532 ILCSYPWARPTIKDCFTNSWLQDA 3555
Cdd:cd06657    253 LLVRDPAQRATAAELLKHPFLAKA 276

Catalytic domain of the Serine/Threonine Kinases, Thousand-and-One Amino acids proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAO proteins possess mitogen-activated protein kinase (MAPK) kinase kinase activity. They activate the MAPKs, p38 and c-Jun N-terminal kinase (JNK), by phosphorylating and activating the respective MAP/ERK kinases (MEKs, also known as MKKs or MAPKKs), MEK3/MEK6 and MKK4/MKK7. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. Vertebrates contain three TAO subfamily members, named TAO1, TAO2, and TAO3. The TAO subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270784 [Multi-domain] Cd Length: 258 Bit Score: 90.97 E-value: 1.85e-19

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3298 KPYTFMDEKARGRFGVIRECRENATGNLYMAKIVPY----EPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLIS 3373
Cdd:cd06607      1 KIFEDLREIGHGSFGAVYYARNKRTSEVVAIKKMSYsgkqSTEKWQDIIKEVKFLRQLRHPNTIEYKGCYLREHTAWLVM 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3374 ECCSG---------KELLHslidrfrysEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTF 3444
Cdd:cd06607     81 EYCLGsasdivevhKKPLQ---------EVEIAAICHGALQGLAYLHSHNRIHRDVKAGNILLTEPGTVKLADFGSASLV 151

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3445 NPlfLKQFsppIGTLDYMSPE----MLKGDVVGpPADIWSIGIlTYIMLSGRLPFTENDPAeteariqaakfdLSKLY-- 3518
Cdd:cd06607    152 CP--ANSF---VGTPYWMAPEvilaMDEGQYDG-KVDVWSLGI-TCIELAERKPPLFNMNA------------MSALYhi 212

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*
gi 1207186029 3519 -QNVSQSAS---------LFIKKILCSYPWARPTIKDCFTNSWLQ 3553
Cdd:cd06607    213 aQNDSPTLSsgewsddfrNFVDSCLQKIPQDRPSAEDLLKHPFVT 257

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 9; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek9, also called Nercc1, is primarily a cytoplasmic protein but can also localize in the nucleus. It is involved in modulating chromosome alignment and splitting during mitosis. It interacts with the gamma-tubulin ring complex and the Ran GTPase, and is implicated in microtubule organization. Nek9 associates with FACT (FAcilitates Chromatin Transcription) and modulates interphase progression. It also interacts with Nek6, and Nek7, during mitosis, resulting in their activation. Nek9 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270860 [Multi-domain] Cd Length: 256 Bit Score: 90.95 E-value: 1.96e-19

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3338 KQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLHSLIDRFR--YSEDDVVAYIVQILQGLDYLHSRRI 3415
Cdd:cd08221     43 RRDALNEIDILSLLNHDNIITYYNHFLDGESLFIEMEYCNGGNLHDKIAQQKNqlFPEEVVLWYLYQIVSAVSHIHKAGI 122

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3416 LHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLKQFSpPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPF 3495
Cdd:cd08221    123 LHRDIKTLNIFLTKADLVKLGDFGISKVLDSESSMAES-IVGTPYYMSPELVQGVKYNFKSDIWAVGCVLYELLTLKRTF 201

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1207186029 3496 TENDPAETEARI-QAAKFDLSKLYqnvSQSASLFIKKILCSYPWARPTIKDCFTNSWL 3552
Cdd:cd08221    202 DATNPLRLAVKIvQGEYEDIDEQY---SEEIIQLVHDCLHQDPEDRPTAEELLERPLL 256

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK3 is a MAPK kinase kinase (MAPKKK or MKKK), that phosphorylates and activates the MAPK kinase MEK5 (or MKK5), which in turn phosphorylates and activates ERK5. The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK3 plays an essential role in embryonic angiogenesis and early heart development. In addition, MEKK3 is involved in interleukin-1 receptor and Toll-like receptor 4 signaling. It is also a specific regulator of the proinflammatory cytokines IL-6 and GM-CSF in some immune cells. MEKK3 also regulates calcineurin, which plays a critical role in T cell activation, apoptosis, skeletal myocyte differentiation, and cardiac hypertrophy. The MEKK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270817 [Multi-domain] Cd Length: 271 Bit Score: 91.30 E-value: 2.07e-19

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1666 KEIGRGAFSYVKRVIQKAGKLEYAAKFI-----SARAKRKASALR-ELNILSHLDHERILYFHDAFE---KKNAVIIITE 1736
Cdd:cd06651     13 KLLGQGAFGRVYLCYDVDTGRELAAKQVqfdpeSPETSKEVSALEcEIQLLKNLQHERIVQYYGCLRdraEKTLTIFMEY 92

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1737 LCHEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDFGNAVKF----MPDEA 1812
Cdd:cd06651     93 MPGGSVKDQLKAYGALTESVTRKYTRQILEGMSYLHSNMIVHRDIKGANILR--DSAGNVKLGDFGASKRLqticMSGTG 170

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1813 QYCKYGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVafEESMFTDLCHEAKGFVI 1892
Cdd:cd06651    171 IRSVTGTPYWMSPEVISGEGYGRKADVWSLGCTVVEMLTEKPPWAEYEAMAAIFKIATQPT--NPQLPSHISEHARDFLG 248

                          250       260
                   ....*....|....*....|
gi 1207186029 1893 KLLVADRLRPDANECLRHPW 1912
Cdd:cd06651    249 CIFVEARHRPSAEELLRHPF 268

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK1 is important in the regulation of many cellular processes including cytoskeletal dynamics, cell motility, growth, and proliferation. Although PAK1 has been regarded mainly as a cytosolic protein, recent reports indicate that PAK1 also exists in significant amounts in the nucleus, where it is involved in transcription modulation and in cell cycle regulatory events. PAK1 is also involved in transformation and tumorigenesis. Its overexpression, hyperactivation and increased nuclear accumulation is correlated to breast cancer invasiveness and progression. Nuclear accumulation is also linked to tamoxifen resistance in breast cancer cells. PAK1 belongs to the group I PAKs, which contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270820 [Multi-domain] Cd Length: 296 Bit Score: 91.71 E-value: 2.11e-19

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3289 STLRQGVPQKPYTFMDEKARGRFGVIRECRENATGN-LYMAKIVPYEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPR 3367
Cdd:cd06654     11 SIVSVGDPKKKYTRFEKIGQGASGTVYTAMDVATGQeVAIRQMNLQQQPKKELIINEILVMRENKNPNIVNYLDSYLVGD 90

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3368 YLVLISECCSGKELLhSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPL 3447
Cdd:cd06654     91 ELWVVMEYLAGGSLT-DVVTETCMDEGQIAAVCRECLQALEFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFCAQITPE 169

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1207186029 3448 FLKQfSPPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDP 3500
Cdd:cd06654    170 QSKR-STMVGTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMIEGEPPYLNENP 221

Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMP-activated protein kinase (AMPK). CaMKK2, also called CaMKK beta, is one of the most versatile CaMKs. It is involved in regulating energy balance, glucose metabolism, adiposity, hematopoiesis, inflammation, and cancer. CaMKK2 contains unique N- and C-terminal domains and a central catalytic kinase domain that is followed by a regulatory domain that bears overlapping autoinhibitory and CaM-binding regions. It can be activated by signaling through G-coupled receptors, IP3 receptors, plasma membrane ion channels, and Toll-like receptors. Thus, CaMKK2 acts as a molecular hub that is capable of receiving and decoding signals from diverse pathways. The CaMKK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271101 [Multi-domain] Cd Length: 286 Bit Score: 91.57 E-value: 2.28e-19

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISAR------------AKRKASAL---------------RELNILSHLD 1714
Cdd:cd14199      4 YKLKDEIGKGSYGVVKLAYNEDDNTYYAMKVLSKKklmrqagfprrpPPRGARAApegctqprgpiervyQEIAILKKLD 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1715 HERILYFHDAFEKKNA--VIIITELCHEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHS 1792
Cdd:cd14199     84 HPNVVKLVEVLDDPSEdhLYMVFELVKQGPVMEVPTLKPLSEDQARFYFQDLIKGIEYLHYQKIIHRDVKPSNLLVGEDG 163

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1793 sdQIRICDFGNAVKFMPDEAQYCK-YGTPEFVAPEIVNQTP---VSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNI 1868
Cdd:cd14199    164 --HIKIADFGVSNEFEGSDALLTNtVGTPAFMAPETLSETRkifSGKALDVWAMGVTLYCFVFGQCPFMDERILSLHSKI 241

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*
gi 1207186029 1869 RNYNVAFEESmfTDLCHEAKGFVIKLLVAD-RLRPDANECLRHPW 1912
Cdd:cd14199    242 KTQPLEFPDQ--PDISDDLKDLLFRMLDKNpESRISVPEIKLHPW 284

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated protein kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK-activated protein kinase 3 (MAPKAP3 or MK3) contains an N-terminal proline-rich region that can bind to SH3 domains, a catalytic kinase domain followed by a C-terminal autoinhibitory region that contains nuclear localization (NLS) and nuclear export (NES) signals with a p38 MAPK docking motif that overlaps the NLS. MK3 is a bonafide substrate for the MAPK p38. It is closely related to MK2 and thus far, MK2/3 show indistinguishable substrate specificity. They are mainly involved in the regulation of gene expression and they participate in diverse cellular processes such as endocytosis, cytokine production, cytoskeletal reorganization, cell migration, cell cycle control and chromatin remodeling. They are implicated in inflammation and cance and their substrates include mRNA-AU-rich-element (ARE)-binding proteins (TTP and hnRNP A0), Hsp proteins (Hsp27 and Hsp25) and RSK, among others. MK2/3 are both expressed ubiquitously but MK2 is expressed at significantly higher levels. MK3 activity is only significant when MK2 is absent. The MK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271074 [Multi-domain] Cd Length: 267 Bit Score: 90.82 E-value: 2.41e-19

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1658 LTDYYDVHKEI------GRGAFSYVKRVIQK-AGKLEYAakfiSARAKRKASALRELNILSHLDHERILYfHDAFEKKNA 1730
Cdd:cd14172      1 VTDDYKLSKQVlglgvnGKVLECFHRRTGQKcALKLLYD----SPKARREVEHHWRASGGPHIVHILDVY-ENMHHGKRC 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1731 VIIITElCHE--ELLDRLTKK--STILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSD-QIRICDFGNAV 1805
Cdd:cd14172     76 LLIIME-CMEggELFSRIQERgdQAFTEREASEIMRDIGTAIQYLHSMNIAHRDVKPENLLYTSKEKDaVLKLTDFGFAK 154

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1806 KFMPDEAQYCKYGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRS----SVLNIRNYNVAFEESMFT 1881
Cdd:cd14172    155 ETTVQNALQTPCYTPYYVAPEVLGPEKYDKSCDMWSLGVIMYILLCGFPPFYSNTGQAispgMKRRIRMGQYGFPNPEWA 234

                          250       260       270
                   ....*....|....*....|....*....|..
gi 1207186029 1882 DLCHEAKGFVIKLLVAD-RLRPDANECLRHPW 1912
Cdd:cd14172    235 EVSEEAKQLIRHLLKTDpTERMTITQFMNHPW 266

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409564 [Multi-domain] Cd Length: 91 Bit Score: 85.33 E-value: 2.42e-19

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1123 PLFTRKLDVLEVIEGRNARFDCKVSGTPPPQVIWSHFDRPLEENEDIRILKEGGRHSLIISHVSNEDEGLYTVAARNSHG 1202
Cdd:cd20972      2 PQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKELQNSPDIQIHQEGDLHSLIIAEAFEEDTGRYSCLATNSVG 81

                           90
                   ....*....|
gi 1207186029 1203 EDECAAELYV 1212
Cdd:cd20972     82 SDTTSAEIFV 91

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated protein kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK-activated protein kinase 5 (MAPKAP5 or MK5) is also called PRAK (p38-regulated/activated protein kinase). It contains a catalytic kinase domain followed by a C-terminal autoinhibitory region that contains nuclear localization (NLS) and nuclear export (NES) signals with a p38 MAPK docking motif that overlaps the NLS. MK5 is a ubiquitous protein that is implicated in neuronal morphogenesis, cell migration, and tumor angiogenesis. It interacts with PKA, which induces cytoplasmic translocation of MK5. Its substrates includes p53, ERK3/4, Hsp27, and cytosolic phospholipase A2 (cPLA2). The MAPKAPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271073 [Multi-domain] Cd Length: 289 Bit Score: 91.37 E-value: 2.42e-19

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1658 LTDYYDV--HKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASALREL------NILSHLDHER--ILYFHDAFEK 1727
Cdd:cd14171      2 ILEEYEVnwTQKLGTGISGPVRVCVKKSTGERFALKILLDRPKARTEVRLHMmcsghpNIVQIYDVYAnsVQFPGESSPR 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1728 KNAVIIITELCHEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSD-QIRICDFGNAvK 1806
Cdd:cd14171     82 ARLLIVMELMEGGELFDRISQHRHFTEKQAAQYTKQIALAVQHCHSLNIAHRDLKPENLLLKDNSEDaPIKLCDFGFA-K 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1807 FMPDEAQYCKYgTPEFVAPEIVN---------------QTPVS--KATDIWPIGVLTYLCLTGVSPFAGENDRSSVLN-- 1867
Cdd:cd14171    161 VDQGDLMTPQF-TPYYVAPQVLEaqrrhrkersgiptsPTPYTydKSCDMWSLGVIIYIMLCGYPPFYSEHPSRTITKdm 239

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*....
gi 1207186029 1868 ---IRNYNVAFEESMFTDLCHEAKGFVIKLLVAD-RLRPDANECLRHPW 1912
Cdd:cd14171    240 krkIMTGSYEFPEEEWSQISEMAKDIVRKLLCVDpEERMTIEEVLHHPW 288

Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase (CDK), Bypass UAS Requirement 1, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BUR1, also called SGV1, is a yeast CDK that is functionally equivalent to mammalian CDK9. It associates with the cyclin BUR2. BUR genes were orginally identified in a genetic screen as factors involved in general transcription. The BUR1/BUR2 complex phosphorylates the C-terminal domain of RNA polymerase II. In addition, this complex regulates histone modification by phosporylating Rad6 and mediating the association of the Paf1 complex with chromatin. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The BUR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270849 [Multi-domain] Cd Length: 311 Bit Score: 91.61 E-value: 2.77e-19

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLY-MAKIVPYEpeSKQ----TVLQEYDILKSLHHEKIMALHE-AYVTPR------ 3367
Cdd:cd07866     10 YEILGKLGEGTFGEVYKARQIKTGRVVaLKKILMHN--EKDgfpiTALREIKILKKLKHPNVVPLIDmAVERPDkskrkr 87

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3368 ---YLVLISECCSGKELLHSliDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTF 3444
Cdd:cd07866     88 gsvYMVTPYMDHDLSGLLEN--PSVKLTESQIKCYMLQLLEGINYLHENHILHRDIKAANILIDNQGILKIADFGLARPY 165

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1207186029 3445 -NPLFLKQFSPPIGTLDYMS---------PEMLKGDV-VGPPADIWSIGILTYIMLSGR 3492
Cdd:cd07866    166 dGPPPNPKGGGGGGTRKYTNlvvtrwyrpPELLLGERrYTTAVDIWGIGCVFAEMFTRR 224

Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.

Pssm-ID: 197581 [Multi-domain] Cd Length: 257 Bit Score: 90.28 E-value: 2.86e-19

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  1666 KEIGRGAFSYVKR----VIQKAGKLEYAAKFISARAKRKASA--LRELNILSHLDHERILYFHDAFEKKNAVIIITELC- 1738
Cdd:smart00219    5 KKLGEGAFGEVYKgklkGKGGKKKVEVAVKTLKEDASEQQIEefLREARIMRKLDHPNVVKLLGVCTEEEPLYIVMEYMe 84

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  1739 HEELLDRL-TKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHssDQIRICDFGNAvKFMPDEAQYCKY 1817
Cdd:smart00219   85 GGDLLSYLrKNRPKLSLSDLLSFALQIARGMEYLESKNFIHRDLAARNCLVGEN--LVVKISDFGLS-RDLYDDDYYRKR 161

                           170       180       190       200
                    ....*....|....*....|....*....|....*....|....*
gi 1207186029  1818 GTPEFV---APEIVNQTPVSKATDIWPIGVLTY-LCLTGVSPFAG 1858
Cdd:smart00219  162 GGKLPIrwmAPESLKEGKFTSKSDVWSFGVLLWeIFTLGEQPYPG 206

Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 2 and 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKL2, also called p56 KKIAMRE, is expressed in testis, kidney, lung, and brain. It functions mainly in mature neurons and plays an important role in learning and memory. Inactivation of CDKL3, also called NKIAMRE (NKIATRE in rat), by translocation is associated with mild mental retardation. It has been reported that CDKL3 is lost in leukemic cells having a chromosome arm 5q deletion, and may contribute to the transformed phenotype. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL2/3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270836 [Multi-domain] Cd Length: 286 Bit Score: 90.94 E-value: 3.00e-19

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQK-AGKLEYAAKFISARAKR--KASALRELNILSHLDHERILYFHDAFEKKNAVIIITELC 1738
Cdd:cd07846      3 YENLGLVGEGSYGMVMKCRHKeTGQIVAIKKFLESEDDKmvKKIAMREIKMLKQLRHENLVNLIEVFRRKKRWYLVFEFV 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1739 HEELLDRLTKKSTILESE-IRSSVRQLLEGINYLHQLDILHLDIKPDNILMAdhSSDQIRICDFGNAVKFMPDEAQYCKY 1817
Cdd:cd07846     83 DHTVLDDLEKYPNGLDESrVRKYLFQILRGIDFCHSHNIIHRDIKPENILVS--QSGVVKLCDFGFARTLAAPGEVYTDY 160

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*.
gi 1207186029 1818 -GTPEFVAPE-IVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGEND 1861
Cdd:cd07846    161 vATRWYRAPElLVGDTKYGKAVDVWAVGCLVTEMLTGEPLFPGDSD 206

Catalytic domain of Male germ cell-Associated Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of human MAK and MAK-related kinase (MRK), Saccharomyces cerevisiae Ime2p, Schizosaccharomyces pombe Mei4-dependent protein 3 (Mde3) and Pit1, Caenorhabditis elegans dyf-5, Arabidopsis thaliana MHK, and similar proteins. These proteins play important roles during meiosis. MAK is highly expressed in testicular cells specifically in the meiotic phase, but is not essential for spermatogenesis and fertility. It functions as a coactivator of the androgen receptor in prostate cells. MRK, also called Intestinal Cell Kinase (ICK), is expressed ubiquitously, with highest expression in the ovary and uterus. A missense mutation in MRK causes endocrine-cerebro-osteodysplasia, suggesting that this protein plays an important role in the development of many organs. MAK and MRK may be involved in regulating cell cycle and cell fate. Ime2p is a meiosis-specific kinase that is important during meiotic initiation and during the later stages of meiosis. Mde3 functions downstream of the transcription factor Mei-4 which is essential for meiotic prophase I. The MAK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270824 [Multi-domain] Cd Length: 283 Bit Score: 91.06 E-value: 3.01e-19

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLY----MAKivPYEPESKQTVLQEydiLKSL----HHEKIMALHEAYVTPRYLVL 3371
Cdd:cd07830      1 YKVIKQLGDGTFGSVYLARNKETGELVaikkMKK--KFYSWEECMNLRE---VKSLrklnEHPNIVKLKEVFRENDELYF 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3372 ISECCsgKELLHSLI---DRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPlf 3448
Cdd:cd07830     76 VFEYM--EGNLYQLMkdrKGKPFSESVIRSIIYQILQGLAHIHKHGFFHRDLKPENLLVSGPEVVKIADFGLAREIRS-- 151

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3449 lkqfSPP----IGTLDYMSPEM-LKGDVVGPPADIWSIGILTYIMLSGRLPF---TEND-----------PAETE----- 3504
Cdd:cd07830    152 ----RPPytdyVSTRWYRAPEIlLRSTSYSSPVDIWALGCIMAELYTLRPLFpgsSEIDqlykicsvlgtPTKQDwpegy 227

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1207186029 3505 ---ARI-----QAAKFDLSKLYQNVSQSASLFIKKILCSYPWARPTIKDCFTNSWL 3552
Cdd:cd07830    228 klaSKLgfrfpQFAPTSLHQLIPNASPEAIDLIKDMLRWDPKKRPTASQALQHPYF 283

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409565 [Multi-domain] Cd Length: 88 Bit Score: 84.93 E-value: 3.01e-19

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1553 DLDVNVGETPRFAVVVEGKPVPDILWYKGDTLLSESSHFTFVYD-DNECSLVVLNTQADDSGVYTCTAKNLAGSVSCKAE 1631
Cdd:cd20973      6 DKEVVEGSAARFDCKVEGYPDPEVKWMKDDNPIVESRRFQIDQDeDGLCSLIISDVCGDDSGKYTCKAVNSLGEATCSAE 85


                   ...
gi 1207186029 1632 LTV 1634
Cdd:cd20973     86 LTV 88

Catalytic domain of Fungal Nak1-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Schizosaccharomyces pombe Nak1, Saccharomyces cerevisiae Kic1p (kinase that interacts with Cdc31p) and related proteins. Nak1 (also called N-rich kinase 1), is required by fission yeast for polarizing the tips of actin cytoskeleton and is involved in cell growth, cell separation, cell morphology and cell-cycle progression. Kic1p is required by budding yeast for cell integrity and morphogenesis. Kic1p interacts with Cdc31p, the yeast homologue of centrin, and phosphorylates substrates in a Cdc31p-dependent manner. The Nak1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270822 [Multi-domain] Cd Length: 277 Bit Score: 91.00 E-value: 3.06e-19

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3299 PYTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPESKQT--VLQEYDILKSLHH---EKIMALHEAYVTPRYLVLIS 3373
Cdd:cd06917      2 LYRRLELVGRGSYGAVYRGYHVKTGRVVALKVLNLDTDDDDVsdIQKEVALLSQLKLgqpKNIIKYYGSYLKGPSLWIIM 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3374 ECCSGKELlHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLKQfS 3453
Cdd:cd06917     82 DYCEGGSI-RTLMRAGPIAERYIAVIMREVLVALKFIHKDGIIHRDIKAANILVTNTGNVKLCDFGVAASLNQNSSKR-S 159

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*....
gi 1207186029 3454 PPIGTLDYMSPE-MLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPA 3501
Cdd:cd06917    160 TFVGTPYWMAPEvITEGKYYDTKADIWSLGITTYEMATGNPPYSDVDAL 208

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 8; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek8 contains an N-terminal kinase catalytic domain and a C-terminal RCC1 (regulator of chromosome condensation) domain. A double point mutation in Nek8 causes cystic kidney disease in mice that genetically resembles human autosomal recessive polycystic kidney disease (ARPKD). Nek8 is also associated with a rare form of juvenile renal cystic disease, nephronophthisis type 9. It has been suggested that a defect in the ciliary localization of Nek8 contributes to the development of cysts manifested by these diseases. Nek8 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270859 [Multi-domain] Cd Length: 256 Bit Score: 90.18 E-value: 3.09e-19

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARA---KRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITELC 1738
Cdd:cd08220      2 YEKIRVVGRGAYGTVYLCRRKDDNKLVIIKQIPVEQmtkEERQAALNEVKVLSMLHHPNIIEYYESFLEDKALMIVMEYA 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1739 HE-ELLDRLTKKSTIL--ESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSdQIRICDFGNAVKFMPDEAQYC 1815
Cdd:cd08220     82 PGgTLFEYIQQRKGSLlsEEEILHFFVQILLALHHVHSKQILHRDLKTQNILLNKKRT-VVKIGDFGISKILSSKSKAYT 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1816 KYGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDlchEAKGFVIKLL 1895
Cdd:cd08220    161 VVGTPCYISPELCEGKPYNQKSDIWALGCVLYELASLKRAFEAANLPALVLKIMRGTFAPISDRYSE---ELRHLILSML 237

                          250
                   ....*....|....*..
gi 1207186029 1896 VAD-RLRPDANECLRHP 1911
Cdd:cd08220    238 HLDpNKRPTLSEIMAQP 254

Catalytic domain of the Protein Tyrosine Kinases, Fungal Wee1 proteins; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of fungal Wee1 proteins, also called Swe1 in budding yeast and Mik1 in fission yeast. Yeast Wee1 is required to control cell size. Wee1 is a cell cycle checkpoint kinase that helps keep the cyclin-dependent kinase CDK1 in an inactive state through phosphorylation of an N-terminal tyr (Y15) residue. During the late G2 phase, CDK1 is activated and mitotic entry is promoted by the removal of this inhibitory phosphorylation by the phosphatase Cdc25. Although Wee1 is functionally a tyr kinase, it is more closely related to serine/threonine kinases (STKs). It contains a catalytic kinase domain sandwiched in between N- and C-terminal regulatory domains. It is regulated by phosphorylation and degradation, and its expression levels are also controlled by circadian clock proteins. The fungal Wee1 subfamily is part of a larger superfamily that includes the catalytic domains of STKs, other PTKs, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270954 [Multi-domain] Cd Length: 278 Bit Score: 90.56 E-value: 3.45e-19

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGK-LEYAAKFIS---ARAKRKASALRELNILSHLD---HERILYFHDAFEKKNAVIII 1734
Cdd:cd14052      2 FANVELIGSGEFSQVYKVSERVPTgKVYAVKKLKpnyAGAKDRLRRLEEVSILRELTldgHDNIVQLIDSWEYHGHLYIQ 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1735 TELCHEELLDR----LTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSdqIRICDFGNAVKFmPD 1810
Cdd:cd14052     82 TELCENGSLDVflseLGLLGRLDEFRVWKILVELSLGLRFIHDHHFVHLDLKPANVLITFEGT--LKIGDFGMATVW-PL 158

                          170       180       190
                   ....*....|....*....|....*....|....*
gi 1207186029 1811 EAQYCKYGTPEFVAPEIVNQTPVSKATDIWPIGVL 1845
Cdd:cd14052    159 IRGIEREGDREYIAPEILSEHMYDKPADIFSLGLI 193

Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MST3 phosphorylates the STK NDR and may play a role in cell cycle progression and cell morphology. It may also regulate paxillin and consequently, cell migration. MST3 is present in human placenta, where it plays an essential role in the oxidative stress-induced apoptosis of trophoblasts in normal spontaneous delivery. Dysregulation of trophoblast apoptosis may result in pregnancy complications such as preeclampsia and intrauterine growth retardation. The MST3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270809 [Multi-domain] Cd Length: 277 Bit Score: 90.90 E-value: 3.48e-19

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3296 PQKPYTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEP--ESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLIS 3373
Cdd:cd06641      2 PEELFTKLEKIGKGSFGEVFKGIDNRTQKVVAIKIIDLEEaeDEIEDIQQEITVLSQCDSPYVTKYYGSYLKDTKLWIIM 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3374 ECCSGKELLhSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLKQfS 3453
Cdd:cd06641     82 EYLGGGSAL-DLLEPGPLDETQIATILREILKGLDYLHSEKKIHRDIKAANVLLSEHGEVKLADFGVAGQLTDTQIKR-N 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3454 PPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIqaAKFDLSKLYQNVSQSASLFIKKIL 3533
Cdd:cd06641    160 *FVGTPFWMAPEVIKQSAYDSKADIWSLGITAIELARGEPPHSELHPMKVLFLI--PKNNPPTLEGNYSKPLKEFVEACL 237

                          250       260       270
                   ....*....|....*....|....*....|....*
gi 1207186029 3534 CSYPWARPTIKDCftnswLQDAYLMRLRRQTLTFT 3568
Cdd:cd06641    238 NKEPSFRPTAKEL-----LKHKFILRNAKKTSYLT 267

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK3 is a MAPK kinase kinase (MAPKKK or MKKK), that phosphorylates and activates the MAPK kinase MEK5 (or MKK5), which in turn phosphorylates and activates ERK5. The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK3 plays an essential role in embryonic angiogenesis and early heart development. In addition, MEKK3 is involved in interleukin-1 receptor and Toll-like receptor 4 signaling. It is also a specific regulator of the proinflammatory cytokines IL-6 and GM-CSF in some immune cells. MEKK3 also regulates calcineurin, which plays a critical role in T cell activation, apoptosis, skeletal myocyte differentiation, and cardiac hypertrophy. The MEKK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270817 [Multi-domain] Cd Length: 271 Bit Score: 90.53 E-value: 3.68e-19

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3296 PQKPYTFMDEK--ARGRFGVIRECRENATGNLYMAKIVPYEPESKQTVLQ------EYDILKSLHHEKIMALHEAYV--T 3365
Cdd:cd06651      3 PSAPINWRRGKllGQGAFGRVYLCYDVDTGRELAAKQVQFDPESPETSKEvsalecEIQLLKNLQHERIVQYYGCLRdrA 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3366 PRYLVLISECCSGKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFN 3445
Cdd:cd06651     83 EKTLTIFMEYMPGGSVKDQLKAYGALTESVTRKYTRQILEGMSYLHSNMIVHRDIKGANILRDSAGNVKLGDFGASKRLQ 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3446 PLFLK--QFSPPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIqAAKFDLSKLYQNVSQ 3523
Cdd:cd06651    163 TICMSgtGIRSVTGTPYWMSPEVISGEGYGRKADVWSLGCTVVEMLTEKPPWAEYEAMAAIFKI-ATQPTNPQLPSHISE 241

                          250       260       270
                   ....*....|....*....|....*....|
gi 1207186029 3524 SASLFIKKILCSYPwARPTIKDCFTNSWLQ 3553
Cdd:cd06651    242 HARDFLGCIFVEAR-HRPSAEELLRHPFAQ 270

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors, which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. GRKs play important roles in the cardiovascular, immune, respiratory, skeletal, and nervous systems. They contain a central catalytic domain, flanked by N- and C-terminal extensions. The N-terminus contains an RGS (regulator of G protein signaling) homology (RH) domain and several motifs. The C-terminus diverges among different groups of GRKs. There are seven types of GRKs, named GRK1 to GRK7, which are subdivided into three main groups: visual (GRK1/7); beta-adrenergic receptor kinases (GRK2/3); and GRK4-like (GRK4/5/6). Expression of GRK2/3/5/6 is widespread while GRK1/4/7 show a limited tissue distribution. The substrate spectrum of the widely expressed GRKs partially overlaps. The GRK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270729 [Multi-domain] Cd Length: 278 Bit Score: 90.66 E-value: 3.77e-19

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYVKRVIQKA-GKLEYAAKFISARAKRK---ASALRELNILSHLDHERILYFHDAFEKKNAVIIITELCHE-EL 1742
Cdd:cd05577      1 LGRGGFGEVCACQVKAtGKMYACKKLDKKRIKKKkgeTMALNEKIILEKVSSPFIVSLAYAFETKDKLCLVLTLMNGgDL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1743 LDRLTKKST--ILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSsdQIRICDFGNAVKFMPDEAQYCKYGTP 1820
Cdd:cd05577     81 KYHIYNVGTrgFSEARAIFYAAEIICGLEHLHNRFIVYRDLKPENILLDDHG--HVRISDLGLAVEFKGGKKIKGRVGTH 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1821 EFVAPEIV-NQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDLCHEAKGFVIKLL---V 1896
Cdd:cd05577    159 GYMAPEVLqKEVAYDFSVDWFALGCMLYEMIAGRSPFRQRKEKVDKEELKRRTLEMAVEYPDSFSPEARSLCEGLLqkdP 238

                          250       260
                   ....*....|....*....|....
gi 1207186029 1897 ADRL---RPDANECLRHPWFKTLN 1917
Cdd:cd05577    239 ERRLgcrGGSADEVKEHPFFRSLN 262

Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase (IKK); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The IKK complex functions as a master regulator of Nuclear Factor-KappaB (NF-kB) proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. It is composed of two kinases, IKKalpha and IKKbeta, and the regulatory subunit IKKgamma or NEMO (NF-kB Essential MOdulator). IKKs facilitate the release of NF-kB dimers from an inactive state, allowing them to migrate to the nucleus where they regulate gene transcription. There are two IKK pathways that regulate NF-kB signaling, called the classical (involving IKKbeta and NEMO) and non-canonical (involving IKKalpha) pathways. The classical pathway regulates the majority of genes activated by NF-kB. The IKK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).

Pssm-ID: 270891 [Multi-domain] Cd Length: 289 Bit Score: 90.59 E-value: 4.66e-19

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYVKRVIQKAGKLEYAAK----FISARAKRKASALRELNILSHLDHERILYFHDAFEKKNAV------IIITEL 1737
Cdd:cd13989      1 LGSGGFGYVTLWKHQDTGEYVAIKkcrqELSPSDKNRERWCLEVQIMKKLNHPNVVSARDVPPELEKLspndlpLLAMEY 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1738 CH----EELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSDQI-RICDFGNAVKFmpDEA 1812
Cdd:cd13989     81 CSggdlRKVLNQPENCCGLKESEVRTLLSDISSAISYLHENRIIHRDLKPENIVLQQGGGRVIyKLIDLGYAKEL--DQG 158

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*.
gi 1207186029 1813 QYCK--YGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPF 1856
Cdd:cd13989    159 SLCTsfVGTLQYLAPELFESKKYTCTVDYWSFGTLAFECITGYRPF 204

Catalytic domain of Numb-Associated Kinase (NAK)-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Drosophila melanogaster NAK, human BMP-2-inducible protein kinase (BMP2K or BIKe) and similar vertebrate proteins, as well as the Saccharomyces cerevisiae proteins Prk1, Actin-regulating kinase 1 (Ark1), and Akl1. NAK was the first characterized member of this subfamily. It plays a role in asymmetric cell division through its association with Numb. It also regulates the localization of Dlg, a protein essential for septate junction formation. BMP2K contains a nuclear localization signal and a kinase domain that is capable of phosphorylating itself and myelin basic protein. The expression of the BMP2K gene is increase during BMP-2-induced osteoblast differentiation. It may function to control the rate of differentiation. Prk1, Ark1, and Akl1 comprise a subfamily of yeast proteins that are important regulators of the actin cytoskeleton and endocytosis. They share an N-terminal kinase domain but no significant homology in other regions of their sequences. The NAK-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270939 [Multi-domain] Cd Length: 277 Bit Score: 90.42 E-value: 4.81e-19

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3307 ARGRFGVIRECRENATGNLYMAK--IVPYEPESkQTVLQEYDILKSLH-HEKIMALHEAYVTPR----YLVLI-SECCSG 3378
Cdd:cd14037     12 AEGGFAHVYLVKTSNGGNRAALKrvYVNDEHDL-NVCKREIEIMKRLSgHKNIVGYIDSSANRSgngvYEVLLlMEYCKG 90

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3379 KELLHSLIDRF--RYSEDDVVAYIVQILQGLDYLHSRR--ILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPL------- 3447
Cdd:cd14037     91 GGVIDLMNQRLqtGLTESEILKIFCDVCEAVAAMHYLKppLIHRDLKVENVLISDSGNYKLCDFGSATTKILPpqtkqgv 170

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3448 -FLKQFSPPIGTLDYMSPEML---KGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAEtearIQAAKFDLSKLYQNVSQ 3523
Cdd:cd14037    171 tYVEEDIKKYTTLQYRAPEMIdlyRGKPITEKSDIWALGCLLYKLCFYTTPFEESGQLA----ILNGNFTFPDNSRYSKR 246

                          250       260
                   ....*....|....*....|
gi 1207186029 3524 SASLfIKKILCSYPWARPTI 3543
Cdd:cd14037    247 LHKL-IRYMLEEDPEKRPNI 265

Catalytic domain of the Serine/Threonine Kinase, Nuclear Dbf2-Related kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NDR2 (also called STK38-like) plays a role in proper centrosome duplication. In addition, it is involved in regulating neuronal growth and differentiation, as well as in facilitating neurite outgrowth. NDR2 is also implicated in fear conditioning as it contributes to the coupling of neuronal morphological changes with fear-memory consolidation. NDR kinase contains an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Like many other AGC kinases, NDR kinase requires phosphorylation at two sites, the activation loop (A-loop) and the hydrophobic motif (HM), for activity. The NDR2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270776 [Multi-domain] Cd Length: 366 Bit Score: 92.04 E-value: 5.45e-19

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1660 DYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFIsarakRKASALRELNIlSHLDHER-----------ILYFHDAFEKK 1728
Cdd:cd05627      2 DDFESLKVIGRGAFGEVRLVQKKDTGHIYAMKIL-----RKADMLEKEQV-AHIRAERdilveadgawvVKMFYSFQDKR 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1729 NAVIIITELCHEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDFG------ 1802
Cdd:cd05627     76 NLYLIMEFLPGGDMMTLLMKKDTLSEEATQFYIAETVLAIDAIHQLGFIHRDIKPDNLLL--DAKGHVKLSDFGlctglk 153

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1803 ---------NAVKFMPD---------------------EAQYCKYGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTG 1852
Cdd:cd05627    154 kahrtefyrNLTHNPPSdfsfqnmnskrkaetwkknrrQLAYSTVGTPDYIAPEVFMQTGYNKLCDWWSLGVIMYEMLIG 233

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1207186029 1853 VSPFAGENDRSSVLNIRNYNVAFEESMFTDLCHEAKGFVIKLLVADRLR---PDANECLRHPWFKTLN 1917
Cdd:cd05627    234 YPPFCSETPQETYRKVMNWKETLVFPPEVPISEKAKDLILRFCTDAENRigsNGVEEIKSHPFFEGVD 301

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK5 is unusual in that it is regulated by non-cyclin proteins, p35 and p39. It is highly expressed in the nervous system and is critical in normal neural development and function. It plays a role in neuronal migration and differentiation, and is also important in synaptic plasticity and learning. CDK5 also participates in protecting against cell death and promoting angiogenesis. Impaired CDK5 activity is implicated in Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, Huntington's disease and acute neuronal injury. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143344 [Multi-domain] Cd Length: 284 Bit Score: 90.18 E-value: 5.49e-19

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPESK---QTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECC 3376
Cdd:cd07839      2 YEKLEKIGEGTYGTVFKAKNRETHEIVALKRVRLDDDDEgvpSSALREICLLKELKHKNIVRLYDVLHSDKKLTLVFEYC 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3377 SG--KELLHSL---IDRfryseDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNpLFLKQ 3451
Cdd:cd07839     82 DQdlKKYFDSCngdIDP-----EIVKSFMFQLLKGLAFCHSHNVLHRDLKPQNLLINKNGELKLADFGLARAFG-IPVRC 155

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1207186029 3452 FSPPIGTLDYMSPEMLKG-DVVGPPADIWSIG-ILTYIMLSGRLPFTENDPAETEARI 3507
Cdd:cd07839    156 YSAEVVTLWYRPPDVLFGaKLYSTSIDMWSAGcIFAELANAGRPLFPGNDVDDQLKRI 213

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek6 is required for the transition from metaphase to anaphase. It also plays important roles in mitotic spindle formation and cytokinesis. Activated by Nek9 during mitosis, Nek6 phosphorylates Eg5, a kinesin that is important for spindle bipolarity. Nek6 localizes to spindle microtubules during metaphase and anaphase, and to the midbody during cytokinesis. It is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270865 [Multi-domain] Cd Length: 268 Bit Score: 90.09 E-value: 5.50e-19

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVI----QKAGKLEYAAKFISARAKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITEL 1737
Cdd:cd08228      4 FQIEKKIGRGQFSEVYRATclldRKPVALKKVQIFEMMDAKARQDCVKEIDLLKQLNHPNVIKYLDSFIEDNELNIVLEL 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1738 CHEELLDRLTK-----KSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMAdhSSDQIRICDFGNAvKFMPDE- 1811
Cdd:cd08228     84 ADAGDLSQMIKyfkkqKRLIPERTVWKYFVQLCSAVEHMHSRRVMHRDIKPANVFIT--ATGVVKLGDLGLG-RFFSSKt 160

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*....
gi 1207186029 1812 -AQYCKYGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGE 1859
Cdd:cd08228    161 tAAHSLVGTPYYMSPERIHENGYNFKSDIWSLGCLLYEMAALQSPFYGD 209

Protein kinase; unclassified specificity; Phosphotransferases. The specificity of this class of kinases can not be predicted. Possible dual-specificity Ser/Thr/Tyr kinase.

Pssm-ID: 214568 [Multi-domain] Cd Length: 258 Bit Score: 89.53 E-value: 5.69e-19

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  3301 TFMDEKARGRFGVIRECRenATGNLYMAKI--------VPYEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLI 3372
Cdd:smart00221    2 TLGKKLGEGAFGEVYKGT--LKGKGDGKEVevavktlkEDASEQQIEEFLREARIMRKLDHPNIVKLLGVCTEEEPLMIV 79

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  3373 SECCSGKELLHSLIDR--FRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLK 3450
Cdd:smart00221   80 MEYMPGGDLLDYLRKNrpKELSLSDLLSFALQIARGMEYLESKNFIHRDLAARNCLVGENLVVKISDFGLSRDLYDDDYY 159

                           170       180       190       200       210       220
                    ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  3451 QFSPPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLS-GRLPFTENDPAETEARIQA 3509
Cdd:smart00221  160 KVKGGKLPIRWMAPESLKEGKFTSKSDVWSFGVLLWEIFTlGEEPYPGMSNAEVLEYLKK 219

Catalytic domain of the Dual-specificity protein kinase, Myt1; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. Myt1 is a cytoplasmic cell cycle checkpoint kinase that can keep the cyclin-dependent kinase CDK1 in an inactive state through phosphorylation of N-terminal thr (T14) and tyr (Y15) residues, leading to the delay of meiosis I entry. Meiotic progression is ensured by a two-step inhibition and downregulation of Myt1 by CDK1/XRINGO and p90Rsk during oocyte maturation. In addition, Myt1 targets cyclin B1/B2 and is essential for Golgi and ER assembly during telophase. In Drosophila, Myt1 may be a downstream target of Notch during eye development. The Myt1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270952 [Multi-domain] Cd Length: 249 Bit Score: 89.29 E-value: 5.78e-19

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKivpyepESKQTVLQEYDILKSL----HHEKI------MALHEAYVTPRYL 3369
Cdd:cd14050      3 FTILSKLGEGSFGEVFKVRSREDGKLYAVK------RSRSRFRGEKDRKRKLeeveRHEKLgehpncVRFIKAWEEKGIL 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3370 VLISECCSGK-----ELLHSLidrfrySEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGsaqtf 3444
Cdd:cd14050     77 YIQTELCDTSlqqycEETHSL------PESEVWNILLDLLKGLKHLHDHGLIHLDIKPANIFLSKDGVCKLGDFG----- 145

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3445 npLFLKQFSPPIGTLD-----YMSPEMLKGDvVGPPADIWSIGIlTYIMLSGRLPFTENDPAETEARiqaaKFDL-SKLY 3518
Cdd:cd14050    146 --LVVELDKEDIHDAQegdprYMAPELLQGS-FTKAADIFSLGI-TILELACNLELPSGGDGWHQLR----QGYLpEEFT 217

                          250       260
                   ....*....|....*....|....*..
gi 1207186029 3519 QNVSQSASLFIKKILCSYPWARPTIKD 3545
Cdd:cd14050    218 AGLSPELRSIIKLMMDPDPERRPTAED 244

Catalytic domain of Serine/Threonine Kinase 25 (also called Yeast Sps1/Ste20-related kinase 1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK25 is also called Ste20/oxidant stress response kinase 1 (SOK1) or yeast Sps1/Ste20-related kinase 1 (YSK1). It is localized in the Golgi apparatus through its interaction with the Golgi matrix protein GM130. It may be involved in the regulation of cell migration and polarization. STK25 binds and phosphorylates CCM3 (cerebral cavernous malformation 3), also called PCD10 (programmed cell death 10), and may play a role in apoptosis. Human STK25 is a candidate gene responsible for pseudopseudohypoparathyroidism (PPHP), a disease that shares features with the Albright hereditary osteodystrophy (AHO) phenotype. The STK25 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270810 [Multi-domain] Cd Length: 277 Bit Score: 90.12 E-value: 6.18e-19

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3296 PQKPYTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEP--ESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLIS 3373
Cdd:cd06642      2 PEELFTKLERIGKGSFGEVYKGIDNRTKEVVAIKIIDLEEaeDEIEDIQQEITVLSQCDSPYITRYYGSYLKGTKLWIIM 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3374 ECCSGKELLhSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLKQfS 3453
Cdd:cd06642     82 EYLGGGSAL-DLLKPGPLEETYIATILREILKGLDYLHSERKIHRDIKAANVLLSEQGDVKLADFGVAGQLTDTQIKR-N 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3454 PPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIqaAKFDLSKLYQNVSQSASLFIKKIL 3533
Cdd:cd06642    160 TFVGTPFWMAPEVIKQSAYDFKADIWSLGITAIELAKGEPPNSDLHPMRVLFLI--PKNSPPTLEGQHSKPFKEFVEACL 237

                          250       260       270
                   ....*....|....*....|....*....|.
gi 1207186029 3534 CSYPWARPTIKDCftnswLQDAYLMRLRRQT 3564
Cdd:cd06642    238 NKDPRFRPTAKEL-----LKHKFITRYTKKT 263

Catalytic domain of the Dual-specificity Mitotic checkpoint protein kinase, Monopolar spindle 1 (also called TTK); Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TTK/Mps1 is a spindle checkpoint kinase that was first discovered due to its necessity in centrosome duplication in budding yeast. It was later found to function in the spindle assembly checkpoint, which monitors the proper attachment of chromosomes to the mitotic spindle. In yeast, substrates of Mps1 include the spindle pole body components Spc98p, Spc110p, and Spc42p. The TTK/Mps1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271033 [Multi-domain] Cd Length: 271 Bit Score: 89.58 E-value: 6.93e-19

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1661 YYDVHKEIGRGAFSYVKRVIQKAGKLeYAAK---FISARAKRKASALRELNILSHLDHE-RI--LYFHDAFEKKNAVIII 1734
Cdd:cd14131      2 PYEILKQLGKGGSSKVYKVLNPKKKI-YALKrvdLEGADEQTLQSYKNEIELLKKLKGSdRIiqLYDYEVTDEDDYLYMV 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1735 TELCHEELLDRLTKK--STILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSsdqIRICDFGNAVKFMPD-- 1810
Cdd:cd14131     81 MECGEIDLATILKKKrpKPIDPNFIRYYWKQMLEAVHTIHEEGIVHSDLKPANFLLVKGR---LKLIDFGIAKAIQNDtt 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1811 ----EAQyckYGTPEFVAPEIVNQT----------PVSKATDIWPIGVLTYLCLTGVSPFAG-ENDRSSVLNIRNYNVAF 1875
Cdd:cd14131    158 sivrDSQ---VGTLNYMSPEAIKDTsasgegkpksKIGRPSDVWSLGCILYQMVYGKTPFQHiTNPIAKLQAIIDPNHEI 234

                          250       260       270
                   ....*....|....*....|....*....|....*....
gi 1207186029 1876 EESMFT--DLCHEAKgfviKLLVAD-RLRPDANECLRHP 1911
Cdd:cd14131    235 EFPDIPnpDLIDVMK----RCLQRDpKKRPSIPELLNHP 269

Catalytic domain of the Protein Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGK3 (also called cytokine-independent survival kinase or CISK) is expressed in most tissues and is most abundant in the embryo and adult heart and spleen. It was originally discovered in a screen for antiapoptotic genes. It phosphorylates and inhibits the proapoptotic proteins, Bad and FKHRL1. SGK3 also regulates many transporters, ion channels, and receptors. It plays a critical role in hair follicle morphogenesis and hair cycling. The SGK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270755 [Multi-domain] Cd Length: 326 Bit Score: 90.79 E-value: 7.04e-19

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1666 KEIGRGAFSyvkRVIQKAGKLE---YAAKFISARA----KRKASALRELNIL-SHLDHERILYFHDAFEKKNAVIIITEL 1737
Cdd:cd05604      2 KVIGKGSFG---KVLLAKRKRDgkyYAVKVLQKKVilnrKEQKHIMAERNVLlKNVKHPFLVGLHYSFQTTDKLYFVLDF 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1738 CHE-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDFG---NAVKFMPDEAQ 1813
Cdd:cd05604     79 VNGgELFFHLQRERSFPEPRARFYAAEIASALGYLHSINIVYRDLKPENILL--DSQGHIVLTDFGlckEGISNSDTTTT 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1814 YCkyGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYnvafEESMFTDLCHEAKGFVIK 1893
Cdd:cd05604    157 FC--GTPEYLAPEVIRKQPYDNTVDWWCLGSVLYEMLYGLPPFYCRDTAEMYENILHK----PLVLRPGISLTAWSILEE 230

                          250       260
                   ....*....|....*....|....*....
gi 1207186029 1894 LLVADR-----LRPDANECLRHPWFKTLN 1917
Cdd:cd05604    231 LLEKDRqlrlgAKEDFLEIKNHPFFESIN 259

Catalytic domain of the Serine/Threonine Kinase, Nemo-Like Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NLK is an atypical mitogen-activated protein kinase (MAPK) that is not regulated by a MAPK kinase. It functions downstream of the MAPK kinase kinase Tak1, which also plays a role in activating the JNK and p38 MAPKs. The Tak1/NLK pathways are regulated by Wnts, a family of secreted proteins that is critical in the control of asymmetric division and cell polarity. NLK can phosphorylate transcription factors from the TCF/LEF family, inhibiting their ability to activate the transcription of target genes. In prostate cancer cells, NLK is involved in regulating androgen receptor-mediated transcription and its expression is altered during cancer progression. MAPKs are important mediators of cellular responses to extracellular signals. The NLK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173748 [Multi-domain] Cd Length: 372 Bit Score: 91.73 E-value: 7.06e-19

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1666 KEIGRGAFSYV---------KRVIQKagKLEYAAKFISArAKRkasALRELNILSHLDHERILYFHDAFEKKNA-----V 1731
Cdd:cd07853      6 RPIGYGAFGVVwsvtdprdgKRVALK--KMPNVFQNLVS-CKR---VFRELKMLCFFKHDNVLSALDILQPPHIdpfeeI 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1732 IIITELCHEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDFGNAVKFMPDE 1811
Cdd:cd07853     80 YVVTELMQSDLHKIIVSPQPLSSDHVKVFLYQILRGLKYLHSAGILHRDIKPGNLLV--NSNCVLKICDFGLARVEEPDE 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1812 AqycKYGTPEFV-----APEIVNQTP-VSKATDIWPIG------------------------VLTYLCLTGVSPF--AGE 1859
Cdd:cd07853    158 S---KHMTQEVVtqyyrAPEILMGSRhYTSAVDIWSVGcifaellgrrilfqaqspiqqldlITDLLGTPSLEAMrsACE 234

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1207186029 1860 NDRSSVLNiRNYNVAFEESMF---TDLCHEAKGFVIKLLVADRL-RPDANECLRHPW 1912
Cdd:cd07853    235 GARAHILR-GPHKPPSLPVLYtlsSQATHEAVHLLCRMLVFDPDkRISAADALAHPY 290

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK1 (also called rhodopsin kinase) belongs to the visual group of GRKs and is expressed in retinal cells. It phosphorylates rhodopsin in rod cells, which leads to termination of the phototransduction cascade. Mutations in GRK1 are associated to a recessively inherited form of stationary nightblindness called Oguchi disease. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors, which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270759 [Multi-domain] Cd Length: 288 Bit Score: 89.94 E-value: 7.37e-19

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3302 FMDEK--ARGRFGVIRECRENATGNLYMAKIVPYEPESK----QTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISEC 3375
Cdd:cd05608      3 FLDFRvlGKGGFGEVSACQMRATGKLYACKKLNKKRLKKrkgyEGAMVEKRILAKVHSRFIVSLAYAFQTKTDLCLVMTI 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3376 CSGKELLHSLI----DRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAqtfnpLFLKQ 3451
Cdd:cd05608     83 MNGGDLRYHIYnvdeENPGFQEPRACFYTAQIISGLEHLHQRRIIYRDLKPENVLLDDDGNVRISDLGLA-----VELKD 157

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*...
gi 1207186029 3452 FSPPI----GTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPF 3495
Cdd:cd05608    158 GQTKTkgyaGTPGFMAPELLLGEEYDYSVDYFTLGVTLYEMIAARGPF 205

Catalytic domain of the Serine/Threonine Kinase, Cell Division Cycle 7 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Cdc7 kinase (or Hsk1 in fission yeast) is a critical regulator in the initiation of DNA replication. It forms a complex with a Dbf4-related regulatory subunit, a cyclin-like molecule that activates the kinase in late G1 phase, and is also referred to as Dbf4-dependent kinase (DDK). Its main targets are mini-chromosome maintenance (MCM) proteins. Cdc7 kinase may also have additional roles in meiosis, checkpoint responses, the maintenance and repair of chromosome structures, and cancer progression. The Cdc7 kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270921 [Multi-domain] Cd Length: 252 Bit Score: 89.20 E-value: 7.54e-19

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1660 DYYDVHKEIGRGAFS--YVKRVIQKAGKLEYAAKFISARAKRKASA----LRELNILSHLD-HERILYFHDAFEKKNAVI 1732
Cdd:cd14019      1 NKYRIIEKIGEGTFSsvYKAEDKLHDLYDRNKGRLVALKHIYPTSSpsriLNELECLERLGgSNNVSGLITAFRNEDQVV 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1733 IITE-LCHEELLDRLTKKSTileSEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMaDHSSDQIRICDFGNAVKFMPDE 1811
Cdd:cd14019     81 AVLPyIEHDDFRDFYRKMSL---TDIRIYLRNLFKALKHVHSFGIIHRDVKPGNFLY-NRETGKGVLVDFGLAQREEDRP 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1812 AQYC-KYGTPEFVAPEI----VNQTPvskATDIWPIGVlTYLC-LTGV-SPFAGENDRSSVL---NIRNYNVAFEesmft 1881
Cdd:cd14019    157 EQRApRAGTRGFRAPEVlfkcPHQTT---AIDIWSAGV-ILLSiLSGRfPFFFSSDDIDALAeiaTIFGSDEAYD----- 227

                          250       260       270
                   ....*....|....*....|....*....|...
gi 1207186029 1882 dlcheakgFVIKLLVAD-RLRPDANECLRHPWF 1913
Cdd:cd14019    228 --------LLDKLLELDpSKRITAEEALKHPFF 252

Catalytic domain of the Dual-specificity Mitotic checkpoint protein kinase, Monopolar spindle 1 (also called TTK); Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TTK/Mps1 is a spindle checkpoint kinase that was first discovered due to its necessity in centrosome duplication in budding yeast. It was later found to function in the spindle assembly checkpoint, which monitors the proper attachment of chromosomes to the mitotic spindle. In yeast, substrates of Mps1 include the spindle pole body components Spc98p, Spc110p, and Spc42p. The TTK/Mps1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271033 [Multi-domain] Cd Length: 271 Bit Score: 89.58 E-value: 7.61e-19

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3320 NATGNLYMAKIVPYEPESKQTV---LQEYDILKSL-HHEKIMALHEAYVTPR--YLVLISEC--CSGKELLHSLIDRfRY 3391
Cdd:cd14131     22 NPKKKIYALKRVDLEGADEQTLqsyKNEIELLKKLkGSDRIIQLYDYEVTDEddYLYMVMECgeIDLATILKKKRPK-PI 100

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3392 SEDDVVAYIVQILQGLDYLHSRRILHLDIKPEN-IIVTymNVVKIIDFGSAQ-----TFNPLFLKQfsppIGTLDYMSPE 3465
Cdd:cd14131    101 DPNFIRYYWKQMLEAVHTIHEEGIVHSDLKPANfLLVK--GRLKLIDFGIAKaiqndTTSIVRDSQ----VGTLNYMSPE 174

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|
gi 1207186029 3466 MLKGDV----------VGPPADIWSIGILTYIMLSGRLPF 3495
Cdd:cd14131    175 AIKDTSasgegkpkskIGRPSDVWSLGCILYQMVYGKTPF 214

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 2 or Protein Kinase regulated by RNA; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKR (or EIF2AK2) contains an N-terminal double-stranded RNA (dsRNA) binding domain and a C-terminal catalytic kinase domain. It is activated by dsRNA, which is produced as a replication intermediate in virally infected cells. It plays a key role in mediating innate immune responses to viral infection. PKR is also directly activated by PACT (protein activator of PKR) and heparin, and is inhibited by viral proteins and RNAs. PKR also regulates transcription and signal transduction in diseased cells, playing roles in tumorigenesis and neurodegenerative diseases. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. The PKR subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270949 [Multi-domain] Cd Length: 267 Bit Score: 89.47 E-value: 8.32e-19

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAK---FISARAKRkasalrELNILSHLDHERILYFH---------------- 1722
Cdd:cd14047      8 FKEIELIGSGGFGQVFKAKHRIDGKTYAIKrvkLNNEKAER------EVKALAKLDHPNIVRYNgcwdgfdydpetsssn 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1723 DAFEKKNAVIIITELCHEELLDRLTKK---STILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADhsSDQIRIC 1799
Cdd:cd14047     82 SSRSKTKCLFIQMEFCEKGTLESWIEKrngEKLDKVLALEIFEQITKGVEYIHSKKLIHRDLKPSNIFLVD--TGKVKIG 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1800 DFGNAVKFMPDEAQYCKYGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLtgvSPFAGENDRSSVL-NIRNYNVAfeeS 1878
Cdd:cd14047    160 DFGLVTSLKNDGKRTKSKGTLSYMSPEQISSQDYGKEVDIYALGLILFELL---HVCDSAFEKSKFWtDLRNGILP---D 233

                          250       260       270
                   ....*....|....*....|....*....|...
gi 1207186029 1879 MFTDLCHEAKGFVIKLLVAD-RLRPDANECLRH 1910
Cdd:cd14047    234 IFDKRYKIEKTIIKKMLSKKpEDRPNASEILRT 266

Catalytic domain of the Protein Serine/Threonine Kinase, G protein-coupled Receptor Kinase 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK7 (also called iodopsin kinase) belongs to the visual group of GRKs. It is primarily found in the retina and plays a role in the regulation of opsin light receptors. GRK7 is located in retinal cone outer segments and plays an important role in regulating photoresponse of the cones. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors, which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK7 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270758 [Multi-domain] Cd Length: 286 Bit Score: 89.58 E-value: 8.85e-19

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1661 YYDVHKEIGRGAFSYVKRV-IQKAGKLEYAAKFISARAKRKAS---ALRELNILSHLDHERILYFHDAFEKKNAVIIITE 1736
Cdd:cd05607      3 YFYEFRVLGKGGFGEVCAVqVKNTGQMYACKKLDKKRLKKKSGekmALLEKEILEKVNSPFIVSLAYAFETKTHLCLVMS 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1737 LCHEELLD----RLTKKSTILESEIRSSVrQLLEGINYLHQLDILHLDIKPDNILMADHSsdQIRICDFGNAVKFMPDEA 1812
Cdd:cd05607     83 LMNGGDLKyhiyNVGERGIEMERVIFYSA-QITCGILHLHSLKIVYRDMKPENVLLDDNG--NCRLSDLGLAVEVKEGKP 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1813 QYCKYGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYN----VAFEESMFTDlchEAK 1888
Cdd:cd05607    160 ITQRAGTNGYMAPEILKEESYSYPVDWFAMGCSIYEMVAGRTPFRDHKEKVSKEELKRRTledeVKFEHQNFTE---EAK 236

                          250       260       270
                   ....*....|....*....|....*....|....*
gi 1207186029 1889 GfVIKLLVA----DRL--RPDANECLRHPWFKTLN 1917
Cdd:cd05607    237 D-ICRLFLAkkpeNRLgsRTNDDDPRKHEFFKSIN 270

Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase Kinases 12 and 13; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP3K12 is also called MAPK upstream kinase (MUK), dual leucine zipper-bearing kinase (DLK) or leucine-zipper protein kinase (ZPK). It is involved in the c-Jun N-terminal kinase (JNK) pathway that directly regulates axonal regulation through the phosphorylation of microtubule-associated protein 1B (MAP1B). It also regulates the differentiation of many cell types including adipocytes and may play a role in adipogenesis. MAP3K13, also called leucine zipper-bearing kinase (LZK), directly phosphorylates and activates MKK7, which in turn activates the JNK pathway. It also activates NF-kB through IKK activation and this activity is enhanced by antioxidant protein-1 (AOP-1). MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAP2Ks (MAPKKs or MKKs), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The MAP3K12/13 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270961 [Multi-domain] Cd Length: 237 Bit Score: 88.32 E-value: 8.89e-19

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1697 AKRKASALRELNI--LSHLDHERILYFHDAFEKKNAVIIITELC-HEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQ 1773
Cdd:cd14059     20 AVKKVRDEKETDIkhLRKLNHPNIIKFKGVCTQAPCYCILMEYCpYGQLYEVLRAGREITPSLLVDWSKQIASGMNYLHL 99

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1774 LDILHLDIKPDNILMAdhSSDQIRICDFGNAVKFMPDEAQYCKYGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGV 1853
Cdd:cd14059    100 HKIIHRDLKSPNVLVT--YNDVLKISDFGTSKELSEKSTKMSFAGTVAWMAPEVIRNEPCSEKVDIWSFGVVLWELLTGE 177


                   ...
gi 1207186029 1854 SPF 1856
Cdd:cd14059    178 IPY 180

Catalytic domain of the Serine/Threonine Kinase, Ste20-Like Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SLK promotes apoptosis through apoptosis signal-regulating kinase 1 (ASK1) and the mitogen-activated protein kinase (MAPK) p38. It acts as a MAPK kinase kinase by phosphorylating ASK1, resulting in the phosphorylation of p38. SLK also plays a role in mediating actin reorganization. It is part of a microtubule-associated complex that is targeted at adhesion sites, and is required in focal adhesion turnover and in regulating cell migration. The SLK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270811 [Multi-domain] Cd Length: 283 Bit Score: 89.70 E-value: 9.63e-19

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3296 PQKPYTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPESK-QTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISE 3374
Cdd:cd06643      3 PEDFWEIVGELGDGAFGKVYKAQNKETGILAAAKVIDTKSEEElEDYMVEIDILASCDHPNIVKLLDAFYYENNLWILIE 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3375 CCSGKELLHSLIDRFR-YSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFG-SAQtfNPLFLKQF 3452
Cdd:cd06643     83 FCAGGAVDAVMLELERpLTEPQIRVVCKQTLEALVYLHENKIIHRDLKAGNILFTLDGDIKLADFGvSAK--NTRTLQRR 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3453 SPPIGTLDYMSPEML-----KGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIqaAKFDLSKLYQNVSQSASL 3527
Cdd:cd06643    161 DSFIGTPYWMAPEVVmcetsKDRPYDYKADVWSLGVTLIEMAQIEPPHHELNPMRVLLKI--AKSEPPTLAQPSRWSPEF 238


                   ....*...
gi 1207186029 3528 --FIKKIL 3533
Cdd:cd06643    239 kdFLRKCL 246

Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C alpha; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-alpha is expressed in many tissues and is associated with cell proliferation, apoptosis, and cell motility. It plays a role in the signaling of the growth factors PDGF, VEGF, EGF, and FGF. Abnormal levels of PKC-alpha have been detected in many transformed cell lines and several human tumors. In addition, PKC-alpha is required for HER2 dependent breast cancer invasion. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. PKCs undergo three phosphorylations in order to take mature forms. In addition, cPKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. The cPKC-alpha subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270766 [Multi-domain] Cd Length: 341 Bit Score: 90.44 E-value: 1.11e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVpyepeSKQTVLQEYDILKSLHHEKIMA----------LHEAYVTPRYL 3369
Cdd:cd05615     12 FNFLMVLGKGSFGKVMLAERKGSDELYAIKIL-----KKDVVIQDDDVECTMVEKRVLAlqdkppfltqLHSCFQTVDRL 86

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3370 VLISECCSGKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQ--TFNPL 3447
Cdd:cd05615     87 YFVMEYVNGGDLMYHIQQVGKFKEPQAVFYAAEISVGLFFLHKKGIIYRDLKLDNVMLDSEGHIKIADFGMCKehMVEGV 166

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3448 FLKQFSppiGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLSKlyqNVSQSASL 3527
Cdd:cd05615    167 TTRTFC---GTPDYIAPEIIAYQPYGRSVDWWAYGVLLYEMLAGQPPFDGEDEDELFQSIMEHNVSYPK---SLSKEAVS 240

                          250
                   ....*....|...
gi 1207186029 3528 FIKKILCSYPWAR 3540
Cdd:cd05615    241 ICKGLMTKHPAKR 253

Catalytic domain of the Serine/Threonine kinase, TANK Binding Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TBK1 is also called T2K and NF-kB-activating kinase. It is widely expressed in most cell types and acts as an IkappaB kinase (IKK)-activating kinase responsible for NF-kB activation in response to growth factors. It plays a role in modulating inflammatory responses through the NF-kB pathway. TKB1 is also a major player in innate immune responses since it functions as a virus-activated kinase necessary for establishing an antiviral state. It phosphorylates IRF-3 and IRF-7, which are important transcription factors for inducing type I interferon during viral infection. In addition, TBK1 may also play roles in cell transformation and oncogenesis. The TBK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270890 [Multi-domain] Cd Length: 316 Bit Score: 89.86 E-value: 1.16e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKIvpYEPESKQTVL----QEYDILKSLHHEKIMALH--EAYVTPRYLVLISECCSGKEL 3381
Cdd:cd13988      3 QGATANVFRGRHKKTGDLYAVKV--FNNLSFMRPLdvqmREFEVLKKLNHKNIVKLFaiEEELTTRHKVLVMELCPCGSL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3382 LHSLID---RFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTY----MNVVKIIDFGSAQTFNPlfLKQFSP 3454
Cdd:cd13988     81 YTVLEEpsnAYGLPESEFLIVLRDVVAGMNHLRENGIVHRDIKPGNIMRVIgedgQSVYKLTDFGAARELED--DEQFVS 158

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*....
gi 1207186029 3455 PIGTLDYMSPEMLKGDVV--------GPPADIWSIGILTYIMLSGRLPF 3495
Cdd:cd13988    159 LYGTEEYLHPDMYERAVLrkdhqkkyGATVDLWSIGVTFYHAATGSLPF 207

mitogen-activated protein kinase kinase; Provisional

Pssm-ID: 215036 [Multi-domain] Cd Length: 353 Bit Score: 90.65 E-value: 1.26e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKIV--PYEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLHSL 3385
Cdd:PLN00034    84 SGAGGTVYKVIHRPTGRLYALKVIygNHEDTVRRQICREIEILRDVNHPNVVKCHDMFDHNGEIQVLLEFMDGGSLEGTH 163

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3386 IDRFRYSEDdvVAYivQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGS----AQTFNPLflkqfSPPIGTLDY 3461
Cdd:PLN00034   164 IADEQFLAD--VAR--QILSGIAYLHRRHIVHRDIKPSNLLINSAKNVKIADFGVsrilAQTMDPC-----NSSVGTIAY 234

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|.
gi 1207186029 3462 MSPEMLKGDVV-----GPPADIWSIG--ILTYIMlsGRLPF 3495
Cdd:PLN00034   235 MSPERINTDLNhgaydGYAGDIWSLGvsILEFYL--GRFPF 273

protein kinase A catalytic subunit; Provisional

Pssm-ID: 140289 [Multi-domain] Cd Length: 329 Bit Score: 89.88 E-value: 1.53e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1657 RLTDYyDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISA----RAKRKASALRELNILSHLDHERILYFHDAFEKKNAVI 1732
Cdd:PTZ00263    16 KLSDF-EMGETLGTGSFGRVRIAKHKGTGEYYAIKCLKKreilKMKQVQHVAQEKSILMELSHPFIVNMMCSFQDENRVY 94

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1733 IITE-LCHEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDFGNAvKFMPDE 1811
Cdd:PTZ00263    95 FLLEfVVGGELFTHLRKAGRFPNDVAKFYHAELVLAFEYLHSKDIIYRDLKPENLLL--DNKGHVKVTDFGFA-KKVPDR 171

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*
gi 1207186029 1812 AqYCKYGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPF 1856
Cdd:PTZ00263   172 T-FTLCGTPEYLAPEVIQSKGHGKAVDWWTMGVLLYEFIAGYPPF 215

Catalytic domain of the Serine/Threonine Kinase, Yeast Sps1/Ste20-related Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. YSK4 is a putative MAPKKK, whose mammalian gene has been isolated. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The YSK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270801 [Multi-domain] Cd Length: 266 Bit Score: 88.26 E-value: 1.62e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYVKRVIQKAGKLeYAAKFI------SARAKRKASALR-ELNILSHLDHERILYFHDAFEKKNAVIIITELCHE 1740
Cdd:cd06631      9 LGKGAYGTVYCGLTSTGQL-IAVKQVeldtsdKEKAEKEYEKLQeEVDLLKTLKHVNIVGYLGTCLEDNVVSIFMEFVPG 87

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1741 ELLDRLTKKSTILESEI-RSSVRQLLEGINYLHQLDILHLDIKPDNI-LMadhSSDQIRICDFGNAVKF-----MPDEAQ 1813
Cdd:cd06631     88 GSIASILARFGALEEPVfCRYTKQILEGVAYLHNNNVIHRDIKGNNImLM---PNGVIKLIDFGCAKRLcinlsSGSQSQ 164

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1814 YCK--YGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNyNVAFEESMFTDLCHEAKGFV 1891
Cdd:cd06631    165 LLKsmRGTPYWMAPEVINETGHGRKSDIWSIGCTVFEMATGKPPWADMNPMAAIFAIGS-GRKPVPRLPDKFSPEARDFV 243

                          250       260
                   ....*....|....*....|..
gi 1207186029 1892 IKLLVAD-RLRPDANECLRHPW 1912
Cdd:cd06631    244 HACLTRDqDERPSAEQLLKHPF 265

Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMP-activated protein kinase (AMPK). CaMKK2, also called CaMKK beta, is one of the most versatile CaMKs. It is involved in regulating energy balance, glucose metabolism, adiposity, hematopoiesis, inflammation, and cancer. CaMKK2 contains unique N- and C-terminal domains and a central catalytic kinase domain that is followed by a regulatory domain that bears overlapping autoinhibitory and CaM-binding regions. It can be activated by signaling through G-coupled receptors, IP3 receptors, plasma membrane ion channels, and Toll-like receptors. Thus, CaMKK2 acts as a molecular hub that is capable of receiving and decoding signals from diverse pathways. The CaMKK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271101 [Multi-domain] Cd Length: 286 Bit Score: 88.87 E-value: 1.65e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIV-----------PYEPESK----------------QTVLQEYDILKSLH 3352
Cdd:cd14199      4 YKLKDEIGKGSYGVVKLAYNEDDNTYYAMKVLskkklmrqagfPRRPPPRgaraapegctqprgpiERVYQEIAILKKLD 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3353 HEKIMALHEAYVTPR--YLVLISECCSGKELLHSLIDRfRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYM 3430
Cdd:cd14199     84 HPNVVKLVEVLDDPSedHLYMVFELVKQGPVMEVPTLK-PLSEDQARFYFQDLIKGIEYLHYQKIIHRDVKPSNLLVGED 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3431 NVVKIIDFGSAQTF--NPLFLkqfSPPIGTLDYMSPEML---KGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEA 3505
Cdd:cd14199    163 GHIKIADFGVSNEFegSDALL---TNTVGTPAFMAPETLsetRKIFSGKALDVWAMGVTLYCFVFGQCPFMDERILSLHS 239

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*...
gi 1207186029 3506 RIQAAKFDLSKlYQNVSQSASLFIKKILCSYPWARPTIKDCFTNSWLQ 3553
Cdd:cd14199    240 KIKTQPLEFPD-QPDISDDLKDLLFRMLDKNPESRISVPEIKLHPWVT 286

Catalytic domain of Extracellular signal-Regulated Kinase 1 and 2-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the mitogen-activated protein kinases (MAPKs) ERK1, ERK2, baker's yeast Fus3, and similar proteins. MAPK pathways are important mediators of cellular responses to extracellular signals. ERK1/2 activation is preferentially by mitogenic factors, differentiation stimuli, and cytokines, through a kinase cascade involving the MAPK kinases MEK1/2 and a MAPK kinase kinase from the Raf family. ERK1/2 have numerous substrates, many of which are nuclear and participate in transcriptional regulation of many cellular processes. They regulate cell growth, cell proliferation, and cell cycle progression from G1 to S phase. Although the distinct roles of ERK1 and ERK2 have not been fully determined, it is known that ERK2 can maintain most functions in the absence of ERK1, and that the deletion of ERK2 is embryonically lethal. The MAPK, Fus3, regulates yeast mating processes including mating-specific gene expression, G1 arrest, mating projection, and cell fusion. This ERK1/2-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270839 [Multi-domain] Cd Length: 336 Bit Score: 90.06 E-value: 1.69e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKAS--ALRELNILSHLDHERILYFHD-----AFEKKNAVIII 1734
Cdd:cd07849      7 YQNLSYIGEGAYGMVCSAVHKPTGQKVAIKKISPFEHQTYClrTLREIKILLRFKHENIIGILDiqrppTFESFKDVYIV 86

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1735 TELChEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDFGNAVKFMPDEAQY 1814
Cdd:cd07849     87 QELM-ETDLYKLIKTQHLSNDHIQYFLYQILRGLKYIHSANVLHRDLKPSNLLL--NTNCDLKICDFGLARIADPEHDHT 163

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1815 CKygTPEFV------APEI-VNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNI------------------- 1868
Cdd:cd07849    164 GF--LTEYVatrwyrAPEImLNSKGYTKAIDIWSVGCILAEMLSNRPLFPGKDYLHQLNLIlgilgtpsqedlnciislk 241

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1207186029 1869 -RNY--------NVAFeESMFTDLCHEAKGFVIKLLVAD-RLRPDANECLRHPW 1912
Cdd:cd07849    242 aRNYikslpfkpKVPW-NKLFPNADPKALDLLDKMLTFNpHKRITVEEALAHPY 294

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK2 plays a role in pro-apoptotic signaling. It is cleaved and activated by caspases leading to morphological changes during apoptosis. PAK2 is also activated in response to a variety of stresses including DNA damage, hyperosmolarity, serum starvation, and contact inhibition, and may play a role in coordinating the stress response. PAK2 also contributes to cancer cell invasion through a mechanism distinct from that of PAK1. It belongs to the group I PAKs, which contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 132986 [Multi-domain] Cd Length: 296 Bit Score: 89.01 E-value: 1.72e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1648 EASILRKMRRLTDY------YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAK-RKASALRELNILSHLDHERILY 1720
Cdd:cd06655      1 DEEIMEKLRTIVSIgdpkkkYTRYEKIGQGASGTVFTAIDVATGQEVAIKQINLQKQpKKELIINEILVMKELKNPNIVN 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1721 FHDAFEKKNAVIIITELCHEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSdqIRICD 1800
Cdd:cd06655     81 FLDSFLVGDELFVVMEYLAGGSLTDVVTETCMDEAQIAAVCRECLQALEFLHANQVIHRDIKSDNVLLGMDGS--VKLTD 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1801 FGNAVKFMPDEAQYCKY-GTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNyNVAFEESM 1879
Cdd:cd06655    159 FGFCAQITPEQSKRSTMvGTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPYLNENPLRALYLIAT-NGTPELQN 237

                          250       260       270
                   ....*....|....*....|....*....|....*.
gi 1207186029 1880 FTDLCHEAKGFVIKLLVAD-RLRPDANECLRHPWFK 1914
Cdd:cd06655    238 PEKLSPIFRDFLNRCLEMDvEKRGSAKELLQHPFLK 273

Catalytic domain of Fungal Nuclear Dbf2-Related kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This group is composed of fungal NDR-like proteins including Saccharomyces cerevisiae CBK1 (or CBK1p), Schizosaccharomyces pombe Orb6 (or Orb6p), Ustilago maydis Ukc1 (or Ukc1p), and Neurospora crassa Cot1. Like NDR kinase, group members contain an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. CBK1 is an essential component in the RAM (regulation of Ace2p activity and cellular morphogenesis) network. CBK1 and Orb6 play similar roles in coordinating cell morphology with cell cycle progression. Ukc1 is involved in morphogenesis, pathogenicity, and pigment formation. Cot1 plays a role in polar tip extension.The fungal NDR subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270778 [Multi-domain] Cd Length: 377 Bit Score: 90.68 E-value: 1.75e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1660 DYYDVhKEIGRGAFSYVKRVIQKA-GKLeYAAKFI--SARAKRK--ASALRELNILSHLDHERILYFHDAFEKKNAVIII 1734
Cdd:cd05629      2 DFHTV-KVIGKGAFGEVRLVQKKDtGKI-YAMKTLlkSEMFKKDqlAHVKAERDVLAESDSPWVVSLYYSFQDAQYLYLI 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1735 TE-LCHEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDFGNAVKF------ 1807
Cdd:cd05629     80 MEfLPGGDLMTMLIKYDTFSEDVTRFYMAECVLAIEAVHKLGFIHRDIKPDNILI--DRGGHIKLSDFGLSTGFhkqhds 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1808 ------------------------------MPDEAQ------------YCKYGTPEFVAPEIVNQTPVSKATDIWPIGVL 1845
Cdd:cd05629    158 ayyqkllqgksnknridnrnsvavdsinltMSSKDQiatwkknrrlmaYSTVGTPDYIAPEIFLQQGYGQECDWWSLGAI 237

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1207186029 1846 TYLCLTGVSPFAGENDRSSVLNIrnynVAFEESM-FTDLCH---EAKGFVIKLLVA--DRL-RPDANECLRHPWFKTLN 1917
Cdd:cd05629    238 MFECLIGWPPFCSENSHETYRKI----INWRETLyFPDDIHlsvEAEDLIRRLITNaeNRLgRGGAHEIKSHPFFRGVD 312

Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. A splice variant of TLK1, called TLK1B, is expressed in the presence of double strand breaks (DSBs). It lacks the N-terminal part of TLK1, but is expected to phosphorylate the same substrates. TLK1/1B interacts with Rad9, which is critical in DNA damage-activated checkpoint response, and plays a role in the repair of linearized DNA with incompatible ends. TLKs play important functions during the cell cycle and are implicated in chromatin remodeling, DNA replication and repair, and mitosis. The TLK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270942 [Multi-domain] Cd Length: 299 Bit Score: 88.96 E-value: 1.99e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1658 LTDYYDVHKEIGRGAFSYVKRVIQKAGKlEYAAKFI-----SARAKRKAS----ALRELNILSHLDHERILYFHDAFE-K 1727
Cdd:cd14040      4 LNERYLLLHLLGRGGFSEVYKAFDLYEQ-RYAAVKIhqlnkSWRDEKKENyhkhACREYRIHKELDHPRIVKLYDYFSlD 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1728 KNAVIIITELCHEELLDRLTKKSTIL-ESEIRSSVRQLLEGINYLHQLD--ILHLDIKPDNILMADHSS-DQIRICDFGN 1803
Cdd:cd14040     83 TDTFCTVLEYCEGNDLDFYLKQHKLMsEKEARSIVMQIVNALRYLNEIKppIIHYDLKPGNILLVDGTAcGEIKITDFGL 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1804 AvKFMPDEAQYCK--------YGTPEFVAPE--IVNQTP--VSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNiRNY 1871
Cdd:cd14040    163 S-KIMDDDSYGVDgmdltsqgAGTYWYLPPEcfVVGKEPpkISNKVDVWSVGVIFFQCLYGRKPFGHNQSQQDILQ-ENT 240

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*.
gi 1207186029 1872 NVAFEESMF---TDLCHEAKGFVIKLLVADRL-RPDANECLRHPWF 1913
Cdd:cd14040    241 ILKATEVQFpvkPVVSNEAKAFIRRCLAYRKEdRFDVHQLASDPYL 286

Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyze the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyze the reverse process. Protein kinases fall into three broad classes, characterized with respect to substrate specificity; Serine/threonine-protein kinases, tyrosine-protein kinases, and dual specificity protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins). This entry represents the catalytic domain found in a number of serine/threonine- and tyrosine-protein kinases. It does not include the catalytic domain of dual specificity kinases.

Pssm-ID: 462242 [Multi-domain] Cd Length: 258 Bit Score: 87.94 E-value: 2.00e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3301 TFMDEKARGRFGVIRECRENATGNLYMA----KIVP--YEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISE 3374
Cdd:pfam07714    2 TLGEKLGEGAFGEVYKGTLKGEGENTKIkvavKTLKegADEEEREDFLEEASIMKKLDHPNIVKLLGVCTQGEPLYIVTE 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3375 CCSGKELLHSLIDRFR-YSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFG------SAQTFNPL 3447
Cdd:pfam07714   82 YMPGGDLLDFLRKHKRkLTLKDLLSMALQIAKGMEYLESKNFVHRDLAARNCLVSENLVVKISDFGlsrdiyDDDYYRKR 161

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1207186029 3448 FLKQFSPPigtldYMSPEMLKGDVVGPPADIWSIGILTYIMLS-GRLPFTENDPAETEARIQA 3509
Cdd:pfam07714  162 GGGKLPIK-----WMAPESLKDGKFTSKSDVWSFGVLLWEIFTlGEQPYPGMSNEEVLEFLED 219

Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ROCK2 was the first identified target of activated RhoA, and was found to play a role in stress fiber and focal adhesion formation. It is prominently expressed in the brain, heart, and skeletal muscles. It is implicated in vascular and neurological disorders, such as hypertension and vasospasm of the coronary and cerebral arteries. ROCK2 is also activated by caspase-2 cleavage, resulting in thrombin-induced microparticle generation in response to cell activation. Mice deficient in ROCK2 show intrauterine growth retardation and embryonic lethality because of placental dysfunction. ROCK contains an N-terminal extension, a catalytic kinase domain, and a C-terminal extension, which contains a coiled-coil region encompassing a Rho-binding domain (RBD) and a pleckstrin homology (PH) domain. ROCK is auto-inhibited by the RBD and PH domain interacting with the catalytic domain, and is activated via interaction with Rho GTPases. The ROCK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270771 [Multi-domain] Cd Length: 379 Bit Score: 90.44 E-value: 2.12e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3307 ARGRFGVIRECRENATGNLYMAKIVPYEPESKQT----VLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELL 3382
Cdd:cd05621     61 GRGAFGEVQLVRHKASQKVYAMKLLSKFEMIKRSdsafFWEERDIMAFANSPWVVQLFCAFQDDKYLYMVMEYMPGGDLV 140

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3383 HsLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLKQFSPPIGTLDYM 3462
Cdd:cd05621    141 N-LMSNYDVPEKWAKFYTAEVVLALDAIHSMGLIHRDVKPDNMLLDKYGHLKLADFGTCMKMDETGMVHCDTAVGTPDYI 219

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1207186029 3463 SPEMLK---GD-VVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLSkLYQNVSQSASlfIKKILCSY 3536
Cdd:cd05621    220 SPEVLKsqgGDgYYGRECDWWSVGVFLFEMLVGDTPFYADSLVGTYSKIMDHKNSLN-FPDDVEISKH--AKNLICAF 294

Catalytic domain of the Serine/Threonine Kinases, Raf (Rapidly Accelerated Fibrosarcoma) kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Raf kinases act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. They function in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. Aberrant expression or activation of components in this pathway are associated with tumor initiation, progression, and metastasis. Raf proteins contain a Ras binding domain, a zinc finger cysteine-rich domain, and a catalytic kinase domain. Vertebrates have three Raf isoforms (A-, B-, and C-Raf) with different expression profiles, modes of regulation, and abilities to function in the ERK cascade, depending on cellular context and stimuli. They have essential and non-overlapping roles during embryo- and organogenesis. Knockout of each isoform results in a lethal phenotype or abnormality in most mouse strains. The Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270964 [Multi-domain] Cd Length: 253 Bit Score: 87.83 E-value: 2.21e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3309 GRFGVIRECRENATGNLYMAKIVPYEPESKQTVLQEYDILKSLHHEKIMaLHEAYVTPRYLVLISECCSGKEL---LHSL 3385
Cdd:cd14062      4 GSFGTVYKGRWHGDVAVKKLNVTDPTPSQLQAFKNEVAVLRKTRHVNIL-LFMGYMTKPQLAIVTQWCEGSSLykhLHVL 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3386 IDRFRYSEDDVVAYivQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAqTFNPLF--LKQFSPPIGTLDYMS 3463
Cdd:cd14062     83 ETKFEMLQLIDIAR--QTAQGMDYLHAKNIIHRDLKSNNIFLHEDLTVKIGDFGLA-TVKTRWsgSQQFEQPTGSILWMA 159

                          170       180       190
                   ....*....|....*....|....*....|....*
gi 1207186029 3464 PEMLKGDVVGP---PADIWSIGILTYIMLSGRLPF 3495
Cdd:cd14062    160 PEVIRMQDENPysfQSDVYAFGIVLYELLTGQLPY 194

Catalytic domain of the Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGK2 shows a more restricted distribution than SGK1 and is most abundantly expressed in epithelial tissues including kidney, liver, pancreas, and the choroid plexus of the brain. In vitro cellular assays show that SGK2 can stimulate the activity of ion channels, the glutamate transporter EEAT4, and the glutamate receptors, GluR6 and GLUR1. The SGK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270754 [Multi-domain] Cd Length: 321 Bit Score: 89.26 E-value: 2.44e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1666 KEIGRGAFSYVKRVIQKAGKLEYAAKFISARA----KRKASALRELNIL-SHLDHERILYFHDAFEKKNAVIIITELCHE 1740
Cdd:cd05603      1 KVIGKGSFGKVLLAKRKCDGKFYAVKVLQKKTilkkKEQNHIMAERNVLlKNLKHPFLVGLHYSFQTSEKLYFVLDYVNG 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1741 -ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDFGNAVKFM-PDEAQYCKYG 1818
Cdd:cd05603     81 gELFFHLQRERCFLEPRARFYAAEVASAIGYLHSLNIIYRDLKPENILL--DCQGHVVLTDFGLCKEGMePEETTSTFCG 158

                          170       180       190
                   ....*....|....*....|....*....|....*...
gi 1207186029 1819 TPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPF 1856
Cdd:cd05603    159 TPEYLAPEVLRKEPYDRTVDWWCLGAVLYEMLYGLPPF 196

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek7 is required for mitotic spindle formation and cytokinesis. It is enriched in the centrosome and is critical for microtubule nucleation. Nek7 is activated by Nek9 during mitosis, and may regulate the p70 ribosomal S6 kinase. It is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270866 [Multi-domain] Cd Length: 292 Bit Score: 88.55 E-value: 2.46e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3334 EPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELlHSLIDRFRYS-----EDDVVAYIVQILQGLD 3408
Cdd:cd08229     64 DAKARADCIKEIDLLKQLNHPNVIKYYASFIEDNELNIVLELADAGDL-SRMIKHFKKQkrlipEKTVWKYFVQLCSALE 142

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3409 YLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLKQFSpPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIM 3488
Cdd:cd08229    143 HMHSRRVMHRDIKPANVFITATGVVKLGDLGLGRFFSSKTTAAHS-LVGTPYYMSPERIHENGYNFKSDIWSLGCLLYEM 221


                   ....*..
gi 1207186029 3489 LSGRLPF 3495
Cdd:cd08229    222 AALQSPF 228

Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase kinase kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP4K3 plays a role in the nutrient-responsive pathway of mTOR (mammalian target of rapamycin) signaling. MAP4K3 is required in the activation of S6 kinase by amino acids and for the phosphorylation of the mTOR-regulated inhibitor of eukaryotic initiation factor 4E. mTOR regulates ribosome biogenesis and protein translation, and is frequently deregulated in cancer. MAP4Ks are involved in MAPK signaling pathways by activating a MAPK kinase kinase. Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Members of this subfamily contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. The MAP4K3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270812 [Multi-domain] Cd Length: 272 Bit Score: 87.79 E-value: 2.68e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3296 PQKPYTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEP-ESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISE 3374
Cdd:cd06645      9 PQEDFELIQRIGSGTYGDVYKARNVNTGELAAIKVIKLEPgEDFAVVQQEIIMMKDCKHSNIVAYFGSYLRRDKLWICME 88

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3375 CCSGKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLKQFSp 3454
Cdd:cd06645     89 FCGGGSLQDIYHVTGPLSESQIAYVSRETLQGLYYLHSKGKMHRDIKGANILLTDNGHVKLADFGVSAQITATIAKRKS- 167

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3455 PIGTLDYMSPEMLKGDVVG---PPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLSKLYQNVSQSASL--FI 3529
Cdd:cd06645    168 FIGTPYWMAPEVAAVERKGgynQLCDIWAVGITAIELAELQPPMFDLHPMRALFLMTKSNFQPPKLKDKMKWSNSFhhFV 247

                          250
                   ....*....|...
gi 1207186029 3530 KKILCSYPWARPT 3542
Cdd:cd06645    248 KMALTKNPKKRPT 260

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK6 is widely expressed in many tissues and is expressed as multiple splice variants with different domain architectures. It is post-translationally palmitoylated and localized in the membrane. GRK6 plays important roles in the regulation of dopamine, M3 muscarinic, opioid, and chemokine receptor signaling. It also plays maladaptive roles in addiction and Parkinson's disease. GRK6-deficient mice exhibit altered dopamine receptor regulation, decreased lymphocyte chemotaxis, and increased acute inflammation and neutrophil chemotaxis. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270779 [Multi-domain] Cd Length: 285 Bit Score: 88.16 E-value: 2.76e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1665 HKEIGRGAFSYVKRV-IQKAGKLEYAAKFISARAKRK---ASALRELNILSHLDHERILYFHDAFEKKNAV-IIITELCH 1739
Cdd:cd05630      5 YRVLGKGGFGEVCACqVRATGKMYACKKLEKKRIKKRkgeAMALNEKQILEKVNSRFVVSLAYAYETKDALcLVLTLMNG 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1740 EELLDRLTKKSTILESEIRSS--VRQLLEGINYLHQLDILHLDIKPDNILMADHSsdQIRICDFGNAVKFMPDEAQYCKY 1817
Cdd:cd05630     85 GDLKFHIYHMGQAGFPEARAVfyAAEICCGLEDLHRERIVYRDLKPENILLDDHG--HIRISDLGLAVHVPEGQTIKGRV 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1818 GTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDLCHEAKGFVIKLLVA 1897
Cdd:cd05630    163 GTVGYMAPEVVKNERYTFSPDWWALGCLLYEMIAGQSPFQQRKKKIKREEVERLVKEVPEEYSEKFSPQARSLCSMLLCK 242

                          250       260
                   ....*....|....*....|....*.
gi 1207186029 1898 DRLR------PDANECLRHPWFKTLN 1917
Cdd:cd05630    243 DPAErlgcrgGGAREVKEHPLFKKLN 268

Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyze the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyze the reverse process. Protein kinases fall into three broad classes, characterized with respect to substrate specificity; Serine/threonine-protein kinases, tyrosine-protein kinases, and dual specificity protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins). This entry represents the catalytic domain found in a number of serine/threonine- and tyrosine-protein kinases. It does not include the catalytic domain of dual specificity kinases.

Pssm-ID: 462242 [Multi-domain] Cd Length: 258 Bit Score: 87.55 E-value: 2.78e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1665 HKEIGRGAFSYVKR----VIQKAGKLEYAAKFI--SARAKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITELC 1738
Cdd:pfam07714    4 GEKLGEGAFGEVYKgtlkGEGENTKIKVAVKTLkeGADEEEREDFLEEASIMKKLDHPNIVKLLGVCTQGEPLYIVTEYM 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1739 -HEELLDRLTKKSTILESEIRSSV-RQLLEGINYLHQLDILHLDIKPDNILMADhsSDQIRICDFGNAvKFMPDEAQYCK 1816
Cdd:pfam07714   84 pGGDLLDFLRKHKRKLTLKDLLSMaLQIAKGMEYLESKNFVHRDLAARNCLVSE--NLVVKISDFGLS-RDIYDDDYYRK 160

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*..
gi 1207186029 1817 YGTPEF----VAPEIVNQTPVSKATDIWPIGVLTY-LCLTGVSPFAG 1858
Cdd:pfam07714  161 RGGGKLpikwMAPESLKDGKFTSKSDVWSFGVLLWeIFTLGEQPYPG 207

Catalytic domain of PCTAIRE-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-like proteins show unusual expression patterns with high levels in post-mitotic tissues, suggesting that they may be involved in regulating post-mitotic cellular events. They share sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The association of PCTAIRE-like proteins with cyclins has not been widely studied, although PFTAIRE-1 has been shown to function as a CDK which is regulated by cyclin D3 as well as the membrane-associated cyclin Y. The PCTAIRE-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270835 [Multi-domain] Cd Length: 286 Bit Score: 88.21 E-value: 3.26e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPESKQ--TVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISEccs 3377
Cdd:cd07844      2 YKKLDKLGEGSYATVYKGRSKLTGQLVALKEIRLEHEEGApfTAIREASLLKDLKHANIVTLHDIIHTKKTLTLVFE--- 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3378 gkeLLHSliDRFRYSED--------DVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTfNPLFL 3449
Cdd:cd07844     79 ---YLDT--DLKQYMDDcggglsmhNVRLFLFQLLRGLAYCHQRRVLHRDLKPQNLLISERGELKLADFGLARA-KSVPS 152

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*..
gi 1207186029 3450 KQFSPPIGTLDYMSPEMLKGDV-VGPPADIWSIGILTYIMLSGRLPF 3495
Cdd:cd07844    153 KTYSNEVVTLWYRPPDVLLGSTeYSTSLDMWGVGCIFYEMATGRPLF 199

Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.

Pssm-ID: 197581 [Multi-domain] Cd Length: 257 Bit Score: 87.20 E-value: 3.54e-18

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  3301 TFMDEKARGRFGVIRECRenATGNLYMAKI--------VPYEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLI 3372
Cdd:smart00219    2 TLGKKLGEGAFGEVYKGK--LKGKGGKKKVevavktlkEDASEQQIEEFLREARIMRKLDHPNVVKLLGVCTEEEPLYIV 79

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  3373 SECCSG---KELLHSLIDRFrySEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFG-SAQTFNPLF 3448
Cdd:smart00219   80 MEYMEGgdlLSYLRKNRPKL--SLSDLLSFALQIARGMEYLESKNFIHRDLAARNCLVGENLVVKISDFGlSRDLYDDDY 157

                           170       180       190       200       210       220
                    ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1207186029  3449 LKQFSPPIgTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLS-GRLPFTENDPAETEARIQA 3509
Cdd:smart00219  158 YRKRGGKL-PIRWMAPESLKEGKFTSKSDVWSFGVLLWEIFTlGEQPYPGMSNEEVLEYLKN 218

Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-2 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-2 is specifically expressed in neurons in the central nervous system, mainly in terminally differentiated neurons. It associates with Trap (Tudor repeat associator with PCTAIRE-2) and could play a role in regulating mitochondrial function in neurons. PCTAIRE-2 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PCTAIRE-2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143377 [Multi-domain] Cd Length: 309 Bit Score: 88.13 E-value: 3.99e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPESKQ--TVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCS 3377
Cdd:cd07872      8 YIKLEKLGEGTYATVFKGRSKLTENLVALKEIRLEHEEGApcTAIREVSLLKDLKHANIVTLHDIVHTDKSLTLVFEYLD 87

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3378 gKELLHSLIDRFR-YSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTfNPLFLKQFSPPI 3456
Cdd:cd07872     88 -KDLKQYMDDCGNiMSMHNVKIFLYQILRGLAYCHRRKVLHRDLKPQNLLINERGELKLADFGLARA-KSVPTKTYSNEV 165

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|
gi 1207186029 3457 GTLDYMSPEMLKGDV-VGPPADIWSIGILTYIMLSGRLPF 3495
Cdd:cd07872    166 VTLWYRPPDVLLGSSeYSTQIDMWGVGCIFFEMASGRPLF 205

Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAO3 is also known as JIK (c-Jun N-terminal kinase inhibitory kinase) or KFC (kinase from chicken). It specifically activates JNK, presumably by phosphorylating and activating MKK4/MKK7. In Saccharomyces cerevisiae, TAO3 is a component of the RAM (regulation of Ace2p activity and cellular morphogenesis) signaling pathway. TAO3 is upregulated in retinal ganglion cells after axotomy, and may play a role in apoptosis. TAO proteins possess mitogen-activated protein kinase (MAPK) kinase kinase activity. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. The TAO3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270803 [Multi-domain] Cd Length: 313 Bit Score: 88.17 E-value: 4.09e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3296 PQKPYTFMDEKARGRFGVIRECRENATGNLYMAKIVPYE----PESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVL 3371
Cdd:cd06633     19 PEEIFVDLHEIGHGSFGAVYFATNSHTNEVVAIKKMSYSgkqtNEKWQDIIKEVKFLQQLKHPNTIEYKGCYLKDHTAWL 98

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3372 ISECC--SGKELLHslIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPlfL 3449
Cdd:cd06633     99 VMEYClgSASDLLE--VHKKPLQEVEIAAITHGALQGLAYLHSHNMIHRDIKAGNILLTEPGQVKLADFGSASIASP--A 174

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3450 KQFsppIGTLDYMSPE----MLKGDVVGpPADIWSIGIlTYIMLSGRLPFTENDPAETeARIQAAKFDLSKLYQNV-SQS 3524
Cdd:cd06633    175 NSF---VGTPYWMAPEvilaMDEGQYDG-KVDIWSLGI-TCIELAERKPPLFNMNAMS-ALYHIAQNDSPTLQSNEwTDS 248

                          250
                   ....*....|....*...
gi 1207186029 3525 ASLFIKKILCSYPWARPT 3542
Cdd:cd06633    249 FRGFVDYCLQKIPQERPS 266

Catalytic domain of the Serine/Threonine Kinase, Nemo-Like Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NLK is an atypical mitogen-activated protein kinase (MAPK) that is not regulated by a MAPK kinase. It functions downstream of the MAPK kinase kinase Tak1, which also plays a role in activating the JNK and p38 MAPKs. The Tak1/NLK pathways are regulated by Wnts, a family of secreted proteins that is critical in the control of asymmetric division and cell polarity. NLK can phosphorylate transcription factors from the TCF/LEF family, inhibiting their ability to activate the transcription of target genes. In prostate cancer cells, NLK is involved in regulating androgen receptor-mediated transcription and its expression is altered during cancer progression. MAPKs are important mediators of cellular responses to extracellular signals. The NLK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173748 [Multi-domain] Cd Length: 372 Bit Score: 89.42 E-value: 4.21e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3337 SKQTVLQEYDILKSLHHEKIMALHEAyVTPRYLVLISECCSGKELLHS-----LIDRFRYSEDDVVAYIVQILQGLDYLH 3411
Cdd:cd07853     42 SCKRVFRELKMLCFFKHDNVLSALDI-LQPPHIDPFEEIYVVTELMQSdlhkiIVSPQPLSSDHVKVFLYQILRGLKYLH 120

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3412 SRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLKQFSPPIGTLDYMSPEMLKGDV-VGPPADIWSIGILTYIMLS 3490
Cdd:cd07853    121 SAGILHRDIKPGNLLVNSNCVLKICDFGLARVEEPDESKHMTQEVVTQYYRAPEILMGSRhYTSAVDIWSVGCIFAELLG 200

                          170
                   ....*....|..
gi 1207186029 3491 GRLPFTENDPAE 3502
Cdd:cd07853    201 RRILFQAQSPIQ 212

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK4 has a limited tissue distribution. It is mainly found in the testis, but is also present in the cerebellum and kidney. It is expressed as multiple splice variants with different domain architectures and is post-translationally palmitoylated and localized in the membrane. GRK4 polymorphisms are associated with hypertension and salt sensitivity, as they cause hyperphosphorylation, desensitization, and internalization of the dopamine 1 (D1) receptor while increasing the expression of the angiotensin II type 1 receptor. GRK4 plays a crucial role in the D1 receptor regulation of sodium excretion and blood pressure. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173720 [Multi-domain] Cd Length: 285 Bit Score: 87.74 E-value: 4.59e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKIVPYEPESKQT----VLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLH 3383
Cdd:cd05631     10 KGGFGEVCACQVRATGKMYACKKLEKKRIKKRKgeamALNEKRILEKVNSRFVVSLAYAYETKDALCLVLTIMNGGDLKF 89

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3384 SLIDRFR--YSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLflKQFSPPIGTLDY 3461
Cdd:cd05631     90 HIYNMGNpgFDEQRAIFYAAELCCGLEDLQRERIVYRDLKPENILLDDRGHIRISDLGLAVQIPEG--ETVRGRVGTVGY 167

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3462 MSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTE-NDPAETEARIQAAKFDLSKLYQNVSQSASLFIKKILCSYPWAR 3540
Cdd:cd05631    168 MAPEVINNEKYTFSPDWWGLGCLIYEMIQGQSPFRKrKERVKREEVDRRVKEDQEEYSEKFSEDAKSICRMLLTKNPKER 247

Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PKC beta isoforms (I and II), generated by alternative splicing of a single gene, are preferentially activated by hyperglycemia-induced DAG (1,2-diacylglycerol) in retinal tissues. This is implicated in diabetic microangiopathy such as ischemia, neovascularization, and abnormal vasodilator function. PKC-beta also plays an important role in VEGF signaling. In addition, glucose regulates proliferation in retinal endothelial cells via PKC-betaI. PKC-beta is also being explored as a therapeutic target in cancer. It contributes to tumor formation and is involved in the tumor host mechanisms of inflammation and angiogenesis. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. PKCs undergo three phosphorylations in order to take mature forms. In addition, cPKCs depend on calcium, DAG, and in most cases, phosphatidylserine (PS) for activation. The cPKC-beta subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270767 [Multi-domain] Cd Length: 323 Bit Score: 88.52 E-value: 4.60e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYVKRVIQKAGKLEYAAKFIsarakRKASALRELNILSHLDHERIL----------YFHDAFEKKNAVIIITEL 1737
Cdd:cd05616      8 LGKGSFGKVMLAERKGTDELYAVKIL-----KKDVVIQDDDVECTMVEKRVLalsgkppfltQLHSCFQTMDRLYFVMEY 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1738 CHE-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDFGNAVKFMPD---EAQ 1813
Cdd:cd05616     83 VNGgDLMYHIQQVGRFKEPHAVFYAAEIAIGLFFLQSKGIIYRDLKLDNVML--DSEGHIKIADFGMCKENIWDgvtTKT 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1814 YCkyGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDLCHEAKGFVIK 1893
Cdd:cd05616    161 FC--GTPDYIAPEIIAYQPYGKSVDWWAFGVLLYEMLAGQAPFEGEDEDELFQSIMEHNVAYPKSMSKEAVAICKGLMTK 238

Catalytic domain of G protein-coupled Receptor Kinase 4-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of the GRK4-like group include GRK4, GRK5, GRK6, and similar GRKs. They contain an N-terminal RGS homology (RH) domain and a catalytic domain, but lack a G protein betagamma-subunit binding domain. They are localized to the plasma membrane through post-translational lipid modification or direct binding to PIP2. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK4-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270756 [Multi-domain] Cd Length: 285 Bit Score: 87.41 E-value: 4.97e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKIVpyepESKQT--------VLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGK 3379
Cdd:cd05605     10 KGGFGEVCACQVRATGKMYACKKL----EKKRIkkrkgeamALNEKQILEKVNSRFVVSLAYAYETKDALCLVLTIMNGG 85

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3380 EL---LHSLiDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFnplflkqfsPP- 3455
Cdd:cd05605     86 DLkfhIYNM-GNPGFEEERAVFYAAEITCGLEHLHSERIVYRDLKPENILLDDHGHVRISDLGLAVEI---------PEg 155

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*.
gi 1207186029 3456 ------IGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPF 3495
Cdd:cd05605    156 etirgrVGTVGYMAPEVVKNERYTFSPDWWGLGCLIYEMIEGQAPF 201

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 2 or Heme-Regulated Inhibitor kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HRI (or EIF2AK1) contains an N-terminal regulatory heme-binding domain and a C-terminal catalytic kinase domain. It is suppressed under normal conditions by binding of the heme iron, and is activated during heme deficiency. It functions as a critical regulator that ensures balanced synthesis of globins and heme, in order to form stable hemoglobin during erythroid differentiation and maturation. HRI also protects cells and enhances survival under iron-deficient conditions. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. The HRI subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270951 [Multi-domain] Cd Length: 284 Bit Score: 87.18 E-value: 5.45e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPESKQ---TVLQEYDILKSLHHEKIMALHEAYVTPRYLVL-ISEC 3375
Cdd:cd14049      8 FEEIARLGKGGYGKVYKVRNKLDGQYYAIKKILIKKVTKRdcmKVLREVKVLAGLQHPNIVGYHTAWMEHVQLMLyIQMQ 87

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3376 CSGKELLHSLIDR---FRYSEDDVVAY-----------IVQILQGLDYLHSRRILHLDIKPENIIVTYMNV-VKIIDFGS 3440
Cdd:cd14049     88 LCELSLWDWIVERnkrPCEEEFKSAPYtpvdvdvttkiLQQLLEGVTYIHSMGIVHRDLKPRNIFLHGSDIhVRIGDFGL 167

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3441 A-----------QTFNPLFLKQFSPPIGTLDYMSPEMLKGDVVGPPADIWSIGIltyIMLSGRLPF-TENDPAETEARIQ 3508
Cdd:cd14049    168 AcpdilqdgndsTTMSRLNGLTHTSGVGTCLYAAPEQLEGSHYDFKSDMYSIGV---ILLELFQPFgTEMERAEVLTQLR 244

                          250       260       270
                   ....*....|....*....|....*....|....
gi 1207186029 3509 AAKFDLSKLYQNVSQSAslFIKKILCSYPWARPT 3542
Cdd:cd14049    245 NGQIPKSLCKRWPVQAK--YIKLLTSTEPSERPS 276

Catalytic domain of the Serine/Threonine Kinase, Classical (or Conventional) Protein Kinase C; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. cPKCs are potent kinases for histones, myelin basic protein, and protamine. They depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. cPKCs contain a calcium-binding C2 region in their regulatory domain. There are four cPKC isoforms, named alpha, betaI, betaII, and gamma. PKC-gamma is mainly expressed in neuronal tissues. It plays a role in protection from ischemia. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. The cPKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270739 [Multi-domain] Cd Length: 320 Bit Score: 88.22 E-value: 5.45e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1767 GINYLHQLDILHLDIKPDNILMadHSSDQIRICDFGNAVKFMPDEAQYCKY-GTPEFVAPEIVNQTPVSKATDIWPIGVL 1845
Cdd:cd05587    109 GLFFLHSKGIIYRDLKLDNVML--DAEGHIKIADFGMCKEGIFGGKTTRTFcGTPDYIAPEIIAYQPYGKSVDWWAYGVL 186

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1207186029 1846 TYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDLCHEAKGFVIKlLVADRL--RPDANECLR-HPWFKTLNKGK 1920
Cdd:cd05587    187 LYEMLAGQPPFDGEDEDELFQSIMEHNVSYPKSLSKEAVSICKGLLTK-HPAKRLgcGPTGERDIKeHPFFRRIDWEK 263

Catalytic domain of the Serine/Threonine Kinase, B-Raf (Rapidly Accelerated Fibrosarcoma) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. B-Raf activates ERK with the strongest magnitude, compared with other Raf kinases. Mice embryos deficient in B-Raf die around midgestation due to vascular hemorrhage caused by apoptotic endothelial cells. Mutations in B-Raf have been implicated in initiating tumorigenesis and tumor progression, and are found in malignant cutaneous melanoma, papillary thyroid cancer, as well as in ovarian and colorectal carcinomas. Most oncogenic B-Raf mutations are located at the activation loop of the kinase and surrounding regions; the V600E mutation accounts for around 90% of oncogenic mutations. The V600E mutant constitutively activates MEK, resulting in sustained activation of ERK. B-Raf is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. They function in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. The B-Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271053 [Multi-domain] Cd Length: 274 Bit Score: 87.04 E-value: 5.57e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3295 VPQKPYTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPESKQTVLQEYDILKSLHHEKIMaLHEAYVTPRYLVLISE 3374
Cdd:cd14151      5 IPDGQITVGQRIGSGSFGTVYKGKWHGDVAVKMLNVTAPTPQQLQAFKNEVGVLRKTRHVNIL-LFMGYSTKPQLAIVTQ 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3375 CCSGKELLHSL-IDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLF-LKQF 3452
Cdd:cd14151     84 WCEGSSLYHHLhIIETKFEMIKLIDIARQTAQGMDYLHAKSIIHRDLKSNNIFLHEDLTVKIGDFGLATVKSRWSgSHQF 163

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*..
gi 1207186029 3453 SPPIGTLDYMSPEMLKGDVVGP---PADIWSIGILTYIMLSGRLPFT 3496
Cdd:cd14151    164 EQLSGSILWMAPEVIRMQDKNPysfQSDVYAFGIVLYELMTGQLPYS 210

cyclin-dependent kinase A; Provisional

Pssm-ID: 177649 [Multi-domain] Cd Length: 294 Bit Score: 87.57 E-value: 5.58e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPESK---QTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECC 3376
Cdd:PLN00009     4 YEKVEKIGEGTYGVVYKARDRVTNETIALKKIRLEQEDEgvpSTAIREISLLKEMQHGNIVRLQDVVHSEKRLYLVFEYL 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3377 SG--KELLHSLIDrFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVT-YMNVVKIIDFGSAQTFNpLFLKQFS 3453
Cdd:PLN00009    84 DLdlKKHMDSSPD-FAKNPRLIKTYLYQILRGIAYCHSHRVLHRDLKPQNLLIDrRTNALKLADFGLARAFG-IPVRTFT 161

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1207186029 3454 PPIGTLDYMSPEMLKGD-VVGPPADIWSIGILTYIMLSGRLPFtendPAETE 3504
Cdd:PLN00009   162 HEVVTLWYRAPEILLGSrHYSTPVDIWSVGCIFAEMVNQKPLF----PGDSE 209

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 81.15 E-value: 6.01e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1249 PDFVKPLYDMDVVEGREAVLRCKVAGLPYPTITWFHNGKRIDSTEDRKMTQFRDVHSLVVRCVCHAHGGVYKCVISNKVG 1328
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTYEGGTYTLTISNVQPDDSGKYTCVATNSAG 80

                           90
                   ....*....|
gi 1207186029 1329 KATCYSHLYV 1338
Cdd:pfam07679   81 EAEASAELTV 90

Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase (CDK), Bypass UAS Requirement 1, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BUR1, also called SGV1, is a yeast CDK that is functionally equivalent to mammalian CDK9. It associates with the cyclin BUR2. BUR genes were orginally identified in a genetic screen as factors involved in general transcription. The BUR1/BUR2 complex phosphorylates the C-terminal domain of RNA polymerase II. In addition, this complex regulates histone modification by phosporylating Rad6 and mediating the association of the Paf1 complex with chromatin. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The BUR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270849 [Multi-domain] Cd Length: 311 Bit Score: 87.76 E-value: 6.91e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1655 MRRLTDYYDVHKeIGRGAFSYVKRVIQKAGKLEYAAKFI---SARAKRKASALRELNILSHLDHERILYFHDAF------ 1725
Cdd:cd07866      4 CSKLRDYEILGK-LGEGTFGEVYKARQIKTGRVVALKKIlmhNEKDGFPITALREIKILKKLKHPNVVPLIDMAverpdk 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1726 --EKKNAVIIITELCHEELLDRLTKKSTILE-SEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSsdQIRICDFG 1802
Cdd:cd07866     83 skRKRGSVYMVTPYMDHDLSGLLENPSVKLTeSQIKCYMLQLLEGINYLHENHILHRDIKAANILIDNQG--ILKIADFG 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1803 NAVKFMpDEAQYCKYGTPE-------------FVAPEIV----NQTPvskATDIWPIG---------------------- 1843
Cdd:cd07866    161 LARPYD-GPPPNPKGGGGGgtrkytnlvvtrwYRPPELLlgerRYTT---AVDIWGIGcvfaemftrrpilqgksdidql 236

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1844 -VLTYLCLT-------GVSPFAG-ENDRSSVLNIRNYNVAFEESM--FTDLCHeakgfviKLLVAD-RLRPDANECLRHP 1911
Cdd:cd07866    237 hLIFKLCGTpteetwpGWRSLPGcEGVHSFTNYPRTLEERFGKLGpeGLDLLS-------KLLSLDpYKRLTASDALEHP 309


                   ..
gi 1207186029 1912 WF 1913
Cdd:cd07866    310 YF 311

Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TLKs play important functions during the cell cycle and are implicated in chromatin remodeling, DNA replication and repair, and mitosis. They phosphorylate and regulate Anti-silencing function 1 protein (Asf1), a histone H3/H4 chaperone that helps facilitate the assembly of chromatin following DNA replication during S phase. TLKs also phosphorylate the H3 histone tail and are essential in transcription. Vertebrates contain two subfamily members, TLK1 and TLK2. The TLK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).

Pssm-ID: 270943 [Multi-domain] Cd Length: 309 Bit Score: 87.42 E-value: 7.44e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1658 LTDYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKF----ISARAKRKAS----ALRELNILSHLDHERILYFHDAFE-KK 1728
Cdd:cd14041      4 LNDRYLLLHLLGRGGFSEVYKAFDLTEQRYVAVKIhqlnKNWRDEKKENyhkhACREYRIHKELDHPRIVKLYDYFSlDT 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1729 NAVIIITELCHEELLDRLTKKSTIL-ESEIRSSVRQLLEGINYLHQLD--ILHLDIKPDNILMADHSS-DQIRICDFGNA 1804
Cdd:cd14041     84 DSFCTVLEYCEGNDLDFYLKQHKLMsEKEARSIIMQIVNALKYLNEIKppIIHYDLKPGNILLVNGTAcGEIKITDFGLS 163

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1805 vKFMPD---------EAQYCKYGTPEFVAPE--IVNQTP--VSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNiRNY 1871
Cdd:cd14041    164 -KIMDDdsynsvdgmELTSQGAGTYWYLPPEcfVVGKEPpkISNKVDVWSVGVIFYQCLYGRKPFGHNQSQQDILQ-ENT 241

                          250       260
                   ....*....|....*....|....*...
gi 1207186029 1872 NVAFEESMFTD---LCHEAKGFVIKLLV 1896
Cdd:cd14041    242 ILKATEVQFPPkpvVTPEAKAFIRRCLA 269

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 80.63 E-value: 8.07e-18

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  1131 VLEVIEGRNARFDCKVSGTPPPQVIWSHFD-RPLEENEDIRILKEGGRHSLIISHVSNEDEGLYTVAARNSHGEDECAAE 1209
Cdd:smart00410    3 SVTVKEGESVTLSCEASGSPPPEVTWYKQGgKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGTT 82


                    ...
gi 1207186029  1210 LYV 1212
Cdd:smart00410   83 LTV 85

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK5 is mainly expressed in the brain. It is not required for viability, but together with PAK6, it is required for normal levels of locomotion and activity, and for learning and memory. PAK5 cooperates with Inca (induced in neural crest by AP2) in the regulation of cell adhesion and cytoskeletal organization in the embryo and in neural crest cells during craniofacial development. PAK5 may also play a role in controlling the signaling of Raf-1, an effector of Ras, at the mitochondria. PAK5 belongs to the group II PAKs, which contain a PBD (p21-binding domain) and a C-terminal catalytic domain, but do not harbor an AID (autoinhibitory domain) or SH3 binding sites. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 132989 [Multi-domain] Cd Length: 292 Bit Score: 87.02 E-value: 8.11e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3296 PQKPYTFMD---EKARGRFGVIRECRENATGNLYMAKIVPYEPESKQTVL-QEYDILKSLHHEKIMALHEAYVTPRYLVL 3371
Cdd:cd06658     17 PGDPREYLDsfiKIGEGSTGIVCIATEKHTGKQVAVKKMDLRKQQRRELLfNEVVIMRDYHHENVVDMYNSYLVGDELWV 96

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3372 ISECCSGKELLhSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLKQ 3451
Cdd:cd06658     97 VMEFLEGGALT-DIVTHTRMNEEQIATVCLSVLRALSYLHNQGVIHRDIKSDSILLTSDGRIKLSDFGFCAQVSKEVPKR 175

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3452 FSPpIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLSKLYQNVSQSASLFIKK 3531
Cdd:cd06658    176 KSL-VGTPYWMAPEVISRLPYGTEVDIWSLGIMVIEMIDGEPPYFNEPPLQAMRRIRDNLPPRVKDSHKVSSVLRGFLDL 254

                          250       260
                   ....*....|....*....|....
gi 1207186029 3532 ILCSYPWARPTIKDCFTNSWLQDA 3555
Cdd:cd06658    255 MLVREPSQRATAQELLQHPFLKLA 278

Catalytic domain of the Serine/Threonine Kinases, Novel Protein Kinase C theta, delta, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-theta is selectively expressed in T-cells and plays an important and non-redundant role in several aspects of T-cell biology. PKC-delta plays a role in cell cycle regulation and programmed cell death in many cell types. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. There are four nPKC isoforms, delta, epsilon, eta, and theta. The nPKC-theta-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270744 [Multi-domain] Cd Length: 320 Bit Score: 87.44 E-value: 8.80e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1767 GINYLHQLDILHLDIKPDNILMadHSSDQIRICDFGNAVKFMPDEAQ---YCkyGTPEFVAPEIVNQTPVSKATDIWPIG 1843
Cdd:cd05592    108 GLQFLHSRGIIYRDLKLDNVLL--DREGHIKIADFGMCKENIYGENKastFC--GTPDYIAPEILKGQKYNQSVDWWSFG 183

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1844 VLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESmftdLCHEAKGFVIKLLVAD-RLRPDANECLR-----HPWFKTLN 1917
Cdd:cd05592    184 VLLYEMLIGQSPFHGEDEDELFWSICNDTPHYPRW----LTKEAASCLSLLLERNpEKRLGVPECPAgdirdHPFFKTID 259


                   ...
gi 1207186029 1918 KGK 1920
Cdd:cd05592    260 WDK 262

Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinases 4 (also called ERK4) and 6 (also called ERK3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK4 (also called ERK4 or p63MAPK) and MAPK6 (also called ERK3 or p97MAPK) are atypical MAPKs that are not regulated by MAPK kinases. MAPK6 is expressed ubiquitously with highest amounts in brain and skeletal muscle. It may be involved in the control of cell differentiation by negatively regulating cell cycle progression in certain conditions. It may also play a role in glucose-induced insulin secretion. MAPK6 and MAPK4 cooperate to regulate the activity of MAPK-activated protein kinase 5 (MK5), leading to its relocation to the cytoplasm and exclusion from the nucleus. The MAPK6/MK5 and MAPK4/MK5 pathways may play critical roles in embryonic and post-natal development. MAPKs are important mediators of cellular responses to extracellular signals. The MAPK4/6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143359 [Multi-domain] Cd Length: 342 Bit Score: 87.91 E-value: 9.15e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1661 YYDVhKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKA-SALRELNILSHLDHERILYFHDAFEKKN---------- 1729
Cdd:cd07854      7 YMDL-RPLGCGSNGLVFSAVDSDCDKRVAVKKIVLTDPQSVkHALREIKIIRRLDHDNIVKVYEVLGPSGsdltedvgsl 85

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1730 ---AVIIITELCHEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMadhSSDQ--IRICDFGNA 1804
Cdd:cd07854     86 telNSVYIVQEYMETDLANVLEQGPLSEEHARLFMYQLLRGLKYIHSANVLHRDLKPANVFI---NTEDlvLKIGDFGLA 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1805 VKFMPDEAQ--YCKYG--TPEFVAPEIVNQ-TPVSKATDIWPIGVLTYLCLTGVSPFAG------------------END 1861
Cdd:cd07854    163 RIVDPHYSHkgYLSEGlvTKWYRSPRLLLSpNNYTKAIDMWAAGCIFAEMLTGKPLFAGaheleqmqlilesvpvvrEED 242

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1207186029 1862 RSSVLN-----IRNYNVAFEESMFTDLC---HEAKGFVIKLLVADRL-RPDANECLRHPWFK 1914
Cdd:cd07854    243 RNELLNvipsfVRNDGGEPRRPLRDLLPgvnPEALDFLEQILTFNPMdRLTAEEALMHPYMS 304

Catalytic domain of Suppressor of loss of cAMP-dependent protein kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Schizosaccharomyces pombe Sck1 and similar fungal proteins. Sck1 plays a role in trehalase activation triggered by glucose and a nitrogen source. Trehalase catalyzes the cleavage of the disaccharide trehalose to glucose. Trehalose, as a carbohydrate reserve and stress metabolite, plays an important role in the response of yeast to environmental changes. The Sck1-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270738 [Multi-domain] Cd Length: 330 Bit Score: 87.63 E-value: 9.95e-18

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKIVpyepeSKQTVLQEYDILKSLHHEKIM------------ALHEAYVTPRYLVLISEC 3375
Cdd:cd05586      3 KGTFGQVYQVRKKDTRRIYAMKVL-----SKKVIVAKKEVAHTIGERNILvrtaldespfivGLKFSFQTPTDLYLVTDY 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3376 CSGKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTfNPLFLKQFSPP 3455
Cdd:cd05586     78 MSGGELFWHLQKEGRFSEDRAKFYIAELVLALEHLHKNDIVYRDLKPENILLDANGHIALCDFGLSKA-DLTDNKTTNTF 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3456 IGTLDYMSPEMLKGDV-VGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLSKlyQNVSQSASLFIKKILC 3534
Cdd:cd05586    157 CGTTEYLAPEVLLDEKgYTKMVDFWSLGVLVFEMCCGWSPFYAEDTQQMYRNIAFGKVRFPK--DVLSDEGRSFVKGLLN 234


                   ....*.
gi 1207186029 3535 SYPWAR 3540
Cdd:cd05586    235 RNPKHR 240

Protein kinase; unclassified specificity; Phosphotransferases. The specificity of this class of kinases can not be predicted. Possible dual-specificity Ser/Thr/Tyr kinase.

Pssm-ID: 214568 [Multi-domain] Cd Length: 258 Bit Score: 86.06 E-value: 9.98e-18

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  1666 KEIGRGAFSYVKR----VIQKAGKLEYAAKFISARAKRKASA--LRELNILSHLDHERILYFHDAFEKKNAVIIITELC- 1738
Cdd:smart00221    5 KKLGEGAFGEVYKgtlkGKGDGKEVEVAVKTLKEDASEQQIEefLREARIMRKLDHPNIVKLLGVCTEEEPLMIVMEYMp 84

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  1739 HEELLDRL--TKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHssDQIRICDFGNAvKFMPDEAQYCK 1816
Cdd:smart00221   85 GGDLLDYLrkNRPKELSLSDLLSFALQIARGMEYLESKNFIHRDLAARNCLVGEN--LVVKISDFGLS-RDLYDDDYYKV 161

                           170       180       190       200
                    ....*....|....*....|....*....|....*....|....*.
gi 1207186029  1817 YGTPEFV---APEIVNQTPVSKATDIWPIGVLTY-LCLTGVSPFAG 1858
Cdd:smart00221  162 KGGKLPIrwmAPESLKEGKFTSKSDVWSFGVLLWeIFTLGEEPYPG 207

Catalytic domain of the Serine/Threonine Kinase, C-Raf (Rapidly Accelerated Fibrosarcoma) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. C-Raf, also known as Raf-1 or c-Raf-1, is ubiquitously expressed and was the first Raf identified. It was characterized as the acquired oncogene from an acutely transforming murine sarcoma virus (3611-MSV) and the transforming agent from the avian retrovirus MH2. C-Raf-deficient mice embryos die around midgestation with increased apoptosis of embryonic tissues, especially in the fetal liver. One of the main functions of C-Raf is restricting caspase activation to promote survival in response to specific stimuli such as Fas stimulation, macrophage apoptosis, and erythroid differentiation. C-Raf is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. It functions in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. The C-Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271051 [Multi-domain] Cd Length: 283 Bit Score: 86.62 E-value: 1.01e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3309 GRFGVIRECRENATGNLYMAKIVPYEPESKQTVLQEYDILKSLHHEKIMaLHEAYVTPRYLVLISECCSGKEL---LHSL 3385
Cdd:cd14149     23 GSFGTVYKGKWHGDVAVKILKVVDPTPEQFQAFRNEVAVLRKTRHVNIL-LFMGYMTKDNLAIVTQWCEGSSLykhLHVQ 101

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3386 IDRFRYSEddVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLF-LKQFSPPIGTLDYMSP 3464
Cdd:cd14149    102 ETKFQMFQ--LIDIARQTAQGMDYLHAKNIIHRDMKSNNIFLHEGLTVKIGDFGLATVKSRWSgSQQVEQPTGSILWMAP 179

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1207186029 3465 EMLKGDVVGP---PADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKF---DLSKLYQNVSQS 3524
Cdd:cd14149    180 EVIRMQDNNPfsfQSDVYSYGIVLYELMTGELPYSHINNRDQIIFMVGRGYaspDLSKLYKNCPKA 245

Catalytic domain of Cyclin-Dependent protein Kinase 9-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDK9 and CDK12 from higher eukaryotes, yeast BUR1, C-type plant CDKs (CdkC), and similar proteins. CDK9, BUR1, and CdkC are functionally equivalent. They act as a kinase for the C-terminal domain of RNA polymerase II and participate in regulating mutliple steps of gene expression including transcription elongation and RNA processing. CDK9 and CdkC associate with T-type cyclins while BUR1 associates with the cyclin BUR2. CDK12 is a unique CDK that contains an arginine/serine-rich (RS) domain, which is predominantly found in splicing factors. CDK12 interacts with cyclins L1 and L2, and participates in regulating transcription and alternative splicing. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK9-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270832 [Multi-domain] Cd Length: 291 Bit Score: 86.46 E-value: 1.14e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVI-QKAGKLeYAAKFISARAKRKA---SALRELNILSHLDHERILYFHD------AFEKKNAV 1731
Cdd:cd07840      1 YEKIAQIGEGTYGQVYKARnKKTGEL-VALKKIRMENEKEGfpiTAIREIKLLQKLDHPNVVRLKEivtskgSAKYKGSI 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1732 IIITELC-HE--ELLDRLTKKSTilESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSsdQIRICDFGNAVKFM 1808
Cdd:cd07840     80 YMVFEYMdHDltGLLDNPEVKFT--ESQIKCYMKQLLEGLQYLHSNGILHRDIKGSNILINNDG--VLKLADFGLARPYT 155

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1809 PDEAQYCKYG--TPEFVAPEIV-NQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRS------------------SVLN 1867
Cdd:cd07840    156 KENNADYTNRviTLWYRPPELLlGATRYGPEVDMWSVGCILAELFTGKPIFQGKTELEqlekifelcgspteenwpGVSD 235

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1207186029 1868 IRNYNV---------AFEESMFTDLCHEAKGFVIKLLVAD-RLRPDANECLRHPWF 1913
Cdd:cd07840    236 LPWFENlkpkkpykrRLREVFKNVIDPSALDLLDKLLTLDpKKRISADQALQHEYF 291

Catalytic domain of the Serine/Threonine kinase, TANK Binding Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TBK1 is also called T2K and NF-kB-activating kinase. It is widely expressed in most cell types and acts as an IkappaB kinase (IKK)-activating kinase responsible for NF-kB activation in response to growth factors. It plays a role in modulating inflammatory responses through the NF-kB pathway. TKB1 is also a major player in innate immune responses since it functions as a virus-activated kinase necessary for establishing an antiviral state. It phosphorylates IRF-3 and IRF-7, which are important transcription factors for inducing type I interferon during viral infection. In addition, TBK1 may also play roles in cell transformation and oncogenesis. The TBK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270890 [Multi-domain] Cd Length: 316 Bit Score: 87.16 E-value: 1.19e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYVKRVIQKAGKLEYAAK-FISARAKRKASA-LRELNILSHLDHE---RILYFHDAFEKKNAVIIItELCHE-- 1740
Cdd:cd13988      1 LGQGATANVFRGRHKKTGDLYAVKvFNNLSFMRPLDVqMREFEVLKKLNHKnivKLFAIEEELTTRHKVLVM-ELCPCgs 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1741 --ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNIL--MADHSSDQIRICDFGNAVKFMPDEAQYCK 1816
Cdd:cd13988     80 lyTVLEEPSNAYGLPESEFLIVLRDVVAGMNHLRENGIVHRDIKPGNIMrvIGEDGQSVYKLTDFGAARELEDDEQFVSL 159

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*...
gi 1207186029 1817 YGTPEFVAPEIVNQTPVSKAT--------DIWPIGVLTYLCLTGVSPF 1856
Cdd:cd13988    160 YGTEEYLHPDMYERAVLRKDHqkkygatvDLWSIGVTFYHAATGSLPF 207

Catalytic domain of the Serine/Threonine Kinase, Cell Division Cycle 2-like 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDC2L1, also called PITSLRE, exists in different isoforms which are named using the alias CDK11(p). The CDC2L1 gene produces two protein products, CDK11(p110) and CDK11(p58). CDC2L1 is also represented by the caspase-processed CDK11(p46). CDK11(p110), the major isoform, associates with cyclin L and is expressed throughout the cell cycle. It is involved in RNA processing and the regulation of transcription. CDK11(p58) associates with cyclin D3 and is expressed during the G2/M phase of the cell cycle. It plays roles in spindle morphogenesis, centrosome maturation, sister chromatid cohesion, and the completion of mitosis. CDK11(p46) is formed from the larger isoforms by caspases during TNFalpha- and Fas-induced apoptosis. It functions as a downstream effector kinase in apoptotic signaling pathways and interacts with eukaryotic initiation factor 3f (eIF3f), p21-activated kinase (PAK1), and Ran-binding protein (RanBPM). CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDC2L1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173741 [Multi-domain] Cd Length: 293 Bit Score: 86.51 E-value: 1.22e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1702 SALRELNILSHLDHERILYFHDAF--EKKNAVIIITELCHEELLDRL-TKKSTILESEIRSSVRQLLEGINYLHQLDILH 1778
Cdd:cd07843     50 TSLREINILLKLQHPNIVTVKEVVvgSNLDKIYMVMEYVEHDLKSLMeTMKQPFLQSEVKCLMLQLLSGVAHLHDNWILH 129

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1779 LDIKPDNILMadHSSDQIRICDFGNAVKFMPDEAQYckygTPEFV-----APEIVNQTPV-SKATDIWPIGVLTYLCLTG 1852
Cdd:cd07843    130 RDLKTSNLLL--NNRGILKICDFGLAREYGSPLKPY----TQLVVtlwyrAPELLLGAKEySTAIDMWSVGCIFAELLTK 203

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1853 VSPFAGENDR---------------------SSVLNIRNYNvaFEESM-------FTDLCHEAKGFVI--KLLVAD-RLR 1901
Cdd:cd07843    204 KPLFPGKSEIdqlnkifkllgtptekiwpgfSELPGAKKKT--FTKYPynqlrkkFPALSLSDNGFDLlnRLLTYDpAKR 281

                          250
                   ....*....|..
gi 1207186029 1902 PDANECLRHPWF 1913
Cdd:cd07843    282 ISAEDALKHPYF 293

Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAO3 is also known as JIK (c-Jun N-terminal kinase inhibitory kinase) or KFC (kinase from chicken). It specifically activates JNK, presumably by phosphorylating and activating MKK4/MKK7. In Saccharomyces cerevisiae, TAO3 is a component of the RAM (regulation of Ace2p activity and cellular morphogenesis) signaling pathway. TAO3 is upregulated in retinal ganglion cells after axotomy, and may play a role in apoptosis. TAO proteins possess mitogen-activated protein kinase (MAPK) kinase kinase activity. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. The TAO3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270803 [Multi-domain] Cd Length: 313 Bit Score: 87.01 E-value: 1.31e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1640 YKDDPMEDeasilrkmrrltdYYDVHkEIGRGAF--------SYVKRVIqKAGKLEYAAKFISARAKrkaSALRELNILS 1711
Cdd:cd06633     15 YKDDPEEI-------------FVDLH-EIGHGSFgavyfatnSHTNEVV-AIKKMSYSGKQTNEKWQ---DIIKEVKFLQ 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1712 HLDHERILYFHDAFEKKNAVIIITELCHEELLDRL-TKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMAD 1790
Cdd:cd06633     77 QLKHPNTIEYKGCYLKDHTAWLVMEYCLGSASDLLeVHKKPLQEVEIAAITHGALQGLAYLHSHNMIHRDIKAGNILLTE 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1791 hsSDQIRICDFGNAVKFMPDEAqycKYGTPEFVAPEIV---NQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLN 1867
Cdd:cd06633    157 --PGQVKLADFGSASIASPANS---FVGTPYWMAPEVIlamDEGQYDGKVDIWSLGITCIELAERKPPLFNMNAMSALYH 231

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*
gi 1207186029 1868 I-RNYNVAFEESMFTDlchEAKGFV-IKLLVADRLRPDANECLRH 1910
Cdd:cd06633    232 IaQNDSPTLQSNEWTD---SFRGFVdYCLQKIPQERPSSAELLRH 273

N-terminal Catalytic domain of the Serine/Threonine Kinase, Class IIIB myosin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Class IIIB myosin is expressed highly in retina. It is also present in the brain and testis. The human class IIIB myosin gene maps to a region that overlaps the locus for Bardet-Biedl syndrome, which is characterized by dysmorphic extremities, retinal dystrophy, obesity, male hypogenitalism, and renal abnormalities. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain. They may play an important role in maintaining the structural integrity of photoreceptor cell microvilli. They may also function as cargo carriers during light-dependent translocation, in photoreceptor cells, of proteins such as transducin and arrestin. The class III myosin subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270808 [Multi-domain] Cd Length: 291 Bit Score: 86.20 E-value: 1.46e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3296 PQKPYTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPESKQTVLQEYDILKSL--HHEKIMALHEAYVTPRY----L 3369
Cdd:cd06639     20 PSDTWDIIETIGKGTYGKVYKVTNKKDGSLAAVKILDPISDVDEEIEAEYNILRSLpnHPNVVKFYGMFYKADQYvggqL 99

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3370 VLISECCSG---KELLHSLIDRFRYSEDDVVAYIV-QILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFG-SAQTF 3444
Cdd:cd06639    100 WLVLELCNGgsvTELVKGLLKCGQRLDEAMISYILyGALLGLQHLHNNRIIHRDVKGNNILLTTEGGVKLVDFGvSAQLT 179

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1207186029 3445 NPLFLKQFSppIGTLDYMSPEMLKGD-----VVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARI 3507
Cdd:cd06639    180 SARLRRNTS--VGTPFWMAPEVIACEqqydySYDARCDVWSLGITAIELADGDPPLFDMHPVKALFKI 245

Catalytic domain of the Serine/Threonine Kinase, A-Raf (Rapidly Accelerated Fibrosarcoma) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. A-Raf cooperates with C-Raf in regulating ERK transient phosphorylation that is associated with cyclin D expression and cell cycle progression. Mice deficient in A-Raf are born alive but show neurological and intestinal defects. A-Raf demonstrates low kinase activity to MEK, compared with B- and C-Raf, and may also have alternative functions other than in the ERK signaling cascade. It regulates the M2 type pyruvate kinase, a key glycolytic enzyme. It also plays a role in endocytic membrane trafficking. A-Raf is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. It functions in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. The A-Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271052 [Multi-domain] Cd Length: 265 Bit Score: 85.45 E-value: 1.68e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3309 GRFGVIRECRENATGNLYMAKIVPYEPESKQTVLQEYDILKSLHHEKIMaLHEAYVTPRYLVLISECCSGKELLHSL-ID 3387
Cdd:cd14150     11 GSFGTVFRGKWHGDVAVKILKVTEPTPEQLQAFKNEMQVLRKTRHVNIL-LFMGFMTRPNFAIITQWCEGSSLYRHLhVT 89

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3388 RFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAqTFNPLF--LKQFSPPIGTLDYMSPE 3465
Cdd:cd14150     90 ETRFDTMQLIDVARQTAQGMDYLHAKNIIHRDLKSNNIFLHEGLTVKIGDFGLA-TVKTRWsgSQQVEQPSGSILWMAPE 168

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1207186029 3466 MLKGDVVGP---PADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKF---DLSKLYQNVSQS 3524
Cdd:cd14150    169 VIRMQDTNPysfQSDVYAYGVVLYELMSGTLPYSNINNRDQIIFMVGRGYlspDLSKLSSNCPKA 233

serine/threonine-protein kinase 1; Provisional

Pssm-ID: 223069 [Multi-domain] Cd Length: 267 Bit Score: 85.29 E-value: 1.72e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1720 YF---HDAFEKKNAVIIITELCHE-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMaDHSSDQ 1795
Cdd:PHA03390    70 NFiklYYSVTTLKGHVLIMDYIKDgDLFDLLKKEGKLSEAEVKKIIRQLVEALNDLHKHNIIHNDIKLENVLY-DRAKDR 148

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1796 IRICDFGnavkfmpdeaqYCKY--------GTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRS---S 1864
Cdd:PHA03390   149 IYLCDYG-----------LCKIigtpscydGTLDYFSPEKIKGHNYDVSFDWWAVGVLTYELLTGKHPFKEDEDEEldlE 217

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1207186029 1865 VLNIRNYN-VAFEESMFTDlcheAKGFVIKLLVAD---RLRpDANECLRHPWFK 1914
Cdd:PHA03390   218 SLLKRQQKkLPFIKNVSKN----ANDFVQSMLKYNinyRLT-NYNEIIKHPFLK 266

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK5 is widely expressed in many tissues. It associates with the membrane though an N-terminal PIP2 binding domain and also binds phospholipids via its C-terminus. GRK5 deficiency is associated with early Alzheimer's disease in humans and mouse models. GRK5 also plays a crucial role in the pathogenesis of sporadic Parkinson's disease. It participates in the regulation and desensitization of PDGFRbeta, a receptor tyrosine kinase involved in a variety of downstream cellular effects including cell growth, chemotaxis, apoptosis, and angiogenesis. GRK5 also regulates Toll-like receptor 4, which is involved in innate and adaptive immunity. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270780 [Multi-domain] Cd Length: 313 Bit Score: 86.56 E-value: 1.77e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3307 ARGRFGVIRECRENATGNLYMAKIVPYEPESKQT----VLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELL 3382
Cdd:cd05632     11 GKGGFGEVCACQVRATGKMYACKRLEKKRIKKRKgesmALNEKQILEKVNSQFVVNLAYAYETKDALCLVLTIMNGGDLK 90

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3383 HSLIDRFR--YSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPlfLKQFSPPIGTLD 3460
Cdd:cd05632     91 FHIYNMGNpgFEEERALFYAAEILCGLEDLHRENTVYRDLKPENILLDDYGHIRISDLGLAVKIPE--GESIRGRVGTVG 168

                          170       180       190
                   ....*....|....*....|....*....|....*
gi 1207186029 3461 YMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPF 3495
Cdd:cd05632    169 YMAPEVLNNQRYTLSPDYWGLGCLIYEMIEGQSPF 203

Catalytic domain of the Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGKs are activated by insulin and growth factors via phosphoinositide 3-kinase and PDK1. They activate ion channels, ion carriers, and the Na-K-ATPase, as well as regulate the activity of enzymes and transcription factors. SGKs play important roles in transport, hormone release, neuroexcitability, cell proliferation, and apoptosis. There are three isoforms of SGK, named SGK1, SGK2, and SGK3 (also called cytokine-independent survival kinase CISK). The SGK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270727 [Multi-domain] Cd Length: 323 Bit Score: 86.60 E-value: 1.95e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKIVPYEP-----ESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELL 3382
Cdd:cd05575      5 KGSFGKVLLARHKAEGKLYAVKVLQKKAilkrnEVKHIMAERNVLLKNVKHPFLVGLHYSFQTKDKLYFVLDYVNGGELF 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3383 HSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFG----------SAQTFnplflkqf 3452
Cdd:cd05575     85 FHLQRERHFPEPRARFYAAEIASALGYLHSLNIIYRDLKPENILLDSQGHVVLTDFGlckegiepsdTTSTF-------- 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3453 sppIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFdlsKLYQNVSQSASLFIKKI 3532
Cdd:cd05575    157 ---CGTPEYLAPEVLRKQPYDRTVDWWCLGAVLYEMLYGLPPFYSRDTAEMYDNILHKPL---RLRTNVSPSARDLLEGL 230


                   .
gi 1207186029 3533 L 3533
Cdd:cd05575    231 L 231

Catalytic domain of the Serine/Threonine Kinase, PFTAIRE-1 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PFTAIRE-1 is widely expressed except in the spleen and thymus. It is highly expressed in the brain, heart, pancreas, testis, and ovary, and is localized in the cytoplasm. It is regulated by cyclin D3 and is inhibited by the p21 cell cycle inhibitor. It has also been shown to interact with the membrane-associated cyclin Y, which recruits the protein to the plasma membrane. PFTAIRE-1 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PFTAIRE-1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143374 [Multi-domain] Cd Length: 303 Bit Score: 85.90 E-value: 2.04e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1660 DYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKA--SALRELNILSHLDHERILYFHDAFEKKNAVIIITEL 1737
Cdd:cd07869      5 DSYEKLEKLGEGSYATVYKGKSKVNGKLVALKVIRLQEEEGTpfTAIREASLLKGLKHANIVLLHDIIHTKETLTLVFEY 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1738 CHEELLDRLTKKSTILESE-IRSSVRQLLEGINYLHQLDILHLDIKPDNILMADhsSDQIRICDFGNA-VKFMPDEAQYC 1815
Cdd:cd07869     85 VHTDLCQYMDKHPGGLHPEnVKLFLFQLLRGLSYIHQRYILHRDLKPQNLLISD--TGELKLADFGLArAKSVPSHTYSN 162

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*..
gi 1207186029 1816 KYGTPEFVAPEI-VNQTPVSKATDIWPIGVLTYLCLTGVSPFAGEND 1861
Cdd:cd07869    163 EVVTLWYRPPDVlLGSTEYSTCLDMWGVGCIFVEMIQGVAAFPGMKD 209

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C theta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-theta is selectively expressed in T-cells and plays an important and non-redundant role in several aspects of T-cell biology. Although T-cells also express other PKC isoforms, PKC-theta is unique in that upon antigen stimulation, it is translocated to the plasma membrane at the immunological synapse, where it mediates signals essential for T-cell activation. It is essential for TCR-induced proliferation, cytokine production, T-cell survival, and the differentiation and effector function of T-helper (Th) cells, particularly Th2 and Th17. PKC-theta is being developed as a therapeutic target for Th2-mediated allergic inflammation and Th17-mediated autoimmune diseases. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270770 [Multi-domain] Cd Length: 331 Bit Score: 86.52 E-value: 2.21e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1660 DYYDVHKEIGRGAFSYVKrviqkAGKLEYAAKFISARAKRKASALR---------ELNILS-HLDHERILYFHDAFEKKN 1729
Cdd:cd05619      5 EDFVLHKMLGKGSFGKVF-----LAELKGTNQFFAIKALKKDVVLMdddvectmvEKRVLSlAWEHPFLTHLFCTFQTKE 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1730 AVIIITEL------------CHEELLDRltkkSTILESEIrssvrqlLEGINYLHQLDILHLDIKPDNILMadHSSDQIR 1797
Cdd:cd05619     80 NLFFVMEYlnggdlmfhiqsCHKFDLPR----ATFYAAEI-------ICGLQFLHSKGIVYRDLKLDNILL--DKDGHIK 146

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1798 ICDFGNAVKFMPDEAQYCKY-GTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFE 1876
Cdd:cd05619    147 IADFGMCKENMLGDAKTSTFcGTPDYIAPEILLGQKYNTSVDWWSFGVLLYEMLIGQSPFHGQDEEELFQSIRMDNPFYP 226

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....
gi 1207186029 1877 ESmftdLCHEAKGFVIKLLVAD---RLRPDANeCLRHPWFKTLN 1917
Cdd:cd05619    227 RW----LEKEAKDILVKLFVREperRLGVRGD-IRQHPFFREIN 265

Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PIM gene locus was discovered as a result of the cloning of retroviral intergration sites in murine Moloney leukemia virus, leading to the identification of PIM kinases. They are constitutively active STKs with a broad range of cellular targets and are overexpressed in many haematopoietic malignancies and solid cancers. Vertebrates contain three distinct PIM kinase genes (PIM1-3); each gene may result in mutliple protein isoforms. There are two PIM1 and three PIM2 isoforms as a result of alternative translation initiation sites, while there is only one PIM3 protein. Compound knockout mice deficient of all three PIM kinases that survive the perinatal period show a profound reduction in body size, indicating that PIMs are important for body growth. The PIM subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270907 [Multi-domain] Cd Length: 255 Bit Score: 84.60 E-value: 2.41e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASALR-------ELNIL---SHLDHERILYFHDAFEKKNAV 1731
Cdd:cd14005      2 YEVGDLLGKGGFGTVYSGVRIRDGLPVAVKFVPKSRVTEWAMINgpvpvplEIALLlkaSKPGVPGVIRLLDWYERPDGF 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1732 IIITE---LChEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMaDHSSDQIRICDFGNAvKFM 1808
Cdd:cd14005     82 LLIMErpePC-QDLFDFITERGALSENLARIIFRQVVEAVRHCHQRGVLHRDIKDENLLI-NLRTGEVKLIDFGCG-ALL 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1809 PDeAQYCKY-GTPEFVAPE-IVNQTPVSKATDIWPIGVLTYLCLTGVSPFagENDrssvLNIRNYNVAFEESMFTDLCHe 1886
Cdd:cd14005    159 KD-SVYTDFdGTRVYSPPEwIRHGRYHGRPATVWSLGILLYDMLCGDIPF--END----EQILRGNVLFRPRLSKECCD- 230

                          250       260
                   ....*....|....*....|....*...
gi 1207186029 1887 akgFVIKLLVAD-RLRPDANECLRHPWF 1913
Cdd:cd14005    231 ---LISRCLQFDpSKRPSLEQILSHPWF 255

Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ROCK is also referred to as Rho-associated kinase or simply as Rho kinase. It contains an N-terminal extension, a catalytic kinase domain, and a long C-terminal extension, which contains a coiled-coil region encompassing a Rho-binding domain (RBD) and a pleckstrin homology (PH) domain. ROCK is auto-inhibited by the RBD and PH domain interacting with the catalytic domain. It is activated via interaction with Rho GTPases and is involved in many cellular functions including contraction, adhesion, migration, motility, proliferation, and apoptosis. The ROCK subfamily consists of two isoforms, ROCK1 and ROCK2, which may be functionally redundant in some systems, but exhibit different tissue distributions. Both isoforms are ubiquitously expressed in most tissues, but ROCK2 is more prominent in brain and skeletal muscle while ROCK1 is more pronounced in the liver, testes, and kidney. Studies in knockout mice result in different phenotypes, suggesting that the two isoforms do not compensate for each other during embryonic development. The ROCK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270747 [Multi-domain] Cd Length: 352 Bit Score: 86.66 E-value: 2.44e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1646 EDEASILRKMRRLTDYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISA--RAKRKASAL--RELNILSHLDHERILYF 1721
Cdd:cd05596     12 EKPVNEITKLRMNAEDFDVIKVIGRGAFGEVQLVRHKSTKKVYAMKLLSKfeMIKRSDSAFfwEERDIMAHANSEWIVQL 91

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1722 HDAFEKKNAVIIITELCHEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDF 1801
Cdd:cd05596     92 HYAFQDDKYLYMVMDYMPGGDLVNLMSNYDVPEKWARFYTAEVVLALDAIHSMGFVHRDVKPDNMLL--DASGHLKLADF 169

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1802 GNAVKFMPDEAQYCK--YGTPEFVAPEIVNQTPV----SKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNY--NV 1873
Cdd:cd05596    170 GTCMKMDKDGLVRSDtaVGTPDYISPEVLKSQGGdgvyGRECDWWSVGVFLYEMLVGDTPFYADSLVGTYGKIMNHknSL 249

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*
gi 1207186029 1874 AFEESMftDLCHEAKGFVIKLLV--ADRL-RPDANECLRHPWFKT 1915
Cdd:cd05596    250 QFPDDV--EISKDAKSLICAFLTdrEVRLgRNGIEEIKAHPFFKN 292

Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK2 is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK) and is also called MAP3K10. MAP3Ks phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLK2 is abundant in brain, skeletal muscle, and testis. It functions upstream of the MAPK, c-Jun N-terminal kinase. It binds hippocalcin, a calcium-sensor protein that protects neurons against calcium-induced cell death. Both MLK2 and hippocalcin may be associated with the pathogenesis of Parkinson's disease. MLK2 also binds to normal huntingtin (Htt), which is important in neuronal transcription, development, and survival. MLK2 does not bind to the polyglutamine-expanded Htt, which is implicated in the pathogeneis of Huntington's disease, leading to neuronal toxicity. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The MLK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).

Pssm-ID: 271050 [Multi-domain] Cd Length: 258 Bit Score: 84.65 E-value: 2.50e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3329 KIVPYEPE-----SKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLHSLIDRfRYSEDDVVAYIVQI 3403
Cdd:cd14148     23 KAARQDPDediavTAENVRQEARLFWMLQHPNIIALRGVCLNPPHLCLVMEYARGGALNRALAGK-KVPPHVLVNWAVQI 101

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3404 LQGLDYLHSRR---ILHLDIKPENIIVT--------YMNVVKIIDFGSAQTFNPLflKQFSPPiGTLDYMSPEMLKGDVV 3472
Cdd:cd14148    102 ARGMNYLHNEAivpIIHRDLKSSNILILepienddlSGKTLKITDFGLAREWHKT--TKMSAA-GTYAWMAPEVIRLSLF 178

                          170       180
                   ....*....|....*....|....*..
gi 1207186029 3473 GPPADIWSIGILTYIMLSGRLPFTEND 3499
Cdd:cd14148    179 SKSSDVWSFGVLLWELLTGEVPYREID 205

Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MST3 phosphorylates the STK NDR and may play a role in cell cycle progression and cell morphology. It may also regulate paxillin and consequently, cell migration. MST3 is present in human placenta, where it plays an essential role in the oxidative stress-induced apoptosis of trophoblasts in normal spontaneous delivery. Dysregulation of trophoblast apoptosis may result in pregnancy complications such as preeclampsia and intrauterine growth retardation. The MST3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270809 [Multi-domain] Cd Length: 277 Bit Score: 85.12 E-value: 2.75e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1666 KEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKA--SALRELNILSHLDHERILYFHDAFEKKNAVIIITE-LCHEEL 1742
Cdd:cd06641     10 EKIGKGSFGEVFKGIDNRTQKVVAIKIIDLEEAEDEieDIQQEITVLSQCDSPYVTKYYGSYLKDTKLWIIMEyLGGGSA 89

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1743 LDrLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSsdQIRICDFGNAVKFMPDEAQYCKY-GTPE 1821
Cdd:cd06641     90 LD-LLEPGPLDETQIATILREILKGLDYLHSEKKIHRDIKAANVLLSEHG--EVKLADFGVAGQLTDTQIKRN*FvGTPF 166

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1822 FVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDLCHEakgFVIKLLVAD-RL 1900
Cdd:cd06641    167 WMAPEVIKQSAYDSKADIWSLGITAIELARGEPPHSELHPMKVLFLIPKNNPPTLEGNYSKPLKE---FVEACLNKEpSF 243

                          250       260       270
                   ....*....|....*....|....*....|....*..
gi 1207186029 1901 RPDANECLRHPWFKTLNKGKSISTESLKKFlsrRKWQ 1937
Cdd:cd06641    244 RPTAKELLKHKFILRNAKKTSYLTELIDRY---KRWK 277

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 79.22 E-value: 2.80e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029   55 PVFIRKMRNAAVGTGCDIRLKVAVAGDPQPTLYWYHND------DLVNMDNQEYGG-LWIRDCKPSDAGLYTCIATNHLG 127
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGqplrssDRFKVTYEGGTYtLTISNVQPDDSGKYTCVATNSAG 80

                           90
                   ....*....|
gi 1207186029  128 EARSSAVLAV 137
Cdd:pfam07679   81 EAEASAELTV 90

Catalytic domain of the Protein Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGK3 (also called cytokine-independent survival kinase or CISK) is expressed in most tissues and is most abundant in the embryo and adult heart and spleen. It was originally discovered in a screen for antiapoptotic genes. It phosphorylates and inhibits the proapoptotic proteins, Bad and FKHRL1. SGK3 also regulates many transporters, ion channels, and receptors. It plays a critical role in hair follicle morphogenesis and hair cycling. The SGK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270755 [Multi-domain] Cd Length: 326 Bit Score: 86.17 E-value: 2.84e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAK-----IVPYEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELL 3382
Cdd:cd05604      6 KGSFGKVLLAKRKRDGKYYAVKvlqkkVILNRKEQKHIMAERNVLLKNVKHPFLVGLHYSFQTTDKLYFVLDFVNGGELF 85

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3383 HSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFG----------SAQTFnplflkqf 3452
Cdd:cd05604     86 FHLQRERSFPEPRARFYAAEIASALGYLHSINIVYRDLKPENILLDSQGHIVLTDFGlckegisnsdTTTTF-------- 157

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3453 sppIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAE 3502
Cdd:cd05604    158 ---CGTPEYLAPEVIRKQPYDNTVDWWCLGSVLYEMLYGLPPFYCRDTAE 204

Catalytic domain of the Serine/Threonine kinase, NF-kappaB Inducing Kinase (NIK); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NIK, also called mitogen activated protein kinase kinase kinase 14 (MAP3K14), phosphorylates and activates Inhibitor of NF-KappaB Kinase (IKK) alpha, which is a regulator of NF-kB proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. NIK is essential in the IKKalpha-mediated non-canonical NF-kB signaling pathway, in which IKKalpha processes the IkB-like C-terminus of NF-kB2/p100 to produce p52, allowing the p52/RelB dimer to migrate to the nucleus where it regulates gene transcription. NIK also plays an important role in Toll-like receptor 7/9 signaling cascades. The NIK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270893 [Multi-domain] Cd Length: 268 Bit Score: 84.87 E-value: 2.86e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKIVPYEpeskQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLHSLID 3387
Cdd:cd13991     16 RGSFGEVHRMEDKQTGFQCAVKKVRLE----VFRAEELMACAGLTSPRVVPLYGAVREGPWVNIFMDLKEGGSLGQLIKE 91

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3388 RFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTY-MNVVKIIDFGSAQTFNP------LFLKQFSPpiGTLD 3460
Cdd:cd13991     92 QGCLPEDRALHYLGQALEGLEYLHSRKILHGDVKADNVLLSSdGSDAFLCDFGHAECLDPdglgksLFTGDYIP--GTET 169

                          170       180       190
                   ....*....|....*....|....*....|....*..
gi 1207186029 3461 YMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTE 3497
Cdd:cd13991    170 HMAPEVVLGKPCDAKVDVWSSCCMMLHMLNGCHPWTQ 206

Catalytic domain of Cyclin-Dependent protein Kinase 4 and 6-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK4 and CDK6 partner with D-type cyclins to regulate the early G1 phase of the cell cycle. They are the first kinases activated by mitogenic signals to release cells from the G0 arrested state. CDK4 and CDK6 are both expressed ubiquitously, associate with all three D cyclins (D1, D2 and D3), and phosphorylate the retinoblastoma (pRb) protein. They are also regulated by the INK4 family of inhibitors which associate with either the CDK alone or the CDK/cyclin complex. CDK4 and CDK6 show differences in subcellular localization, sensitivity to some inhibitors, timing in activation, tumor selectivity, and possibly substrate profiles. Although CDK4 and CDK6 seem to show some redundancy, they also have discrete, nonoverlapping functions. CDK6 plays an important role in cell differentiation. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK4/6-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270831 [Multi-domain] Cd Length: 287 Bit Score: 85.02 E-value: 2.94e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRK---ASALRELNILSHLD---HERILYFHDAF-----EKKNA 1730
Cdd:cd07838      1 YEEVAEIGEGAYGTVYKARDLQDGRFVALKKVRVPLSEEgipLSTIREIALLKQLEsfeHPNVVRLLDVChgprtDRELK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1731 VIIITELCHEELLDRLTK--KSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMAdhSSDQIRICDFGNAVKFM 1808
Cdd:cd07838     81 LTLVFEHVDQDLATYLDKcpKPGLPPETIKDLMRQLLRGLDFLHSHRIVHRDLKPQNILVT--SDGQVKLADFGLARIYS 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1809 PDEAQyckygTPEFV-----APEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGEND--------------------RS 1863
Cdd:cd07838    159 FEMAL-----TSVVVtlwyrAPEVLLQSSYATPVDMWSVGCIFAELFNRRPLFRGSSEadqlgkifdviglpseeewpRN 233

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1207186029 1864 SVL---NIRNYNVAFEESMFTDLCHEAKGFVIKLLVAD-RLRPDANECLRHPWF 1913
Cdd:cd07838    234 SALprsSFPSYTPRPFKSFVPEIDEEGLDLLKKMLTFNpHKRISAFEALQHPYF 287

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 5; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK5 (also called MEK5) is a dual-specificity PK that phosphorylates its downstream target, extracellular signal-regulated kinase 5 (ERK5), on specific threonine and tyrosine residues. MKK5 is activated by MEKK2 and MEKK3 in response to mitogenic and stress stimuli. The ERK5 cascade promotes cell proliferation, differentiation, neuronal survival, and neuroprotection. This cascade plays an essential role in heart development. Mice deficient in either ERK5 or MKK5 die around embryonic day 10 due to cardiovascular defects including underdevelopment of the myocardium. In addition, MKK5 is associated with metastasis and unfavorable prognosis in prostate cancer. The MKK5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 132950 [Multi-domain] Cd Length: 279 Bit Score: 84.93 E-value: 3.17e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3302 FMDEKARGRFGVIRECRENATGNLYMAKIVPYE--PESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGK 3379
Cdd:cd06619      5 YQEILGHGNGGTVYKAYHLLTRRILAVKVIPLDitVELQKQIMSELEILYKCDSPYIIGFYGAFFVENRISICTEFMDGG 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3380 ELlhsliDRFRYSEDDVVAYI-VQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFG-SAQTFNPLfLKQFsppIG 3457
Cdd:cd06619     85 SL-----DVYRKIPEHVLGRIaVAVVKGLTYLWSLKILHRDVKPSNMLVNTRGQVKLCDFGvSTQLVNSI-AKTY---VG 155

                          170       180       190
                   ....*....|....*....|....*....|....*...
gi 1207186029 3458 TLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPF 3495
Cdd:cd06619    156 TNAYMAPERISGEQYGIHSDVWSLGISFMELALGRFPY 193

Catalytic domain of the Protein Serine/Threonine Kinase, p21-activated kinase 3; Serine/threonine kinases (STKs), p21-activated kinase (PAK) 3, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs from higher eukaryotes are classified into two groups (I and II), according to their biochemical and structural features. PAK3 belongs to group I. Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). PAK3 is highly expressed in the brain. It is implicated in neuronal plasticity, synapse formation, dendritic spine morphogenesis, cell cycle progression, neuronal migration, and apoptosis. Inactivating mutations in the PAK3 gene cause X-linked non-syndromic mental retardation, the severity of which depends on the site of the mutation.

Pssm-ID: 132987 [Multi-domain] Cd Length: 297 Bit Score: 85.16 E-value: 3.26e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1648 EASILRKMRRLTDYYDVHKE------IGRGAFSYVKRVIQKAGKLEYAAKFISARAK-RKASALRELNILSHLDHERILY 1720
Cdd:cd06656      1 DEEILEKLRSIVSVGDPKKKytrfekIGQGASGTVYTAIDIATGQEVAIKQMNLQQQpKKELIINEILVMRENKNPNIVN 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1721 FHDAFEKKNAVIIITELCHEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSdqIRICD 1800
Cdd:cd06656     81 YLDSYLVGDELWVVMEYLAGGSLTDVVTETCMDEGQIAAVCRECLQALDFLHSNQVIHRDIKSDNILLGMDGS--VKLTD 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1801 FGNAVKFMPDEAQYCKY-GTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNyNVAFEESM 1879
Cdd:cd06656    159 FGFCAQITPEQSKRSTMvGTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPYLNENPLRALYLIAT-NGTPELQN 237

                          250       260       270
                   ....*....|....*....|....*....|....*.
gi 1207186029 1880 FTDLCHEAKGFVIKLLVAD-RLRPDANECLRHPWFK 1914
Cdd:cd06656    238 PERLSAVFRDFLNRCLEMDvDRRGSAKELLQHPFLK 273

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase N; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKN has a C-terminal catalytic domain that is highly homologous to PKCs. Its unique N-terminal regulatory region contains antiparallel coiled-coil (ACC) domains. In mammals, there are three PKN isoforms from different genes (designated PKN-alpha, beta, and gamma), which show different enzymatic properties, tissue distribution, and varied functions. PKN can be activated by the small GTPase Rho, and by fatty acids such as arachidonic and linoleic acids. It is involved in many biological processes including cytokeletal regulation, cell adhesion, vesicle transport, glucose transport, regulation of meiotic maturation and embryonic cell cycles, signaling to the nucleus, and tumorigenesis. The PKN subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270741 [Multi-domain] Cd Length: 326 Bit Score: 85.82 E-value: 3.31e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1767 GINYLHQLDILHLDIKPDNILMadHSSDQIRICDFG---NAVKFMPDEAQYCkyGTPEFVAPEIVNQTPVSKATDIWPIG 1843
Cdd:cd05589    113 GLQFLHEHKIVYRDLKLDNLLL--DTEGYVKIADFGlckEGMGFGDRTSTFC--GTPEFLAPEVLTDTSYTRAVDWWGLG 188

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1844 VLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTdlchEAKGFVIKLLVAD---RL---RPDANECLRHPWFKTLN 1917
Cdd:cd05589    189 VLIYEMLVGESPFPGDDEEEVFDSIVNDEVRYPRFLST----EAISIMRRLLRKNperRLgasERDAEDVKKQPFFRNID 264

Catalytic domain of the Serine/Threonine Kinase, Group I p21-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Group I PAKs, also called conventional PAKs, include PAK1, PAK2, and PAK3. Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). They interact with the SH3 domain containing proteins Nck, Grb2 and PIX. Binding of group I PAKs to activated GTPases leads to conformational changes that destabilize the AID, allowing autophosphorylation and full activation of the kinase domain. Known group I PAK substrates include MLCK, Bad, Raf, MEK1, LIMK, Merlin, Vimentin, Myc, Stat5a, and Aurora A, among others. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs are implicated in the regulation of many cellular processes including growth factor receptor-mediated proliferation, cell polarity, cell motility, cell death and survival, and actin cytoskeleton organization. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270814 [Multi-domain] Cd Length: 261 Bit Score: 84.59 E-value: 3.42e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAK-RKASALRELNILSHLDHERILYFHDAFEKKNAVIIITE-LCH 1739
Cdd:cd06647      9 YTRFEKIGQGASGTVYTAIDVATGQEVAIKQMNLQQQpKKELIINEILVMRENKNPNIVNYLDSYLVGDELWVVMEyLAG 88

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1740 EELLDRLTKkSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSdqIRICDFGNAVKFMPDEAQYCKY-G 1818
Cdd:cd06647     89 GSLTDVVTE-TCMDEGQIAAVCRECLQALEFLHSNQVIHRDIKSDNILLGMDGS--VKLTDFGFCAQITPEQSKRSTMvG 165

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1819 TPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGEND-RSSVLNIRNYNVAFEE-----SMFTDlcheakgFVI 1892
Cdd:cd06647    166 TPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPYLNENPlRALYLIATNGTPELQNpeklsAIFRD-------FLN 238

                          250       260
                   ....*....|....*....|...
gi 1207186029 1893 KLLVAD-RLRPDANECLRHPWFK 1914
Cdd:cd06647    239 RCLEMDvEKRGSAKELLQHPFLK 261

Catalytic domain of the Serine/Threonine Kinase, Fungal Mitogen-Activated Protein Kinase MPK1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the MAPKs MPK1 from Saccharomyces cerevisiae, Pmk1 from Schizosaccharomyces pombe, and similar proteins. MPK1 (also called Slt2) and Pmk1 (also called Spm1) are stress-activated MAPKs that regulate the cell wall integrity pathway, and are therefore important in the maintainance of cell shape, cell wall construction, morphogenesis, and ion homeostasis. MPK1 is activated in response to cell wall stress including heat stimulation, osmotic shock, UV irradiation, and any agents that interfere with cell wall biogenesis such as chitin antagonists, caffeine, or zymolase. MPK1 is regulated by the MAP2Ks Mkk1/2, which are regulated by the MAP3K Bck1. Pmk1 is also activated by multiple stresses including elevated temperatures, hyper- or hypotonic stress, glucose deprivation, exposure to cell-wall damaging compounds, and oxidative stress. It is regulated by the MAP2K Pek1, which is regulated by the MAP3K Mkh1. MAPKs are important mediators of cellular responses to extracellular signals. The MPK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173750 [Multi-domain] Cd Length: 332 Bit Score: 85.92 E-value: 3.78e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1661 YYDVHKEIGRGAFSYV--KRVIQKAGKLEYAAKFIS------ARAKRkasALRELNILSHL-DHERI--LY-----FHDA 1724
Cdd:cd07857      1 RYELIKELGQGAYGIVcsARNAETSEEETVAIKKITnvfskkILAKR---ALRELKLLRHFrGHKNItcLYdmdivFPGN 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1725 FekkNAVIIITELCHEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDFGNA 1804
Cdd:cd07857     78 F---NELYLYEELMEADLHQIIRSGQPLTDAHFQSFIYQILCGLKYIHSANVLHRDLKPGNLLV--NADCELKICDFGLA 152

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1207186029 1805 VKFMPDEAQYCKYGTpEFV------APEI-VNQTPVSKATDIWPIGVLTYLCLTGVSPFAGEN 1860
Cdd:cd07857    153 RGFSENPGENAGFMT-EYVatrwyrAPEImLSFQSYTKAIDVWSVGCILAELLGRKPVFKGKD 214

Catalytic domain of the Serine/Threonine Kinase, Large Tumor Suppressor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LATS was originally identified in Drosophila using a screen for genes whose inactivation led to overproliferation of cells. In tetrapods, there are two LATS isoforms, LATS1 and LATS2. Inactivation of LATS1 in mice results in the development of various tumors, including sarcomas and ovarian cancer. LATS functions as a tumor suppressor and is implicated in cell cycle regulation. The LATS subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270749 [Multi-domain] Cd Length: 333 Bit Score: 85.83 E-value: 3.82e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKIVpyepeSKQTVLQ---------EYDILKSLHHEKIMALHEAYVTPRYLVLISECCSG 3378
Cdd:cd05598     11 VGAFGEVSLVRKKDTNALYAMKTL-----RKKDVLKrnqvahvkaERDILAEADNEWVVKLYYSFQDKENLYFVMDYIPG 85

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3379 KELLhSLIDRFRYSEDDVVA-YIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTF----NPLFLKQFS 3453
Cdd:cd05598     86 GDLM-SLLIKKGIFEEDLARfYIAELVCAIESVHKMGFIHRDIKPDNILIDRDGHIKLTDFGLCTGFrwthDSKYYLAHS 164

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3454 PpIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLSKLYQ-NVSQSASLFIKKI 3532
Cdd:cd05598    165 L-VGTPNYIAPEVLLRTGYTQLCDWWSVGVILYEMLVGQPPFLAQTPAETQLKVINWRTTLKIPHEaNLSPEAKDLILRL 243


                   ...
gi 1207186029 3533 LCS 3535
Cdd:cd05598    244 CCD 246

Catalytic domain of the Serine/Threonine kinase, Inositol-requiring protein 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRE1, also called Endoplasmic reticulum (ER)-to-nucleus signaling protein (or ERN), is an ER-localized type I transmembrane protein with kinase and endoribonuclease domains in the cytoplasmic side. It acts as an ER stress sensor and is the oldest and most conserved component of the unfolded protein response (UPR) in eukaryotes. The UPR is activated when protein misfolding is detected in the ER in order to decrease the synthesis of new proteins and increase the capacity of the ER to cope with the stress. During ER stress, IRE1 dimerizes and forms oligomers, allowing the kinase domain to undergo trans-autophosphorylation. This leads to a conformational change that stimulates its endoribonuclease activity and results in the cleavage of its mRNA substrate, HAC1 in yeast and XBP1 in metazoans, promoting a splicing event that enables translation into a transcription factor which activates the UPR. Mammals contain two IRE1 proteins, IRE1alpha (or ERN1) and IRE1beta (or ERN2). The Ire1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270884 [Multi-domain] Cd Length: 269 Bit Score: 84.25 E-value: 4.00e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3388 RFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNV-----VKIIDFGSAQT--FNPLFLKQFSPPIGTLD 3460
Cdd:cd13982     93 LFLRPGLEPVRLLRQIASGLAHLHSLNIVHRDLKPQNILISTPNAhgnvrAMISDFGLCKKldVGRSSFSRRSGVAGTSG 172

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3461 YMSPEMLKGDVVGPPA---DIWSIGILTYIMLS-GRLPFteNDPAETEARIQAAKFDLSKLYQNVSQS--ASLFIKKILC 3534
Cdd:cd13982    173 WIAPEMLSGSTKRRQTravDIFSLGCVFYYVLSgGSHPF--GDKLEREANILKGKYSLDKLLSLGEHGpeAQDLIERMID 250

                          170
                   ....*....|..
gi 1207186029 3535 SYPWARPTIKDC 3546
Cdd:cd13982    251 FDPEKRPSAEEV 262

Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MST4 is sometimes referred to as MASK (MST3 and SOK1-related kinase). It plays a role in mitogen-activated protein kinase (MAPK) signaling during cytoskeletal rearrangement, morphogenesis, and apoptosis. It influences cell growth and transformation by modulating the extracellular signal-regulated kinase (ERK) pathway. MST4 may also play a role in tumor formation and progression. It localizes in the Golgi apparatus by interacting with the Golgi matrix protein GM130 and may play a role in cell migration. The MST4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 132971 [Multi-domain] Cd Length: 277 Bit Score: 84.72 E-value: 4.10e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKA--SALRELNILSHLDHERILYFHDAFEKKNAVIIITE-LCHEELLD 1744
Cdd:cd06640     12 IGKGSFGEVFKGIDNRTQQVVAIKIIDLEEAEDEieDIQQEITVLSQCDSPYVTKYYGSYLKGTKLWIIMEyLGGGSALD 91

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1745 rLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSsdQIRICDFGNAVKFMPDEAQYCKY-GTPEFV 1823
Cdd:cd06640     92 -LLRAGPFDEFQIATMLKEILKGLDYLHSEKKIHRDIKAANVLLSEQG--DVKLADFGVAGQLTDTQIKRNTFvGTPFWM 168

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1824 APEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAfeeSMFTDLCHEAKGFVIKLLVAD-RLRP 1902
Cdd:cd06640    169 APEVIQQSAYDSKADIWSLGITAIELAKGEPPNSDMHPMRVLFLIPKNNPP---TLVGDFSKPFKEFIDACLNKDpSFRP 245

                          250       260       270
                   ....*....|....*....|....*....|....*
gi 1207186029 1903 DANECLRHPWFKTLNKGKSISTESLKKFlsrRKWQ 1937
Cdd:cd06640    246 TAKELLKHKFIVKNAKKTSYLTELIDRF---KRWK 277

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPKs serve as important mediators of cellular responses to extracellular signals. They control critical cellular functions including differentiation, proliferation, migration, and apoptosis. They are also implicated in the pathogenesis of many diseases including multiple types of cancer, stroke, diabetes, and chronic inflammation. Typical MAPK pathways involve a triple kinase core cascade comprising of the MAPK, which is phosphorylated and activated by a MAPK kinase (MAP2K or MKK), which itself is phosphorylated and activated by a MAPK kinase kinase (MAP3K or MKKK). Each cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. There are three typical MAPK subfamilies: Extracellular signal-Regulated Kinase (ERK), c-Jun N-terminal Kinase (JNK), and p38. Some MAPKs are atypical in that they are not regulated by MAP2Ks. These include MAPK4, MAPK6, NLK, and ERK7. The MAPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270828 [Multi-domain] Cd Length: 329 Bit Score: 85.65 E-value: 4.20e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3341 VLQEYDILKSLHHEKIMALHEAYVTPR-------YLVLiseccsgkEL----LHSLIDRFRYSEDDVVAYIV-QILQGLD 3408
Cdd:cd07834     46 ILREIKILRHLKHENIIGLLDILRPPSpeefndvYIVT--------ELmetdLHKVIKSPQPLTDDHIQYFLyQILRGLK 117

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1207186029 3409 YLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLKQF-SPPIGTLDYMSPE-MLKGDVVGPPADIWSIG 3482
Cdd:cd07834    118 YLHSAGVIHRDLKPSNILVNSNCDLKICDFGLARGVDPDEDKGFlTEYVVTRWYRAPElLLSSKKYTKAIDIWSVG 193

Catalytic domain of Yeast Protein Kinase 1-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of fungal proteins with similarity to the AGC STKs, Saccharomyces cerevisiae YPK1 and Schizosaccharomyces pombe Gad8p. YPK1 is required for cell growth and acts as a downstream kinase in the sphingolipid-mediated signaling pathway of yeast. It also plays a role in efficient endocytosis and in the maintenance of cell wall integrity. Gad8p is a downstream target of Tor1p, the fission yeast homolog of mTOR. It plays a role in cell growth and sexual development. The YPK1-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270737 [Multi-domain] Cd Length: 313 Bit Score: 85.32 E-value: 4.79e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAK-IVPYEPESKQTV---LQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLH 3383
Cdd:cd05585      4 KGSFGKVMQVRKKDTSRIYALKtIRKAHIVSRSEVthtLAERTVLAQVDCPFIVPLKFSFQSPEKLYLVLAFINGGELFH 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3384 SLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQtFNPLFLKQFSPPIGTLDYMS 3463
Cdd:cd05585     84 HLQREGRFDLSRARFYTAELLCALECLHKFNVIYRDLKPENILLDYTGHIALCDFGLCK-LNMKDDDKTNTFCGTPEYLA 162

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....
gi 1207186029 3464 PEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARI 3507
Cdd:cd05585    163 PELLLGHGYTKAVDWWTLGVLLYEMLTGLPPFYDENTNEMYRKI 206

Catalytic domain of the Serine/Threonine Kinase, Nuclear Dbf2-Related kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NDR1 (also called STK38) plays a role in proper centrosome duplication. It is highly expressed in thymus, muscle, lung and spleen. It is not an essential protein because mice deficient of NDR1 remain viable and fertile. However, these mice develop T-cell lymphomas and appear to be hypersenstive to carcinogenic treatment. NDR1 appears to also act as a tumor suppressor. NDR kinase contains an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Like many other AGC kinases, NDR kinase requires phosphorylation at two sites, the activation loop (A-loop) and the hydrophobic motif (HM), for activity. The NDR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270777 [Multi-domain] Cd Length: 376 Bit Score: 86.25 E-value: 4.88e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1666 KEIGRGAFSYVKRVIQKAGKLEYAAKFIsarakRKASALRELNIlSHLDHER-----------ILYFHDAFEKKNAVIII 1734
Cdd:cd05628      7 KVIGRGAFGEVRLVQKKDTGHVYAMKIL-----RKADMLEKEQV-GHIRAERdilveadslwvVKMFYSFQDKLNLYLIM 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1735 TELCHEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDFG------------ 1802
Cdd:cd05628     81 EFLPGGDMMTLLMKKDTLTEEETQFYIAETVLAIDSIHQLGFIHRDIKPDNLLL--DSKGHVKLSDFGlctglkkahrte 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1803 ---NAVKFMPD---------------------EAQYCKYGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAG 1858
Cdd:cd05628    159 fyrNLNHSLPSdftfqnmnskrkaetwkrnrrQLAFSTVGTPDYIAPEVFMQTGYNKLCDWWSLGVIMYEMLIGYPPFCS 238

                          250
                   ....*....|...
gi 1207186029 1859 ENDRSSVLNIRNY 1871
Cdd:cd05628    239 ETPQETYKKVMNW 251

Catalytic domain of Cyclin-Dependent protein Kinase 8-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDK8, CDC2L6, and similar proteins. CDK8 functions as a negative or positive regulator of transcription, depending on the scenario. Together with its regulator, cyclin C, it reversibly associates with the multi-subunit core Mediator complex, a cofactor that is involved in regulating RNA polymerase II-dependent transcription. CDC2L6 also associates with Mediator in complexes lacking CDK8. In VP16-dependent transcriptional activation, CDK8 and CDC2L6 exerts opposing effects by positive and negative regulation, respectively, in similar conditions. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK8-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270834 [Multi-domain] Cd Length: 316 Bit Score: 85.03 E-value: 5.12e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKL--EYAAKFISARAKRKA----SALRELNILSHLDHERILYFHDAFEKKN--AVII 1733
Cdd:cd07842      2 YEIEGCIGRGTYGRVYKAKRKNGKDgkEYAIKKFKGDKEQYTgisqSACREIALLRELKHENVVSLVEVFLEHAdkSVYL 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1734 ITELCHEELLD-----RLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNIL-MADHSSD-QIRICDFGNAVK 1806
Cdd:cd07842     82 LFDYAEHDLWQiikfhRQAKRVSIPPSMVKSLLWQILNGIHYLHSNWVLHRDLKPANILvMGEGPERgVVKIGDLGLARL 161

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1207186029 1807 FM-PDEAQYckYGTPEFV-----APEIV----NQTpvsKATDIWPIGVLTYLCLTGVSPFAGEND 1861
Cdd:cd07842    162 FNaPLKPLA--DLDPVVVtiwyrAPELLlgarHYT---KAIDIWAIGCIFAELLTLEPIFKGREA 221

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK2, also called beta-adrenergic receptor kinase (beta-ARK) or beta-ARK1, is important in regulating several cardiac receptor responses. It plays a role in cardiac development and in hypertension. Deletion of GRK2 in mice results in embryonic lethality, caused by hypoplasia of the ventricular myocardium. GRK2 also plays important roles in the liver (as a regulator of portal blood pressure), in immune cells, and in the nervous system. Altered GRK2 expression has been reported in several disorders including major depression, schizophrenia, bipolar disorder, and Parkinsonism. GRK2 contains an N-terminal RGS homology (RH) domain, a central catalytic domain, and C-terminal pleckstrin homology (PH) domain that mediates PIP2 and G protein betagamma-subunit translocation to the membrane. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. TheGRK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271125 [Multi-domain] Cd Length: 321 Bit Score: 85.10 E-value: 5.41e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3307 ARGRFGVIRECRENATGNLYMAKIVP---YEPESKQTVLQEYDILKSLHHEK----IMALHEAYVTPRYLVLISECCSGK 3379
Cdd:cd14223      9 GRGGFGEVYGCRKADTGKMYAMKCLDkkrIKMKQGETLALNERIMLSLVSTGdcpfIVCMSYAFHTPDKLSFILDLMNGG 88

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3380 ELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPlflKQFSPPIGTL 3459
Cdd:cd14223     89 DLHYHLSQHGVFSEAEMRFYAAEIILGLEHMHSRFVVYRDLKPANILLDEFGHVRISDLGLACDFSK---KKPHASVGTH 165

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|
gi 1207186029 3460 DYMSPEML-KGDVVGPPADIWSIGILTYIMLSGRLPFTEN 3498
Cdd:cd14223    166 GYMAPEVLqKGVAYDSSADWFSLGCMLFKLLRGHSPFRQH 205

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 2 or Heme-Regulated Inhibitor kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HRI (or EIF2AK1) contains an N-terminal regulatory heme-binding domain and a C-terminal catalytic kinase domain. It is suppressed under normal conditions by binding of the heme iron, and is activated during heme deficiency. It functions as a critical regulator that ensures balanced synthesis of globins and heme, in order to form stable hemoglobin during erythroid differentiation and maturation. HRI also protects cells and enhances survival under iron-deficient conditions. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. The HRI subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270951 [Multi-domain] Cd Length: 284 Bit Score: 84.48 E-value: 5.46e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASA---LRELNILSHLDHERILYFHDAF-EKKNAVIIIT-ELCHEEL 1742
Cdd:cd14049     14 LGKGGYGKVYKVRNKLDGQYYAIKKILIKKVTKRDCmkvLREVKVLAGLQHPNIVGYHTAWmEHVQLMLYIQmQLCELSL 93

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1743 LDRLTKKSTILESEIRSS--------------VRQLLEGINYLHQLDILHLDIKPDNILMadHSSD-QIRICDFGNAVK- 1806
Cdd:cd14049     94 WDWIVERNKRPCEEEFKSapytpvdvdvttkiLQQLLEGVTYIHSMGIVHRDLKPRNIFL--HGSDiHVRIGDFGLACPd 171

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1807 -FMPDEAQYCK-----------YGTPEFVAPEIVNQTPVSKATDIWPIGVLTylcLTGVSPFAGENDRSSVL-NIRNYNV 1873
Cdd:cd14049    172 iLQDGNDSTTMsrlnglthtsgVGTCLYAAPEQLEGSHYDFKSDMYSIGVIL---LELFQPFGTEMERAEVLtQLRNGQI 248

                          250       260       270
                   ....*....|....*....|....*....|....*....
gi 1207186029 1874 AfeesmfTDLCHEAKGFV--IKLLVADR--LRPDANECL 1908
Cdd:cd14049    249 P------KSLCKRWPVQAkyIKLLTSTEpsERPSASQLL 281

Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase Pho85; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Pho85 is a multifunctional CDK in yeast. It is regulated by 10 different cyclins (Pcls) and plays a role in G1 progression, cell polarity, phosphate and glycogen metabolism, gene expression, and in signaling changes in the environment. It is not essential for yeast viability and is the functional homolog of mammalian CDK5, which plays a role in central nervous system development. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The Pho85 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143341 [Multi-domain] Cd Length: 284 Bit Score: 84.45 E-value: 5.62e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1701 ASALRELNILSHLDHERILYFHDAFEKKNAVIIITELCHEEL---LDRLTKKSTILESEIRSSVRQLLEGINYLHQLDIL 1777
Cdd:cd07836     43 STAIREISLMKELKHENIVRLHDVIHTENKLMLVFEYMDKDLkkyMDTHGVRGALDPNTVKSFTYQLLKGIAFCHENRVL 122

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1778 HLDIKPDNILMadHSSDQIRICDFGNAVKF-MPDEAQYCKYGTPEFVAPEIVNQTPV-SKATDIWPIGVLTYLCLTGVSP 1855
Cdd:cd07836    123 HRDLKPQNLLI--NKRGELKLADFGLARAFgIPVNTFSNEVVTLWYRAPDVLLGSRTySTSIDIWSVGCIMAEMITGRPL 200

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1856 FAGENDRSSVLNIRN------------------YNVAFEESMFTDLCH---EAKGFVIKLLvaDRL-------RPDANEC 1907
Cdd:cd07836    201 FPGTNNEDQLLKIFRimgtptestwpgisqlpeYKPTFPRYPPQDLQQlfpHADPLGIDLL--HRLlqlnpelRISAHDA 278


                   ....*.
gi 1207186029 1908 LRHPWF 1913
Cdd:cd07836    279 LQHPWF 284

Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMP-activated protein kinase (AMPK). CaMKK1, also called CaMKK alpha, is involved in the regulation of glucose uptake in skeletal muscles, independently of AMPK and PKB activation. It also play roles in learning and memory. Studies on CaMKK1 knockout mice reveal deficits in fear conditioning. The CaMKK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271102 [Multi-domain] Cd Length: 284 Bit Score: 84.23 E-value: 6.23e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIV-----------PYEP-----------ESKQT-----VLQEYDILKSLH 3352
Cdd:cd14200      2 YKLQSEIGKGSYGVVKLAYNESDDKYYAMKVLskkkllkqygfPRRPpprgskaaqgeQAKPLaplerVYQEIAILKKLD 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3353 HEKIMALHEAYVTPrylvliseccsGKELLHSLIDRFR------------YSEDDVVAYIVQILQGLDYLHSRRILHLDI 3420
Cdd:cd14200     82 HVNIVKLIEVLDDP-----------AEDNLYMVFDLLRkgpvmevpsdkpFSEDQARLYFRDIVLGIEYLHYQKIVHRDI 150

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3421 KPENIIVTYMNVVKIIDFGSAQTF--NPlflKQFSPPIGTLDYMSPEMLKGD---VVGPPADIWSIGILTYIMLSGRLPF 3495
Cdd:cd14200    151 KPSNLLLGDDGHVKIADFGVSNQFegND---ALLSSTAGTPAFMAPETLSDSgqsFSGKALDVWAMGVTLYCFVYGKCPF 227

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1207186029 3496 TENDPAETEARIQAAKFDLSKLYQnVSQSASLFIKKILCSYPWARPTIKDCFTNSWL 3552
Cdd:cd14200    228 IDEFILALHNKIKNKPVEFPEEPE-ISEELKDLILKMLDKNPETRITVPEIKVHPWV 283

Catalytic domain of Serine/Threonine Kinase 25 (also called Yeast Sps1/Ste20-related kinase 1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK25 is also called Ste20/oxidant stress response kinase 1 (SOK1) or yeast Sps1/Ste20-related kinase 1 (YSK1). It is localized in the Golgi apparatus through its interaction with the Golgi matrix protein GM130. It may be involved in the regulation of cell migration and polarization. STK25 binds and phosphorylates CCM3 (cerebral cavernous malformation 3), also called PCD10 (programmed cell death 10), and may play a role in apoptosis. Human STK25 is a candidate gene responsible for pseudopseudohypoparathyroidism (PPHP), a disease that shares features with the Albright hereditary osteodystrophy (AHO) phenotype. The STK25 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270810 [Multi-domain] Cd Length: 277 Bit Score: 83.95 E-value: 6.35e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKA--SALRELNILSHLDHERILYFHDAFEKKNAVIIITE-LCHEELLD 1744
Cdd:cd06642     12 IGKGSFGEVYKGIDNRTKEVVAIKIIDLEEAEDEieDIQQEITVLSQCDSPYITRYYGSYLKGTKLWIIMEyLGGGSALD 91

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1745 rLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSdqIRICDFGNAVKFMPDEAQYCKY-GTPEFV 1823
Cdd:cd06642     92 -LLKPGPLEETYIATILREILKGLDYLHSERKIHRDIKAANVLLSEQGD--VKLADFGVAGQLTDTQIKRNTFvGTPFWM 168

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1824 APEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDlchEAKGFVIKLLVAD-RLRP 1902
Cdd:cd06642    169 APEVIKQSAYDFKADIWSLGITAIELAKGEPPNSDLHPMRVLFLIPKNSPPTLEGQHSK---PFKEFVEACLNKDpRFRP 245

                          250       260       270
                   ....*....|....*....|....*....|....*
gi 1207186029 1903 DANECLRHPWFKTLNKGKSISTESLKKFlsrRKWQ 1937
Cdd:cd06642    246 TAKELLKHKFITRYTKKTSFLTELIDRY---KRWK 277

Catalytic domain of the Serine/Threonine Kinases, Mixed Lineage Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Mammals have four MLKs (MLK1-4), mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The MLK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270963 [Multi-domain] Cd Length: 258 Bit Score: 83.60 E-value: 6.66e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3328 AKIVPYEPESK--QTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLHSLIDRfRYSEDDVVAYIVQILQ 3405
Cdd:cd14061     25 ARQDPDEDISVtlENVRQEARLFWMLRHPNIIALRGVCLQPPNLCLVMEYARGGALNRVLAGR-KIPPHVLVDWAIQIAR 103

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3406 GLDYLHSRR---ILHLDIKPENIIVTYM--------NVVKIIDFGSAQTfnpLFLKQFSPPIGTLDYMSPEMLKGDVVGP 3474
Cdd:cd14061    104 GMNYLHNEApvpIIHRDLKSSNILILEAienedlenKTLKITDFGLARE---WHKTTRMSAAGTYAWMAPEVIKSSTFSK 180

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3475 PADIWSIGILTYIMLSGRLPFTENDPaeteariqaakfdLSKLYQNVSQSASLFIKKIlCSYPWARpTIKDCftnsWLQD 3554
Cdd:cd14061    181 ASDVWSYGVLLWELLTGEVPYKGIDG-------------LAVAYGVAVNKLTLPIPST-CPEPFAQ-LMKDC----WQPD 241


                   ..
gi 1207186029 3555 AY 3556
Cdd:cd14061    242 PH 243

Catalytic domain of the Serine/Threonine Kinase, p38alpha Mitogen-Activated Protein Kinase (also called MAPK14); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38alpha/MAPK14 is expressed in most tissues and is the major isoform involved in the immune and inflammatory response. It is the central p38 MAPK involved in myogenesis. It plays a role in regulating cell cycle check-point transition and promoting cell differentiation. p38alpha also regulates cell proliferation and death through crosstalk with the JNK pathway. Its substrates include MAPK activated protein kinase 2 (MK2), MK5, and the transcription factors ATF2 and Mitf. p38 kinases MAPKs, serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38alpha subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143382 [Multi-domain] Cd Length: 345 Bit Score: 85.09 E-value: 7.03e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1660 DYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFIS------ARAKRkasALRELNILSHLDHERILYFHDAF------EK 1727
Cdd:cd07877     17 ERYQNLSPVGSGAYGSVCAAFDTKTGLRVAVKKLSrpfqsiIHAKR---TYRELRLLKHMKHENVIGLLDVFtparslEE 93

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1728 KNAVIIITELCHEELlDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNilMADHSSDQIRICDFGNAVKf 1807
Cdd:cd07877     94 FNDVYLVTHLMGADL-NNIVKCQKLTDDHVQFLIYQILRGLKYIHSADIIHRDLKPSN--LAVNEDCELKILDFGLARH- 169

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1808 mPDEAQYCKYGTPEFVAPEI-VNQTPVSKATDIWPIGVLTYLCLTGVSPFAGEN--------------------DRSSVL 1866
Cdd:cd07877    170 -TDDEMTGYVATRWYRAPEImLNWMHYNQTVDIWSVGCIMAELLTGRTLFPGTDhidqlklilrlvgtpgaellKKISSE 248

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1207186029 1867 NIRNYNVAFE-------ESMFTDLCHEAKGFVIKLLVADR-LRPDANECLRHPWF 1913
Cdd:cd07877    249 SARNYIQSLTqmpkmnfANVFIGANPLAVDLLEKMLVLDSdKRITAAQALAHAYF 303

Catalytic domain of the Serine/Threonine Kinase, PFTAIRE-2 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PFTAIRE-2 is also referred to as ALS2CR7 (amyotrophic lateral sclerosis 2 (juvenile) chromosome region candidate 7). It may be associated with amyotrophic lateral sclerosis 2 (ALS2), an autosomal recessive form of juvenile ALS. The function of PFTAIRE-2 is not yet known. It shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PFTAIRE-2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270852 [Multi-domain] Cd Length: 286 Bit Score: 83.86 E-value: 7.42e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1666 KEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKA--SALRELNILSHLDHERILYFHDAFEKKNAVIIITELCHEELL 1743
Cdd:cd07870      6 EKLGEGSYATVYKGISRINGQLVALKVISMKTEEGVpfTAIREASLLKGLKHANIVLLHDIIHTKETLTFVFEYMHTDLA 85

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1744 DRLTKKSTILES-EIRSSVRQLLEGINYLHQLDILHLDIKPDNILMAdhSSDQIRICDFGNA-VKFMPDEAQYCKYGTPE 1821
Cdd:cd07870     86 QYMIQHPGGLHPyNVRLFMFQLLRGLAYIHGQHILHRDLKPQNLLIS--YLGELKLADFGLArAKSIPSQTYSSEVVTLW 163

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|.
gi 1207186029 1822 FVAPEIV-NQTPVSKATDIWPIGVLTYLCLTGVSPFAGEND 1861
Cdd:cd07870    164 YRPPDVLlGATDYSSALDIWGAGCIFIEMLQGQPAFPGVSD 204

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C delta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-delta plays a role in cell cycle regulation and programmed cell death in many cell types. It slows down cell proliferation, inducing cell cycle arrest and enhancing cell differentiation. PKC-delta is also involved in the regulation of transcription as well as immune and inflammatory responses. It plays a central role in the genotoxic stress response that leads to DNA damaged-induced apoptosis. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC-delta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173710 [Multi-domain] Cd Length: 316 Bit Score: 84.61 E-value: 7.97e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKIVpyepeSKQTVLQEYDILKSLHHEKIMAL----------HEAYVTPRYLVLISECCS 3377
Cdd:cd05620      5 KGSFGKVLLAELKGKGEYFAVKAL-----KKDVVLIDDDVECTMVEKRVLALawenpflthlYCTFQTKEHLFFVMEFLN 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3378 GKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTfNPLFLKQFSPPIG 3457
Cdd:cd05620     80 GGDLMFHIQDKGRFDLYRATFYAAEIVCGLQFLHSKGIIYRDLKLDNVMLDRDGHIKIADFGMCKE-NVFGDNRASTFCG 158

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*
gi 1207186029 3458 TLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAE 3502
Cdd:cd05620    159 TPDYIAPEILQGLKYTFSVDWWSFGVLLYEMLIGQSPFHGDDEDE 203

Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RIP kinases serve as essential sensors of cellular stress. They are involved in regulating NF-kappaB and MAPK signaling, and are implicated in mediating cellular processes such as apoptosis, necroptosis, differentiation, and survival. RIP kinases contain a homologous N-terminal kinase domain and varying C-terminal domains. Higher vertebrates contain multiple RIP kinases, with mammals harboring at least five members. RIP1 and RIP2 harbor C-terminal domains from the Death domain (DD) superfamily while RIP4 contains ankyrin (ANK) repeats. RIP3 contain a RIP homotypic interaction motif (RHIM) that facilitates binding to RIP1. RIP1 and RIP3 are important in apoptosis and necroptosis, while RIP2 and RIP4 play roles in keratinocyte differentiation and inflammatory immune responses. The RIP subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270880 [Multi-domain] Cd Length: 263 Bit Score: 83.27 E-value: 8.64e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKIVPYEP---ESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSG---KEL 3381
Cdd:cd13978      3 SGGFGTVSKARHVSWFGMVAIKCLHSSPnciEERKALLKEAEKMERARHSYVLPLLGVCVERRSLGLVMEYMENgslKSL 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3382 LHSLID------RFRYseddvvayIVQILQGLDYLH--SRRILHLDIKPENIIVTYMNVVKIIDFGSAQtFNPLFLKQ-- 3451
Cdd:cd13978     83 LEREIQdvpwslRFRI--------IHEIALGMNFLHnmDPPLLHHDLKPENILLDNHFHVKISDFGLSK-LGMKSISAnr 153

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3452 --FSPPI-GTLDYMSPEMLKgDVVGPP---ADIWSIGILTYIMLSGRLPFtENdpAETEARIQAAKF--------DLSKL 3517
Cdd:cd13978    154 rrGTENLgGTPIYMAPEAFD-DFNKKPtskSDVYSFAIVIWAVLTRKEPF-EN--AINPLLIMQIVSkgdrpsldDIGRL 229

                          250       260       270
                   ....*....|....*....|....*....|...
gi 1207186029 3518 YQN--VSQSASLFIKkilC--SYPWARPTIKDC 3546
Cdd:cd13978    230 KQIenVQELISLMIR---CwdGNPDARPTFLEC 259

N-terminal Catalytic domain of the Serine/Threonine Kinase, Class IIIA myosin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Class IIIA myosin is highly expressed in retina and in inner ear hair cells. It is localized to the distal ends of actin-bundled structures. Mutations in human myosin IIIA are responsible for progressive nonsyndromic hearing loss. Human myosin IIIA possesses ATPase and kinase activities, and the ability to move actin filaments in a motility assay. It may function as a cellular transporter capable of moving along actin bundles in sensory cells. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain. Class III myosins may play an important role in maintaining the structural integrity of photoreceptor cell microvilli. In photoreceptor cells, they may also function as cargo carriers during light-dependent translocation of proteins such as transducin and arrestin. The class III myosin subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 132969 [Multi-domain] Cd Length: 286 Bit Score: 83.91 E-value: 8.64e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3296 PQKPYTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPESKQTVLQEYDILKSLH-HEKIMALHEAY-----VTPRYL 3369
Cdd:cd06638     16 PSDTWEIIETIGKGTYGKVFKVLNKKNGSKAAVKILDPIHDIDEEIEAEYNILKALSdHPNVVKFYGMYykkdvKNGDQL 95

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3370 VLISECCSG---KELLHSLIDRFRYSEDDVVAYIV-QILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFG-SAQTF 3444
Cdd:cd06638     96 WLVLELCNGgsvTDLVKGFLKRGERMEEPIIAYILhEALMGLQHLHVNKTIHRDVKGNNILLTTEGGVKLVDFGvSAQLT 175

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3445 NPLFLKQFSppIGTLDYMSPEMLKGD-----VVGPPADIWSIGILTYIMLSGRLPFTENDPaeTEARIQAAKFDLSKLYQ 3519
Cdd:cd06638    176 STRLRRNTS--VGTPFWMAPEVIACEqqldsTYDARCDVWSLGITAIELGDGDPPLADLHP--MRALFKIPRNPPPTLHQ 251

                          250       260
                   ....*....|....*....|....*...
gi 1207186029 3520 NVSQSASL--FIKKILCSYPWARPTIKD 3545
Cdd:cd06638    252 PELWSNEFndFIRKCLTKDYEKRPTVSD 279

Catalytic domain of the Serine/Threonine kinase, NF-kappaB Inducing Kinase (NIK); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NIK, also called mitogen activated protein kinase kinase kinase 14 (MAP3K14), phosphorylates and activates Inhibitor of NF-KappaB Kinase (IKK) alpha, which is a regulator of NF-kB proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. NIK is essential in the IKKalpha-mediated non-canonical NF-kB signaling pathway, in which IKKalpha processes the IkB-like C-terminus of NF-kB2/p100 to produce p52, allowing the p52/RelB dimer to migrate to the nucleus where it regulates gene transcription. NIK also plays an important role in Toll-like receptor 7/9 signaling cascades. The NIK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270893 [Multi-domain] Cd Length: 268 Bit Score: 83.33 E-value: 8.76e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1665 HKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRkasaLRELNILSHLDHERILYFHDAFEKKNAVIIITELCHEELLD 1744
Cdd:cd13991     11 QLRIGRGSFGEVHRMEDKQTGFQCAVKKVRLEVFR----AEELMACAGLTSPRVVPLYGAVREGPWVNIFMDLKEGGSLG 86

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1745 RLTKKSTIL-ESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSDQIrICDFGNAVKFMPDEAQYCKY------ 1817
Cdd:cd13991     87 QLIKEQGCLpEDRALHYLGQALEGLEYLHSRKILHGDVKADNVLLSSDGSDAF-LCDFGHAECLDPDGLGKSLFtgdyip 165

                          170       180       190
                   ....*....|....*....|....*....|....*....
gi 1207186029 1818 GTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPF 1856
Cdd:cd13991    166 GTETHMAPEVVLGKPCDAKVDVWSSCCMMLHMLNGCHPW 204

Catalytic domain of the Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGKs are activated by insulin and growth factors via phosphoinositide 3-kinase and PDK1. They activate ion channels, ion carriers, and the Na-K-ATPase, as well as regulate the activity of enzymes and transcription factors. SGKs play important roles in transport, hormone release, neuroexcitability, cell proliferation, and apoptosis. There are three isoforms of SGK, named SGK1, SGK2, and SGK3 (also called cytokine-independent survival kinase CISK). The SGK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270727 [Multi-domain] Cd Length: 323 Bit Score: 84.68 E-value: 9.07e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1666 KEIGRGAFSYVKRVIQKAGKLEYAAKFISARA--KRKASA--LRELNIL-SHLDHERILYFHDAFEKKNAVIIITELCHE 1740
Cdd:cd05575      1 KVIGKGSFGKVLLARHKAEGKLYAVKVLQKKAilKRNEVKhiMAERNVLlKNVKHPFLVGLHYSFQTKDKLYFVLDYVNG 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1741 -ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDFGNAVKFMPDE---AQYCk 1816
Cdd:cd05575     81 gELFFHLQRERHFPEPRARFYAAEIASALGYLHSLNIIYRDLKPENILL--DSQGHVVLTDFGLCKEGIEPSdttSTFC- 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1817 yGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTdlchEAKGFVIKLLV 1896
Cdd:cd05575    158 -GTPEYLAPEVLRKQPYDRTVDWWCLGAVLYEMLYGLPPFYSRDTAEMYDNILHKPLRLRTNVSP----SARDLLEGLLQ 232

                          250       260
                   ....*....|....*....|....*.
gi 1207186029 1897 ADRLR-----PDANECLRHPWFKTLN 1917
Cdd:cd05575    233 KDRTKrlgsgNDFLEIKNHSFFRPIN 258

Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK3 is a mitogen-activated protein kinase kinase kinases (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLK3 activates multiple MAPK pathways and plays a role in apoptosis, proliferation, migration, and differentiation, depending on the cellular context. It is highly expressed in breast cancer cells and its signaling through c-Jun N-terminal kinase has been implicated in the migration, invasion, and malignancy of cancer cells. MLK3 also functions as a negative regulator of Inhibitor of Nuclear Factor-KappaB Kinase (IKK) and consequently, it also impacts inflammation and immunity. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation.The MLK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271049 [Multi-domain] Cd Length: 267 Bit Score: 83.15 E-value: 9.32e-17

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3309 GRFGVIRecRENATGNLYMAKIVPYEPE-----SKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLH 3383
Cdd:cd14147     14 GGFGKVY--RGSWRGELVAVKAARQDPDedisvTAESVRQEARLFAMLAHPNIIALKAVCLEEPNLCLVMEYAAGGPLSR 91

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3384 SLIDRfRYSEDDVVAYIVQILQGLDYLHSRRI---LHLDIKPENIIVTYMNV--------VKIIDFGSAQTFNPLflKQF 3452
Cdd:cd14147     92 ALAGR-RVPPHVLVNWAVQIARGMHYLHCEALvpvIHRDLKSNNILLLQPIEnddmehktLKITDFGLAREWHKT--TQM 168

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|...
gi 1207186029 3453 SPPiGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPF 3495
Cdd:cd14147    169 SAA-GTYAWMAPEVIKASTFSKGSDVWSFGVLLWELLTGEVPY 210

Catalytic domain of the Protein Serine/Threonine Kinase, Serum- and Glucocorticoid-induced Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SGK1 is ubiquitously expressed and is under transcriptional control of numerous stimuli including cell stress (cell shrinkage), serum, hormones (gluco- and mineralocorticoids), gonadotropins, growth factors, interleukin-6, and other cytokines. It plays roles in sodium retention and potassium elimination in the kidney, nutrient transport, salt sensitivity, memory consolidation, and cardiac repolarization. A common SGK1 variant is associated with increased blood pressure and body weight. SGK1 may also contribute to tumor growth, neurodegeneration, fibrosing disease, and ischemia. The SGK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270753 [Multi-domain] Cd Length: 339 Bit Score: 84.68 E-value: 1.06e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3282 PIGKPGDstlrqgvpqkpYTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEP-----ESKQTVLQEYDILKSLHHEKI 3356
Cdd:cd05602      2 PHAKPSD-----------FHFLKVIGKGSFGKVLLARHKSDEKFYAVKVLQKKAilkkkEEKHIMSERNVLLKNVKHPFL 70

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3357 MALHEAYVTPRYLVLISECCSGKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKII 3436
Cdd:cd05602     71 VGLHFSFQTTDKLYFVLDYINGGELFYHLQRERCFLEPRARFYAAEIASALGYLHSLNIVYRDLKPENILLDSQGHIVLT 150

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3437 DFGSAQTfNPLFLKQFSPPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLSK 3516
Cdd:cd05602    151 DFGLCKE-NIEPNGTTSTFCGTPEYLAPEVLHKQPYDRTVDWWCLGAVLYEMLYGLPPFYSRNTAEMYDNILNKPLQLKP 229

                          250       260       270
                   ....*....|....*....|....*....|..
gi 1207186029 3517 lyqNVSQSASLFIKKILCSYPWARPTIKDCFT 3548
Cdd:cd05602    230 ---NITNSARHLLEGLLQKDRTKRLGAKDDFT 258

Catalytic domain of the Serine/Threonine Kinase, PFTAIRE-2 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PFTAIRE-2 is also referred to as ALS2CR7 (amyotrophic lateral sclerosis 2 (juvenile) chromosome region candidate 7). It may be associated with amyotrophic lateral sclerosis 2 (ALS2), an autosomal recessive form of juvenile ALS. The function of PFTAIRE-2 is not yet known. It shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PFTAIRE-2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270852 [Multi-domain] Cd Length: 286 Bit Score: 83.47 E-value: 1.10e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPESKQ--TVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISEccs 3377
Cdd:cd07870      2 YLNLEKLGEGSYATVYKGISRINGQLVALKVISMKTEEGVpfTAIREASLLKGLKHANIVLLHDIIHTKETLTFVFE--- 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3378 gkeLLHSLIDRFRYSED------DVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTfNPLFLKQ 3451
Cdd:cd07870     79 ---YMHTDLAQYMIQHPgglhpyNVRLFMFQLLRGLAYIHGQHILHRDLKPQNLLISYLGELKLADFGLARA-KSIPSQT 154

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1207186029 3452 FSPPIGTLDYMSPEMLKGDV-VGPPADIWSIGILTYIMLSGR--LPFTENDPAETE 3504
Cdd:cd07870    155 YSSEVVTLWYRPPDVLLGATdYSSALDIWGAGCIFIEMLQGQpaFPGVSDVFEQLE 210

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 77.68 E-value: 1.11e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1029 IIRPVRDVMVKAGETALFECHVIGPQDTDVDWLSDGKLIQPAlLNCKMHFDGKRCRLLLNSVHEDDSGTYTCKLSTAKEE 1108
Cdd:pfam07679    3 FTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSS-DRFKVTYEGGTYTLTISNVQPDDSGKYTCVATNSAGE 81


                   ....*....
gi 1207186029 1109 LTSSAKLKV 1117
Cdd:pfam07679   82 AEASAELTV 90

N-terminal Catalytic domain of Class III myosin-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Class III myosins are motor proteins with an N-terminal kinase catalytic domain and a C-terminal actin-binding motor domain. Class III myosins are present in the photoreceptors of invertebrates and vertebrates and in the auditory hair cells of mammals. The kinase domain of myosin III can phosphorylate several cytoskeletal proteins, conventional myosin regulatory light chains, and can autophosphorylate the C-terminal motor domain. Myosin III may play an important role in maintaining the structural integrity of photoreceptor cell microvilli. It may also function as a cargo carrier during light-dependent translocation, in photoreceptor cells, of proteins such as transducin and arrestin. The Drosophila class III myosin, called NinaC (Neither inactivation nor afterpotential protein C), is critical in normal adaptation and termination of photoresponse. Vertebrates contain two isoforms of class III myosin, IIIA and IIIB. This subfamily also includes mammalian NIK-like embryo-specific kinase (NESK), Traf2- and Nck-interacting kinase (TNIK), and mitogen-activated protein kinase (MAPK) kinase kinase kinase 4/6. MAP4Ks are involved in some MAPK signaling pathways by activating a MAPK kinase kinase. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. The class III myosin-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270785 [Multi-domain] Cd Length: 275 Bit Score: 83.12 E-value: 1.15e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1659 TDYYDVHKEIGRGAFSYVKRVIQ-KAGKLeYAAKFISARAKRKASALRELNILSHL-DHERILYFHDAFEKKNAVI---- 1732
Cdd:cd06608      5 AGIFELVEVIGEGTYGKVYKARHkKTGQL-AAIKIMDIIEDEEEEIKLEINILRKFsNHPNIATFYGAFIKKDPPGgddq 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1733 --IITELCH----EELLDRLTKKSTILESEIRSSV-RQLLEGINYLHQLDILHLDIKPDNILMADhsSDQIRICDFGnaV 1805
Cdd:cd06608     84 lwLVMEYCGggsvTDLVKGLRKKGKRLKEEWIAYIlRETLRGLAYLHENKVIHRDIKGQNILLTE--EAEVKLVDFG--V 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1806 KFMPDEAQYCK---YGTPEFVAPEIV--NQTPVSKAT---DIWPIGVLTYLCLTGVSPFAGEN-DRSSVLNIRNYNVAFE 1876
Cdd:cd06608    160 SAQLDSTLGRRntfIGTPYWMAPEVIacDQQPDASYDarcDVWSLGITAIELADGKPPLCDMHpMRALFKIPRNPPPTLK 239

                          250       260       270
                   ....*....|....*....|....*....|....*..
gi 1207186029 1877 ESmfTDLCHEAKGFVIKLLVAD-RLRPDANECLRHPW 1912
Cdd:cd06608    240 SP--EKWSKEFNDFISECLIKNyEQRPFTEELLEHPF 274

Catalytic domain of G protein-coupled Receptor Kinase 4-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of the GRK4-like group include GRK4, GRK5, GRK6, and similar GRKs. They contain an N-terminal RGS homology (RH) domain and a catalytic domain, but lack a G protein betagamma-subunit binding domain. They are localized to the plasma membrane through post-translational lipid modification or direct binding to PIP2. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK4-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270756 [Multi-domain] Cd Length: 285 Bit Score: 83.56 E-value: 1.18e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYVKRVIQKA-GKLeYAAKFISAR--AKRK--ASALRELNILSHLDHERILYFHDAFEKKNAV-IIITELCHEE 1741
Cdd:cd05605      8 LGKGGFGEVCACQVRAtGKM-YACKKLEKKriKKRKgeAMALNEKQILEKVNSRFVVSLAYAYETKDALcLVLTIMNGGD 86

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1742 LLDRL--TKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSsdQIRICDFGNAVKFMPDEAQYCKYGT 1819
Cdd:cd05605     87 LKFHIynMGNPGFEEERAVFYAAEITCGLEHLHSERIVYRDLKPENILLDDHG--HVRISDLGLAVEIPEGETIRGRVGT 164

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1820 PEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAG--------ENDRSSVLNIRNYNVAFEEsmftdlchEAKGFV 1891
Cdd:cd05605    165 VGYMAPEVVKNERYTFSPDWWGLGCLIYEMIEGQAPFRArkekvkreEVDRRVKEDQEEYSEKFSE--------EAKSIC 236

                          250       260       270
                   ....*....|....*....|....*....|..
gi 1207186029 1892 IKLLVAD---RL---RPDANECLRHPWFKTLN 1917
Cdd:cd05605    237 SQLLQKDpktRLgcrGEGAEDVKSHPFFKSIN 268

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 77.68 E-value: 1.18e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  928 PAFLAVIGDQSVIEGQEVTMSVLVTGQPKPMLYWLRDRVTIKTGTRHIVQEtEEGNFEMIIKSAQRSDTGVYTCKIINEY 1007
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRFKVTY-EGGTYTLTISNVQPDDSGKYTCVATNSA 79

                           90
                   ....*....|.
gi 1207186029 1008 GTKQCEGKLEV 1018
Cdd:pfam07679   80 GEAEASAELTV 90

Catalytic domain of Cyclin-Dependent protein Kinase 8-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDK8, CDC2L6, and similar proteins. CDK8 functions as a negative or positive regulator of transcription, depending on the scenario. Together with its regulator, cyclin C, it reversibly associates with the multi-subunit core Mediator complex, a cofactor that is involved in regulating RNA polymerase II-dependent transcription. CDC2L6 also associates with Mediator in complexes lacking CDK8. In VP16-dependent transcriptional activation, CDK8 and CDC2L6 exerts opposing effects by positive and negative regulation, respectively, in similar conditions. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK8-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270834 [Multi-domain] Cd Length: 316 Bit Score: 83.87 E-value: 1.19e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECR--ENATGNLYMAKivPYEPESKQTV------LQEYDILKSLHHEKIMALHEAYVTP--RYL 3369
Cdd:cd07842      2 YEIEGCIGRGTYGRVYKAKrkNGKDGKEYAIK--KFKGDKEQYTgisqsaCREIALLRELKHENVVSLVEVFLEHadKSV 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3370 VLISECCSgKELLHslIDRFRYSEDDVV--AYIV-----QILQGLDYLHSRRILHLDIKPENIIVT----YMNVVKIIDF 3438
Cdd:cd07842     80 YLLFDYAE-HDLWQ--IIKFHRQAKRVSipPSMVksllwQILNGIHYLHSNWVLHRDLKPANILVMgegpERGVVKIGDL 156

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1207186029 3439 GSAQTFNPLfLKQFS---PPIGTLDYMSPEMLKGDVVGPPA-DIWSIGILTYIMLSGRLPF 3495
Cdd:cd07842    157 GLARLFNAP-LKPLAdldPVVVTIWYRAPELLLGARHYTKAiDIWAIGCIFAELLTLEPIF 216

Catalytic domain of the Serine/Threonine Kinase, beta-adrenergic receptor kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The beta-ARK group is composed of GRK2, GRK3, and similar proteins. GRK2 and GRK3 are both widely expressed in many tissues, although GRK2 is present at higher levels. They contain an N-terminal RGS homology (RH) domain, a central catalytic domain, and C-terminal pleckstrin homology (PH) domain that mediates PIP2 and G protein betagamma-subunit translocation to the membrane. GRK2 (also called beta-ARK or beta-ARK1) is important in regulating several cardiac receptor responses. It plays a role in cardiac development and in hypertension. Deletion of GRK2 in mice results in embryonic lethality, caused by hypoplasia of the ventricular myocardium. GRK2 also plays important roles in the liver (as a regulator of portal blood pressure), in immune cells, and in the nervous system. Altered GRK2 expression has been reported in several disorders including major depression, schizophrenia, bipolar disorder, and Parkinsonism. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The beta-ARK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270757 [Multi-domain] Cd Length: 279 Bit Score: 83.26 E-value: 1.22e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKIVpyepESKQTVLQEYDILKSlhHEKIM--------------ALHEAYVTPRYLVLIS 3373
Cdd:cd05606      4 RGGFGEVYGCRKADTGKMYAMKCL----DKKRIKMKQGETLAL--NERIMlslvstggdcpfivCMTYAFQTPDKLCFIL 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3374 ECCSGKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPlflKQFS 3453
Cdd:cd05606     78 DLMNGGDLHYHLSQHGVFSEAEMRFYAAEVILGLEHMHNRFIVYRDLKPANILLDEHGHVRISDLGLACDFSK---KKPH 154

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*.
gi 1207186029 3454 PPIGTLDYMSPEML-KGDVVGPPADIWSIGILTYIMLSGRLPFTEN 3498
Cdd:cd05606    155 ASVGTHGYMAPEVLqKGVAYDSSADWFSLGCMLYKLLKGHSPFRQH 200

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 3 or PKR-like Endoplasmic Reticulum Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PERK (or EIF2AK3) is a type-I ER transmembrane protein containing a luminal domain bound with the chaperone BiP under unstressed conditions and a cytoplasmic catalytic kinase domain. In response to the accumulation of misfolded or unfolded proteins in the ER, PERK is activated through the release of BiP, allowing it to dimerize and autophosphorylate. It functions as the central regulator of translational control during the Unfolded Protein Response (UPR) pathway. In addition to the eIF-2 alpha subunit, PERK also phosphorylates Nrf2, a leucine zipper transcription factor which regulates cellular redox status and promotes cell survival during the UPR. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. The PERK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270950 [Multi-domain] Cd Length: 281 Bit Score: 83.38 E-value: 1.23e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAK--IVPYEPESKQTVLQEYDILKSLHHEKIMALHEAYV-TPR----------YLVLISE 3374
Cdd:cd14048     16 RGGFGVVFEAKNKVDDCNYAVKriRLPNNELAREKVLREVRALAKLDHPGIVRYFNAWLeRPPegwqekmdevYLYIQMQ 95

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3375 CCSgKELLHSLIDRFRYSEDDVVAY----IVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFN---PL 3447
Cdd:cd14048     96 LCR-KENLKDWMNRRCTMESRELFVclniFKQIASAVEYLHSKGLIHRDLKPSNVFFSLDDVVKVGDFGLVTAMDqgePE 174

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3448 FLKQFSPP--------IGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLsgrLPF-TENDPAETEARIQAAKFDLsKLY 3518
Cdd:cd14048    175 QTVLTPMPayakhtgqVGTRLYMSPEQIHGNQYSEKVDIFALGLILFELI---YSFsTQMERIRTLTDVRKLKFPA-LFT 250

                          250       260       270
                   ....*....|....*....|....*....|.
gi 1207186029 3519 QNVSQSaSLFIKKILCSYPWARPTIKDCFTN 3549
Cdd:cd14048    251 NKYPEE-RDMVQQMLSPSPSERPEAHEVIEH 280

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 3 or PKR-like Endoplasmic Reticulum Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PERK (or EIF2AK3) is a type-I ER transmembrane protein containing a luminal domain bound with the chaperone BiP under unstressed conditions and a cytoplasmic catalytic kinase domain. In response to the accumulation of misfolded or unfolded proteins in the ER, PERK is activated through the release of BiP, allowing it to dimerize and autophosphorylate. It functions as the central regulator of translational control during the Unfolded Protein Response (UPR) pathway. In addition to the eIF-2 alpha subunit, PERK also phosphorylates Nrf2, a leucine zipper transcription factor which regulates cellular redox status and promotes cell survival during the UPR. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. The PERK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270950 [Multi-domain] Cd Length: 281 Bit Score: 83.00 E-value: 1.33e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1656 RRLTDYyDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISA--RAKRKASALRELNILSHLDHERILYFHDAF-------- 1725
Cdd:cd14048      3 RFLTDF-EPIQCLGRGGFGVVFEAKNKVDDCNYAVKRIRLpnNELAREKVLREVRALAKLDHPGIVRYFNAWlerppegw 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1726 -EKKNAVI--IITELCHEELLDRLTKKSTILESEIRSS----VRQLLEGINYLHQLDILHLDIKPDNILMadhSSDQ-IR 1797
Cdd:cd14048     82 qEKMDEVYlyIQMQLCRKENLKDWMNRRCTMESRELFVclniFKQIASAVEYLHSKGLIHRDLKPSNVFF---SLDDvVK 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1798 ICDFG------------NAVKFMPDEAQYCK-YGTPEFVAPEIVNQTPVSKATDIWPIG-VLTYLcltgVSPFAGENDRS 1863
Cdd:cd14048    159 VGDFGlvtamdqgepeqTVLTPMPAYAKHTGqVGTRLYMSPEQIHGNQYSEKVDIFALGlILFEL----IYSFSTQMERI 234

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*....
gi 1207186029 1864 SVL-NIRNYNVAfeeSMFTDLCHEAKGFVIKLLVADRL-RPDANECLRH 1910
Cdd:cd14048    235 RTLtDVRKLKFP---ALFTNKYPEERDMVQQMLSPSPSeRPEAHEVIEH 280

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. There are three PKB isoforms from different genes, PKB-alpha (or Akt1), PKB-beta (or Akt2), and PKB-gamma (or Akt3). PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. It is activated downstream of phosphoinositide 3-kinase (PI3K) and plays important roles in diverse cellular functions including cell survival, growth, proliferation, angiogenesis, motility, and migration. PKB also has a central role in a variety of human cancers, having been implicated in tumor initiation, progression, and metastasis. The PKB subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and PI3K.

Pssm-ID: 270723 [Multi-domain] Cd Length: 322 Bit Score: 83.94 E-value: 1.41e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1666 KEIGRGAFSYVKRVIQKAGKLEYAAKFISAR---AKRK-ASALRELNILSHLDHERILYFHDAFEKKNAVIIITELCHE- 1740
Cdd:cd05571      1 KVLGKGTFGKVILCREKATGELYAIKILKKEviiAKDEvAHTLTENRVLQNTRHPFLTSLKYSFQTNDRLCFVMEYVNGg 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1741 ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSsdQIRICDFG---NAVKFMPDEAQYCky 1817
Cdd:cd05571     81 ELFFHLSRERVFSEDRTRFYGAEIVLALGYLHSQGIVYRDLKLENLLLDKDG--HIKITDFGlckEEISYGATTKTFC-- 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1818 GTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFagendrssvlNIRNYNVAFEESMFTD------LCHEAKGFV 1891
Cdd:cd05571    157 GTPEYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPF----------YNRDHEVLFELILMEEvrfpstLSPEAKSLL 226

                          250       260       270
                   ....*....|....*....|....*....|..
gi 1207186029 1892 IKLLVAD---RL---RPDANECLRHPWFKTLN 1917
Cdd:cd05571    227 AGLLKKDpkkRLgggPRDAKEIMEHPFFASIN 258

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409564 [Multi-domain] Cd Length: 91 Bit Score: 77.24 E-value: 1.43e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  780 APVFEFPLQDTVASTGTEVLLKCIISGTPLPEVIWKKDNTEVKNSPTHVVKIEGERHSLLIKWTKPSDAGTYTVTAVNEV 859
Cdd:cd20972      1 PPQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKELQNSPDIQIHQEGDLHSLIIAEAFEEDTGRYSCLATNSV 80

                           90
                   ....*....|.
gi 1207186029  860 GEVSSSATLFI 870
Cdd:cd20972     81 GSDTTSAEIFV 91

Catalytic domain of the Serine/Threonine Kinases, Plant TEY Mitogen-Activated Protein Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Plant MAPKs are typed based on the conserved phosphorylation motif present in the activation loop, TEY and TDY. This subfamily represents the TEY subtype of plant MAPKs and is further subdivided into three groups (A, B, and C). Group A is represented by AtMPK3, AtMPK6, Nicotiana tabacum BTF4 (NtNTF4), among others. They are mostly involved in environmental and hormonal responses. AtMPK3 and AtMPK6 are also key regulators for stomatal development and patterning. Group B is represented by AtMPK4, AtMPK13, and NtNTF6, among others. They may be involved in both cell division and environmental stress response. AtMPK4 also participates in regulating innate immunity. Group C is represented by AtMPK1, AtMPK2, NtNTF3, Oryza sativa MAPK4 (OsMAPK4), among others. They may also be involved in stress responses. AtMPK1 and AtMPK2 are activated following mechanical injury and in the presence of stress chemicals such as jasmonic acid, hydrogen peroxide and abscisic acid. OsMAPK4 is also called OsMSRMK3 for Multiple Stress-Responsive MAPK3. In plants, MAPKs are associated with physiological, developmental, hormonal, and stress responses. Some plants show numerous gene duplications of MAPKs; Arabidopsis thaliana harbors at least 20 MAPKs, named AtMPK1-20. The TEY MAPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143363 [Multi-domain] Cd Length: 337 Bit Score: 83.96 E-value: 1.51e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1666 KEIGRGAFSYVKRVIQKAGKLEYAAKFIS------ARAKRkasALRELNILSHLDHERILYFHDAF-----EKKNAVIII 1734
Cdd:cd07858     11 KPIGRGAYGIVCSAKNSETNEKVAIKKIAnafdnrIDAKR---TLREIKLLRHLDHENVIAIKDIMppphrEAFNDVYIV 87

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1735 TELCHEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDFGNA------VKFM 1808
Cdd:cd07858     88 YELMDTDLHQIIRSSQTLSDDHCQYFLYQLLRGLKYIHSANVLHRDLKPSNLLL--NANCDLKICDFGLArttsekGDFM 165

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1809 PDEaqyckYGTPEFVAPE-IVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGEN---------------DRSSVLNIRNYN 1872
Cdd:cd07858    166 TEY-----VVTRWYRAPElLLNCSEYTTAIDVWSVGCIFAELLGRKPLFPGKDyvhqlklitellgspSEEDLGFIRNEK 240

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1207186029 1873 -------------VAFEEsMFTDLCHEAKGFVIKLLVAD-RLRPDANECLRHPWFKTL 1916
Cdd:cd07858    241 arryirslpytprQSFAR-LFPHANPLAIDLLEKMLVFDpSKRITVEEALAHPYLASL 297

Catalytic domain of the Protein Serine/Threonine Kinase, Microtubule-associated serine/threonine kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAST kinases contain an N-terminal domain of unknown function, a central catalytic domain, and a C-terminal PDZ domain that mediates protein-protein interactions. There are four mammalian MAST kinases, named MAST1-MAST4. MAST1 is also called syntrophin-associated STK (SAST) while MAST2 is also called MAST205. MAST kinases are cytoskeletal associated kinases of unknown function that are also expressed at neuromuscular junctions and postsynaptic densities. MAST1, MAST2, and MAST3 bind and phosphorylate the tumor suppressor PTEN, and may contribute to the regulation and stabilization of PTEN. MAST2 is involved in the regulation of the Fc-gamma receptor of the innate immune response in macrophages, and may also be involved in the regulation of the Na+/H+ exchanger NHE3. The MAST kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270760 [Multi-domain] Cd Length: 280 Bit Score: 82.84 E-value: 1.53e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARA----KRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITEL 1737
Cdd:cd05609      2 FETIKLISNGAYGAVYLVRHRETRQRFAMKKINKQNlilrNQIQQVFVERDILTFAENPFVVSMYCSFETKRHLCMVMEY 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1738 CHEELLDRLTKKSTILESEI-RSSVRQLLEGINYLHQLDILHLDIKPDNILMAdhSSDQIRICDFG-------------- 1802
Cdd:cd05609     82 VEGGDCATLLKNIGPLPVDMaRMYFAETVLALEYLHSYGIVHRDLKPDNLLIT--SMGHIKLTDFGlskiglmslttnly 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1803 ------NAVKFMpdEAQYCkyGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFE 1876
Cdd:cd05609    160 eghiekDTREFL--DKQVC--GTPEYIAPEVILRQGYGKPVDWWAMGIILYEFLVGCVPFFGDTPEELFGQVISDEIEWP 235

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*..
gi 1207186029 1877 ESmftD--LCHEAKGFVIKLL---VADRL-RPDANECLRHPWFKTLN 1917
Cdd:cd05609    236 EG---DdaLPDDAQDLITRLLqqnPLERLgTGGAEEVKQHPFFQDLD 279

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK4 partners with all three D-type cyclins (D1, D2, and D3) and is also regulated by INK4 inhibitors. It is active towards the retinoblastoma (pRb) protein and plays a role in regulating the early G1 phase of the cell cycle. It is expressed ubiquitously and is localized in the nucleus. CDK4 also shows kinase activity towards Smad3, a signal transducer of TGF-beta signaling which modulates transcription and plays a role in cell proliferation and apoptosis. CDK4 is inhibited by the p21 inhibitor and is specifically mutated in human melanoma. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143368 [Multi-domain] Cd Length: 288 Bit Score: 83.09 E-value: 1.53e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPESKQ---TVLQEYDILKSLhhekimalhEAYVTPRYLVLISECC 3376
Cdd:cd07863      2 YEPVAEIGVGAYGTVYKARDPHSGHFVALKSVRVQTNEDGlplSTVREVALLKRL---------EAFDHPNIVRLMDVCA 72

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3377 SGK---ELLHSLIdrFRYSEDDVVAYI-----------------VQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKII 3436
Cdd:cd07863     73 TSRtdrETKVTLV--FEHVDQDLRTYLdkvpppglpaetikdlmRQFLRGLDFLHANCIVHRDLKPENILVTSGGQVKLA 150

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1207186029 3437 DFGSAQTFNplFLKQFSPPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIqaakFDL 3514
Cdd:cd07863    151 DFGLARIYS--CQMALTPVVVTLWYRAPEVLLQSTYATPVDMWSVGCIFAEMFRRKPLFCGNSEADQLGKI----FDL 222

Catalytic domain of the Serine/Threonine Kinase, p38beta Mitogen-Activated Protein Kinase (also called MAPK11); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38beta/MAPK11 is widely expressed in tissues and shows more similarity with p38alpha than with the other isoforms. Both are sensitive to pyridinylimidazoles and share some common substrates such as MAPK activated protein kinase 2 (MK2) and the transcription factors ATF2, c-Fos and, ELK-1. p38beta is involved in regulating the activation of the cyclooxygenase-2 promoter and the expression of TGFbeta-induced alpha-smooth muscle cell actin. p38 kinases are mitogen-activated protein kinases (MAPKs), serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38beta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143383 [Multi-domain] Cd Length: 343 Bit Score: 83.95 E-value: 1.85e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAF-----SYVKRVIQKAGKLEYAAKFISARAKRKAsaLRELNILSHLDHERILYFHDAF------EKKNAVIIITE 1736
Cdd:cd07878     23 VGSGAYgsvcsAYDTRLRQKVAVKKLSRPFQSLIHARRT--YRELRLLKHMKHENVIGLLDVFtpatsiENFNEVYLVTN 100

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1737 LCHEELlDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNIlmADHSSDQIRICDFGNAVKfmPDEAQYCK 1816
Cdd:cd07878    101 LMGADL-NNIVKCQKLSDEHVQFLIYQLLRGLKYIHSAGIIHRDLKPSNV--AVNEDCELRILDFGLARQ--ADDEMTGY 175

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*
gi 1207186029 1817 YGTPEFVAPEI-VNQTPVSKATDIWPIGVLTYLCLTGVSPFAGEN 1860
Cdd:cd07878    176 VATRWYRAPEImLNWMHYNQTVDIWSVGCIMAELLKGKALFPGND 220

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK3, also called beta-adrenergic receptor kinase 2 (beta-ARK2), is widely expressed in many tissues. It is involved in modulating the cholinergic response of airway smooth muscles, and also plays a role in dopamine receptor regulation. GRK3-deficient mice show a lack of olfactory receptor desensitization and altered regulation of the M2 muscarinic airway. GRK3 promoter polymorphisms may also be associated with bipolar disorder. GRK3 contains an N-terminal RGS homology (RH) domain, a central catalytic domain, and C-terminal pleckstrin homology (PH) domain that mediates PIP2 and G protein betagamma-subunit translocation to the membrane. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270781 [Multi-domain] Cd Length: 346 Bit Score: 83.96 E-value: 1.89e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3307 ARGRFGVIRECRENATGNLYMAKIVP---YEPESKQTVLQEYDILKSLHHEK----IMALHEAYVTPRYLVLISECCSGK 3379
Cdd:cd05633     14 GRGGFGEVYGCRKADTGKMYAMKCLDkkrIKMKQGETLALNERIMLSLVSTGdcpfIVCMTYAFHTPDKLCFILDLMNGG 93

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3380 ELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPlflKQFSPPIGTL 3459
Cdd:cd05633     94 DLHYHLSQHGVFSEKEMRFYATEIILGLEHMHNRFVVYRDLKPANILLDEHGHVRISDLGLACDFSK---KKPHASVGTH 170

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|
gi 1207186029 3460 DYMSPEML-KGDVVGPPADIWSIGILTYIMLSGRLPFTEN 3498
Cdd:cd05633    171 GYMAPEVLqKGTAYDSSADWFSLGCMLFKLLRGHSPFRQH 210

Catalytic domain of the Protein Tyrosine Kinases, Fungal Wee1 proteins; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of fungal Wee1 proteins, also called Swe1 in budding yeast and Mik1 in fission yeast. Yeast Wee1 is required to control cell size. Wee1 is a cell cycle checkpoint kinase that helps keep the cyclin-dependent kinase CDK1 in an inactive state through phosphorylation of an N-terminal tyr (Y15) residue. During the late G2 phase, CDK1 is activated and mitotic entry is promoted by the removal of this inhibitory phosphorylation by the phosphatase Cdc25. Although Wee1 is functionally a tyr kinase, it is more closely related to serine/threonine kinases (STKs). It contains a catalytic kinase domain sandwiched in between N- and C-terminal regulatory domains. It is regulated by phosphorylation and degradation, and its expression levels are also controlled by circadian clock proteins. The fungal Wee1 subfamily is part of a larger superfamily that includes the catalytic domains of STKs, other PTKs, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270954 [Multi-domain] Cd Length: 278 Bit Score: 82.47 E-value: 1.99e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3320 NATGNLYMAKIVPY---EPESKQTVLQEYDILKSLH---HEKIMALHEAYVTPRYLVLISECCSGKEL--------LHSL 3385
Cdd:cd14052     23 VPTGKVYAVKKLKPnyaGAKDRLRRLEEVSILRELTldgHDNIVQLIDSWEYHGHLYIQTELCENGSLdvflselgLLGR 102

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3386 IDRFRyseddVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFnplflkqfsPPI------GTL 3459
Cdd:cd14052    103 LDEFR-----VWKILVELSLGLRFIHDHHFVHLDLKPANVLITFEGTLKIGDFGMATVW---------PLIrgiereGDR 168

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3460 DYMSPEMLKGDVVGPPADIWSIGILTY-IMLSGRLPftEN-------------------DPAETEARIQAAKFDLSKLYQ 3519
Cdd:cd14052    169 EYIAPEILSEHMYDKPADIFSLGLILLeAAANVVLP--DNgdawqklrsgdlsdaprlsSTDLHSASSPSSNPPPDPPNM 246

                          250       260
                   ....*....|....*....|....*..
gi 1207186029 3520 NV-SQSASLFIKKILCSYPWARPTIKD 3545
Cdd:cd14052    247 PIlSGSLDRVVRWMLSPEPDRRPTADD 273

Catalytic domain of the Serine/Threonine Kinase, Classical Protein Kinase C alpha; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-alpha is expressed in many tissues and is associated with cell proliferation, apoptosis, and cell motility. It plays a role in the signaling of the growth factors PDGF, VEGF, EGF, and FGF. Abnormal levels of PKC-alpha have been detected in many transformed cell lines and several human tumors. In addition, PKC-alpha is required for HER2 dependent breast cancer invasion. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. PKCs undergo three phosphorylations in order to take mature forms. In addition, cPKCs depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. The cPKC-alpha subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270766 [Multi-domain] Cd Length: 341 Bit Score: 83.89 E-value: 2.05e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1657 RLTDYyDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISA----RAKRKASALRELNILSHLDHERIL-YFHDAFEKKNAV 1731
Cdd:cd05615      8 RLTDF-NFLMVLGKGSFGKVMLAERKGSDELYAIKILKKdvviQDDDVECTMVEKRVLALQDKPPFLtQLHSCFQTVDRL 86

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1732 IIITELCHE-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDFGNAVKFMPD 1810
Cdd:cd05615     87 YFVMEYVNGgDLMYHIQQVGKFKEPQAVFYAAEISVGLFFLHKKGIIYRDLKLDNVML--DSEGHIKIADFGMCKEHMVE 164

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1811 ---EAQYCkyGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDLCHEA 1887
Cdd:cd05615    165 gvtTRTFC--GTPDYIAPEIIAYQPYGRSVDWWAYGVLLYEMLAGQPPFDGEDEDELFQSIMEHNVSYPKSLSKEAVSIC 242


                   ....*.
gi 1207186029 1888 KGFVIK 1893
Cdd:cd05615    243 KGLMTK 248

Catalytic domain of the Serine/Threonine Kinase, Extracellular signal-Regulated Kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ERK5 (also called Big MAPK1 (BMK1) or MAPK7) has a unique C-terminal extension, making it approximately twice as big as other MAPKs. This extension contains transcriptional activation capability which is inhibited by the N-terminal half. ERK5 is activated in response to growth factors and stress by a cascade that leads to its phosphorylation by the MAP2K MEK5, which in turn is regulated by the MAP3Ks MEKK2 and MEKK3. Activated ERK5 phosphorylates its targets including myocyte enhancer factor 2 (MEF2), Sap1a, c-Myc, and RSK. It plays a role in EGF-induced cell proliferation during the G1/S phase transition. Studies on knockout mice revealed that ERK5 is essential for cardiovascular development and plays an important role in angiogenesis. It is also critical for neural differentiation and survival. The ERK5 pathway has been implicated in the pathogenesis of many diseases including cancer, cardiac hypertrophy, and atherosclerosis. MAPKs are important mediators of cellular responses to extracellular signals. The ERK5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270842 [Multi-domain] Cd Length: 336 Bit Score: 83.57 E-value: 2.24e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1657 RLTDYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFIS------ARAKRkasALRELNILSHLDHERILYFHDAFEKKNA 1730
Cdd:cd07855      2 DVGDRYEPIETIGSGAYGVVCSAIDTKSGQKVAIKKIPnafdvvTTAKR---TLRELKILRHFKHDNIIAIRDILRPKVP 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1731 ------VIIITELcHEELLDRLTKKSTILESE-IRSSVRQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDFGN 1803
Cdd:cd07855     79 yadfkdVYVVLDL-MESDLHHIIHSDQPLTLEhIRYFLYQLLRGLKYIHSANVIHRDLKPSNLLV--NENCELKIGDFGM 155

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1804 AVKFMPDEAQYCKYGTpEFV------APEIVNQTP-VSKATDIWPIGVL--------------TY-------LCLTGvSP 1855
Cdd:cd07855    156 ARGLCTSPEEHKYFMT-EYVatrwyrAPELMLSLPeYTQAIDMWSVGCIfaemlgrrqlfpgkNYvhqlqliLTVLG-TP 233

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1207186029 1856 FAGENDRSSVLNIRNYNVAFE-------ESMFTDLCHEAKGFVIKLLVAD-RLRPDANECLRHPWFKTL 1916
Cdd:cd07855    234 SQAVINAIGADRVRRYIQNLPnkqpvpwETLYPKADQQALDLLSQMLRFDpSERITVAEALQHPFLAKY 302

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 76.53 E-value: 2.50e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 2861 PVFHIKLRDHVLLEGDPVTLSCLPAGSPHPHISWMKDKKPLEIDPRMnMISCPDGRQLLMIMKTTKKDAGLYECVAANPL 2940
Cdd:pfam07679    1 PKFTQKPKDVEVQEGESARFTCTVTGTPDPEVSWFKDGQPLRSSDRF-KVTYEGGTYTLTISNVQPDDSGKYTCVATNSA 79


                   ....*....
gi 1207186029 2941 ATVTSSCVV 2949
Cdd:pfam07679   80 GEAEASAEL 88

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409565 [Multi-domain] Cd Length: 88 Bit Score: 76.46 E-value: 2.91e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1132 LEVIEGRNARFDCKVSGTPPPQVIWSHFDRPLEENEDIRILKEG-GRHSLIISHVSNEDEGLYTVAARNSHGEDECAAEL 1210
Cdd:cd20973      7 KEVVEGSAARFDCKVEGYPDPEVKWMKDDNPIVESRRFQIDQDEdGLCSLIISDVCGDDSGKYTCKAVNSLGEATCSAEL 86


                   ..
gi 1207186029 1211 YV 1212
Cdd:cd20973     87 TV 88

Catalytic domain of the Serine/Threonine Kinase, p38 Mitogen-Activated Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38 kinases are mitogen-activated protein kinases (MAPKs), serving as important mediators of cellular responses to extracellular signals. They function in the regulation of the cell cycle, cell development, cell differentiation, senescence, tumorigenesis, apoptosis, pain development and pain progression, and immune responses. p38 kinases are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. p38 substrates include other protein kinases and factors that regulate transcription, nuclear export, mRNA stability and translation. p38 kinases are drug targets for the inflammatory diseases psoriasis, rheumatoid arthritis, and chronic pulmonary disease. Vertebrates contain four isoforms of p38, named alpha, beta, gamma, and delta, which show varying substrate specificity and expression patterns. p38alpha and p38beta are ubiquitously expressed, p38gamma is predominantly found in skeletal muscle, and p38delta is found in the heart, lung, testis, pancreas, and small intestine. The p38 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143356 [Multi-domain] Cd Length: 343 Bit Score: 83.11 E-value: 3.42e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1660 DYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAK-----FISA-RAKRkasALRELNILSHLDHERILYFHDAF------EK 1727
Cdd:cd07851     15 DRYQNLSPVGSGAYGQVCSAFDTKTGRKVAIKklsrpFQSAiHAKR---TYRELRLLKHMKHENVIGLLDVFtpasslED 91

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1728 KNAVIIITELCHEELlDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSsdQIRICDFGNAVKF 1807
Cdd:cd07851     92 FQDVYLVTHLMGADL-NNIVKCQKLSDDHIQFLVYQILRGLKYIHSAGIIHRDLKPSNLAVNEDC--ELKILDFGLARHT 168

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1808 MPDEAQYCkyGTPEFVAPEIV-NQTPVSKATDIWPIGVLTYLCLTGVSPFAGEN-----------------------DRS 1863
Cdd:cd07851    169 DDEMTGYV--ATRWYRAPEIMlNWMHYNQTVDIWSVGCIMAELLTGKTLFPGSDhidqlkrimnlvgtpdeellkkiSSE 246

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1207186029 1864 SVLN-IRNYNVaFEESMFTDLCHEAKGFVI----KLLVAD-RLRPDANECLRHPWFK 1914
Cdd:cd07851    247 SARNyIQSLPQ-MPKKDFKEVFSGANPLAIdlleKMLVLDpDKRITAAEALAHPYLA 302

Catalytic domain of the Serine/Threonine Kinase, Classical (or Conventional) Protein Kinase C; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. cPKCs are potent kinases for histones, myelin basic protein, and protamine. They depend on calcium, DAG (1,2-diacylglycerol), and in most cases, phosphatidylserine (PS) for activation. cPKCs contain a calcium-binding C2 region in their regulatory domain. There are four cPKC isoforms, named alpha, betaI, betaII, and gamma. PKC-gamma is mainly expressed in neuronal tissues. It plays a role in protection from ischemia. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. The cPKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270739 [Multi-domain] Cd Length: 320 Bit Score: 82.83 E-value: 3.49e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKIVpyepeSKQTVLQEYDILKSLHHEKIMAL----------HEAYVTPRYLVLISECCS 3377
Cdd:cd05587      6 KGSFGKVMLAERKGTDELYAIKIL-----KKDVIIQDDDVECTMVEKRVLALsgkppfltqlHSCFQTMDRLYFVMEYVN 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3378 GKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQ--TFNPLFLKQFSpp 3455
Cdd:cd05587     81 GGDLMYHIQQVGKFKEPVAVFYAAEIAVGLFFLHSKGIIYRDLKLDNVMLDAEGHIKIADFGMCKegIFGGKTTRTFC-- 158

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1207186029 3456 iGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIqaakfdlskLYQNVSQSASL 3527
Cdd:cd05587    159 -GTPDYIAPEIIAYQPYGKSVDWWAYGVLLYEMLAGQPPFDGEDEDELFQSI---------MEHNVSYPKSL 220

C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myotilin. Mytolin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to the latter family contain multiple Ig-like domains and function as scaffolds, modulating the actin cytoskeleton. Myotilin is most abundant in skeletal and cardiac muscle and is involved in maintaining sarcomere integrity. It binds to alpha-actinin, filamin, and actin. Mutations in myotilin lead to muscle disorders. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409473 Cd Length: 92 Bit Score: 76.35 E-value: 3.57e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  781 PVFEFPLQDTVASTGTEVLLKCIISGTPLPEVIWKKDNTEVKNSPTHVVKIEGE--RHSLLIKWTKPSDAGTYTVTAVNE 858
Cdd:cd05892      1 PMFIQKPQNKKVLEGDPVRLECQISAIPPPQIFWKKNNEMLQYNTDRISLYQDNcgRICLLIQNANKKDAGWYTVSAVNE 80

                           90
                   ....*....|
gi 1207186029  859 VGEVSSSATL 868
Cdd:cd05892     81 AGVVSCNARL 90

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK1 is important in the regulation of many cellular processes including cytoskeletal dynamics, cell motility, growth, and proliferation. Although PAK1 has been regarded mainly as a cytosolic protein, recent reports indicate that PAK1 also exists in significant amounts in the nucleus, where it is involved in transcription modulation and in cell cycle regulatory events. PAK1 is also involved in transformation and tumorigenesis. Its overexpression, hyperactivation and increased nuclear accumulation is correlated to breast cancer invasiveness and progression. Nuclear accumulation is also linked to tamoxifen resistance in breast cancer cells. PAK1 belongs to the group I PAKs, which contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270820 [Multi-domain] Cd Length: 296 Bit Score: 82.08 E-value: 3.74e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1648 EASILRKMRRLTDYYDVHKE------IGRGAFSYVKRVIQKAGKLEYAAKFISARAK-RKASALRELNILSHLDHERILY 1720
Cdd:cd06654      2 DEEILEKLRSIVSVGDPKKKytrfekIGQGASGTVYTAMDVATGQEVAIRQMNLQQQpKKELIINEILVMRENKNPNIVN 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1721 FHDAFEKKNAVIIITELCHEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSdqIRICD 1800
Cdd:cd06654     82 YLDSYLVGDELWVVMEYLAGGSLTDVVTETCMDEGQIAAVCRECLQALEFLHSNQVIHRDIKSDNILLGMDGS--VKLTD 159

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1207186029 1801 FGNAVKFMPDEAQYCKY-GTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGEN 1860
Cdd:cd06654    160 FGFCAQITPEQSKRSTMvGTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMIEGEPPYLNEN 220

Catalytic domain of the Serine/Threonine kinase, Leucine-Rich Repeat Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LRRKs are also classified as ROCO proteins because they contain a ROC (Ras of complex proteins)/GTPase domain followed by a COR (C-terminal of ROC) domain of unknown function. In addition, LRRKs contain a catalytic kinase domain and protein-protein interaction motifs including a WD40 domain, LRRs and ankyrin (ANK) repeats. LRRKs possess both GTPase and kinase activities, with the ROC domain acting as a molecular switch for the kinase domain, cycling between a GTP-bound state which drives kinase activity and a GDP-bound state which decreases the activity. Vertebrates contain two members, LRRK1 and LRRK2, which show complementary expression in the brain. Mutations in LRRK2 are linked to both familial and sporadic forms of Parkinson's disease. The normal roles of LRRKs are not clearly defined. They may be involved in mitogen-activated protein kinase (MAPK) pathways, protein translation control, programmed cell death pathways, and cytoskeletal dynamics. The LRRK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270902 [Multi-domain] Cd Length: 275 Bit Score: 81.51 E-value: 4.03e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3343 QEYDILKSLHHEKIMALHEAYVTPRYLVL-----------ISE-CCSGKELLHSLIDRFRYseddvvayivQILQGLDYL 3410
Cdd:cd14000     59 QELTVLSHLHHPSIVYLLGIGIHPLMLVLelaplgsldhlLQQdSRSFASLGRTLQQRIAL----------QVADGLRYL 128

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3411 HSRRILHLDIKPENIIVTYMNV-----VKIIDFGSAQTFNPLFLKQFSppiGTLDYMSPEMLKGDVV-GPPADIWSIGIL 3484
Cdd:cd14000    129 HSAMIIYRDLKSHNVLVWTLYPnsaiiIKIADYGISRQCCRMGAKGSE---GTPGFRAPEIARGNVIyNEKVDVFSFGML 205

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1207186029 3485 TYIMLSGRLPFTENDPAETEARIQAAKFDLSKLYQNVSQSASL-FIKKILCSYPWARPT 3542
Cdd:cd14000    206 LYEILSGGAPMVGHLKFPNEFDIHGGLRPPLKQYECAPWPEVEvLMKKCWKENPQQRPT 264

Catalytic domain of Numb-Associated Kinase (NAK)-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Drosophila melanogaster NAK, human BMP-2-inducible protein kinase (BMP2K or BIKe) and similar vertebrate proteins, as well as the Saccharomyces cerevisiae proteins Prk1, Actin-regulating kinase 1 (Ark1), and Akl1. NAK was the first characterized member of this subfamily. It plays a role in asymmetric cell division through its association with Numb. It also regulates the localization of Dlg, a protein essential for septate junction formation. BMP2K contains a nuclear localization signal and a kinase domain that is capable of phosphorylating itself and myelin basic protein. The expression of the BMP2K gene is increase during BMP-2-induced osteoblast differentiation. It may function to control the rate of differentiation. Prk1, Ark1, and Akl1 comprise a subfamily of yeast proteins that are important regulators of the actin cytoskeleton and endocytosis. They share an N-terminal kinase domain but no significant homology in other regions of their sequences. The NAK-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270939 [Multi-domain] Cd Length: 277 Bit Score: 81.56 E-value: 4.52e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1664 VHKEIGRGAFSYVKRVIQKAGKLEYAAKFISAR-------AKRKASALREL----NILSHLDHERILYFHDAFEkknaVI 1732
Cdd:cd14037      7 IEKYLAEGGFAHVYLVKTSNGGNRAALKRVYVNdehdlnvCKREIEIMKRLsghkNIVGYIDSSANRSGNGVYE----VL 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1733 IITELCHE-ELLD----RLTKKSTilESEIRSSVRQLLEGINYLHQLD--ILHLDIKPDNILMADhsSDQIRICDFGNA- 1804
Cdd:cd14037     83 LLMEYCKGgGVIDlmnqRLQTGLT--ESEILKIFCDVCEAVAAMHYLKppLIHRDLKVENVLISD--SGNYKLCDFGSAt 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1805 VKFMP----DEAQYC-----KYGTPEFVAPEIVN---QTPVSKATDIWPIGVLTY-LCLTgVSPFaGEndrSSVLNIRNY 1871
Cdd:cd14037    159 TKILPpqtkQGVTYVeedikKYTTLQYRAPEMIDlyrGKPITEKSDIWALGCLLYkLCFY-TTPF-EE---SGQLAILNG 233

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|.
gi 1207186029 1872 NVAFEE-SMFTDLCHeakGFVIKLLVAD-RLRPDANECLRH 1910
Cdd:cd14037    234 NFTFPDnSRYSKRLH---KLIRYMLEEDpEKRPNIYQVSYE 271

Catalytic domain of Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. They can be classified into receptor and non-receptor tyr kinases. PTKs play important roles in many cellular processes including, lymphocyte activation, epithelium growth and maintenance, metabolism control, organogenesis regulation, survival, proliferation, differentiation, migration, adhesion, motility, and morphogenesis. Receptor tyr kinases (RTKs) are integral membrane proteins which contain an extracellular ligand-binding region, a transmembrane segment, and an intracellular tyr kinase domain. RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain, leading to intracellular signaling. Some RTKs are orphan receptors with no known ligands. Non-receptor (or cytoplasmic) tyr kinases are distributed in different intracellular compartments and are usually multi-domain proteins containing a catalytic tyr kinase domain as well as various regulatory domains such as SH3 and SH2. PTKs are usually autoinhibited and require a mechanism for activation. In many PTKs, the phosphorylation of tyr residues in the activation loop is essential for optimal activity. Aberrant expression of PTKs is associated with many development abnormalities and cancers.The PTK family is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270623 [Multi-domain] Cd Length: 262 Bit Score: 81.05 E-value: 4.61e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRenATGNLYMAKIV-------PYEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKE 3380
Cdd:cd00192      5 EGAFGEVYKGK--LKGGDGKTVDVavktlkeDASESERKDFLKEARVMKKLGHPNVVRLLGVCTEEEPLYLVMEYMEGGD 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3381 LLHSLIDRFRY---------SEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFG-SAQTFNPLFLK 3450
Cdd:cd00192     83 LLDFLRKSRPVfpspepstlSLKDLLSFAIQIAKGMEYLASKKFVHRDLAARNCLVGEDLVVKISDFGlSRDIYDDDYYR 162

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*....
gi 1207186029 3451 QFSP---PIgtlDYMSPEMLKGDVVGPPADIWSIGILTY-IMLSGRLPF 3495
Cdd:cd00192    163 KKTGgklPI---RWMAPESLKDGIFTSKSDVWSFGVLLWeIFTLGATPY 208

Catalytic domain of the Serine/Threonine Kinase, Nuclear Dbf2-Related kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NDR2 (also called STK38-like) plays a role in proper centrosome duplication. In addition, it is involved in regulating neuronal growth and differentiation, as well as in facilitating neurite outgrowth. NDR2 is also implicated in fear conditioning as it contributes to the coupling of neuronal morphological changes with fear-memory consolidation. NDR kinase contains an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Like many other AGC kinases, NDR kinase requires phosphorylation at two sites, the activation loop (A-loop) and the hydrophobic motif (HM), for activity. The NDR2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270776 [Multi-domain] Cd Length: 366 Bit Score: 83.18 E-value: 4.80e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3307 ARGRFGVIRECRENATGNLYMAKIVP----YEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELL 3382
Cdd:cd05627     11 GRGAFGEVRLVQKKDTGHIYAMKILRkadmLEKEQVAHIRAERDILVEADGAWVVKMFYSFQDKRNLYLIMEFLPGGDMM 90

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3383 HSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLKQF------SPP- 3455
Cdd:cd05627     91 TLLMKKDTLSEEATQFYIAETVLAIDAIHQLGFIHRDIKPDNLLLDAKGHVKLSDFGLCTGLKKAHRTEFyrnlthNPPs 170

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1207186029 3456 ---------------------------IGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARI 3507
Cdd:cd05627    171 dfsfqnmnskrkaetwkknrrqlaystVGTPDYIAPEVFMQTGYNKLCDWWSLGVIMYEMLIGYPPFCSETPQETYRKV 249

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 10; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK10, also called PISSLRE, is essential for cell growth and proliferation, and acts through the G2/M phase of the cell cycle. CDK10 has also been identified as an important factor in endocrine therapy resistance in breast cancer. CDK10 silencing increases the transcription of c-RAF and the activation of the p42/p44 MAPK pathway, which leads to antiestrogen resistance. Patients who express low levels of CDK10 relapse early on tamoxifen. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK10 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173742 [Multi-domain] Cd Length: 309 Bit Score: 82.03 E-value: 4.85e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1656 RRLTDYYDVHKeIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKA---SALRELNILSHLDHERILYFHDAFEKK--NA 1730
Cdd:cd07845      4 RSVTEFEKLNR-IGEGTYGIVYRARDTTSGEIVALKKVRMDNERDGipiSSLREITLLLNLRHPNIVELKEVVVGKhlDS 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1731 VIIITELCHEE---LLDRLTkkSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSsdQIRICDFGNAVKF 1807
Cdd:cd07845     83 IFLVMEYCEQDlasLLDNMP--TPFSESQVKCLMLQLLRGLQYLHENFIIHRDLKVSNLLLTDKG--CLKIADFGLARTY 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1808 MPDEAQYckygTPEFV-----APEIV----NQTpvsKATDIWPIGVLTYLCLTGVSPFAGE----------------NDR 1862
Cdd:cd07845    159 GLPAKPM----TPKVVtlwyrAPELLlgctTYT---TAIDMWAVGCILAELLAHKPLLPGKseieqldliiqllgtpNES 231

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1207186029 1863 -----SSVLNIRNYNVA-----FEESMFTDLCHEAKGFVIKLLVAD-RLRPDANECLRHPWFKT 1915
Cdd:cd07845    232 iwpgfSDLPLVGKFTLPkqpynNLKHKFPWLSEAGLRLLNFLLMYDpKKRATAEEALESSYFKE 295

Catalytic domain of the Serine/Threonine Kinase, Apoptosis signal-regulating kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily are mitogen-activated protein kinase (MAPK) kinase kinases (MAPKKKs or MKKKs) and include ASK1, ASK2, and MAPKKK15. ASK1 (also called MAPKKK5) functions in the c-Jun N-terminal kinase (JNK) and p38 MAPK signaling pathways by directly activating their respective MAPKKs, MKK4/MKK7 and MKK3/MKK6. It plays important roles in cytokine and stress responses, as well as in reactive oxygen species-mediated cellular responses. ASK1 is implicated in various diseases mediated by oxidative stress including inschemic heart disease, hypertension, vessel injury, brain ischemia, Fanconi anemia, asthma, and pulmonary edema, among others. ASK2 (also called MAPKKK6) functions only in a heteromeric complex with ASK1, and can activate ASK1 by direct phosphorylation. The function of MAPKKK15 is still unknown. The ASK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270794 [Multi-domain] Cd Length: 268 Bit Score: 80.92 E-value: 5.25e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKE---IGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASAL-RELNILSHLDHERILYFHDAFEKKNAVIIITEL 1737
Cdd:cd06624      7 YDESGErvvLGKGTFGVVYAARDLSTQVRIAIKEIPERDSREVQPLhEEIALHSRLSHKNIVQYLGSVSEDGFFKIFMEQ 86

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1738 CHEELLDRLTK-KSTIL---ESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSdQIRICDFGNAvKFMPDEAQ 1813
Cdd:cd06624     87 VPGGSLSALLRsKWGPLkdnENTIGYYTKQILEGLKYLHDNKIVHRDIKGDNVLVNTYSG-VVKISDFGTS-KRLAGINP 164

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1814 YCKY--GTPEFVAPEIVNQTP--VSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLnirnynvaFEESMF-------TD 1882
Cdd:cd06624    165 CTETftGTLQYMAPEVIDKGQrgYGPPADIWSLGCTIIEMATGKPPFIELGEPQAAM--------FKVGMFkihpeipES 236

                          250       260       270
                   ....*....|....*....|....*....|
gi 1207186029 1883 LCHEAKGFVIKLLVADRL-RPDANECLRHP 1911
Cdd:cd06624    237 LSEEAKSFILRCFEPDPDkRATASDLLQDP 266

Catalytic domain of the Serine/Threonine Kinase, Mixed lineage kinase-Like mitogen-activated protein Triple Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLTK, also called zipper sterile-alpha-motif kinase (ZAK), contains a catalytic kinase domain and a leucine zipper. There are two alternatively-spliced variants, MLTK-alpha and MLTK-beta. MLTK-alpha contains a sterile-alpha-motif (SAM) at the C-terminus. MLTK regulates the c-Jun N-terminal kinase, extracellular signal-regulated kinase, p38 MAPK, and NF-kB pathways. ZAK is the MAP3K involved in the signaling cascade that leads to the ribotoxic stress response initiated by cellular damage due to Shiga toxins and ricin. It may also play a role in cell transformation and cancer development. MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals.The MLTK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270962 [Multi-domain] Cd Length: 242 Bit Score: 80.39 E-value: 5.33e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3317 CRENATGNLYMAKIVPYEPE-SKQTVLQ---EYDILKSLHHEKIMALHEAYVTPRYLVLISECCSgkelLHSLIDRFRYS 3392
Cdd:cd14060      1 CGGGSFGSVYRAIWVSQDKEvAVKKLLKiekEAEILSVLSHRNIIQFYGAILEAPNYGIVTEYAS----YGSLFDYLNSN 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3393 E------DDVVAYIVQILQGLDYLHSR---RILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLKQFsppIGTLDYMS 3463
Cdd:cd14060     77 EseemdmDQIMTWATDIAKGMHYLHMEapvKVIHRDLKSRNVVIAADGVLKICDFGASRFHSHTTHMSL---VGTFPWMA 153

                          170       180       190
                   ....*....|....*....|....*....|..
gi 1207186029 3464 PEMLKGDVVGPPADIWSIGILTYIMLSGRLPF 3495
Cdd:cd14060    154 PEVIQSLPVSETCDTYSYGVVLWEMLTREVPF 185

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated protein kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK-activated protein kinase 2 (MAPKAP2 or MK2) contains an N-terminal proline-rich region that can bind to SH3 domains, a catalytic kinase domain followed by a C-terminal autoinhibitory region that contains nuclear localization (NLS) and nuclear export (NES) signals with a p38 MAPK docking motif that overlaps the NLS. MK2 is a bonafide substrate for the MAPK p38. It is closely related to MK3 and thus far, MK2/3 show indistinguishable substrate specificity. They are mainly involved in the regulation of gene expression and they participate in diverse cellular processes such as endocytosis, cytokine production, cytoskeletal reorganization, cell migration, cell cycle control and chromatin remodeling. They are implicated in inflammation and cance and their substrates include mRNA-AU-rich-element (ARE)-binding proteins (TTP and hnRNP A0), Hsp proteins (Hsp27 and Hsp25) and RSK, among others. MK2/3 are both expressed ubiquitously but MK2 is expressed at significantly higher levels. The MK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271072 [Multi-domain] Cd Length: 303 Bit Score: 81.62 E-value: 5.70e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1660 DYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFIS--ARAKRKASALRELNILSHLdHERILYFHDAFEKKNAVIIITE- 1736
Cdd:cd14170      2 DYKVTSQVLGLGINGKVLQIFNKRTQEKFALKMLQdcPKARREVELHWRASQCPHI-VRIVDVYENLYAGRKCLLIVMEc 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1737 LCHEELLDRLTKK--STILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSDQI-RICDFGNAVKFMPDEAQ 1813
Cdd:cd14170     81 LDGGELFSRIQDRgdQAFTEREASEIMKSIGEAIQYLHSINIAHRDVKPENLLYTSKRPNAIlKLTDFGFAKETTSHNSL 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1814 YCKYGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRS----SVLNIRNYNVAFEESMFTDLCHEAKG 1889
Cdd:cd14170    161 TTPCYTPYYVAPEVLGPEKYDKSCDMWSLGVIMYILLCGYPPFYSNHGLAispgMKTRIRMGQYEFPNPEWSEVSEEVKM 240

                          250       260
                   ....*....|....*....|....
gi 1207186029 1890 FVIKLLVAD-RLRPDANECLRHPW 1912
Cdd:cd14170    241 LIRNLLKTEpTQRMTITEFMNHPW 264

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 2 or Protein Kinase regulated by RNA; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKR (or EIF2AK2) contains an N-terminal double-stranded RNA (dsRNA) binding domain and a C-terminal catalytic kinase domain. It is activated by dsRNA, which is produced as a replication intermediate in virally infected cells. It plays a key role in mediating innate immune responses to viral infection. PKR is also directly activated by PACT (protein activator of PKR) and heparin, and is inhibited by viral proteins and RNAs. PKR also regulates transcription and signal transduction in diseased cells, playing roles in tumorigenesis and neurodegenerative diseases. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. The PKR subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270949 [Multi-domain] Cd Length: 267 Bit Score: 81.00 E-value: 6.16e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPESkqtVLQEYDILKSLHHEKIMALHEAYVTP------------- 3366
Cdd:cd14047      8 FKEIELIGSGGFGQVFKAKHRIDGKTYAIKRVKLNNEK---AEREVKALAKLDHPNIVRYNGCWDGFdydpetsssnssr 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3367 ---RYLVLISECCSgKELLHSLIDRFRYSEDDVVAYIV---QILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFG- 3439
Cdd:cd14047     85 sktKCLFIQMEFCE-KGTLESWIEKRNGEKLDKVLALEifeQITKGVEYIHSKKLIHRDLKPSNIFLVDTGKVKIGDFGl 163

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3440 SAQTFNPLflkQFSPPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQaakfDLSKLYQ 3519
Cdd:cd14047    164 VTSLKNDG---KRTKSKGTLSYMSPEQISSQDYGKEVDIYALGLILFELLHVCDSAFEKSKFWTDLRNG----ILPDIFD 236

                          250       260
                   ....*....|....*....|....*.
gi 1207186029 3520 NVSQSASLFIKKILCSYPWARPTIKD 3545
Cdd:cd14047    237 KRYKIEKTIIKKMLSKKPEDRPNASE 262

Catalytic domain of the Serine/Threonine Kinases, Fungal Mitogen-Activated Protein Kinases Sty1 and Hog1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the MAPKs Sty1 from Schizosaccharomyces pombe, Hog1 from Saccharomyces cerevisiae, and similar proteins. Sty1 and Hog1 are stress-activated MAPKs that partipate in transcriptional regulation in response to stress. Sty1 is activated in response to oxidative stress, osmotic stress, and UV radiation. It is regulated by the MAP2K Wis1, which is activated by the MAP3Ks Wis4 and Win1, which receive signals of the stress condition from membrane-spanning histidine kinases Mak1-3. Activated Sty1 stabilizes the Atf1 transcription factor and induces transcription of Atf1-dependent genes of the core environmetal stress response. Hog1 is the key element in the high osmolarity glycerol (HOG) pathway and is activated upon hyperosmotic stress. Activated Hog1 accumulates in the nucleus and regulates stress-induced transcription. The HOG pathway is mediated by two transmembrane osmosensors, Sln1 and Sho1. MAPKs are important mediators of cellular responses to extracellular signals. The Sty1/Hog1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270843 [Multi-domain] Cd Length: 328 Bit Score: 82.23 E-value: 6.20e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATG-NLYMAKIV-PYE-PESKQTVLQEYDILKSLHHEKIMALHEAYVTPR---YLVlis 3373
Cdd:cd07856     12 YSDLQPVGMGAFGLVCSARDQLTGqNVAVKKIMkPFStPVLAKRTYRELKLLKHLRHENIISLSDIFISPLediYFV--- 88

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3374 eccsgKELLHSLIDRF---RYSEDDVVAYIV-QILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPlfl 3449
Cdd:cd07856     89 -----TELLGTDLHRLltsRPLEKQFIQYFLyQILRGLKYVHSAGVIHRDLKPSNILVNENCDLKICDFGLARIQDP--- 160

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1207186029 3450 kQFSPPIGTLDYMSPE-MLKGDVVGPPADIWSIGILTYIMLSGRLPFTEND 3499
Cdd:cd07856    161 -QMTGYVSTRYYRAPEiMLTWQKYDVEVDIWSAGCIFAEMLEGKPLFPGKD 210

cAMP-dependent protein kinase catalytic subunit; Provisional

Pssm-ID: 173616 [Multi-domain] Cd Length: 340 Bit Score: 81.95 E-value: 7.47e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3341 VLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDI 3420
Cdd:PTZ00426    78 VFSERKILNYINHPFCVNLYGSFKDESYLYLVLEFVIGGEFFTFLRRNKRFPNDVGCFYAAQIVLIFEYLQSLNIVYRDL 157

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3421 KPENIIVTYMNVVKIIDFGSAQTFNplflKQFSPPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDP 3500
Cdd:PTZ00426   158 KPENLLLDKDGFIKMTDFGFAKVVD----TRTYTLCGTPEYIAPEILLNVGHGKAADWWTLGIFIYEILVGCPPFYANEP 233

serine/threonine kinase US3; Provisional

Pssm-ID: 165478 [Multi-domain] Cd Length: 391 Bit Score: 82.74 E-value: 7.48e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3289 STLRQGVPQKPYTFMDEKARGRFGVIRECRENATgnlymAKIVPYEPESKQTVLQEYDILKSLHHEKIMALHEAY----- 3363
Cdd:PHA03212    83 AEARAGIEKAGFSILETFTPGAEGFAFACIDNKT-----CEHVVIKAGQRGGTATEAHILRAINHPSIIQLKGTFtynkf 157

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3364 ---VTPRYLVliseccsgkELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGS 3440
Cdd:PHA03212   158 tclILPRYKT---------DLYCYLAAKRNIAICDILAIERSVLRAIQYLHENRIIHRDIKAENIFINHPGDVCLGDFGA 228

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1207186029 3441 AQTFNPLFLKQFSPPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTEND 3499
Cdd:PHA03212   229 ACFPVDINANKYYGWAGTIATNAPELLARDPYGPAVDIWSAGIVLFEMATCHDSLFEKD 287

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek7 is required for mitotic spindle formation and cytokinesis. It is enriched in the centrosome and is critical for microtubule nucleation. Nek7 is activated by Nek9 during mitosis, and may regulate the p70 ribosomal S6 kinase. It is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270866 [Multi-domain] Cd Length: 292 Bit Score: 81.23 E-value: 7.60e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAK----FISARAKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITEL 1737
Cdd:cd08229     26 FRIEKKIGRGQFSEVYRATCLLDGVPVALKkvqiFDLMDAKARADCIKEIDLLKQLNHPNVIKYYASFIEDNELNIVLEL 105

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1738 CHEELLDRLTK-----KSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMAdhSSDQIRICDFGNAVKFMPDE- 1811
Cdd:cd08229    106 ADAGDLSRMIKhfkkqKRLIPEKTVWKYFVQLCSALEHMHSRRVMHRDIKPANVFIT--ATGVVKLGDLGLGRFFSSKTt 183

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*...
gi 1207186029 1812 AQYCKYGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGE 1859
Cdd:cd08229    184 AAHSLVGTPYYMSPERIHENGYNFKSDIWSLGCLLYEMAALQSPFYGD 231

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409405 [Multi-domain] Cd Length: 91 Bit Score: 75.22 E-value: 7.66e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  781 PVFEFPLQDTVASTGTEVLLKCIISGTPLPEVIWKKDNTEVKNSPTHVVKI-EGERHSLLIKWTKPSDAGTYTVTAVNEV 859
Cdd:cd05744      1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKMLVrENGRHSLIIEPVTKRDAGIYTCIARNRA 80

                           90
                   ....*....|.
gi 1207186029  860 GEVSSSATLFI 870
Cdd:cd05744     81 GENSFNAELVV 91

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK4 regulates cell morphology and cytoskeletal organization. It is essential for embryonic viability and proper neural development. Mice lacking PAK4 die due to defects in the fetal heart. In addition, their spinal cord motor neurons showed failure to differentiate and migrate. PAK4 also plays a role in cell survival and tumorigenesis. It is overexpressed in many primary tumors including colon, esophageal, and mammary tumors. PAK4 has also been implicated in viral and bacterial infection pathways. PAK4 belongs to the group II PAKs, which contain a PBD (p21-binding domain) and a C-terminal catalytic domain, but do not harbor an AID (autoinhibitory domain) or SH3 binding sites. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 132988 [Multi-domain] Cd Length: 292 Bit Score: 81.22 E-value: 7.86e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1661 YYDVHKEIGRGAFSYV-KRVIQKAGKLEYAAKFISARAKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITELCH 1739
Cdd:cd06657     21 YLDNFIKIGEGSTGIVcIATVKSSGKLVAVKKMDLRKQQRRELLFNEVVIMRDYQHENVVEMYNSYLVGDELWVVMEFLE 100

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1740 EELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMAdhSSDQIRICDFGNAVKfMPDEAQYCK--Y 1817
Cdd:cd06657    101 GGALTDIVTHTRMNEEQIAAVCLAVLKALSVLHAQGVIHRDIKSDSILLT--HDGRVKLSDFGFCAQ-VSKEVPRRKslV 177

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1818 GTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNyNVAFEESMFTDLCHEAKGFVIKLLVA 1897
Cdd:cd06657    178 GTPYWMAPELISRLPYGPEVDIWSLGIMVIEMVDGEPPYFNEPPLKAMKMIRD-NLPPKLKNLHKVSPSLKGFLDRLLVR 256

                          250
                   ....*....|....*..
gi 1207186029 1898 D-RLRPDANECLRHPWF 1913
Cdd:cd06657    257 DpAQRATAAELLKHPFL 273

N-terminal Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 and 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. MAP4K4 is also called Nck Interacting kinase (NIK). It facilitates the activation of the MAPKs, extracellular signal-regulated kinase (ERK) 1, ERK2, and c-Jun N-terminal kinase (JNK), by phosphorylating and activating MEKK1. MAP4K4 plays a role in tumor necrosis factor (TNF) alpha-induced insulin resistance. MAP4K4 silencing in skeletal muscle cells from type II diabetic patients restores insulin-mediated glucose uptake. MAP4K4, through JNK, also plays a broad role in cell motility, which impacts inflammation, homeostasis, as well as the invasion and spread of cancer. MAP4K4 is found to be highly expressed in most tumor cell lines relative to normal tissue. MAP4K6 (also called MINK for Misshapen/NIKs-related kinase) is activated after Ras induction and mediates activation of p38 MAPK. MAP4K6 plays a role in cell cycle arrest, cytoskeleton organization, cell adhesion, and cell motility. The MAP4K4/6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270806 [Multi-domain] Cd Length: 282 Bit Score: 80.82 E-value: 7.92e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3289 STLRQgvPQKPYTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPESKQTVLQEYDILKSL-HHEKIMALHEAYVTPR 3367
Cdd:cd06636      9 SALRD--PAGIFELVEVVGNGTYGQVYKGRHVKTGQLAAIKVMDVTEDEEEEIKLEINMLKKYsHHRNIATYYGAFIKKS 86

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3368 ------YLVLISECCsGKELLHSLIDRFRYS--EDDVVAYIV-QILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDF 3438
Cdd:cd06636     87 ppghddQLWLVMEFC-GAGSVTDLVKNTKGNalKEDWIAYICrEILRGLAHLHAHKVIHRDIKGQNVLLTENAEVKLVDF 165

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1207186029 3439 GSAQTFNPLFLKQfSPPIGTLDYMSPEMLKGDvVGPPA------DIWSIGILTYIMLSGRLPFTENDP 3500
Cdd:cd06636    166 GVSAQLDRTVGRR-NTFIGTPYWMAPEVIACD-ENPDAtydyrsDIWSLGITAIEMAEGAPPLCDMHP 231

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MEK1 and MEK2 are MAPK kinases (MAPKKs or MKKs), and are dual-specificity PKs that phosphorylate and activate the downstream targets, ERK1 and ERK2, on specific threonine and tyrosine residues. The ERK cascade starts with extracellular signals including growth factors, hormones, and neurotransmitters, which act through receptors and ion channels to initiate intracellular signaling that leads to the activation at the MAPKKK (Raf-1 or MOS) level, which leads to the transmission of signals to MEK1/2, and finally to ERK1/2. The ERK cascade plays an important role in cell proliferation, differentiation, oncogenic transformation, and cell cycle control, as well as in apoptosis and cell survival under certain conditions. This cascade has also been implicated in synaptic plasticity, migration, morphological determination, and stress response immunological reactions. Gain-of-function mutations in genes encoding ERK cascade proteins, including MEK1/2, cause cardiofaciocutaneous (CFC) syndrome, a condition leading to multiple congenital anomalies and mental retardation in patients. The MEK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 132946 [Multi-domain] Cd Length: 308 Bit Score: 81.33 E-value: 7.94e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3305 EKARGRFGVIRECRENATGnLYMA-KIVPYE--PESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKEL 3381
Cdd:cd06615      8 ELGAGNGGVVTKVLHRPSG-LIMArKLIHLEikPAIRNQIIRELKVLHECNSPYIVGFYGAFYSDGEISICMEHMDGGSL 86

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3382 LHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRR-ILHLDIKPENIIVTYMNVVKIIDFG-SAQTFNPLfLKQFsppIGTL 3459
Cdd:cd06615     87 DQVLKKAGRIPENILGKISIAVLRGLTYLREKHkIMHRDVKPSNILVNSRGEIKLCDFGvSGQLIDSM-ANSF---VGTR 162

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*.
gi 1207186029 3460 DYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEA 3505
Cdd:cd06615    163 SYMSPERLQGTHYTVQSDIWSLGLSLVEMAIGRYPIPPPDAKELEA 208

Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PIM gene locus was discovered as a result of the cloning of retroviral intergration sites in murine Moloney leukemia virus, leading to the identification of PIM kinases. They are constitutively active STKs with a broad range of cellular targets and are overexpressed in many haematopoietic malignancies and solid cancers. Vertebrates contain three distinct PIM kinase genes (PIM1-3); each gene may result in mutliple protein isoforms. There are three PIM2 isoforms resulting from alternative translation initiation sites. PIM2 is highly expressed in leukemia and lymphomas and has been shown to promote the survival and proliferation of tumor cells. The PIM2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271003 [Multi-domain] Cd Length: 257 Bit Score: 79.89 E-value: 9.94e-16

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3353 HEKIMALHEAYVTPR-YLVLISECCSGKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIV-TYM 3430
Cdd:cd14101     66 HRGVIRLLDWFEIPEgFLLVLERPQHCQDLFDYITERGALDESLARRFFKQVVEAVQHCHSKGVVHRDIKDENILVdLRT 145

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3431 NVVKIIDFGSAQTFNPLFLKQFSppiGTLDYMSPE-MLKGDVVGPPADIWSIGILTYIMLSGRLPFtendpaETEARIQA 3509
Cdd:cd14101    146 GDIKLIDFGSGATLKDSMYTDFD---GTRVYSPPEwILYHQYHALPATVWSLGILLYDMVCGDIPF------ERDTDILK 216

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....
gi 1207186029 3510 AKFDLSKlyqNVSQSASLFIKKILCSYPWARPTIKDCFTNSWLQ 3553
Cdd:cd14101    217 AKPSFNK---RVSNDCRSLIRSCLAYNPSDRPSLEQILLHPWMM 257

NIMA-related protein kinase; Provisional

Pssm-ID: 140293 [Multi-domain] Cd Length: 478 Bit Score: 83.14 E-value: 1.01e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3327 MAKIVPYEPESKQTVLQ-EYDILKSLHHEKIMALHEAYVTPRYLVLISECCSG----KELLHSLIDRFRYSEDDVVAYIV 3401
Cdd:PTZ00267    97 VAKFVMLNDERQAAYARsELHCLAACDHFGIVKHFDDFKSDDKLLLIMEYGSGgdlnKQIKQRLKEHLPFQEYEVGLLFY 176

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3402 QILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFG-SAQTFNPLFLKQFSPPIGTLDYMSPEMLKGDVVGPPADIWS 3480
Cdd:PTZ00267   177 QIVLALDEVHSRKMMHRDLKSANIFLMPTGIIKLGDFGfSKQYSDSVSLDVASSFCGTPYYLAPELWERKRYSKKADMWS 256

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3481 IGILTYIMLSGRLPFTENDPAETEARIQAAKFDlsKLYQNVSQSASLFIKKILCSYPWARPTIKDCFTNSWLQdaYLMRL 3560
Cdd:PTZ00267   257 LGVILYELLTLHRPFKGPSQREIMQQVLYGKYD--PFPCPVSSGMKALLDPLLSKNPALRPTTQQLLHTEFLK--YVANL 332

                          250       260
                   ....*....|....*....|....*....
gi 1207186029 3561 ----RRQTLTFTTTRLKEFLEQQQHIRAQ 3585
Cdd:PTZ00267   333 fqdiVRHSETISPHDREEILRQLQESGER 361

Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Human TAO2 is also known as prostate-derived Ste20-like kinase (PSK) and was identified in a screen for overexpressed RNAs in prostate cancer. TAO2 possesses mitogen-activated protein kinase (MAPK) kinase kinase activity and activates both p38 and c-Jun N-terminal kinase (JNK), by phosphorylating and activating their respective MAP/ERK kinases, MEK3/MEK6 and MKK4/MKK7. It contains a long C-terminal extension with autoinhibitory segments, and is activated by the release of this inhibition and the phosphorylation of its activation loop serine. TAO2 functions as a regulator of actin cytoskeletal and microtubule organization. In addition, it regulates the transforming growth factor-activated kinase 1 (TAK1), which is a MAPKKK that plays an essential role in the signaling pathways of tumor necrosis factor, interleukin 1, and Toll-like receptor. The TAO2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270804 [Multi-domain] Cd Length: 308 Bit Score: 81.22 E-value: 1.01e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3296 PQKPYTFMDEKARGRFGVIRECRENATGNLYMAKIVPYE----PESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVL 3371
Cdd:cd06634     13 PEKLFSDLREIGHGSFGAVYFARDVRNNEVVAIKKMSYSgkqsNEKWQDIIKEVKFLQKLRHPNTIEYRGCYLREHTAWL 92

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3372 ISECC--SGKELLHslIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLfl 3449
Cdd:cd06634     93 VMEYClgSASDLLE--VHKKPLQEVEIAAITHGALQGLAYLHSHNMIHRDVKAGNILLTEPGLVKLGDFGSASIMAPA-- 168

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3450 kqfSPPIGTLDYMSPE----MLKGDVVGpPADIWSIGIlTYIMLSGRLPFTENDPAETeARIQAAKFDLSKLYQNV-SQS 3524
Cdd:cd06634    169 ---NSFVGTPYWMAPEvilaMDEGQYDG-KVDVWSLGI-TCIELAERKPPLFNMNAMS-ALYHIAQNESPALQSGHwSEY 242

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|.
gi 1207186029 3525 ASLFIKKILCSYPWARPTikdcfTNSWLQDAYLMRLRRQTL 3565
Cdd:cd06634    243 FRNFVDSCLQKIPQDRPT-----SDVLLKHRFLLRERPPTV 278

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409405 [Multi-domain] Cd Length: 91 Bit Score: 74.84 E-value: 1.03e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1249 PDFVKPLYDMDVVEGREAVLRCKVAGLPYPTITWFHNGKRI-DSTEDRKMTQFRDVHSLVVRCVCHAHGGVYKCVISNKV 1327
Cdd:cd05744      1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVrPDSAHKMLVRENGRHSLIIEPVTKRDAGIYTCIARNRA 80

                           90
                   ....*....|.
gi 1207186029 1328 GKATCYSHLYV 1338
Cdd:cd05744     81 GENSFNAELVV 91

Catalytic domain of the Serine/Threonine Kinase, Mixed lineage kinase-Like mitogen-activated protein Triple Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLTK, also called zipper sterile-alpha-motif kinase (ZAK), contains a catalytic kinase domain and a leucine zipper. There are two alternatively-spliced variants, MLTK-alpha and MLTK-beta. MLTK-alpha contains a sterile-alpha-motif (SAM) at the C-terminus. MLTK regulates the c-Jun N-terminal kinase, extracellular signal-regulated kinase, p38 MAPK, and NF-kB pathways. ZAK is the MAP3K involved in the signaling cascade that leads to the ribotoxic stress response initiated by cellular damage due to Shiga toxins and ricin. It may also play a role in cell transformation and cancer development. MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals.The MLTK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270962 [Multi-domain] Cd Length: 242 Bit Score: 79.62 E-value: 1.03e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1669 GRGAFSYVKRVIQKAGKLEYAAKFISARAKrkasalrELNILSHLDHERILYFHDA-FEKKNAVIIITELCHEELLDRL- 1746
Cdd:cd14060      2 GGGSFGSVYRAIWVSQDKEVAVKKLLKIEK-------EAEILSVLSHRNIIQFYGAiLEAPNYGIVTEYASYGSLFDYLn 74

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1747 TKKSTILE-SEIRSSVRQLLEGINYLHQ---LDILHLDIKPDNILMAdhSSDQIRICDFGnAVKFMPDEAQYCKYGTPEF 1822
Cdd:cd14060     75 SNESEEMDmDQIMTWATDIAKGMHYLHMeapVKVIHRDLKSRNVVIA--ADGVLKICDFG-ASRFHSHTTHMSLVGTFPW 151

                          170       180       190
                   ....*....|....*....|....*....|....*.
gi 1207186029 1823 VAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAG 1858
Cdd:cd14060    152 MAPEVIQSLPVSETCDTYSYGVVLWEMLTREVPFKG 187

Catalytic domain of the Serine/Threonine kinase, Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase 8; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP3K8 is also called Tumor progression locus 2 (Tpl2) or Cancer Osaka thyroid (Cot), and was first identified as a proto-oncogene in T-cell lymphoma induced by MoMuL virus and in breast carcinoma induced by MMTV. Activated MAP3K8 induces various MAPK pathways including Extracellular Regulated Kinase (ERK) 1/2, c-Jun N-terminal kinase (JNK), and p38. It plays a pivotal role in innate immunity, linking Toll-like receptors to the production of TNF and the activation of ERK in macrophages. It is also required in interleukin-1beta production and is critical in host defense against Gram-positive bacteria. MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The MAP3K8 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270897 [Multi-domain] Cd Length: 256 Bit Score: 80.05 E-value: 1.10e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKIVPYEpeskQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLHSLID 3387
Cdd:cd13995     14 RGAFGKVYLAQDTKTKKRMACKLIPVE----QFKPSDVEIQACFRHENIAELYGALLWEETVHLFMEAGEGGSVLEKLES 89

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3388 RFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVkIIDFG-SAQTFNPLFLKQfsPPIGTLDYMSPEM 3466
Cdd:cd13995     90 CGPMREFEIIWVTKHVLKGLDFLHSKNIIHHDIKPSNIVFMSTKAV-LVDFGlSVQMTEDVYVPK--DLRGTEIYMSPEV 166

                          170       180       190
                   ....*....|....*....|....*....|....
gi 1207186029 3467 LKGDVVGPPADIWSIGILTYIMLSGRLPFTENDP 3500
Cdd:cd13995    167 ILCRGHNTKADIYSLGATIIHMQTGSPPWVRRYP 200

C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myotilin. Mytolin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to the latter family contain multiple Ig-like domains and function as scaffolds, modulating the actin cytoskeleton. Myotilin is most abundant in skeletal and cardiac muscle and is involved in maintaining sarcomere integrity. It binds to alpha-actinin, filamin, and actin. Mutations in myotilin lead to muscle disorders. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409473 Cd Length: 92 Bit Score: 74.81 E-value: 1.12e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1123 PLFTRKLDVLEVIEGRNARFDCKVSGTPPPQVIWSHFDRPLEENED-IRILKEG-GRHSLIISHVSNEDEGLYTVAARNS 1200
Cdd:cd05892      1 PMFIQKPQNKKVLEGDPVRLECQISAIPPPQIFWKKNNEMLQYNTDrISLYQDNcGRICLLIQNANKKDAGWYTVSAVNE 80

                           90
                   ....*....|..
gi 1207186029 1201 HGEDECAAELYV 1212
Cdd:cd05892     81 AGVVSCNARLDV 92

Catalytic subunit (alpha) of the Serine/Threonine Kinase, Casein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CK2 is a tetrameric protein with two catalytic (alpha) and two regulatory (beta) subunits. It is constitutively active and ubiquitously expressed, and is found in the cytoplasm, nucleus, as well as in the plasma membrane. It phosphorylates a wide variety of substrates including gylcogen synthase, cell cycle proteins, nuclear proteins (e.g. DNA topoisomerase II), and ion channels (e.g. ENaC), among others. It may be considered a master kinase controlling the activity or lifespan of many other kinases and exerting its effect over cell fate, gene expression, protein synthesis and degradation, and viral infection. CK2 is implicated in every stage of the cell cycle and is required for cell cycle progression. It plays crucial roles in cell differentiation, proliferation, and survival, and is thus implicated in cancer. CK2 is not an oncogene by itself but elevated CK2 levels create an environment that enhances the survival of tumor cells. The CK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271034 [Multi-domain] Cd Length: 306 Bit Score: 80.66 E-value: 1.15e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3297 QKPYTFMDEKARGRFGVIRECRENATGNLYMAKIVpyEPESKQTVLQEYDILKSLH-HEKIMALHEAYVTP--RYLVLIS 3373
Cdd:cd14132     17 QDDYEIIRKIGRGKYSEVFEGINIGNNEKVVIKVL--KPVKKKKIKREIKILQNLRgGPNIVKLLDVVKDPqsKTPSLIF 94

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3374 E---CCSGKELLHSLIDrfryseDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMN-VVKIIDFGSAQTFNPlfL 3449
Cdd:cd14132     95 EyvnNTDFKTLYPTLTD------YDIRYYMYELLKALDYCHSKGIMHRDVKPHNIMIDHEKrKLRLIDWGLAEFYHP--G 166

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1207186029 3450 KQFSPPIGTLDYMSPEMLkgdvVGPP-----ADIWSIGILTYIMLSGRLPF 3495
Cdd:cd14132    167 QEYNVRVASRYYKGPELL----VDYQyydysLDMWSLGCMLASMIFRKEPF 213

Catalytic domain of the Serine/Threonine Kinase, MAPK/MAK/MRK Overlapping Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MOK, also called Renal tumor antigen 1 (RAGE-1), is widely expressed and is enriched in testis, kidney, lung, and brain. It is expressed in approximately 50% of renal cell carcinomas (RCC) and is a potential target for immunotherapy. MOK is stabilized by its association with the HSP90 molecular chaperone. It is induced by the transcription factor Cdx2 and may be involved in regulating intestinal epithelial development and differentiation. The MOK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270825 [Multi-domain] Cd Length: 282 Bit Score: 80.39 E-value: 1.18e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQ-KAGKLeYAAKFISARAK--RKASALRELNILSHL-DHERILYFHDA-FEKKNA-VIIIT 1735
Cdd:cd07831      1 YKILGKIGEGTFSEVLKAQSrKTGKY-YAIKCMKKHFKslEQVNNLREIQALRRLsPHPNILRLIEVlFDRKTGrLALVF 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1736 ELCHEELLDRLTKKSTIL-ESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADhssDQIRICDFGNAvkfmpdEAQY 1814
Cdd:cd07831     80 ELMDMNLYELIKGRKRPLpEKRVKNYMYQLLKSLDHMHRNGIFHRDIKPENILIKD---DILKLADFGSC------RGIY 150

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1815 CKYGTPEFV------APE-IVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGEND--------------RSSVL------N 1867
Cdd:cd07831    151 SKPPYTEYIstrwyrAPEcLLTDGYYGPKMDIWAVGCVFFEILSLFPLFPGTNEldqiakihdvlgtpDAEVLkkfrksR 230

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1207186029 1868 IRNYNVAFE-----ESMFTDLCHEAKGFVIKLLVAD-RLRPDANECLRHPWF 1913
Cdd:cd07831    231 HMNYNFPSKkgtglRKLLPNASAEGLDLLKKLLAYDpDERITAKQALRHPYF 282

Catalytic domain of the Serine/Threonine kinase, SINK-homologous inhibitory kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SHIK, also referred to as STK40 or LYK4, is a cytoplasmic and nuclear protein that is involved in the negative regulation of NF-kappaB- and p53-mediated transcription. It was identified as a protein related to SINK, a p65-interacting protein that inhibits p65 phosphorylation by the catalytic subunit of PKA, thereby inhibiting transcriptional competence of NF-kappaB. The SHIK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270876 [Multi-domain] Cd Length: 290 Bit Score: 80.53 E-value: 1.19e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3314 IREC--RENATGNLYMAKIVPYE--PESKQTVLQ-------EYDILKSLHHEKIMALH------EAY------------- 3363
Cdd:cd13974     12 IVQClaRKEGTDDFYTLKILTLEekGEETQEDRQgkmllhtEYSLLSLLHDQDGVVHHhglfqdRACeikedkssnvytg 91

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3364 -VTPRyLVLISECCSGKE----------LLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVT-YMN 3431
Cdd:cd13974     92 rVRKR-LCLVLDCLCAHDfsdktadlinLQHYVIREKRLSEREALVIFYDVVRVVEALHKKNIVHRDLKLGNMVLNkRTR 170

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3432 VVKIIDFGSAQTFNP---LFLKQFSPPIgtldYMSPEMLKGD-VVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARI 3507
Cdd:cd13974    171 KITITNFCLGKHLVSeddLLKDQRGSPA----YISPDVLSGKpYLGKPSDMWALGVVLFTMLYGQFPFYDSIPQELFRKI 246

                          250       260       270
                   ....*....|....*....|....*....|....*
gi 1207186029 3508 QAAKFDLSKLYQnVSQSASLFIKKILCSYPWARPT 3542
Cdd:cd13974    247 KAAEYTIPEDGR-VSENTVCLIRKLLVLNPQKRLT 280

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409543 [Multi-domain] Cd Length: 94 Bit Score: 74.76 E-value: 1.21e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1123 PLFTRKLDVLEVIEGRNARFDCKVSGTPPPQVIWSHFDRPLEENEDIRILK---EGGRHSLIISHVSNEDEGLYTVAARN 1199
Cdd:cd20951      1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIDPSSIPGKYKiesEYGVHVLHIRRVTVEDSAVYSAVAKN 80

                           90
                   ....*....|....
gi 1207186029 1200 SHGEDECAAELYVQ 1213
Cdd:cd20951     81 IHGEASSSASVVVE 94

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase 15 and similar MAPKs; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Human MAPK15 is also called Extracellular signal Regulated Kinase 8 (ERK8) while the rat protein is called ERK7. ERK7 and ERK8 display both similar and different biochemical properties. They autophosphorylate and activate themselves and do not require upstream activating kinases. ERK7 is constitutively active and is not affected by extracellular stimuli whereas ERK8 shows low basal activity and is activated by DNA-damaging agents. ERK7 and ERK8 also have different substrate profiles. Genome analysis shows that they are orthologs with similar gene structures. ERK7 and ERK 8 may be involved in the signaling of some nuclear receptor transcription factors. ERK7 regulates hormone-dependent degradation of estrogen receptor alpha while ERK8 down-regulates the transcriptional co-activation androgen and glucocorticoid receptors. MAPKs are important mediators of cellular responses to extracellular signals. The MAPK15 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270841 [Multi-domain] Cd Length: 337 Bit Score: 81.07 E-value: 1.35e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1648 EASILRKmrrltdyYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFI------SARAKRkasALRELNILSHL-DHERILY 1720
Cdd:cd07852      2 DKHILRR-------YEILKKLGKGAYGIVWKAIDKKTGEVVALKKIfdafrnATDAQR---TFREIMFLQELnDHPNIIK 71

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1721 FHDAFEKKN----------------AVIiitelcheelldrltkKSTILES-EIRSSVRQLLEGINYLHQLDILHLDIKP 1783
Cdd:cd07852     72 LLNVIRAENdkdiylvfeymetdlhAVI----------------RANILEDiHKQYIMYQLLKALKYLHSGGVIHRDLKP 135

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1784 DNILMadhSSD-QIRICDFGNAVKFMPDEAQYCKYGTPEFVA------PEI-VNQTPVSKATDIWPIGvltylC-----L 1850
Cdd:cd07852    136 SNILL---NSDcRVKLADFGLARSLSQLEEDDENPVLTDYVAtrwyraPEIlLGSTRYTKGVDMWSVG-----CilgemL 207

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1851 TGVSPFAGEN------------DRSSVLNIRNYNVAFEESM---------------FTDLCHEAKGFVIKLLVAD-RLRP 1902
Cdd:cd07852    208 LGKPLFPGTStlnqlekiieviGRPSAEDIESIQSPFAATMleslppsrpksldelFPKASPDALDLLKKLLVFNpNKRL 287

                          330
                   ....*....|..
gi 1207186029 1903 DANECLRHPWFK 1914
Cdd:cd07852    288 TAEEALRHPYVA 299

Catalytic domain of the Protein Serine/Threonine Kinase, G protein-coupled Receptor Kinase 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK7 (also called iodopsin kinase) belongs to the visual group of GRKs. It is primarily found in the retina and plays a role in the regulation of opsin light receptors. GRK7 is located in retinal cone outer segments and plays an important role in regulating photoresponse of the cones. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors, which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK7 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270758 [Multi-domain] Cd Length: 286 Bit Score: 80.33 E-value: 1.49e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKIVPYEPESKQT----VLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLH 3383
Cdd:cd05607     12 KGGFGEVCAVQVKNTGQMYACKKLDKKRLKKKSgekmALLEKEILEKVNSPFIVSLAYAFETKTHLCLVMSLMNGGDLKY 91

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3384 SL--IDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLflKQFSPPIGTLDY 3461
Cdd:cd05607     92 HIynVGERGIEMERVIFYSAQITCGILHLHSLKIVYRDMKPENVLLDDNGNCRLSDLGLAVEVKEG--KPITQRAGTNGY 169

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*
gi 1207186029 3462 MSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFteNDPAETEAR 3506
Cdd:cd05607    170 MAPEILKEESYSYPVDWFAMGCSIYEMVAGRTPF--RDHKEKVSK 212

Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK1 is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK) and is also called MAP3K9. MAP3Ks phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Little is known about the specific function of MLK1. It is capable of activating the c-Jun N-terminal kinase pathway. Mice lacking both MLK1 and MLK2 are viable, fertile, and have normal life spans. There could be redundancy in the function of MLKs. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The MLK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271047 [Multi-domain] Cd Length: 270 Bit Score: 79.70 E-value: 1.54e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3336 ESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLHSLIDRfRYSEDDVVAYIVQILQGLDYLHSRRI 3415
Cdd:cd14145     47 QTIENVRQEAKLFAMLKHPNIIALRGVCLKEPNLCLVMEFARGGPLNRVLSGK-RIPPDILVNWAVQIARGMNYLHCEAI 125

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3416 ---LHLDIKPENIIVTYM--------NVVKIIDFGSAQTFNPLflKQFSPPiGTLDYMSPEMLKGDVVGPPADIWSIGIL 3484
Cdd:cd14145    126 vpvIHRDLKSSNILILEKvengdlsnKILKITDFGLAREWHRT--TKMSAA-GTYAWMAPEVIRSSMFSKGSDVWSYGVL 202

                          170
                   ....*....|.
gi 1207186029 3485 TYIMLSGRLPF 3495
Cdd:cd14145    203 LWELLTGEVPF 213

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 9; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek9, also called Nercc1, is primarily a cytoplasmic protein but can also localize in the nucleus. It is involved in modulating chromosome alignment and splitting during mitosis. It interacts with the gamma-tubulin ring complex and the Ran GTPase, and is implicated in microtubule organization. Nek9 associates with FACT (FAcilitates Chromatin Transcription) and modulates interphase progression. It also interacts with Nek6, and Nek7, during mitosis, resulting in their activation. Nek9 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270860 [Multi-domain] Cd Length: 256 Bit Score: 79.40 E-value: 1.54e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFS----YVKR-----VIQKAGKLEYAAKfisaraKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITELC 1738
Cdd:cd08221      8 LGRGAFGeavlYRKTednslVVWKEVNLSRLSE------KERRDALNEIDILSLLNHDNIITYYNHFLDGESLFIEMEYC 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1739 HE-ELLDRLTKKSTIL--ESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMAdhSSDQIRICDFGNAvKFMPDEAQYC 1815
Cdd:cd08221     82 NGgNLHDKIAQQKNQLfpEEVVLWYLYQIVSAVSHIHKAGILHRDIKTLNIFLT--KADLVKLGDFGIS-KVLDSESSMA 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1816 K--YGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDlchEAKGFVIK 1893
Cdd:cd08221    159 EsiVGTPYYMSPELVQGVKYNFKSDIWAVGCVLYELLTLKRTFDATNPLRLAVKIVQGEYEDIDEQYSE---EIIQLVHD 235

                          250       260
                   ....*....|....*....|.
gi 1207186029 1894 LLVAD-RLRPDANECLRHPWF 1913
Cdd:cd08221    236 CLHQDpEDRPTAEELLERPLL 256

Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAO1 is sometimes referred to as prostate-derived sterile 20-like kinase 2 (PSK2). TAO1 activates the p38 MAPK through direct interaction with and activation of MEK3. TAO1 is highly expressed in the brain and may play a role in neuronal apoptosis. TAO1 interacts with the checkpoint proteins BubR1 and Mad2, and plays an important role in regulating mitotic progression, which is required for both chromosome congression and checkpoint-induced anaphase delay. TAO1 may play a role in protecting genomic stability. TAO proteins possess MAPK kinase kinase activity. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. The TAO1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270805 [Multi-domain] Cd Length: 317 Bit Score: 80.86 E-value: 1.59e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3296 PQKPYTFMDEKARGRFGVIRECRENATGNLYMAKIVPYE----PESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVL 3371
Cdd:cd06635     23 PEKLFSDLREIGHGSFGAVYFARDVRTSEVVAIKKMSYSgkqsNEKWQDIIKEVKFLQRIKHPNSIEYKGCYLREHTAWL 102

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3372 ISECC--SGKELLHslIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLfl 3449
Cdd:cd06635    103 VMEYClgSASDLLE--VHKKPLQEIEIAAITHGALQGLAYLHSHNMIHRDIKAGNILLTEPGQVKLADFGSASIASPA-- 178

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3450 kqfSPPIGTLDYMSPE----MLKGDVVGpPADIWSIGIlTYIMLSGRLPFTENDPAETeARIQAAKFDLSKLYQNV-SQS 3524
Cdd:cd06635    179 ---NSFVGTPYWMAPEvilaMDEGQYDG-KVDVWSLGI-TCIELAERKPPLFNMNAMS-ALYHIAQNESPTLQSNEwSDY 252

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|.
gi 1207186029 3525 ASLFIKKILCSYPWARPTikdcfTNSWLQDAYLMRLRRQTL 3565
Cdd:cd06635    253 FRNFVDSCLQKIPQDRPT-----SEELLKHMFVLRERPETV 288

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 10; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. No function has yet been ascribed to Nek10. The gene encoding Nek10 is a putative causative gene for breast cancer; it is located within a breast cancer susceptibility loci on chromosome 3p24. Nek10 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270867 [Multi-domain] Cd Length: 270 Bit Score: 79.85 E-value: 1.60e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLE-YAAKFIS-------ARAKRKASALR----ELNIL-SHLDHERILYFHDAFEKK 1728
Cdd:cd08528      2 YAVLELLGSGAFGCVYKVRKKSNGQTlLALKEINmtnpafgRTEQERDKSVGdiisEVNIIkEQLRHPNIVRYYKTFLEN 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1729 NAVIIITELCH----EELLDRLT-KKSTILESEIRSSVRQLLEGINYLH-QLDILHLDIKPDNILMADhsSDQIRICDFG 1802
Cdd:cd08528     82 DRLYIVMELIEgaplGEHFSSLKeKNEHFTEDRIWNIFVQMVLALRYLHkEKQIVHRDLKPNNIMLGE--DDKVTITDFG 159

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1207186029 1803 NAVKFMPDEAQYCK-YGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGEN 1860
Cdd:cd08528    160 LAKQKGPESSKMTSvVGTILYSCPEIVQNEPYGEKADIWALGCILYQMCTLQPPFYSTN 218

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK4 has a limited tissue distribution. It is mainly found in the testis, but is also present in the cerebellum and kidney. It is expressed as multiple splice variants with different domain architectures and is post-translationally palmitoylated and localized in the membrane. GRK4 polymorphisms are associated with hypertension and salt sensitivity, as they cause hyperphosphorylation, desensitization, and internalization of the dopamine 1 (D1) receptor while increasing the expression of the angiotensin II type 1 receptor. GRK4 plays a crucial role in the D1 receptor regulation of sodium excretion and blood pressure. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173720 [Multi-domain] Cd Length: 285 Bit Score: 80.04 E-value: 1.60e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1665 HKEIGRGAFSYVKRV-IQKAGKLEYAAKFISARAKRK---ASALRELNILSHLDHERILYFHDAFEKKNAV-IIITELCH 1739
Cdd:cd05631      5 YRVLGKGGFGEVCACqVRATGKMYACKKLEKKRIKKRkgeAMALNEKRILEKVNSRFVVSLAYAYETKDALcLVLTIMNG 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1740 EELLDRLTKKSTILESEIRS--SVRQLLEGINYLHQLDILHLDIKPDNILMADHSsdQIRICDFGNAVKFMPDEAQYCKY 1817
Cdd:cd05631     85 GDLKFHIYNMGNPGFDEQRAifYAAELCCGLEDLQRERIVYRDLKPENILLDDRG--HIRISDLGLAVQIPEGETVRGRV 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1818 GTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDLCHEAKGFVIKLLVA 1897
Cdd:cd05631    163 GTVGYMAPEVINNEKYTFSPDWWGLGCLIYEMIQGQSPFRKRKERVKREEVDRRVKEDQEEYSEKFSEDAKSICRMLLTK 242

                          250       260
                   ....*....|....*....|....*.
gi 1207186029 1898 D---RL---RPDANECLRHPWFKTLN 1917
Cdd:cd05631    243 NpkeRLgcrGNGAAGVKQHPIFKNIN 268

Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase (IKK) alpha; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IKKalpha is involved in the non-canonical or alternative pathway of regulating Nuclear Factor-KappaB (NF-kB) proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. The non-canonical pathway functions in cells lacking NEMO (NF-kB Essential MOdulator) and IKKbeta. It is induced by a subset of TNFR family members including CD40, RANK, and B cell-activating factor receptor. IKKalpha processes the Inhibitor of NF-kB (IkB)-like C-terminus of NF-kB2/p100 to produce p52, allowing the p52/RelB dimer to migrate to the nucleus. This pathway is dependent on NIK (NF-kB Inducing Kinase) which phosphorylates and activates IKKalpha. The IKKalpha subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270941 [Multi-domain] Cd Length: 289 Bit Score: 79.96 E-value: 1.65e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3343 QEYDILKSLHHEKIMALHEAYVTPRYLV-----LISECCSG---KELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRR 3414
Cdd:cd14039     40 HEIQIMKKLNHPNVVKACDVPEEMNFLVndvplLAMEYCSGgdlRKLLNKPENCCGLKESQVLSLLSDIGSGIQYLHENK 119

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3415 ILHLDIKPENIIVTYMN---VVKIIDFGSAQTFNPLFL-KQFsppIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLS 3490
Cdd:cd14039    120 IIHRDLKPENIVLQEINgkiVHKIIDLGYAKDLDQGSLcTSF---VGTLQYLAPELFENKSYTVTVDYWSFGTMVFECIA 196


                   ....*...
gi 1207186029 3491 GRLPFTEN 3498
Cdd:cd14039    197 GFRPFLHN 204

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase 1; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MEK1 is a dual-specificity PK and a MAPK kinase (MAPKK or MKK) that phosphorylates and activates the downstream targets, ERK1 and ERK2, on specific threonine and tyrosine residues. The ERK cascade starts with extracellular signals including growth factors, hormones, and neurotransmitters, which act through receptors and ion channels to initiate intracellular signaling that leads to the activation at the MAPKKK (Raf-1 or MOS) level, which leads to the transmission of signals to MEK1, and finally to ERK1/2. The ERK cascade plays an important role in cell proliferation, differentiation, oncogenic transformation, and cell cycle control, as well as in apoptosis and cell survival under certain conditions. Gain-of-function mutations in genes encoding ERK cascade proteins, including MEK1, cause cardiofaciocutaneous (CFC) syndrome, a condition leading to multiple congenital anomalies and mental retardation in patients. MEK1 also plays a role in cell cycle control. The MEK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270816 [Multi-domain] Cd Length: 319 Bit Score: 80.48 E-value: 1.67e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3303 MDEKARGRFGVIRECRENATGNLYMAKIVPYE--PESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKE 3380
Cdd:cd06650     10 ISELGAGNGGVVFKVSHKPSGLVMARKLIHLEikPAIRNQIIRELQVLHECNSPYIVGFYGAFYSDGEISICMEHMDGGS 89

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3381 LLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSR-RILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLKQFsppIGTL 3459
Cdd:cd06650     90 LDQVLKKAGRIPEQILGKVSIAVIKGLTYLREKhKIMHRDVKPSNILVNSRGEIKLCDFGVSGQLIDSMANSF---VGTR 166

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*
gi 1207186029 3460 DYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETE 3504
Cdd:cd06650    167 SYMSPERLQGTHYSVQSDIWSMGLSLVEMAVGRYPIPPPDAKELE 211

Catalytic domain of Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. They can be classified into receptor and non-receptor tyr kinases. PTKs play important roles in many cellular processes including, lymphocyte activation, epithelium growth and maintenance, metabolism control, organogenesis regulation, survival, proliferation, differentiation, migration, adhesion, motility, and morphogenesis. Receptor tyr kinases (RTKs) are integral membrane proteins which contain an extracellular ligand-binding region, a transmembrane segment, and an intracellular tyr kinase domain. RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain, leading to intracellular signaling. Some RTKs are orphan receptors with no known ligands. Non-receptor (or cytoplasmic) tyr kinases are distributed in different intracellular compartments and are usually multi-domain proteins containing a catalytic tyr kinase domain as well as various regulatory domains such as SH3 and SH2. PTKs are usually autoinhibited and require a mechanism for activation. In many PTKs, the phosphorylation of tyr residues in the activation loop is essential for optimal activity. Aberrant expression of PTKs is associated with many development abnormalities and cancers.The PTK family is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270623 [Multi-domain] Cd Length: 262 Bit Score: 79.12 E-value: 2.24e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1666 KEIGRGAFSYVKR---VIQKAGKLEYAAKFI--SARAKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITELCHE 1740
Cdd:cd00192      1 KKLGEGAFGEVYKgklKGGDGKTVDVAVKTLkeDASESERKDFLKEARVMKKLGHPNVVRLLGVCTEEEPLYLVMEYMEG 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1741 -ELLDRLTKKSTILESEIRS--SVRQLL-------EGINYLHQLDILHLDIKPDNILMADHssDQIRICDFGNAvKFMPD 1810
Cdd:cd00192     81 gDLLDFLRKSRPVFPSPEPStlSLKDLLsfaiqiaKGMEYLASKKFVHRDLAARNCLVGED--LVVKISDFGLS-RDIYD 157

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1207186029 1811 EAQYCKYGTPEF----VAPEIVNQTPVSKATDIWPIGVLTYLCLT-GVSPFAG 1858
Cdd:cd00192    158 DDYYRKKTGGKLpirwMAPESLKDGIFTSKSDVWSFGVLLWEIFTlGATPYPG 210

Catalytic subunit (alpha) of the Serine/Threonine Kinase, Casein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CK2 is a tetrameric protein with two catalytic (alpha) and two regulatory (beta) subunits. It is constitutively active and ubiquitously expressed, and is found in the cytoplasm, nucleus, as well as in the plasma membrane. It phosphorylates a wide variety of substrates including gylcogen synthase, cell cycle proteins, nuclear proteins (e.g. DNA topoisomerase II), and ion channels (e.g. ENaC), among others. It may be considered a master kinase controlling the activity or lifespan of many other kinases and exerting its effect over cell fate, gene expression, protein synthesis and degradation, and viral infection. CK2 is implicated in every stage of the cell cycle and is required for cell cycle progression. It plays crucial roles in cell differentiation, proliferation, and survival, and is thus implicated in cancer. CK2 is not an oncogene by itself but elevated CK2 levels create an environment that enhances the survival of tumor cells. The CK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271034 [Multi-domain] Cd Length: 306 Bit Score: 79.51 E-value: 3.52e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1660 DYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKAsaLRELNILSHL-DHERILYFHDAF---EKKNAVIIIT 1735
Cdd:cd14132     18 DDYEIIRKIGRGKYSEVFEGINIGNNEKVVIKVLKPVKKKKI--KREIKILQNLrGGPNIVKLLDVVkdpQSKTPSLIFE 95

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1736 ELCHEELLDRLTKKSTIlesEIRSSVRQLLEGINYLHQLDILHLDIKPDNIlMADHSSDQIRICDFGNAVKFMPDEAQYC 1815
Cdd:cd14132     96 YVNNTDFKTLYPTLTDY---DIRYYMYELLKALDYCHSKGIMHRDVKPHNI-MIDHEKRKLRLIDWGLAEFYHPGQEYNV 171

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1816 KYGTPEFVAPEI-VNQTPVSKATDIWPIGVLTYLCLTGVSP-FAGENDRSSVLNI-------------RNYNVAFEESM- 1879
Cdd:cd14132    172 RVASRYYKGPELlVDYQYYDYSLDMWSLGCMLASMIFRKEPfFHGHDNYDQLVKIakvlgtddlyaylDKYGIELPPRLn 251

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1207186029 1880 -------------FT-----DLC-HEAKGFVIKLLVAD-RLRPDANECLRHPWFK 1914
Cdd:cd14132    252 dilgrhskkpwerFVnsenqHLVtPEALDLLDKLLRYDhQERITAKEAMQHPYFD 306

Catalytic domain of the Serine/Threonine Kinase, PFTAIRE-1 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PFTAIRE-1 is widely expressed except in the spleen and thymus. It is highly expressed in the brain, heart, pancreas, testis, and ovary, and is localized in the cytoplasm. It is regulated by cyclin D3 and is inhibited by the p21 cell cycle inhibitor. It has also been shown to interact with the membrane-associated cyclin Y, which recruits the protein to the plasma membrane. PFTAIRE-1 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PFTAIRE-1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143374 [Multi-domain] Cd Length: 303 Bit Score: 79.35 E-value: 3.84e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPESKQ--TVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCS 3377
Cdd:cd07869      7 YEKLEKLGEGSYATVYKGKSKVNGKLVALKVIRLQEEEGTpfTAIREASLLKGLKHANIVLLHDIIHTKETLTLVFEYVH 86

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3378 GKelLHSLIDRFR--YSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTfNPLFLKQFSPP 3455
Cdd:cd07869     87 TD--LCQYMDKHPggLHPENVKLFLFQLLRGLSYIHQRYILHRDLKPQNLLISDTGELKLADFGLARA-KSVPSHTYSNE 163

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|.
gi 1207186029 3456 IGTLDYMSPEMLKGDV-VGPPADIWSIGILTYIMLSGRLPF 3495
Cdd:cd07869    164 VVTLWYRPPDVLLGSTeYSTCLDMWGVGCIFVEMIQGVAAF 204

Catalytic domain of Serine/Threonine Kinase 16; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK16 is associated with many names including Myristylated and Palmitylated Serine/threonine Kinase 1 (MPSK1), Kinase related to cerevisiae and thaliana (Krct), and Protein Kinase expressed in day 12 fetal liver (PKL12). It is widely expressed in mammals with highest levels found in liver, testis, and kidney. It is localized in the Golgi but is translocated to the nucleus upon disorganization of the Golgi. STK16 is constitutively active and is capable of phosphorylating itself and other substrates. It may be involved in regulating stromal-epithelial interactions during mammary gland ductal morphogenesis. It may also function as a transcriptional co-activator of type-C natriuretic peptide and VEGF. The STK16 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270888 [Multi-domain] Cd Length: 282 Bit Score: 78.88 E-value: 3.94e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKR-KASALREL---------NILSHLDHERIlyfHDAFEKKNAV 1731
Cdd:cd13986      2 YRIQRLLGEGGFSFVYLVEDLSTGRLYALKKILCHSKEdVKEAMREIenyrlfnhpNILRLLDSQIV---KEAGGKKEVY 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1732 IIITELCHEELLD----RLTKKSTILESEIRSSVRQLLEGINYLHQLDIL---HLDIKPDNILMadHSSDQIRICDFGNA 1804
Cdd:cd13986     79 LLLPYYKRGSLQDeierRLVKGTFFPEDRILHIFLGICRGLKAMHEPELVpyaHRDIKPGNVLL--SEDDEPILMDLGSM 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1805 VK------------FMPDEA-QYCkygTPEFVAPEIVN---QTPVSKATDIWPIGVLTYLCLTGVSPFAGENDR--SSVL 1866
Cdd:cd13986    157 NParieiegrrealALQDWAaEHC---TMPYRAPELFDvksHCTIDEKTDIWSLGCTLYALMYGESPFERIFQKgdSLAL 233

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*.
gi 1207186029 1867 NIRNYNVAF-EESMFTDLCHEakgFVIKLLVADRL-RPDANECLRH 1910
Cdd:cd13986    234 AVLSGNYSFpDNSRYSEELHQ---LVKSMLVVNPAeRPSIDDLLSR 276

Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase (IKK) beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IKKbeta is involved in the classical pathway of regulating Nuclear Factor-KappaB (NF-kB) proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. The classical pathway regulates the majority of genes activated by NF-kB including those encoding cytokines, chemokines, leukocyte adhesion molecules, and anti-apoptotic factors. It involves NEMO (NF-kB Essential MOdulator)- and IKKbeta-dependent phosphorylation and degradation of the Inhibitor of NF-kB (IkB), which liberates NF-kB dimers (typified by the p50-p65 heterodimer) from an inactive IkB/dimeric NF-kB complex, enabling them to migrate to the nucleus where they regulate gene transcription. The IKKbeta subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270940 [Multi-domain] Cd Length: 290 Bit Score: 78.85 E-value: 4.01e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3314 IRECRENATgnlymakivpyePESKQTVLQEYDILKSLHHEKIMALHEA-----YVTPRYLVLIS-ECCSGKEL---LHS 3384
Cdd:cd14038     24 IKQCRQELS------------PKNRERWCLEIQIMKRLNHPNVVAARDVpeglqKLAPNDLPLLAmEYCQGGDLrkyLNQ 91

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3385 LIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMN---VVKIIDFGSAQTFNPLFL-KQFsppIGTLD 3460
Cdd:cd14038     92 FENCCGLREGAILTLLSDISSALRYLHENRIIHRDLKPENIVLQQGEqrlIHKIIDLGYAKELDQGSLcTSF---VGTLQ 168

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*....
gi 1207186029 3461 YMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTEN-DPAETEARIQ 3508
Cdd:cd14038    169 YLAPELLEQQKYTVTVDYWSFGTLAFECITGFRPFLPNwQPVQWHGKVR 217

Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase (IKK) alpha; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IKKalpha is involved in the non-canonical or alternative pathway of regulating Nuclear Factor-KappaB (NF-kB) proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. The non-canonical pathway functions in cells lacking NEMO (NF-kB Essential MOdulator) and IKKbeta. It is induced by a subset of TNFR family members including CD40, RANK, and B cell-activating factor receptor. IKKalpha processes the Inhibitor of NF-kB (IkB)-like C-terminus of NF-kB2/p100 to produce p52, allowing the p52/RelB dimer to migrate to the nucleus. This pathway is dependent on NIK (NF-kB Inducing Kinase) which phosphorylates and activates IKKalpha. The IKKalpha subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270941 [Multi-domain] Cd Length: 289 Bit Score: 78.81 E-value: 4.07e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYV---------KRVIQKAGKLEYAAKfisarakRKASALRELNILSHLDHERILYFHDAFEKKNAVI-----I 1733
Cdd:cd14039      1 LGTGGFGNVclyqnqetgEKIAIKSCRLELSVK-------NKDRWCHEIQIMKKLNHPNVVKACDVPEEMNFLVndvplL 73

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1734 ITELCHEELLDRLTKKST----ILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSDQI-RICDFGNAVKFm 1808
Cdd:cd14039     74 AMEYCSGGDLRKLLNKPEnccgLKESQVLSLLSDIGSGIQYLHENKIIHRDLKPENIVLQEINGKIVhKIIDLGYAKDL- 152

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1809 pDEAQYCK--YGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPF 1856
Cdd:cd14039    153 -DQGSLCTsfVGTLQYLAPELFENKSYTVTVDYWSFGTMVFECIAGFRPF 201

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C theta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-theta is selectively expressed in T-cells and plays an important and non-redundant role in several aspects of T-cell biology. Although T-cells also express other PKC isoforms, PKC-theta is unique in that upon antigen stimulation, it is translocated to the plasma membrane at the immunological synapse, where it mediates signals essential for T-cell activation. It is essential for TCR-induced proliferation, cytokine production, T-cell survival, and the differentiation and effector function of T-helper (Th) cells, particularly Th2 and Th17. PKC-theta is being developed as a therapeutic target for Th2-mediated allergic inflammation and Th17-mediated autoimmune diseases. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270770 [Multi-domain] Cd Length: 331 Bit Score: 79.58 E-value: 4.15e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKIVpyepeSKQTVLQEYDILKSLHHEKIMAL---HE-------AYVTPRYLVLISECCS 3377
Cdd:cd05619     15 KGSFGKVFLAELKGTNQFFAIKAL-----KKDVVLMDDDVECTMVEKRVLSLaweHPflthlfcTFQTKENLFFVMEYLN 89

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3378 GKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTfNPLFLKQFSPPIG 3457
Cdd:cd05619     90 GGDLMFHIQSCHKFDLPRATFYAAEIICGLQFLHSKGIVYRDLKLDNILLDKDGHIKIADFGMCKE-NMLGDAKTSTFCG 168

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*
gi 1207186029 3458 TLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAE 3502
Cdd:cd05619    169 TPDYIAPEILLGQKYNTSVDWWSFGVLLYEMLIGQSPFHGQDEEE 213

Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK1 is a MAPK kinase kinase (MAPKKK or MKKK) that phosphorylates and activates activates the ERK1/2 and c-Jun N-terminal kinase (JNK) pathways by activating their respective MAPKKs, MEK1/2 and MKK4/MKK7, respectively. MEKK1 is important in regulating cell survival and apoptosis. MEKK1 also plays a role in cell migration, tissue maintenance and homeostasis, and wound healing. The MEKK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270800 [Multi-domain] Cd Length: 268 Bit Score: 78.24 E-value: 5.19e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFS--YVKRVIqKAGKLeYAAKFIS-------ARAKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITE-L 1737
Cdd:cd06630      8 LGTGAFSscYQARDV-KTGTL-MAVKQVSfcrnsssEQEEVVEAIREEIRMMARLNHPNIVRMLGATQHKSHFNIFVEwM 85

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1738 CHEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMaDHSSDQIRICDFGNAVKFMPD-----EA 1812
Cdd:cd06630     86 AGGSVASLLSKYGAFSENVIINYTLQILRGLAYLHDNQIIHRDLKGANLLV-DSTGQRLRIADFGAAARLASKgtgagEF 164

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1813 QYCKYGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIrnYNVAFEE---SMFTDLCHEAKG 1889
Cdd:cd06630    165 QGQLLGTIAFMAPEVLRGEQYGRSCDVWSVGCVIIEMATAKPPWNAEKISNHLALI--FKIASATtppPIPEHLSPGLRD 242

                          250       260
                   ....*....|....*....|....*.
gi 1207186029 1890 FVIKLLVADR-LRPDANECLRHPWFK 1914
Cdd:cd06630    243 VTLRCLELQPeDRPPARELLKHPVFT 268

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek4 is highly abundant in the testis. Its specific function is unknown. Neks are involved in the regulation of downstream processes following the activation of Cdc2, and many of their functions are cell cycle-related. They play critical roles in microtubule dynamics during ciliogenesis and mitosis. Nek4 is one in a family of 11 different Neks (Nek1-11). The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270862 [Multi-domain] Cd Length: 257 Bit Score: 77.86 E-value: 5.81e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFI----SARAKRKAsALRELNILSHLDHERILYFHDAFEKKNAVI-IITE 1736
Cdd:cd08223      2 YQFLRVIGKGSYGEVWLVRHKRDRKQYVIKKLnlknASKRERKA-AEQEAKLLSKLKHPNIVSYKESFEGEDGFLyIVMG 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1737 LCHE-ELLDRLTKKSTIL--ESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMAdhSSDQIRICDFGNAVKFmpdEAQ 1813
Cdd:cd08223     81 FCEGgDLYTRLKEQKGVLleERQVVEWFVQIAMALQYMHERNILHRDLKTQNIFLT--KSNIIKVGDLGIARVL---ESS 155

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1814 Y----CKYGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNV-AFEESMFTDLCHeak 1888
Cdd:cd08223    156 SdmatTLIGTPYYMSPELFSNKPYNHKSDVWALGCCVYEMATLKHAFNAKDMNSLVYKILEGKLpPMPKQYSPELGE--- 232

                          250       260
                   ....*....|....*....|....*.
gi 1207186029 1889 gfVIKLLVADR--LRPDANECLRHPW 1912
Cdd:cd08223    233 --LIKAMLHQDpeKRPSVKRILRQPY 256

Catalytic domain of the Protein Serine/Threonine Kinase, Microtubule-associated serine/threonine kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAST kinases contain an N-terminal domain of unknown function, a central catalytic domain, and a C-terminal PDZ domain that mediates protein-protein interactions. There are four mammalian MAST kinases, named MAST1-MAST4. MAST1 is also called syntrophin-associated STK (SAST) while MAST2 is also called MAST205. MAST kinases are cytoskeletal associated kinases of unknown function that are also expressed at neuromuscular junctions and postsynaptic densities. MAST1, MAST2, and MAST3 bind and phosphorylate the tumor suppressor PTEN, and may contribute to the regulation and stabilization of PTEN. MAST2 is involved in the regulation of the Fc-gamma receptor of the innate immune response in macrophages, and may also be involved in the regulation of the Na+/H+ exchanger NHE3. The MAST kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270760 [Multi-domain] Cd Length: 280 Bit Score: 78.22 E-value: 6.31e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3339 QTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKE---LLHSLIDrfrYSEDDVVAYIVQILQGLDYLHSRRI 3415
Cdd:cd05609     45 QQVFVERDILTFAENPFVVSMYCSFETKRHLCMVMEYVEGGDcatLLKNIGP---LPVDMARMYFAETVLALEYLHSYGI 121

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3416 LHLDIKPENIIVTYMNVVKIIDFGSAQ------TFNpLF-------LKQFSPP--IGTLDYMSPEMLKGDVVGPPADIWS 3480
Cdd:cd05609    122 VHRDLKPDNLLITSMGHIKLTDFGLSKiglmslTTN-LYeghiekdTREFLDKqvCGTPEYIAPEVILRQGYGKPVDWWA 200

                          170       180
                   ....*....|....*....|..
gi 1207186029 3481 IGILTYIMLSGRLPFTENDPAE 3502
Cdd:cd05609    201 MGIILYEFLVGCVPFFGDTPEE 222

Catalytic domain of the Serine/Threonine Kinase, Extracellular signal-Regulated Kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ERK5 (also called Big MAPK1 (BMK1) or MAPK7) has a unique C-terminal extension, making it approximately twice as big as other MAPKs. This extension contains transcriptional activation capability which is inhibited by the N-terminal half. ERK5 is activated in response to growth factors and stress by a cascade that leads to its phosphorylation by the MAP2K MEK5, which in turn is regulated by the MAP3Ks MEKK2 and MEKK3. Activated ERK5 phosphorylates its targets including myocyte enhancer factor 2 (MEF2), Sap1a, c-Myc, and RSK. It plays a role in EGF-induced cell proliferation during the G1/S phase transition. Studies on knockout mice revealed that ERK5 is essential for cardiovascular development and plays an important role in angiogenesis. It is also critical for neural differentiation and survival. The ERK5 pathway has been implicated in the pathogenesis of many diseases including cancer, cardiac hypertrophy, and atherosclerosis. MAPKs are important mediators of cellular responses to extracellular signals. The ERK5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270842 [Multi-domain] Cd Length: 336 Bit Score: 79.33 E-value: 6.42e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3309 GRFGVIRECRENATGNLYMAKIVPY---EPESKQTVLQEYDILKSLHHEKIMALHEAYVTPR--------YLVL-ISECC 3376
Cdd:cd07855     16 GAYGVVCSAIDTKSGQKVAIKKIPNafdVVTTAKRTLRELKILRHFKHDNIIAIRDILRPKVpyadfkdvYVVLdLMESD 95

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3377 sgkelLHSLIdrfrYS-----EDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSA------QTFN 3445
Cdd:cd07855     96 -----LHHII----HSdqpltLEHIRYFLYQLLRGLKYIHSANVIHRDLKPSNLLVNENCELKIGDFGMArglctsPEEH 166

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3446 PLFLKQFsppIGTLDYMSPE-MLKGDVVGPPADIWSIGILTYIMLSGRLPFTEND---------------PAETEARIQA 3509
Cdd:cd07855    167 KYFMTEY---VATRWYRAPElMLSLPEYTQAIDMWSVGCIFAEMLGRRQLFPGKNyvhqlqliltvlgtpSQAVINAIGA 243

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1207186029 3510 -------------AKFDLSKLYQNVSQSASLFIKKILCSYPWARPTIKDCFTNSWLQ 3553
Cdd:cd07855    244 drvrryiqnlpnkQPVPWETLYPKADQQALDLLSQMLRFDPSERITVAEALQHPFLA 300

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase 2; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MEK2 is a dual-specificity PK and a MAPK kinase (MAPKK or MKK) that phosphorylates and activates the downstream targets, ERK1 and ERK2, on specific threonine and tyrosine residues. The ERK cascade starts with extracellular signals including growth factors, hormones, and neurotransmitters, which act through receptors and ion channels to initiate intracellular signaling that leads to the activation at the MAPKKK (Raf-1 or MOS) level, which leads to the transmission of signals to MEK2, and finally to ERK1/2. The ERK cascade plays an important role in cell proliferation, differentiation, oncogenic transformation, and cell cycle control, as well as in apoptosis and cell survival under certain conditions. Gain-of-function mutations in genes encoding ERK cascade proteins, including MEK2, cause cardiofaciocutaneous (CFC) syndrome, a condition leading to multiple congenital anomalies and mental retardation in patients. The MEK subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 132980 [Multi-domain] Cd Length: 331 Bit Score: 78.94 E-value: 7.22e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3305 EKARGRFGVIRECRENATGNLYMAKIVPYE--PESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELL 3382
Cdd:cd06649     12 ELGAGNGGVVTKVQHKPSGLIMARKLIHLEikPAIRNQIIRELQVLHECNSPYIVGFYGAFYSDGEISICMEHMDGGSLD 91

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3383 HSLIDRFRYSEDDVVAYIVQILQGLDYLHSR-RILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLKQFsppIGTLDY 3461
Cdd:cd06649     92 QVLKEAKRIPEEILGKVSIAVLRGLAYLREKhQIMHRDVKPSNILVNSRGEIKLCDFGVSGQLIDSMANSF---VGTRSY 168

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....
gi 1207186029 3462 MSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEA 3505
Cdd:cd06649    169 MSPERLQGTHYSVQSDIWSMGLSLVELAIGRYPIPPPDAKELEA 212

Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PIM gene locus was discovered as a result of the cloning of retroviral intergration sites in murine Moloney leukemia virus, leading to the identification of PIM kinases. They are constitutively active STKs with a broad range of cellular targets and are overexpressed in many haematopoietic malignancies and solid cancers. Vertebrates contain three distinct PIM kinase genes (PIM1-3); each gene may result in mutliple protein isoforms. There are two PIM1 isoforms resulting from alternative translation initiation sites. PIM1 is the founding member of the PIM subfamily. It is involved in regulating cell growth, differentiation, and apoptosis. It promotes cancer development when overexpressed by inhibiting apoptosis, promoting cell proliferation, and promoting genomic instability. The PIM1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271002 [Multi-domain] Cd Length: 254 Bit Score: 77.32 E-value: 7.39e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3379 KELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTY-MNVVKIIDFGSAQTFNPLFLKQFSppiG 3457
Cdd:cd14100     91 QDLFDFITERGALPEELARSFFRQVLEAVRHCHNCGVLHRDIKDENILIDLnTGELKLIDFGSGALLKDTVYTDFD---G 167

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3458 TLDYMSPEMLKGDVV-GPPADIWSIGILTYIMLSGRLPFtENDpaetEARIQAAKFdlskLYQNVSQSASLFIKKILCSY 3536
Cdd:cd14100    168 TRVYSPPEWIRFHRYhGRSAAVWSLGILLYDMVCGDIPF-EHD----EEIIRGQVF----FRQRVSSECQHLIKWCLALR 238

                          170
                   ....*....|....*.
gi 1207186029 3537 PWARPTIKDCFTNSWL 3552
Cdd:cd14100    239 PSDRPSFEDIQNHPWM 254

Catalytic domain of fungal PBS2-like dual-specificity Mitogen-Activated Protein Kinase Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include the MAPKKs Polymyxin B resistance protein 2 (PBS2) from Saccharomyces cerevisiae, Wis1 from Schizosaccharomyces pombe, and related proteins. PBS2 and Wis1 are components of stress-activated MAPK cascades in budding and fission yeast, respectively. PBS2 is the specific activator of the MAPK Hog1, which plays a central role in the response of budding yeast to stress including exposure to arsenite and hyperosmotic environments. Wis1 phosphorylates and activates the MAPK Sty1 (also called Spc1 or Phh1), which stimulates a transcriptional response to a wide range of cellular insults through the bZip transcription factors Atf1, Pcr1, and Pap1. The PBS2 subfamily is part of a larger superfamily that includes the catalytic domains of STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 132953 [Multi-domain] Cd Length: 286 Bit Score: 77.97 E-value: 7.53e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1660 DYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFI--SARAKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITEL 1737
Cdd:cd06622      1 DEIEVLDELGKGNYGSVYKVLHRPTGVTMAMKEIrlELDESKFNQIIMELDILHKAVSPYIVDFYGAFFIEGAVYMCMEY 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1738 CHEELLDRLTKKST----ILESEIRSSVRQLLEGINYL-HQLDILHLDIKPDNILMadHSSDQIRICDF---GNAVKFMP 1809
Cdd:cd06622     81 MDAGSLDKLYAGGVategIPEDVLRRITYAVVKGLKFLkEEHNIIHRDVKPTNVLV--NGNGQVKLCDFgvsGNLVASLA 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1810 DEAQYCK-YGTPEFVAPEIVNQTPV-SKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDLCHEA 1887
Cdd:cd06622    159 KTNIGCQsYMAPERIKSGGPNQNPTyTVQSDVWSLGLSILEMALGRYPYPPETYANIFAQLSAIVDGDPPTLPSGYSDDA 238

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*...
gi 1207186029 1888 KGFVIKLLVAD-RLRPDANECLRHPWFKTLNKGKSISTESLKKFLSRR 1934
Cdd:cd06622    239 QDFVAKCLNKIpNRRPTYAQLLEHPWLVKYKNADVDMAEWVTGALKRK 286

Catalytic domain of the Serine/Threonine Kinase, Traf2- and Nck-Interacting Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TNIK is an effector of Rap2, a small GTP-binding protein from the Ras family. TNIK specifically activates the c-Jun N-terminal kinase (JNK) pathway and plays a role in regulating the actin cytoskeleton. The TNIK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270807 [Multi-domain] Cd Length: 296 Bit Score: 78.22 E-value: 7.69e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3296 PQKPYTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPESKQTVLQEYDILKSL-HHEKIMALHEAYVTPR------Y 3368
Cdd:cd06637      4 PAGIFELVELVGNGTYGQVYKGRHVKTGQLAAIKVMDVTGDEEEEIKQEINMLKKYsHHRNIATYYGAFIKKNppgmddQ 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3369 LVLISECCsGKELLHSLIDRFRYS--EDDVVAYIV-QILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFN 3445
Cdd:cd06637     84 LWLVMEFC-GAGSVTDLIKNTKGNtlKEEWIAYICrEILRGLSHLHQHKVIHRDIKGQNVLLTENAEVKLVDFGVSAQLD 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3446 PLFLKQfSPPIGTLDYMSPEMLKGDvVGPPA------DIWSIGILTYIMLSGRLPFTENDPAET--------EARIQAAK 3511
Cdd:cd06637    163 RTVGRR-NTFIGTPYWMAPEVIACD-ENPDAtydfksDLWSLGITAIEMAEGAPPLCDMHPMRAlfliprnpAPRLKSKK 240

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|...
gi 1207186029 3512 FdlSKLYQNvsqsaslFIKKILCSYPWARPTIKDCFTNSWLQD 3554
Cdd:cd06637    241 W--SKKFQS-------FIESCLVKNHSQRPSTEQLMKHPFIRD 274

Pseudokinase domain of Kinase Suppressor of Ras; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. KSR is a scaffold protein that functions downstream of Ras and upstream of Raf in the Extracellular signal-Regulated Kinase (ERK) pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. KSR proteins regulate the assembly and activation of the Raf/MEK/ERK module upon Ras activation at the membrane by direct association of its components. They are widely regarded as pseudokinases, but there is some debate in this designation as a few groups have reported detecting kinase catalytic activity for KSRs, specifically KSR1. Vertebrates contain two KSR proteins, KSR1 and KSR2. The KSR subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270965 [Multi-domain] Cd Length: 271 Bit Score: 77.39 E-value: 8.54e-15

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3302 FMDEKARGRFGVIRECRENATGNLYMAKIVPYEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKEL 3381
Cdd:cd14063      4 IKEVIGKGRFGRVHRGRWHGDVAIKLLNIDYLNEEQLEAFKEEVAAYKNTRHDNLVLFMGACMDPPHLAIVTSLCKGRTL 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3382 ---LHSLIDRFRYSEDDVVAyiVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVkIIDFG----SAQTFNPLFLKQFSP 3454
Cdd:cd14063     84 yslIHERKEKFDFNKTVQIA--QQICQGMGYLHAKGIIHKDLKSKNIFLENGRVV-ITDFGlfslSGLLQPGRREDTLVI 160

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1207186029 3455 PIGTLDYMSPEMLKG-----DVVG-----PPADIWSIGILTYIMLSGRLPFTEnDPAE 3502
Cdd:cd14063    161 PNGWLCYLAPEIIRAlspdlDFEEslpftKASDVYAFGTVWYELLAGRWPFKE-QPAE 217

Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase (IKK) beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IKKbeta is involved in the classical pathway of regulating Nuclear Factor-KappaB (NF-kB) proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. The classical pathway regulates the majority of genes activated by NF-kB including those encoding cytokines, chemokines, leukocyte adhesion molecules, and anti-apoptotic factors. It involves NEMO (NF-kB Essential MOdulator)- and IKKbeta-dependent phosphorylation and degradation of the Inhibitor of NF-kB (IkB), which liberates NF-kB dimers (typified by the p50-p65 heterodimer) from an inactive IkB/dimeric NF-kB complex, enabling them to migrate to the nucleus where they regulate gene transcription. The IKKbeta subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270940 [Multi-domain] Cd Length: 290 Bit Score: 77.70 E-value: 1.06e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYVKRVIQKAGKLEYAAKF----ISARAKRKASAlrELNILSHLDHERILYFHDAFEKKNAV------IIITEL 1737
Cdd:cd14038      2 LGTGGFGNVLRWINQETGEQVAIKQcrqeLSPKNRERWCL--EIQIMKRLNHPNVVAARDVPEGLQKLapndlpLLAMEY 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1738 CH----EELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSDQI-RICDFGNAVKFmpDEA 1812
Cdd:cd14038     80 CQggdlRKYLNQFENCCGLREGAILTLLSDISSALRYLHENRIIHRDLKPENIVLQQGEQRLIhKIIDLGYAKEL--DQG 157

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*.
gi 1207186029 1813 QYCK--YGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPF 1856
Cdd:cd14038    158 SLCTsfVGTLQYLAPELLEQQKYTVTVDYWSFGTLAFECITGFRPF 203

Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RIP1 harbors a C-terminal Death domain (DD), which binds death receptors (DRs) including TNF receptor 1, Fas, TNF-related apoptosis-inducing ligand receptor 1 (TRAILR1), and TRAILR2. It also interacts with other DD-containing adaptor proteins such as TRADD and FADD. RIP1 can also recruit other kinases including MEKK1, MEKK3, and RIP3 through an intermediate domain (ID) that bears a RIP homotypic interaction motif (RHIM). RIP1 plays a crucial role in determining a cell's fate, between survival or death, following exposure to stress signals. It is important in the signaling of NF-kappaB and MAPKs, and it links DR-associated signaling to reactive oxygen species (ROS) production. Abnormal RIP1 function may result in ROS accummulation affecting inflammatory responses, innate immunity, stress responses, and cell survival. RIP kinases serve as essential sensors of cellular stress. The RIP1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270929 [Multi-domain] Cd Length: 267 Bit Score: 77.15 E-value: 1.20e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3309 GRFGVIRECRENATGNLYMAKIV--PYEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLH--- 3383
Cdd:cd14027      4 GGFGKVSLCFHRTQGLVVLKTVYtgPNCIEHNEALLEEGKMMNRLRHSRVVKLLGVILEEGKYSLVMEYMEKGNLMHvlk 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3384 ------SLIDRFryseddvvayIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAqTFNPL---------- 3447
Cdd:cd14027     84 kvsvplSVKGRI----------ILEIIEGMAYLHGKGVIHKDLKPENILVDNDFHIKIADLGLA-SFKMWskltkeehne 152

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3448 ---FLKQFSPPIGTLDYMSPEMLKGDVVGP--PADIWSIGILTYIMLSGRLPFtENDPAETE---ARIQAAKFDLSKLYQ 3519
Cdd:cd14027    153 qreVDGTAKKNAGTLYYMAPEHLNDVNAKPteKSDVYSFAIVLWAIFANKEPY-ENAINEDQiimCIKSGNRPDVDDITE 231

                          250       260       270
                   ....*....|....*....|....*....|
gi 1207186029 3520 NVSQSASLFIKKILCSYPWARPTIKDCFTN 3549
Cdd:cd14027    232 YCPREIIDLMKLCWEANPEARPTFPGIEEK 261

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK5 is mainly expressed in the brain. It is not required for viability, but together with PAK6, it is required for normal levels of locomotion and activity, and for learning and memory. PAK5 cooperates with Inca (induced in neural crest by AP2) in the regulation of cell adhesion and cytoskeletal organization in the embryo and in neural crest cells during craniofacial development. PAK5 may also play a role in controlling the signaling of Raf-1, an effector of Ras, at the mitochondria. PAK5 belongs to the group II PAKs, which contain a PBD (p21-binding domain) and a C-terminal catalytic domain, but do not harbor an AID (autoinhibitory domain) or SH3 binding sites. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 132989 [Multi-domain] Cd Length: 292 Bit Score: 77.77 E-value: 1.21e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1660 DYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASAL-RELNILSHLDHERILYFHDAFEKKNAVIIITELC 1738
Cdd:cd06658     22 EYLDSFIKIGEGSTGIVCIATEKHTGKQVAVKKMDLRKQQRRELLfNEVVIMRDYHHENVVDMYNSYLVGDELWVVMEFL 101

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1739 HEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMAdhSSDQIRICDFG---NAVKFMPDEAQYC 1815
Cdd:cd06658    102 EGGALTDIVTHTRMNEEQIATVCLSVLRALSYLHNQGVIHRDIKSDSILLT--SDGRIKLSDFGfcaQVSKEVPKRKSLV 179

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1816 kyGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNyNVAFEESMFTDLCHEAKGFVIKLL 1895
Cdd:cd06658    180 --GTPYWMAPEVISRLPYGTEVDIWSLGIMVIEMIDGEPPYFNEPPLQAMRRIRD-NLPPRVKDSHKVSSVLRGFLDLML 256

                          250       260
                   ....*....|....*....|
gi 1207186029 1896 VAD-RLRPDANECLRHPWFK 1914
Cdd:cd06658    257 VREpSQRATAQELLQHPFLK 276

Catalytic domain of Fungal Sid2p-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This group contains fungal kinases including Schizosaccharomyces pombe Sid2p and Saccharomyces cerevisiae Dbf2p. Group members show similarity to NDR kinases in that they contain an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Sid2p plays a crucial role in the septum initiation network (SIN) and in the initiation of cytokinesis. Dbf2p is important in regulating the mitotic exit network (MEN) and in cytokinesis. The Sid2p-like group is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270751 [Multi-domain] Cd Length: 386 Bit Score: 78.92 E-value: 1.23e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1652 LRKMR---RLTDYyDVHKEIGRGAFSYV----KRVIQKAGKLEYAAKFISARAKRKASALRELNILSHLDHE---RILYf 1721
Cdd:cd05600      1 LRKRRtrlKLSDF-QILTQVGQGGYGSVflarKKDTGEICALKIMKKKVLFKLNEVNHVLTERDILTTTNSPwlvKLLY- 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1722 hdAFEKKNAVIIITE-LCHEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICD 1800
Cdd:cd05600     79 --AFQDPENVYLAMEyVPGGDFRTLLNNSGILSEEHARFYIAEMFAAISSLHQLGYIHRDLKPENFLI--DSSGHIKLTD 154

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1801 FG------------------NAVKFMPDEAQYCKY--------------------GTPEFVAPEIVNQTPVSKATDIWPI 1842
Cdd:cd05600    155 FGlasgtlspkkiesmkirlEEVKNTAFLELTAKErrniyramrkedqnyansvvGSPDYMAPEVLRGEGYDLTVDYWSL 234

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1843 GVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTD------LCHEAKGFVIKLLV--ADRLRpDANECLRHPWFK 1914
Cdd:cd05600    235 GCILFECLVGFPPFSGSTPNETWANLYHWKKTLQRPVYTDpdlefnLSDEAWDLITKLITdpQDRLQ-SPEQIKNHPFFK 313


                   ...
gi 1207186029 1915 TLN 1917
Cdd:cd05600    314 NID 316

Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinases 4 (also called ERK4) and 6 (also called ERK3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK4 (also called ERK4 or p63MAPK) and MAPK6 (also called ERK3 or p97MAPK) are atypical MAPKs that are not regulated by MAPK kinases. MAPK6 is expressed ubiquitously with highest amounts in brain and skeletal muscle. It may be involved in the control of cell differentiation by negatively regulating cell cycle progression in certain conditions. It may also play a role in glucose-induced insulin secretion. MAPK6 and MAPK4 cooperate to regulate the activity of MAPK-activated protein kinase 5 (MK5), leading to its relocation to the cytoplasm and exclusion from the nucleus. The MAPK6/MK5 and MAPK4/MK5 pathways may play critical roles in embryonic and post-natal development. MAPKs are important mediators of cellular responses to extracellular signals. The MAPK4/6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143359 [Multi-domain] Cd Length: 342 Bit Score: 78.28 E-value: 1.39e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3329 KIVPYEPESKQTVLQEYDILKSLHHEKIMALHEAY--------VTPRYLVLISECCSGKEL----LHSLIDRFRYSEDDV 3396
Cdd:cd07854     37 KIVLTDPQSVKHALREIKIIRRLDHDNIVKVYEVLgpsgsdltEDVGSLTELNSVYIVQEYmetdLANVLEQGPLSEEHA 116

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3397 VAYIVQILQGLDYLHSRRILHLDIKPENIIV-TYMNVVKIIDFGSAQTFNPLFLKQ--FSPPIGTLDYMSPEMLkgdvVG 3473
Cdd:cd07854    117 RLFMYQLLRGLKYIHSANVLHRDLKPANVFInTEDLVLKIGDFGLARIVDPHYSHKgyLSEGLVTKWYRSPRLL----LS 192

                          170       180
                   ....*....|....*....|....*..
gi 1207186029 3474 P-----PADIWSIGILTYIMLSGRLPF 3495
Cdd:cd07854    193 PnnytkAIDMWAAGCIFAEMLTGKPLF 219

Catalytic domain of the Serine/Threonine protein kinase, cyclin G-Associated Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GAK, also called auxilin-2, contains an N-terminal kinase domain that phosphorylates the mu subunits of adaptor protein (AP) 1 and AP2. In addition, it contains an auxilin-1-like domain structure consisting of PTEN-like, clathrin-binding, and J domains. Like auxilin-1, GAK facilitates Hsc70-mediated dissociation of clathrin from clathrin-coated vesicles. GAK is expressed ubiquitously and is enriched in the Golgi, unlike auxilin-1 which is nerve-specific. GAK also plays regulatory roles outside of clathrin-mediated membrane traffic including the maintenance of centrosome integrity and chromosome congression, neural patterning, survival of neurons, and immune responses through interaction with the interleukin 12 receptor. It also interacts with the androgen receptor, acting as a transcriptional coactivator, and its expression is significantly increased with the progression of prostate cancer. The GAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270938 [Multi-domain] Cd Length: 282 Bit Score: 77.16 E-value: 1.45e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3307 ARGRFGVIRECRENATGNLYMAK-IVPYEPESKQTVLQEYDILKSLH-HEKIMAL-HEAYVTPR--------YLVLiSEC 3375
Cdd:cd14036      9 AEGGFAFVYEAQDVGTGKEYALKrLLSNEEEKNKAIIQEINFMKKLSgHPNIVQFcSAASIGKEesdqgqaeYLLL-TEL 87

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3376 CSGkellhSLIDRFR-------YSEDDVVAYIVQILQGLDYLHSRR--ILHLDIKPENIIVTYMNVVKIIDFGSAQT--F 3444
Cdd:cd14036     88 CKG-----QLVDFVKkveapgpFSPDTVLKIFYQTCRAVQHMHKQSppIIHRDLKIENLLIGNQGQIKLCDFGSATTeaH 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3445 NPLF-------------LKQFSPPIgtldYMSPEML---KGDVVGPPADIWSIGILTYIMLSGRLPFTENdpaeTEARIQ 3508
Cdd:cd14036    163 YPDYswsaqkrslvedeITRNTTPM----YRTPEMIdlySNYPIGEKQDIWALGCILYLLCFRKHPFEDG----AKLRII 234

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|
gi 1207186029 3509 AAKFDL---SKLYQNVSQsaslFIKKILCSYPWARPTIKD 3545
Cdd:cd14036    235 NAKYTIppnDTQYTVFHD----LIRSTLKVNPEERLSITE 270

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 71.38 E-value: 1.61e-14

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029   935 GDQSVIEGQEVTMSVLVTGQPKPMLYWLRDRVTIKTGTRHIVQETEEGNFEMIIKSAQRSDTGVYTCKIINEYGTKQCEG 1014
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGT 81


                    ....
gi 1207186029  1015 KLEV 1018
Cdd:smart00410   82 TLTV 85

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK6 is regulated by D-type cyclins and INK4 inhibitors. It is active towards the retinoblastoma (pRb) protein, implicating it to function in regulating the early G1 phase of the cell cycle. It is expressed ubiquitously and is localized in the cytoplasm. It is also present in the ruffling edge of spreading fibroblasts and may play a role in cell spreading. It binds to the p21 inhibitor without any effect on its own activity and it is overexpressed in squamous cell carcinomas and neuroblastomas. CDK6 has also been shown to inhibit cell differentiation in many cell types. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270846 [Multi-domain] Cd Length: 290 Bit Score: 77.00 E-value: 1.83e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMA----KIVPYEPESKQTVLQEYDILKSLhhekimalhEAYVTPRYLVLISEC 3375
Cdd:cd07862      3 YECVAEIGEGAYGKVFKARDLKNGGRFVAlkrvRVQTGEEGMPLSTIREVAVLRHL---------ETFEHPNVVRLFDVC 73

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3376 C---SGKELLHSLIdrFRYSEDDVVAYI-----------------VQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKI 3435
Cdd:cd07862     74 TvsrTDRETKLTLV--FEHVDQDLTTYLdkvpepgvptetikdmmFQLLRGLDFLHSHRVVHRDLKPQNILVTSSGQIKL 151

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1207186029 3436 IDFGSAQTFNplFLKQFSPPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARI 3507
Cdd:cd07862    152 ADFGLARIYS--FQMALTSVVVTLWYRAPEVLLQSSYATPVDLWSVGCIFAEMFRRKPLFRGSSDVDQLGKI 221

Catalytic domain of testis-specific serine/threonine kinase 1, TSSK2, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK1 and TSSK2 are expressed specifically in meiotic and postmeiotic spermatogenic cells, respectively. TSSK2 is localized in the sperm neck, equatorial segment, and mid-piece of the sperm tail. Both TSSK1 and TSSK2 phosphorylate their common substrate TSKS (testis-specific-kinase-substrate). TSSK1/TSSK2 double knock-out mice are sterile without manifesting other defects, making these kinases viable targets for male contraception. The TSSK1/2-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271067 [Multi-domain] Cd Length: 263 Bit Score: 76.36 E-value: 1.99e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3343 QEYDILKSLHHEKIMALHEAYVTPR-YLVLISECCSGKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIK 3421
Cdd:cd14165     50 RELEILARLNHKSIIKTYEIFETSDgKVYIVMELGVQGDLLEFIKLRGALPEDVARKMFHQLSSAIKYCHELDIVHRDLK 129

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3422 PENIIVTYMNVVKIIDFGSAQTFNP------LFLKQFSppiGTLDYMSPEMLKGDVVGPPA-DIWSIGILTYIMLSGRLP 3494
Cdd:cd14165    130 CENLLLDKDFNIKLTDFGFSKRCLRdengriVLSKTFC---GSAAYAAPEVLQGIPYDPRIyDIWSLGVILYIMVCGSMP 206

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1207186029 3495 FTENDPAETeARIQA---AKFDLSKlyqNVSQSASLFIKKILCSYPWARPTIKDCFTNSWL 3552
Cdd:cd14165    207 YDDSNVKKM-LKIQKehrVRFPRSK---NLTSECKDLIYRLLQPDVSQRLCIDEVLSHPWL 263

Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C zeta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-zeta plays a critical role in activating the glucose transport response. It is activated by glucose, insulin, and exercise through diverse pathways. PKC-zeta also plays a central role in maintaining cell polarity in yeast and mammalian cells. In addition, it affects actin remodeling in muscle cells. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. aPKCs only require phosphatidylserine (PS) for activation. The aPKC-zeta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270768 [Multi-domain] Cd Length: 357 Bit Score: 77.75 E-value: 2.14e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3291 LRQGVPQKPYTFMDEKARGRFGVIRECRENATGNLYMAKIVPYE----PESKQTVLQEYDILKSLHHEK-IMALHEAYVT 3365
Cdd:cd05617      8 ISQGLGLQDFDLIRVIGRGSYAKVLLVRLKKNDQIYAMKVVKKElvhdDEDIDWVQTEKHVFEQASSNPfLVGLHSCFQT 87

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3366 PRYLVLISECCSGKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFG-SAQTF 3444
Cdd:cd05617     88 TSRLFLVIEYVNGGDLMFHMQRQRKLPEEHARFYAAEICIALNFLHERGIIYRDLKLDNVLLDADGHIKLTDYGmCKEGL 167

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1207186029 3445 NPlfLKQFSPPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPF---TENDPAETE 3504
Cdd:cd05617    168 GP--GDTTSTFCGTPNYIAPEILRGEEYGFSVDWWALGVLMFEMMAGRSPFdiiTDNPDMNTE 228

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 70.67 E-value: 2.18e-14

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1207186029 2860 PPVFHIKLRDHVLLEGDPVTLSCLPAGSPHPHISWMKDKKPLeIDPRMNMISCPDGRQLLMIMKTTKKDAGLYECVAAN 2938
Cdd:pfam13927    1 KPVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPI-SSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

serine/threonine kinase US3; Provisional

Pssm-ID: 177557 [Multi-domain] Cd Length: 357 Bit Score: 77.99 E-value: 2.18e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3311 FGVIRECRENATGNLYMAKiVPYEPES-------KQTVLQEYDILKSLHHEKIMALHEAY--------VTPRYlvlisec 3375
Cdd:PHA03209    68 YTVIKTLTPGSEGRVFVAT-KPGQPDPvvlkigqKGTTLIEAMLLQNVNHPSVIRMKDTLvsgaitcmVLPHY------- 139

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3376 csgKELLHSLIDR--FRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTfnPLFLKQFS 3453
Cdd:PHA03209   140 ---SSDLYTYLTKrsRPLPIDQALIIEKQILEGLRYLHAQRIIHRDVKTENIFINDVDQVCIGDLGAAQF--PVVAPAFL 214

                          170       180       190
                   ....*....|....*....|....*....|....*..
gi 1207186029 3454 PPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLS 3490
Cdd:PHA03209   215 GLAGTVETNAPEVLARDKYNSKADIWSAGIVLFEMLA 251

NIMA-related protein kinase; Provisional

Pssm-ID: 173502 [Multi-domain] Cd Length: 1021 Bit Score: 80.17 E-value: 2.38e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1657 RLTDYyDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARA---KRKASALRELNILSHLDHERILYFHDAFEKK--NAV 1731
Cdd:PTZ00266    11 RLNEY-EVIKKIGNGRFGEVFLVKHKRTQEFFCWKAISYRGlkeREKSQLVIEVNVMRELKHKNIVRYIDRFLNKanQKL 89

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1732 IIITELCHEELLDRLTKK-----STILESEIRSSVRQLLEGINYLHQLD-------ILHLDIKPDNILMAD--------- 1790
Cdd:PTZ00266    90 YILMEFCDAGDLSRNIQKcykmfGKIEEHAIVDITRQLLHALAYCHNLKdgpngerVLHRDLKPQNIFLSTgirhigkit 169

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1791 ------HSSDQIRICDFGNAVKFMPDEAQYCKYGTPEFVAPEIVNQTPVS--KATDIWPIGVLTYLCLTGVSPFAGENDR 1862
Cdd:PTZ00266   170 aqannlNGRPIAKIGDFGLSKNIGIESMAHSCVGTPYYWSPELLLHETKSydDKSDMWALGCIIYELCSGKTPFHKANNF 249

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1863 SSVLNirnynvafEESMFTDLCHEAKGFVIKLLVADRL------RPDANECLRHPWFKTL 1916
Cdd:PTZ00266   250 SQLIS--------ELKRGPDLPIKGKSKELNILIKNLLnlsakeRPSALQCLGYQIIKNV 301

Catalytic domain of the Serine/Threonine Kinase, Group II p21-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Group II PAKs, also called non-conventional PAKs, include PAK4, PAK5, and PAK6. Group II PAKs contain PBD (p21-binding domain) and catalytic domains, but lack other motifs found in group I PAKs, such as an AID (autoinhibitory domain) and SH3 binding sites. Since group II PAKs do not contain an obvious AID, they may be regulated differently from group I PAKs. While group I PAKs interact with the SH3 containing proteins Nck, Grb2 and PIX, no such binding has been demonstrated for group II PAKs. Some known substrates of group II PAKs are also substrates of group I PAKs such as Raf, BAD, LIMK and GEFH1. Unique group II substrates include MARK/Par-1 and PDZ-RhoGEF. Group II PAKs play important roles in filopodia formation, neuron extension, cytoskeletal organization, and cell survival. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270815 [Multi-domain] Cd Length: 261 Bit Score: 75.94 E-value: 2.48e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1661 YYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASAL-RELNILSHLDHERILYFHDAFEKKNAVIIITELCH 1739
Cdd:cd06648      8 DLDNFVKIGEGSTGIVCIATDKSTGRQVAVKKMDLRKQQRRELLfNEVVIMRDYQHPNIVEMYSSYLVGDELWVVMEFLE 87

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1740 EELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMAdhSSDQIRICDFG---NAVKFMPDEAQYCk 1816
Cdd:cd06648     88 GGALTDIVTHTRMNEEQIATVCRAVLKALSFLHSQGVIHRDIKSDSILLT--SDGRVKLSDFGfcaQVSKEVPRRKSLV- 164

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1817 yGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNynvafEESMFTDLCHEA----KGFVI 1892
Cdd:cd06648    165 -GTPYWMAPEVISRLPYGTEVDIWSLGIMVIEMVDGEPPYFNEPPLQAMKRIRD-----NEPPKLKNLHKVsprlRSFLD 238

                          250       260
                   ....*....|....*....|...
gi 1207186029 1893 KLLVADRL-RPDANECLRHPWFK 1914
Cdd:cd06648    239 RMLVRDPAqRATAAELLNHPFLA 261

Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PIM gene locus was discovered as a result of the cloning of retroviral intergration sites in murine Moloney leukemia virus, leading to the identification of PIM kinases. They are constitutively active STKs with a broad range of cellular targets and are overexpressed in many haematopoietic malignancies and solid cancers. Vertebrates contain three distinct PIM kinase genes (PIM1-3); each gene may result in mutliple protein isoforms. There are two PIM1 isoforms resulting from alternative translation initiation sites. PIM1 is the founding member of the PIM subfamily. It is involved in regulating cell growth, differentiation, and apoptosis. It promotes cancer development when overexpressed by inhibiting apoptosis, promoting cell proliferation, and promoting genomic instability. The PIM1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271002 [Multi-domain] Cd Length: 254 Bit Score: 75.78 E-value: 2.80e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISaraKRKASALRELNILSHLDHERILY------------FHDAFEKKN 1729
Cdd:cd14100      2 YQVGPLLGSGGFGSVYSGIRVADGAPVAIKHVE---KDRVSEWGELPNGTRVPMEIVLLkkvgsgfrgvirLLDWFERPD 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1730 AVIIITELCH--EELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMaDHSSDQIRICDFGNAVkf 1807
Cdd:cd14100     79 SFVLVLERPEpvQDLFDFITERGALPEELARSFFRQVLEAVRHCHNCGVLHRDIKDENILI-DLNTGELKLIDFGSGA-- 155

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1808 MPDEAQYCKY-GTPEFVAPE-IVNQTPVSKATDIWPIGVLTYLCLTGVSPFagENDRSsvlnIRNYNVAFEESMFTDlCH 1885
Cdd:cd14100    156 LLKDTVYTDFdGTRVYSPPEwIRFHRYHGRSAAVWSLGILLYDMVCGDIPF--EHDEE----IIRGQVFFRQRVSSE-CQ 228

                          250       260
                   ....*....|....*....|....*..
gi 1207186029 1886 EAKGFVIKLLVADrlRPDANECLRHPW 1912
Cdd:cd14100    229 HLIKWCLALRPSD--RPSFEDIQNHPW 253

Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C iota; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-iota is directly implicated in carcinogenesis. It is critical to oncogenic signaling mediated by Ras and Bcr-Abl. The PKC-iota gene is the target of tumor-specific gene amplification in many human cancers, and has been identified as a human oncogene. In addition to its role in transformed growth, PKC-iota also promotes invasion, chemoresistance, and tumor cell survival. Expression profiling of PKC-iota is a prognostic marker of poor clinical outcome in several human cancers. PKC-iota also plays a role in establishing cell polarity, and has critical embryonic functions. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. aPKCs only require phosphatidylserine (PS) for activation. The aPKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270769 [Multi-domain] Cd Length: 364 Bit Score: 77.77 E-value: 2.91e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVPYE----PESKQTVLQEYDIL-KSLHHEKIMALHEAYVTPRYLVLISE 3374
Cdd:cd05618     22 FDLLRVIGRGSYAKVLLVRLKKTERIYAMKVVKKElvndDEDIDWVQTEKHVFeQASNHPFLVGLHSCFQTESRLFFVIE 101

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3375 CCSGKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFG-SAQTFNPlfLKQFS 3453
Cdd:cd05618    102 YVNGGDLMFHMQRQRKLPEEHARFYSAEISLALNYLHERGIIYRDLKLDNVLLDSEGHIKLTDYGmCKEGLRP--GDTTS 179

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|..
gi 1207186029 3454 PPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPF 3495
Cdd:cd05618    180 TFCGTPNYIAPEILRGEDYGFSVDWWALGVLMFEMMAGRSPF 221

Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jak2 is widely expressed in many tissues and is essential for the signaling of hormone-like cytokines such as growth hormone, erythropoietin, thrombopoietin, and prolactin, as well as some IFNs and cytokines that signal through the IL-3 and gp130 receptors. Disruption of Jak2 in mice results in an embryonic lethal phenotype with multiple defects including erythropoietic and cardiac abnormalities. It is the only Jak gene that results in a lethal phenotype when disrupted in mice. A mutation in the pseudokinase domain of Jak2, V617F, is present in many myeloproliferative diseases, including almost all patients with polycythemia vera, and 50% of patients with essential thrombocytosis and myelofibrosis. Jak2 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal catalytic tyr kinase domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271107 [Multi-domain] Cd Length: 284 Bit Score: 76.21 E-value: 2.93e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3302 FMDEKARGRFGVIRECR----ENATGNLYMAKIVPYEPESK-QTVLQEYDILKSLHHEKIMALHEAYVTP--RYLVLISE 3374
Cdd:cd14205      8 FLQQLGKGNFGSVEMCRydplQDNTGEVVAVKKLQHSTEEHlRDFEREIEILKSLQHDNIVKYKGVCYSAgrRNLRLIME 87

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3375 CC---SGKELLHSLIDRFRYSEddVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTF--NPLFL 3449
Cdd:cd14205     88 YLpygSLRDYLQKHKERIDHIK--LLQYTSQICKGMEYLGTKRYIHRDLATRNILVENENRVKIGDFGLTKVLpqDKEYY 165

                          170       180       190
                   ....*....|....*....|....*....|....*..
gi 1207186029 3450 KQFSPPIGTLDYMSPEMLKGDVVGPPADIWSIGILTY 3486
Cdd:cd14205    166 KVKEPGESPIFWYAPESLTESKFSVASDVWSFGVVLY 202

Catalytic domain of the Serine/Threonine Kinase, Nuclear Dbf2-Related kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NDR1 (also called STK38) plays a role in proper centrosome duplication. It is highly expressed in thymus, muscle, lung and spleen. It is not an essential protein because mice deficient of NDR1 remain viable and fertile. However, these mice develop T-cell lymphomas and appear to be hypersenstive to carcinogenic treatment. NDR1 appears to also act as a tumor suppressor. NDR kinase contains an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Like many other AGC kinases, NDR kinase requires phosphorylation at two sites, the activation loop (A-loop) and the hydrophobic motif (HM), for activity. The NDR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270777 [Multi-domain] Cd Length: 376 Bit Score: 77.77 E-value: 3.12e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3307 ARGRFGVIRECRENATGNLYMAKIVP----YEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELL 3382
Cdd:cd05628     10 GRGAFGEVRLVQKKDTGHVYAMKILRkadmLEKEQVGHIRAERDILVEADSLWVVKMFYSFQDKLNLYLIMEFLPGGDMM 89

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3383 HSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFG----------------------S 3440
Cdd:cd05628     90 TLLMKKDTLTEEETQFYIAETVLAIDSIHQLGFIHRDIKPDNLLLDSKGHVKLSDFGlctglkkahrtefyrnlnhslpS 169

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3441 AQTFNPLFLKQ-------------FSpPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARI 3507
Cdd:cd05628    170 DFTFQNMNSKRkaetwkrnrrqlaFS-TVGTPDYIAPEVFMQTGYNKLCDWWSLGVIMYEMLIGYPPFCSETPQETYKKV 248

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*....
gi 1207186029 3508 QAAKFDLSKLYQ-NVSQSASLFIKKILCSYPW--ARPTIKDCFTNSWLQ 3553
Cdd:cd05628    249 MNWKETLIFPPEvPISEKAKDLILRFCCEWEHriGAPGVEEIKTNPFFE 297

Catalytic domain of Fungal Sid2p-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This group contains fungal kinases including Schizosaccharomyces pombe Sid2p and Saccharomyces cerevisiae Dbf2p. Group members show similarity to NDR kinases in that they contain an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Sid2p plays a crucial role in the septum initiation network (SIN) and in the initiation of cytokinesis. Dbf2p is important in regulating the mitotic exit network (MEN) and in cytokinesis. The Sid2p-like group is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270751 [Multi-domain] Cd Length: 386 Bit Score: 77.76 E-value: 3.24e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3341 VLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDI 3420
Cdd:cd05600     58 VLTERDILTTTNSPWLVKLLYAFQDPENVYLAMEYVPGGDFRTLLNNSGILSEEHARFYIAEMFAAISSLHQLGYIHRDL 137

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3421 KPENIIVTYMNVVKIIDFG-SAQTFNP---LFLKQ-----FSPP---------------------------IGTLDYMSP 3464
Cdd:cd05600    138 KPENFLIDSSGHIKLTDFGlASGTLSPkkiESMKIrleevKNTAfleltakerrniyramrkedqnyansvVGSPDYMAP 217

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3465 EMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARI-------QAAKFDLSKLYQNVSQSASLFIKKILCSYP 3537
Cdd:cd05600    218 EVLRGEGYDLTVDYWSLGCILFECLVGFPPFSGSTPNETWANLyhwkktlQRPVYTDPDLEFNLSDEAWDLITKLITDPQ 297

C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myotilin. Mytolin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to the latter family contain multiple Ig-like domains and function as scaffolds, modulating the actin cytoskeleton. Myotilin is most abundant in skeletal and cardiac muscle and is involved in maintaining sarcomere integrity. It binds to alpha-actinin, filamin, and actin. Mutations in myotilin lead to muscle disorders. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409473 Cd Length: 92 Bit Score: 70.57 E-value: 3.27e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 2861 PVFHIKLRDHVLLEGDPVTLSCLPAGSPHPHISWMKDKKPLEIDP-RMNMISCPDGRQLLMIMKTTKKDAGLYECVAANP 2939
Cdd:cd05892      1 PMFIQKPQNKKVLEGDPVRLECQISAIPPPQIFWKKNNEMLQYNTdRISLYQDNCGRICLLIQNANKKDAGWYTVSAVNE 80

                           90
                   ....*....|....*
gi 1207186029 2940 LATVTSScvvslARL 2954
Cdd:cd05892     81 AGVVSCN-----ARL 90

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 70.23 E-value: 3.31e-14

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  1552 EDLDVNVGETPRFAVVVEGKPVPDILWYK-GDTLLSESSHFTFVYDDNECSLVVLNTQADDSGVYTCTAKNLAGSVSCKA 1630
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPPEVTWYKqGGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGT 81


                    ....
gi 1207186029  1631 ELTV 1634
Cdd:smart00410   82 TLTV 85

Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNK3 shows a restricted expression pattern; it is found at high levels in the pituary glands and is also expressed in the kidney and brain. It has been shown to regulate many ion transporters including members of the SLC12A family of cation-chloride cotransporters such as NCC and NKCC2, the renal potassium channel ROMK, and the epithelial calcium channels TRPV5 and TRPV6. WNK3 appears to sense low-chloride hypotonic stress and under these conditions, it activates SPAK, which directly interacts and phosphorylates cation-chloride cotransporters. WNK3 has also been shown to promote cell survival, possibly through interaction with procaspase-3 and HSP70. WNKs comprise a subfamily of STKs with an unusual placement of the catalytic lysine relative to all other protein kinases. The WNK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270933 [Multi-domain] Cd Length: 275 Bit Score: 75.91 E-value: 3.78e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1667 EIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASALR---ELNILSHLDHERILYFHDAFEK----KNAVIIITELCH 1739
Cdd:cd14031     17 ELGRGAFKTVYKGLDTETWVEVAWCELQDRKLTKAEQQRfkeEAEMLKGLQHPNIVRFYDSWESvlkgKKCIVLVTELMT 96

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1740 EELLDRLTKKSTILESEI-RSSVRQLLEGINYLHQLD--ILHLDIKPDNILMADhSSDQIRICDFGNAVkFMPDEAQYCK 1816
Cdd:cd14031     97 SGTLKTYLKRFKVMKPKVlRSWCRQILKGLQFLHTRTppIIHRDLKCDNIFITG-PTGSVKIGDLGLAT-LMRTSFAKSV 174

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|.
gi 1207186029 1817 YGTPEFVAPEIVNQTpVSKATDIWPIGVLTYLCLTGVSPFA 1857
Cdd:cd14031    175 IGTPEFMAPEMYEEH-YDESVDVYAFGMCMLEMATSEYPYS 214

Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-1 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-1 is expressed ubiquitously and is localized in the cytoplasm. Its kinase activity is cell cycle dependent and peaks at the S and G2 phases. PCTAIRE-1 is highly expressed in the brain and may play a role in regulating neurite outgrowth. It can also associate with Trap (Tudor repeat associator with PCTAIRE-2), a physiological partner of PCTAIRE-2; with p11, a small dimeric protein with similarity to S100; and with 14-3-3 proteins, mediators of phosphorylation-dependent interactions in many different proteins. PCTAIRE-1 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PCTAIRE-1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270854 [Multi-domain] Cd Length: 297 Bit Score: 76.19 E-value: 4.07e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1667 EIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKA--SALRELNILSHLDHERILYFHDAFEKKNAVIIITELCHEELLD 1744
Cdd:cd07873      9 KLGEGTYATVYKGRSKLTDNLVALKEIRLEHEEGApcTAIREVSLLKDLKHANIVTLHDIIHTEKSLTLVFEYLDKDLKQ 88

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1745 RLTKKSTILE-SEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSsdQIRICDFGNA-VKFMPDEAQYCKYGTPEF 1822
Cdd:cd07873     89 YLDDCGNSINmHNVKLFLFQLLRGLAYCHRRKVLHRDLKPQNLLINERG--ELKLADFGLArAKSIPTKTYSNEVVTLWY 166

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1823 VAPEI-VNQTPVSKATDIWPIGVLTYLCLTGVSPFAG--------------------------ENDRSSVLNIRNYNVAF 1875
Cdd:cd07873    167 RPPDIlLGSTDYSTQIDMWGVGCIFYEMSTGRPLFPGstveeqlhfifrilgtpteetwpgilSNEEFKSYNYPKYRADA 246

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....
gi 1207186029 1876 EESMFTDLCHEAKGFVIKLL-VADRLRPDANECLRHPWFKTLNK 1918
Cdd:cd07873    247 LHNHAPRLDSDGADLLSKLLqFEGRKRISAEEAMKHPYFHSLGE 290

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409543 [Multi-domain] Cd Length: 94 Bit Score: 70.53 E-value: 4.16e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029   55 PVFIRKMRNAAVGTGCDIRLKVAVAGDPQPTLYWYHNDDLVNMDNQ--------EYG--GLWIRDCKPSDAGLYTCIATN 124
Cdd:cd20951      1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIDPSSIpgkykiesEYGvhVLHIRRVTVEDSAVYSAVAKN 80

                           90
                   ....*....|...
gi 1207186029  125 HLGEARSSAVLAV 137
Cdd:cd20951     81 IHGEASSSASVVV 93

Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. aPKCs only require phosphatidylserine (PS) for activation. They contain a C2-like region, instead of a calcium-binding (C2) region found in classical PKCs, in their regulatory domain. There are two aPKC isoforms, zeta and iota. aPKCs are involved in many cellular functions including proliferation, migration, apoptosis, polarity maintenance and cytoskeletal regulation. They also play a critical role in the regulation of glucose metabolism and in the pathogenesis of type 2 diabetes. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. The aPKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270740 [Multi-domain] Cd Length: 328 Bit Score: 76.31 E-value: 4.52e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3353 HEKIMALHEAYVTPRYLVLISECCSGKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNV 3432
Cdd:cd05588     55 HPFLVGLHSCFQTESRLFFVIEFVNGGDLMFHMQRQRRLPEEHARFYSAEISLALNFLHEKGIIYRDLKLDNVLLDSEGH 134

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3433 VKIIDFG----------SAQTFnplflkqfsppIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPF-----TE 3497
Cdd:cd05588    135 IKLTDYGmckeglrpgdTTSTF-----------CGTPNYIAPEILRGEDYGFSVDWWALGVLMFEMLAGRSPFdivgsSD 203


                   ....*..
gi 1207186029 3498 NDPAETE 3504
Cdd:cd05588    204 NPDQNTE 210

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409564 [Multi-domain] Cd Length: 91 Bit Score: 70.30 E-value: 4.62e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1249 PDFVKPLYDMDVVEGREAVLRCKVAGLPYPTITWFHNGKRIDSTEDRKMTQFRDVHSLVVRCVCHAHGGVYKCVISNKVG 1328
Cdd:cd20972      2 PQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKELQNSPDIQIHQEGDLHSLIIAEAFEEDTGRYSCLATNSVG 81

                           90
                   ....*....|
gi 1207186029 1329 KATCYSHLYV 1338
Cdd:cd20972     82 SDTTSAEIFV 91

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 69.90 E-value: 4.76e-14

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1207186029  781 PVFEFPLQDTVASTGTEVLLKCIISGTPLPEVIWKKDNTEVKNSPTHVVKIEGERHSLLIKWTKPSDAGTYTVTAVN 857
Cdd:pfam13927    2 PVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase 2 and 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK2 is regulated by cyclin E or cyclin A. Upon activation by cyclin E, it phosphorylates the retinoblastoma (pRb) protein which activates E2F mediated transcription and allows cells to move into S phase. The CDK2/cyclin A complex plays a role in regulating DNA replication. CDK2, together with CDK4, also regulates embryonic cell proliferation. Despite these important roles, mice deleted for the cdk2 gene are viable and normal except for being sterile. This may be due to compensation provided by CDK1 (also called Cdc2), which can also bind cyclin E and drive the G1 to S phase transition. CDK3 is regulated by cyclin C and it phosphorylates pRB specifically during the G0/G1 transition. This phosphorylation is required for cells to exit G0 efficiently and enter the G1 phase. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK2/3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270844 [Multi-domain] Cd Length: 284 Bit Score: 75.62 E-value: 4.76e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1701 ASALRELNILSHLDHERILYFHDAFEKKNAVIIITELCHEEL---LDrLTKKSTILESEIRSSVRQLLEGINYLHQLDIL 1777
Cdd:cd07860     44 STAIREISLLKELNHPNIVKLLDVIHTENKLYLVFEFLHQDLkkfMD-ASALTGIPLPLIKSYLFQLLQGLAFCHSHRVL 122

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1778 HLDIKPDNILMadHSSDQIRICDFGNAVKF-MPDEAQYCKYGTPEFVAPEIVNQTPV-SKATDIWPIGVLTYLCLTGVSP 1855
Cdd:cd07860    123 HRDLKPQNLLI--NTEGAIKLADFGLARAFgVPVRTYTHEVVTLWYRAPEILLGCKYySTAVDIWSLGCIFAEMVTRRAL 200


                   ....*.
gi 1207186029 1856 FAGEND 1861
Cdd:cd07860    201 FPGDSE 206

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 70.11 E-value: 4.98e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1249 PDFV-KPLYDMDVVEGREAVLRCKVAGLPYPTITWFHNGKRID-STEDRKMTQfrdvHSLVVRCVCHAHGGVYKCVISNK 1326
Cdd:cd20978      1 PKFIqKPEKNVVVKGGQDVTLPCQVTGVPQPKITWLHNGKPLQgPMERATVED----GTLTIINVQPEDTGYYGCVATNE 76


                   ...
gi 1207186029 1327 VGK 1329
Cdd:cd20978     77 IGD 79

Catalytic domain of the protein kinase, Dual-specificity tYrosine-phosphorylated and -Regulated Kinase 4; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. DYRK4 is a testis-specific kinase with restricted expression to postmeiotic spermatids. It may function during spermiogenesis, however, it is not required for male fertility. DYRK4 has also been detected in a human teratocarcinoma cell line induced to produce postmitotic neurons. It may have a role in neuronal differentiation. DYRKs autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. They play important roles in cell proliferation, differentiation, survival, and development. The DYRK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271127 [Multi-domain] Cd Length: 341 Bit Score: 76.28 E-value: 5.34e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASALRELNILSHL---DHE---RILYFHDAFEKKNAVIIIT 1735
Cdd:cd14225     45 YEILEVIGKGSFGQVVKALDHKTNEHVAIKIIRNKKRFHHQALVEVKILDALrrkDRDnshNVIHMKEYFYFRNHLCITF 124

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1736 ELCHEELLDrLTKKSTILE---SEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSDQIRICDFGNAVkfMPDEA 1812
Cdd:cd14225    125 ELLGMNLYE-LIKKNNFQGfslSLIRRFAISLLQCLRLLYRERIIHCDLKPENILLRQRGQSSIKVIDFGSSC--YEHQR 201

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1813 QYcKYGTPEFV-APEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGEND 1861
Cdd:cd14225    202 VY-TYIQSRFYrSPEVILGLPYSMAIDMWSLGCILAELYTGYPLFPGENE 250

Catalytic domain of the Serine/Threonine Kinases, Thousand-and-One Amino acids proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAO proteins possess mitogen-activated protein kinase (MAPK) kinase kinase activity. They activate the MAPKs, p38 and c-Jun N-terminal kinase (JNK), by phosphorylating and activating the respective MAP/ERK kinases (MEKs, also known as MKKs or MAPKKs), MEK3/MEK6 and MKK4/MKK7. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. Vertebrates contain three TAO subfamily members, named TAO1, TAO2, and TAO3. The TAO subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270784 [Multi-domain] Cd Length: 258 Bit Score: 74.79 E-value: 5.36e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1661 YYDVHkEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASA----LRELNILSHLDHERILYFHDAFEKKNAVIIITE 1736
Cdd:cd06607      3 FEDLR-EIGHGSFGAVYYARNKRTSEVVAIKKMSYSGKQSTEKwqdiIKEVKFLRQLRHPNTIEYKGCYLREHTAWLVME 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1737 LCHEELLDRL-TKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSsdQIRICDFGNAVkfMPDEAQyC 1815
Cdd:cd06607     82 YCLGSASDIVeVHKKPLQEVEIAAICHGALQGLAYLHSHNRIHRDVKAGNILLTEPG--TVKLADFGSAS--LVCPAN-S 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1816 KYGTPEFVAPEIV---NQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNI-RNYNVAFEESMFTDlchEAKGFV 1891
Cdd:cd06607    157 FVGTPYWMAPEVIlamDEGQYDGKVDVWSLGITCIELAERKPPLFNMNAMSALYHIaQNDSPTLSSGEWSD---DFRNFV 233

                          250       260
                   ....*....|....*....|..
gi 1207186029 1892 IKLLVADRL-RPDANECLRHPW 1912
Cdd:cd06607    234 DSCLQKIPQdRPSAEDLLKHPF 255

Catalytic domain of Fungal Nuclear Dbf2-Related kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This group is composed of fungal NDR-like proteins including Saccharomyces cerevisiae CBK1 (or CBK1p), Schizosaccharomyces pombe Orb6 (or Orb6p), Ustilago maydis Ukc1 (or Ukc1p), and Neurospora crassa Cot1. Like NDR kinase, group members contain an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. CBK1 is an essential component in the RAM (regulation of Ace2p activity and cellular morphogenesis) network. CBK1 and Orb6 play similar roles in coordinating cell morphology with cell cycle progression. Ukc1 is involved in morphogenesis, pathogenicity, and pigment formation. Cot1 plays a role in polar tip extension.The fungal NDR subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270778 [Multi-domain] Cd Length: 377 Bit Score: 76.81 E-value: 5.44e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKIV----PYEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLH 3383
Cdd:cd05629     11 KGAFGEVRLVQKKDTGKIYAMKTLlkseMFKKDQLAHVKAERDVLAESDSPWVVSLYYSFQDAQYLYLIMEFLPGGDLMT 90

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3384 SLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFN----------PLFLKQFS 3453
Cdd:cd05629     91 MLIKYDTFSEDVTRFYMAECVLAIEAVHKLGFIHRDIKPDNILIDRGGHIKLSDFGLSTGFHkqhdsayyqkLLQGKSNK 170

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3454 PP------------------------------------IGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTE 3497
Cdd:cd05629    171 NRidnrnsvavdsinltmsskdqiatwkknrrlmaystVGTPDYIAPEIFLQQGYGQECDWWSLGAIMFECLIGWPPFCS 250

                          250
                   ....*....|
gi 1207186029 3498 NDPAETEARI 3507
Cdd:cd05629    251 ENSHETYRKI 260

Catalytic domain of the Serine/Threonine protein kinase, cyclin G-Associated Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GAK, also called auxilin-2, contains an N-terminal kinase domain that phosphorylates the mu subunits of adaptor protein (AP) 1 and AP2. In addition, it contains an auxilin-1-like domain structure consisting of PTEN-like, clathrin-binding, and J domains. Like auxilin-1, GAK facilitates Hsc70-mediated dissociation of clathrin from clathrin-coated vesicles. GAK is expressed ubiquitously and is enriched in the Golgi, unlike auxilin-1 which is nerve-specific. GAK also plays regulatory roles outside of clathrin-mediated membrane traffic including the maintenance of centrosome integrity and chromosome congression, neural patterning, survival of neurons, and immune responses through interaction with the interleukin 12 receptor. It also interacts with the androgen receptor, acting as a transcriptional coactivator, and its expression is significantly increased with the progression of prostate cancer. The GAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270938 [Multi-domain] Cd Length: 282 Bit Score: 75.24 E-value: 5.50e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1664 VHKEIGRGAFSYVKRVIQKAGKLEYAAK-FISARAKRKASALRELNILSHLD-HERILYFHDA--FEKKNA------VII 1733
Cdd:cd14036      4 IKRVIAEGGFAFVYEAQDVGTGKEYALKrLLSNEEEKNKAIIQEINFMKKLSgHPNIVQFCSAasIGKEESdqgqaeYLL 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1734 ITELCHEELLDRLTK---KSTILESEIRSSVRQLLEGINYLH--QLDILHLDIKPDNILMAdhSSDQIRICDFGNA--VK 1806
Cdd:cd14036     84 LTELCKGQLVDFVKKveaPGPFSPDTVLKIFYQTCRAVQHMHkqSPPIIHRDLKIENLLIG--NQGQIKLCDFGSAttEA 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1807 FMPD-----------EAQYCKYGTPEFVAPEIVN---QTPVSKATDIWPIG-VLTYLCLTGvSPFagenDRSSVLNIRNY 1871
Cdd:cd14036    162 HYPDyswsaqkrslvEDEITRNTTPMYRTPEMIDlysNYPIGEKQDIWALGcILYLLCFRK-HPF----EDGAKLRIINA 236

                          250
                   ....*....|....*..
gi 1207186029 1872 NVAFEES-----MFTDL 1883
Cdd:cd14036    237 KYTIPPNdtqytVFHDL 253

Catalytic domain of fungal PBS2-like dual-specificity Mitogen-Activated Protein Kinase Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include the MAPKKs Polymyxin B resistance protein 2 (PBS2) from Saccharomyces cerevisiae, Wis1 from Schizosaccharomyces pombe, and related proteins. PBS2 and Wis1 are components of stress-activated MAPK cascades in budding and fission yeast, respectively. PBS2 is the specific activator of the MAPK Hog1, which plays a central role in the response of budding yeast to stress including exposure to arsenite and hyperosmotic environments. Wis1 phosphorylates and activates the MAPK Sty1 (also called Spc1 or Phh1), which stimulates a transcriptional response to a wide range of cellular insults through the bZip transcription factors Atf1, Pcr1, and Pap1. The PBS2 subfamily is part of a larger superfamily that includes the catalytic domains of STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 132953 [Multi-domain] Cd Length: 286 Bit Score: 75.27 E-value: 6.50e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3302 FMDEKARGRFGVIRECRENATGNLYMAKIVPYE-PESK-QTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGK 3379
Cdd:cd06622      5 VLDELGKGNYGSVYKVLHRPTGVTMAMKEIRLElDESKfNQIIMELDILHKAVSPYIVDFYGAFFIEGAVYMCMEYMDAG 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3380 EL--LHSLIDRFRYSEDDVVAYIV-QILQGLDYLHSR-RILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLKQfspP 3455
Cdd:cd06622     85 SLdkLYAGGVATEGIPEDVLRRITyAVVKGLKFLKEEhNIIHRDVKPTNVLVNGNGQVKLCDFGVSGNLVASLAKT---N 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3456 IGTLDYMSPEMLKGDvvGPP--------ADIWSIGILTYIMLSGRLPFtendPAETEARIQA-----AKFDLSKLYQNVS 3522
Cdd:cd06622    162 IGCQSYMAPERIKSG--GPNqnptytvqSDVWSLGLSILEMALGRYPY----PPETYANIFAqlsaiVDGDPPTLPSGYS 235

                          250       260       270
                   ....*....|....*....|....*....|
gi 1207186029 3523 QSASLFIKKILCSYPWARPTIKDCFTNSWL 3552
Cdd:cd06622    236 DDAQDFVAKCLNKIPNRRPTYAQLLEHPWL 265

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B alpha (also called Akt1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKB-alpha is predominantly expressed in endothelial cells. It is critical for the regulation of angiogenesis and the maintenance of vascular integrity. It also plays a role in adipocyte differentiation. Mice deficient in PKB-alpha exhibit perinatal morbidity, growth retardation, reduction in body weight accompanied by reduced sizes of multiple organs, and enhanced apoptosis in some cell types. PKB-alpha activity has been reported to be frequently elevated in breast and prostate cancers. In some cancer cells, PKB-alpha may act as a suppressor of metastasis. PKB contains an N-terminal pleckstrin homology (PH) domain and a C-terminal catalytic domain. The PKB-alpha subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270746 [Multi-domain] Cd Length: 356 Bit Score: 76.22 E-value: 6.66e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1646 EDEASILRKMRRLTDY-YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISAR---AKRK-ASALRELNILSHLDHERILY 1720
Cdd:cd05594     10 EMEVSLTKPKHKVTMNdFEYLKLLGKGTFGKVILVKEKATGRYYAMKILKKEvivAKDEvAHTLTENRVLQNSRHPFLTA 89

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1721 FHDAFEKKNAVIIITELCHE-ELLDRLTKKSTILESEIRSSVRQLLEGINYLH-QLDILHLDIKPDNiLMADHSSdQIRI 1798
Cdd:cd05594     90 LKYSFQTHDRLCFVMEYANGgELFFHLSRERVFSEDRARFYGAEIVSALDYLHsEKNVVYRDLKLEN-LMLDKDG-HIKI 167

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1799 CDFGNAVKFMPDEAQYCKY-GTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEE 1877
Cdd:cd05594    168 TDFGLCKEGIKDGATMKTFcGTPEYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGRLPFYNQDHEKLFELILMEEIRFPR 247

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*
gi 1207186029 1878 SmftdLCHEAKGFVIKLLVADRLR------PDANECLRHPWFKTL 1916
Cdd:cd05594    248 T----LSPEAKSLLSGLLKKDPKQrlgggpDDAKEIMQHKFFAGI 288

Catalytic domain of the Serine/Threonine Kinase, Large Tumor Suppressor 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LATS1 functions as a tumor suppressor and is implicated in cell cycle regulation. Inactivation of LATS1 in mice results in the development of various tumors, including sarcomas and ovarian cancer. Promoter methylation, loss of heterozygosity, and missense mutations targeting the LATS1 gene have also been found in human sarcomas and ovarian cancers. In addition, decreased expression of LATS1 is associated with an aggressive phenotype and poor prognosis. LATS1 induces G2 arrest and promotes cytokinesis. It may be a component of the mitotic exit network in higher eukaryotes. The LATS1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270775 [Multi-domain] Cd Length: 382 Bit Score: 76.62 E-value: 7.48e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1666 KEIGRGAFSYVKRVIQKAGKLEYAAKFISAR----AKRKASALRELNILSHLDHERILYFHDAFEKK-NAVIIITELCHE 1740
Cdd:cd05625      7 KTLGIGAFGEVCLARKVDTKALYATKTLRKKdvllRNQVAHVKAERDILAEADNEWVVRLYYSFQDKdNLYFVMDYIPGG 86

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1741 ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDFG--NAVKFMPDEAQY---- 1814
Cdd:cd05625     87 DMMSLLIRMGVFPEDLARFYIAELTCAVESVHKMGFIHRDIKPDNILI--DRDGHIKLTDFGlcTGFRWTHDSKYYqsgd 164

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1815 ------------------CK------------------------YGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTG 1852
Cdd:cd05625    165 hlrqdsmdfsnewgdpenCRcgdrlkplerraarqhqrclahslVGTPNYIAPEVLLRTGYTQLCDWWSVGVILFEMLVG 244

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1207186029 1853 VSPFAGENDRSSVLNIRNYNVAFEESMFTDLCHEAKGFVIKLLVA--DRL-RPDANECLRHPWFKTLNKGKSISTES 1926
Cdd:cd05625    245 QPPFLAQTPLETQMKVINWQTSLHIPPQAKLSPEASDLIIKLCRGpeDRLgKNGADEIKAHPFFKTIDFSSDLRQQS 321

Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RIP kinases serve as essential sensors of cellular stress. They are involved in regulating NF-kappaB and MAPK signaling, and are implicated in mediating cellular processes such as apoptosis, necroptosis, differentiation, and survival. RIP kinases contain a homologous N-terminal kinase domain and varying C-terminal domains. Higher vertebrates contain multiple RIP kinases, with mammals harboring at least five members. RIP1 and RIP2 harbor C-terminal domains from the Death domain (DD) superfamily while RIP4 contains ankyrin (ANK) repeats. RIP3 contain a RIP homotypic interaction motif (RHIM) that facilitates binding to RIP1. RIP1 and RIP3 are important in apoptosis and necroptosis, while RIP2 and RIP4 play roles in keratinocyte differentiation and inflammatory immune responses. The RIP subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270880 [Multi-domain] Cd Length: 263 Bit Score: 74.41 E-value: 9.36e-14

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYVKRVIQKAGKLEYAAKFI---SARAKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITELCHEELLD 1744
Cdd:cd13978      1 LGSGGFGTVSKARHVSWFGMVAIKCLhssPNCIEERKALLKEAEKMERARHSYVLPLLGVCVERRSLGLVMEYMENGSLK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1745 RLtkkstiLESEIRS---SVR-----QLLEGINYLHQLD--ILHLDIKPDNILMADHSsdQIRICDFGNAVKFMPDEAQY 1814
Cdd:cd13978     81 SL------LEREIQDvpwSLRfriihEIALGMNFLHNMDppLLHHDLKPENILLDNHF--HVKISDFGLSKLGMKSISAN 152

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1207186029 1815 CK------YGTPEFVAPEIVN--QTPVSKATDIWPIGVLTYLCLTGVSPFAGE 1859
Cdd:cd13978    153 RRrgtenlGGTPIYMAPEAFDdfNKKPTSKSDVYSFAIVIWAVLTRKEPFENA 205

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 68.51 E-value: 9.44e-14

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  798 VLLKCIISGTPLPEVIWKKDNTEVKNSPTHVVKIEGERHSLLIKWTKPSDAGTYTVTAVNEVGEVSSSAT 867
Cdd:cd00096      1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASASV 70

Catalytic domain of the Serine/Threonine Kinase, p38alpha Mitogen-Activated Protein Kinase (also called MAPK14); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38alpha/MAPK14 is expressed in most tissues and is the major isoform involved in the immune and inflammatory response. It is the central p38 MAPK involved in myogenesis. It plays a role in regulating cell cycle check-point transition and promoting cell differentiation. p38alpha also regulates cell proliferation and death through crosstalk with the JNK pathway. Its substrates include MAPK activated protein kinase 2 (MK2), MK5, and the transcription factors ATF2 and Mitf. p38 kinases MAPKs, serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38alpha subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143382 [Multi-domain] Cd Length: 345 Bit Score: 75.46 E-value: 1.08e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3343 QEYDILKSLHHEKIMALHEAYVTPRYL-----VLISECCSGKELlHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILH 3417
Cdd:cd07877     65 RELRLLKHMKHENVIGLLDVFTPARSLeefndVYLVTHLMGADL-NNIVKCQKLTDDHVQFLIYQILRGLKYIHSADIIH 143

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3418 LDIKPENIIVTYMNVVKIIDFGSAQTFNplflKQFSPPIGTLDYMSPE-MLKGDVVGPPADIWSIGILTYIMLSGRLPFT 3496
Cdd:cd07877    144 RDLKPSNLAVNEDCELKILDFGLARHTD----DEMTGYVATRWYRAPEiMLNWMHYNQTVDIWSVGCIMAELLTGRTLFP 219


                   ...
gi 1207186029 3497 END 3499
Cdd:cd07877    220 GTD 222

Catalytic domain of the Serine/Threonine Kinase, Microtubule-associated serine/threonine-like kinase (also called greatwall kinase); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MASTL kinases in this group carry only a catalytic domain, which contains a long insertion relative to MAST kinases. MASTL, also called greatwall kinase (Gwl), is involved in the regulation of mitotic entry, which is controlled by the coordinated activities of protein kinases and opposing protein phosphatases (PPs). The cyclin B/CDK1 complex induces entry into M-phase while PP2A-B55 shows anti-mitotic activity. MASTL/Gwl is activated downstream of cyclin B/CDK1 and indirectly inhibits PP2A-B55 by phosphorylating the small protein alpha-endosulfine (Ensa) or the cAMP-regulated phosphoprotein 19 (Arpp19), resulting in M-phase progression. Gwl kinase may also play roles in mRNA stabilization and DNA checkpoint recovery. The human MASTL gene has also been named FLJ14813; a missense mutation in FLJ14813 is associated with autosomal dominant thrombocytopenia. The MASTL kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270761 [Multi-domain] Cd Length: 349 Bit Score: 75.30 E-value: 1.23e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3307 ARGRFGVIRECRENATGNLYMAKIV-PYEPESKQTVLQ---EYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELl 3382
Cdd:cd05610     13 SRGAFGKVYLGRKKNNSKLYAVKVVkKADMINKNMVHQvqaERDALALSKSPFIVHLYYSLQSANNVYLVMEYLIGGDV- 91

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3383 HSLIDRFRY-SEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFG---------------------- 3439
Cdd:cd05610     92 KSLLHIYGYfDEEMAVKYISEVALALDYLHRHGIIHRDLKPDNMLISNEGHIKLTDFGlskvtlnrelnmmdilttpsma 171

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3440 -----------------SAQTFN-------PLFLKQFSPPI------GTLDYMSPEMLKGDVVGPPADIWSIGILTYIML 3489
Cdd:cd05610    172 kpkndysrtpgqvlsliSSLGFNtptpyrtPKSVRRGAARVegerilGTPDYLAPELLLGKPHGPAVDWWALGVCLFEFL 251

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1207186029 3490 SGRLPFTENDPAETEARIQAAKFDLSKLYQNVSQSASLFIKKILCSYPWARPTIKDCFTNSWLQDAYLMRLRRQTLTF 3567
Cdd:cd05610    252 TGIPPFNDETPQQVFQNILNRDIPWPEGEEELSVNAQNAIEILLTMDPTKRAGLKELKQHPLFHGVDWENLQNQTMPF 329

Catalytic domain of the protein kinase, Dual-specificity tYrosine-phosphorylated and -Regulated Kinase; Protein Kinases (PKs), Dual-specificity tYrosine-phosphorylated and -Regulated Kinase (DYRK) subfamily, catalytic (c) domain. Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. The DYRK subfamily is part of a larger superfamily that includes the catalytic domains of other protein S/T PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K). DYRKs autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. They play important roles in cell proliferation, differentiation, survival, and development. Vertebrates contain multiple DYRKs (DYRK1-4) and mammals contain two types of DYRK1 proteins, DYRK1A and DYRK1B. DYRK1A is involved in neuronal differentiation and is implicated in the pathogenesis of DS (Down syndrome). DYRK1B plays a critical role in muscle differentiation by regulating transcription, cell motility, survival, and cell cycle progression. It is overexpressed in many solid tumors where it acts as a tumor survival factor. DYRK2 promotes apoptosis in response to DNA damage by phosphorylating the tumor suppressor p53, while DYRK3 promotes cell survival by phosphorylating SIRT1 and promoting p53 deacetylation. DYRK4 is a testis-specific kinase that may function during spermiogenesis.

Pssm-ID: 271112 [Multi-domain] Cd Length: 311 Bit Score: 74.89 E-value: 1.25e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFG-VIReCRENATGNLYMAKIVPYEPESKQTVLQEYDILKSL-HHEK-----IMALHEAYVTPRYLVLISECCSGKe 3380
Cdd:cd14210     23 KGSFGqVVK-CLDHKTGQLVAIKIIRNKKRFHQQALVEVKILKHLnDNDPddkhnIVRYKDSFIFRGHLCIVFELLSIN- 100

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3381 lLHSLI--DRFR-YSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMN--VVKIIDFGSA-----QTFNPL--- 3447
Cdd:cd14210    101 -LYELLksNNFQgLSLSLIRKFAKQILQALQFLHKLNIIHCDLKPENILLKQPSksSIKVIDFGSScfegeKVYTYIqsr 179

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1207186029 3448 FlkqfsppigtldYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFtendPAETE 3504
Cdd:cd14210    180 F------------YRAPEVILGLPYDTAIDMWSLGCILAELYTGYPLF----PGENE 220

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409405 [Multi-domain] Cd Length: 91 Bit Score: 69.06 E-value: 1.27e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  928 PAFLAVIGDQSVIEGQEVTMSVLVTGQPKPMLYWLRDRVTIKTGTRHIVQETEEGNFEMIIKSAQRSDTGVYTCKIINEY 1007
Cdd:cd05744      1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKMLVRENGRHSLIIEPVTKRDAGIYTCIARNRA 80

                           90
                   ....*....|.
gi 1207186029 1008 GTKQCEGKLEV 1018
Cdd:cd05744     81 GENSFNAELVV 91

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNKs are mitogen-activated protein kinases (MAPKs) that are involved in many stress-activated responses including those during inflammation, neurodegeneration, apoptosis, and persistent pain sensitization, among others. They are also essential regulators of physiological and pathological processes and are involved in the pathogenesis of several diseases such as diabetes, atherosclerosis, stroke, Parkinson's and Alzheimer's. Vetebrates harbor three different JNK genes (Jnk1, Jnk2, and Jnk3) that are alternatively spliced to produce at least 10 isoforms. JNKs are specifically activated by the MAPK kinases MKK4 and MKK7, which are in turn activated by upstream MAPK kinase kinases as a result of different stimuli including stresses such as ultraviolet (UV) irradiation, hyperosmolarity, heat shock, or cytokines. JNKs activate a large number of different substrates based on specific stimulus, cell type, and cellular condition, and may be implicated in seemingly contradictory functions. The JNK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270840 [Multi-domain] Cd Length: 337 Bit Score: 75.14 E-value: 1.32e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3343 QEYDILKSLHHEKIMALHEAYvTPR---------YLVLISECCSGKELLHSLIDRFRYSeddvvaYIV-QILQGLDYLHS 3412
Cdd:cd07850     48 RELVLMKLVNHKNIIGLLNVF-TPQksleefqdvYLVMELMDANLCQVIQMDLDHERMS------YLLyQMLCGIKHLHS 120

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3413 RRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLkqFSPPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGR 3492
Cdd:cd07850    121 AGIIHRDLKPSNIVVKSDCTLKILDFGLARTAGTSFM--MTPYVVTRYYRAPEVILGMGYKENVDIWSVGCIMGEMIRGT 198


                   ....*..
gi 1207186029 3493 LPFTEND 3499
Cdd:cd07850    199 VLFPGTD 205

Catalytic domain of Mitogen-activated protein kinase kinase kinase kinase (MAP4K) 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes MAP4K3, MAP4K1, MAP4K2, MAP4K5, and related proteins. Vertebrate members contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. MAP4K1, also called haematopoietic progenitor kinase 1 (HPK1), is a hematopoietic-specific STK involved in many cellular signaling cascades including MAPK, antigen receptor, apoptosis, growth factor, and cytokine signaling. It participates in the regulation of T cell receptor signaling and T cell-mediated immune responses. MAP4K2 was referred to as germinal center (GC) kinase because of its preferred location in GC B cells. MAP4K3 plays a role in the nutrient-responsive pathway of mTOR (mammalian target of rapamycin) signaling. It is required in the activation of S6 kinase by amino acids and for the phosphorylation of the mTOR-regulated inhibitor of eukaryotic initiation factor 4E. MAP4K5, also called germinal center kinase-related enzyme (GCKR), has been shown to activate the MAPK c-Jun N-terminal kinase (JNK). The MAP4K3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270788 [Multi-domain] Cd Length: 259 Bit Score: 73.49 E-value: 1.47e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYV-KRVIQKAGKLEyAAKFISARAKRKASALR-ELNILSHLDHERILYFHDAFEKKNAVIIITELCH 1739
Cdd:cd06613      2 YELIQRIGSGTYGDVyKARNIATGELA-AVKVIKLEPGDDFEIIQqEISMLKECRHPNIVAYFGSYLRRDKLWIVMEYCG 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1740 EELLDRLTKKSTIL-ESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSsdQIRICDFGNAVKFMPDEAQYCKY- 1817
Cdd:cd06613     81 GGSLQDIYQVTGPLsELQIAYVCRETLKGLAYLHSTGKIHRDIKGANILLTEDG--DVKLADFGVSAQLTATIAKRKSFi 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1818 GTPEFVAPEIVN---QTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNvaFEESMFTD------LCHEak 1888
Cdd:cd06613    159 GTPYWMAPEVAAverKGGYDGKCDIWALGITAIELAELQPPMFDLHPMRALFLIPKSN--FDPPKLKDkekwspDFHD-- 234

                          250       260
                   ....*....|....*....|....
gi 1207186029 1889 gFVIKLLVAD-RLRPDANECLRHP 1911
Cdd:cd06613    235 -FIKKCLTKNpKKRPTATKLLQHP 257

Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK4 is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The specific function of MLK4 is yet to be determined. Mutations in the kinase domain of MLK4 have been detected in colorectal cancers. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation.The MLK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271048 [Multi-domain] Cd Length: 268 Bit Score: 73.92 E-value: 1.52e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3337 SKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLHSLIDRF---------RYSEDDVVAYIVQILQGL 3407
Cdd:cd14146     36 TAESVRQEAKLFSMLRHPNIIKLEGVCLEEPNLCLVMEFARGGTLNRALAAANaapgprrarRIPPHILVNWAVQIARGM 115

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3408 DYLHSRR---ILHLDIKPENIIVTYM--------NVVKIIDFGSAQTFNPLflKQFSPPiGTLDYMSPEMLKGDVVGPPA 3476
Cdd:cd14146    116 LYLHEEAvvpILHRDLKSSNILLLEKiehddicnKTLKITDFGLAREWHRT--TKMSAA-GTYAWMAPEVIKSSLFSKGS 192

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3477 DIWSIGILTYIMLSGRLPFTENDpaeteariqaakfDLSKLYQNVSQSASLFIKKIlCSYPWARpTIKDCftnsWLQDAY 3556
Cdd:cd14146    193 DIWSYGVLLWELLTGEVPYRGID-------------GLAVAYGVAVNKLTLPIPST-CPEPFAK-LMKEC----WEQDPH 253


                   .
gi 1207186029 3557 L 3557
Cdd:cd14146    254 I 254

Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-3 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-3 shows a restricted pattern of expression and is present in brain, kidney, and intestine. It is elevated in Alzheimer's disease (AD) and has been shown to associate with paired helical filaments (PHFs) and stimulate Tau phosphorylation. As AD progresses, phosphorylated Tau aggregates and forms PHFs, which leads to the formation of neurofibrillary tangles. In human glioma cells, PCTAIRE-3 induces cell cycle arrest and cell death. PCTAIRE-3 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PCTAIRE-3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270853 [Multi-domain] Cd Length: 288 Bit Score: 74.28 E-value: 1.58e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1657 RLTDYYDVHKeIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKA--SALRELNILSHLDHERILYFHDAFEKKNAVIII 1734
Cdd:cd07871      3 KLETYVKLDK-LGEGTYATVFKGRSKLTENLVALKEIRLEHEEGApcTAIREVSLLKNLKHANIVTLHDIIHTERCLTLV 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1735 TELCHEELLDRLTKKSTILE-SEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSsdQIRICDFGNA-VKFMPDEA 1812
Cdd:cd07871     82 FEYLDSDLKQYLDNCGNLMSmHNVKIFMFQLLRGLSYCHKRKILHRDLKPQNLLINEKG--ELKLADFGLArAKSVPTKT 159

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*..
gi 1207186029 1813 QYCKYGTPEFVAPEI-VNQTPVSKATDIWPIGVLTYLCLTGVSPFAG 1858
Cdd:cd07871    160 YSNEVVTLWYRPPDVlLGSTEYSTPIDMWGVGCILYEMATGRPMFPG 206

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 12; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK12 is also called Cdc2-related protein kinase 7 (CRK7) or Cdc2-related kinase arginine/serine-rich (CrkRS). It is a unique CDK that contains an RS domain, which is predominantly found in splicing factors. CDK12 is widely expressed in tissues. It interacts with cyclins L1 and L2, and plays roles in regulating transcription and alternative splicing. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK12 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270847 [Multi-domain] Cd Length: 302 Bit Score: 74.45 E-value: 1.63e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1656 RRLTDYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKA---SALRELNILSHLDHERILYFHDA-------- 1724
Cdd:cd07864      3 KRCVDKFDIIGIIGEGTYGQVYKAKDKDTGELVALKKVRLDNEKEGfpiTAIREIKILRQLNHRSVVNLKEIvtdkqdal 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1725 -FEK-KNAVIIITELCHEELLDRLTKKSTIL-ESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDF 1801
Cdd:cd07864     83 dFKKdKGAFYLVFEYMDHDLMGLLESGLVHFsEDHIKSFMKQLLEGLNYCHKKNFLHRDIKCSNILL--NNKGQIKLADF 160

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*
gi 1207186029 1802 GNAVKFMPDEAQ-YC-KYGTPEFVAPE-IVNQTPVSKATDIWPIG 1843
Cdd:cd07864    161 GLARLYNSEESRpYTnKVITLWYRPPElLLGEERYGPAIDVWSCG 205

Catalytic domain of the Serine/Threonine Kinase, Traf2- and Nck-Interacting Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TNIK is an effector of Rap2, a small GTP-binding protein from the Ras family. TNIK specifically activates the c-Jun N-terminal kinase (JNK) pathway and plays a role in regulating the actin cytoskeleton. The TNIK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270807 [Multi-domain] Cd Length: 296 Bit Score: 74.37 E-value: 1.64e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1655 MRRLTDYYDVHKEIGRGAFSYVKRVIQ-KAGKLEyAAKFISARAKRKASALRELNILSHLDHER-ILYFHDAFEKKN--- 1729
Cdd:cd06637      1 LRDPAGIFELVELVGNGTYGQVYKGRHvKTGQLA-AIKVMDVTGDEEEEIKQEINMLKKYSHHRnIATYYGAFIKKNppg 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1730 ---AVIIITELCHEELLDRL---TKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSsdQIRICDFGN 1803
Cdd:cd06637     80 mddQLWLVMEFCGAGSVTDLiknTKGNTLKEEWIAYICREILRGLSHLHQHKVIHRDIKGQNVLLTENA--EVKLVDFGV 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1804 AVKFMPDEAQYCKY-GTPEFVAPEIV--NQTPVSK---ATDIWPIGVLTYLCLTGVSPFAGEND-RSSVLNIRNYNVAFE 1876
Cdd:cd06637    158 SAQLDRTVGRRNTFiGTPYWMAPEVIacDENPDATydfKSDLWSLGITAIEMAEGAPPLCDMHPmRALFLIPRNPAPRLK 237

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1207186029 1877 ESMFTDlchEAKGFVIKLLVADR-LRPDANECLRHPWFKTLNKGKSISTEsLKKFLSRRKWQR 1938
Cdd:cd06637    238 SKKWSK---KFQSFIESCLVKNHsQRPSTEQLMKHPFIRDQPNERQVRIQ-LKDHIDRTKKKR 296

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C epsilon; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-epsilon has been shown to behave as an oncoprotein. Its overexpression contributes to neoplastic transformation depending on the cell type. It contributes to oncogenesis by inducing disordered cell growth and inhibiting cell death. It also plays a role in tumor invasion and metastasis. PKC-epsilon has also been found to confer cardioprotection against ischemia and reperfusion-mediated damage. Other cellular functions include the regulation of gene expression, cell adhesion, and cell motility. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC-epsilon subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270743 [Multi-domain] Cd Length: 321 Bit Score: 74.45 E-value: 1.98e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKIVpyepeSKQTVLQEYDILKSLHHEKIMAL----------HEAYVTPRYLVLISECCS 3377
Cdd:cd05591      5 KGSFGKVMLAERKGTDEVYAIKVL-----KKDVILQDDDVDCTMTEKRILALaakhpfltalHSCFQTKDRLFFVMEYVN 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3378 GKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQ--TFNPLFLKQFSpp 3455
Cdd:cd05591     80 GGDLMFQIQRARKFDEPRARFYAAEVTLALMFLHRHGVIYRDLKLDNILLDAEGHCKLADFGMCKegILNGKTTTTFC-- 157

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|
gi 1207186029 3456 iGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPF 3495
Cdd:cd05591    158 -GTPDYIAPEILQELEYGPSVDWWALGVLMYEMMAGQPPF 196

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase 1; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MEK1 is a dual-specificity PK and a MAPK kinase (MAPKK or MKK) that phosphorylates and activates the downstream targets, ERK1 and ERK2, on specific threonine and tyrosine residues. The ERK cascade starts with extracellular signals including growth factors, hormones, and neurotransmitters, which act through receptors and ion channels to initiate intracellular signaling that leads to the activation at the MAPKKK (Raf-1 or MOS) level, which leads to the transmission of signals to MEK1, and finally to ERK1/2. The ERK cascade plays an important role in cell proliferation, differentiation, oncogenic transformation, and cell cycle control, as well as in apoptosis and cell survival under certain conditions. Gain-of-function mutations in genes encoding ERK cascade proteins, including MEK1, cause cardiofaciocutaneous (CFC) syndrome, a condition leading to multiple congenital anomalies and mental retardation in patients. MEK1 also plays a role in cell cycle control. The MEK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270816 [Multi-domain] Cd Length: 319 Bit Score: 74.32 E-value: 2.25e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1660 DYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKR--KASALRELNILSHLDHERILYFHDAFEKKNAVIIITEL 1737
Cdd:cd06650      5 DDFEKISELGAGNGGVVFKVSHKPSGLVMARKLIHLEIKPaiRNQIIRELQVLHECNSPYIVGFYGAFYSDGEISICMEH 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1738 CHEELLDRLTKKSTILESEIRSSVR-QLLEGINYLHQL-DILHLDIKPDNILMadHSSDQIRICDFGNAVKFMpDEAQYC 1815
Cdd:cd06650     85 MDGGSLDQVLKKAGRIPEQILGKVSiAVIKGLTYLREKhKIMHRDVKPSNILV--NSRGEIKLCDFGVSGQLI-DSMANS 161

                          170       180
                   ....*....|....*....|....*....
gi 1207186029 1816 KYGTPEFVAPEIVNQTPVSKATDIWPIGV 1844
Cdd:cd06650    162 FVGTRSYMSPERLQGTHYSVQSDIWSMGL 190

Catalytic domain of the Serine/Threonine kinases, Interleukin-1 Receptor Associated Kinases and related STKs; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. Some IRAKs may also play roles in T- and B-cell signaling, and adaptive immunity. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK-1, -2, and -4 are ubiquitously expressed and are active kinases, while IRAK-M is only induced in monocytes and macrophages and is an inactive kinase. Variations in IRAK genes are linked to diverse diseases including infection, sepsis, cancer, and autoimmune diseases. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain (a pseudokinase domain in the case of IRAK3), and a C-terminal domain; IRAK-4 lacks the C-terminal domain. This subfamily includes plant receptor-like kinases (RLKs) including Arabidopsis thaliana BAK1 and CLAVATA1 (CLV1). BAK1 functions in BR (brassinosteroid)-regulated plant development and in pathways involved in plant resistance to pathogen infection and herbivore attack. CLV1, directly binds small signaling peptides, CLAVATA3 (CLV3) and CLAVATA3/EMBRYO SURROUNDING REGI0N (CLE), to restrict stem cell proliferation: the CLV3-CLV1-WUS (WUSCHEL) module influences stem cell maintenance in the shoot apical meristem, and the CLE40 (CLAVATA3/EMBRYO SURROUNDING REGION40) -ACR4 (CRINKLY4) -CLV1- WOX5 (WUSCHEL-RELATED HOMEOBOX5) module at the root apical meristem. The IRAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270968 [Multi-domain] Cd Length: 272 Bit Score: 73.08 E-value: 2.49e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3335 PESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISEccsgkeLLH--SLIDRFRYSEDDVV-------AYIVQILQ 3405
Cdd:cd14066     31 AASKKEFLTELEMLGRLRHPNLVRLLGYCLESDEKLLVYE------YMPngSLEDRLHCHKGSPPlpwpqrlKIAKGIAR 104

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3406 GLDYLHS---RRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNP-LFLKQFSPPIGTLDYMSPEMLKGDVVGPPADIWSI 3481
Cdd:cd14066    105 GLEYLHEecpPPIIHGDIKSSNILLDEDFEPKLTDFGLARLIPPsESVSKTSAVKGTIGYLAPEYIRTGRVSTKSDVYSF 184

                          170       180
                   ....*....|....*....|....*.
gi 1207186029 3482 GILTYIMLSGRLPFTENDPAETEARI 3507
Cdd:cd14066    185 GVVLLELLTGKPAVDENRENASRKDL 210

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 67.81 E-value: 2.54e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  788 QDTVASTGTEVLLKCIISGTPLPEVIWKKDNTEVKNSPTHVVkiegERHSLLIKWTKPSDAGTYTVTAVNEVGEVSSSAT 867
Cdd:cd05725      5 QNQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGELPKGRYEIL----DDHSLKIRKVTAGDMGSYTCVAENMVGKIEASAT 80


                   .
gi 1207186029  868 L 868
Cdd:cd05725     81 L 81

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 4; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK4 is a dual-specificity PK that phosphorylates and activates the downstream targets, c-Jun N-terminal kinase (JNK) and p38 MAPK, on specific threonine and tyrosine residues. JNK and p38 are collectively known as stress-activated MAPKs, as they are activated in response to a variety of environmental stresses and pro-inflammatory cytokines. Their activation is associated with the induction of cell death. Mice deficient in MKK4 die during embryogenesis and display anemia, severe liver hemorrhage, and abnormal hepatogenesis. MKK4 may also play roles in the immune system and in cardiac hypertrophy. It plays a major role in cancer as a tumor and metastasis suppressor. Under certain conditions, MKK4 is pro-oncogenic. The MKK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270790 [Multi-domain] Cd Length: 291 Bit Score: 73.55 E-value: 2.56e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1667 EIGRGAFSYVKRVIQKAGKLEYAAKFISARA--KRKASALRELN-ILSHLDHERILYFHDAFEKKNAVIIITELChEELL 1743
Cdd:cd06616     13 EIGRGAFGTVNKMLHKPSGTIMAVKRIRSTVdeKEQKRLLMDLDvVMRSSDCPYIVKFYGALFREGDCWICMELM-DISL 91

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1744 DRLTK------KSTILESEIRSSVRQLLEGINYL-HQLDILHLDIKPDNILMADHSSdqIRICDFGNAVKFMPDEAQYCK 1816
Cdd:cd06616     92 DKFYKyvyevlDSVIPEEILGKIAVATVKALNYLkEELKIIHRDVKPSNILLDRNGN--IKLCDFGISGQLVDSIAKTRD 169

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1817 YGTPEFVAPEIVNQTPVSKA----TDIWPIGVLTYLCLTGVSPFAGEND----RSSVLN----IRNYNVAFEESMftdlc 1884
Cdd:cd06616    170 AGCRPYMAPERIDPSASRDGydvrSDVWSLGITLYEVATGKFPYPKWNSvfdqLTQVVKgdppILSNSEEREFSP----- 244

                          250       260       270
                   ....*....|....*....|....*....|..
gi 1207186029 1885 hEAKGFVIKLLVADR-LRPDANECLRHPWFKT 1915
Cdd:cd06616    245 -SFVNFVNLCLIKDEsKRPKYKELLKHPFIKM 275

Catalytic domain of the Serine/Threonine Kinase, p38 Mitogen-Activated Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38 kinases are mitogen-activated protein kinases (MAPKs), serving as important mediators of cellular responses to extracellular signals. They function in the regulation of the cell cycle, cell development, cell differentiation, senescence, tumorigenesis, apoptosis, pain development and pain progression, and immune responses. p38 kinases are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. p38 substrates include other protein kinases and factors that regulate transcription, nuclear export, mRNA stability and translation. p38 kinases are drug targets for the inflammatory diseases psoriasis, rheumatoid arthritis, and chronic pulmonary disease. Vertebrates contain four isoforms of p38, named alpha, beta, gamma, and delta, which show varying substrate specificity and expression patterns. p38alpha and p38beta are ubiquitously expressed, p38gamma is predominantly found in skeletal muscle, and p38delta is found in the heart, lung, testis, pancreas, and small intestine. The p38 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143356 [Multi-domain] Cd Length: 343 Bit Score: 74.25 E-value: 2.77e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3344 EYDILKSLHHEKIMALHEAYvTPR---------YLVLiseccsgkEL----LHSLIDRFRYSEDDVVAYIVQILQGLDYL 3410
Cdd:cd07851     64 ELRLLKHMKHENVIGLLDVF-TPAssledfqdvYLVT--------HLmgadLNNIVKCQKLSDDHIQFLVYQILRGLKYI 134

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3411 HSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNplflKQFSPPIGTLDYMSPE-MLKGDVVGPPADIWSIGILTYIML 3489
Cdd:cd07851    135 HSAGIIHRDLKPSNLAVNEDCELKILDFGLARHTD----DEMTGYVATRWYRAPEiMLNWMHYNQTVDIWSVGCIMAELL 210

                          170
                   ....*....|.
gi 1207186029 3490 SGRLPFTENDP 3500
Cdd:cd07851    211 TGKTLFPGSDH 221

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK1 (also called rhodopsin kinase) belongs to the visual group of GRKs and is expressed in retinal cells. It phosphorylates rhodopsin in rod cells, which leads to termination of the phototransduction cascade. Mutations in GRK1 are associated to a recessively inherited form of stationary nightblindness called Oguchi disease. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors, which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270759 [Multi-domain] Cd Length: 288 Bit Score: 73.38 E-value: 2.88e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1660 DYYDVHKEIGRGAFSYVKRVIQKA-GKLeYAAKFISAR--AKRKA--SALRELNILSHLDHERILYFHDAFEKKNAVIII 1734
Cdd:cd05608      1 DWFLDFRVLGKGGFGEVSACQMRAtGKL-YACKKLNKKrlKKRKGyeGAMVEKRILAKVHSRFIVSLAYAFQTKTDLCLV 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1735 TELC-------HEELLDRltKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADhsSDQIRICDFGNAVKF 1807
Cdd:cd05608     80 MTIMnggdlryHIYNVDE--ENPGFQEPRACFYTAQIISGLEHLHQRRIIYRDLKPENVLLDD--DGNVRISDLGLAVEL 155

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1808 MPDEAQYCKY-GTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPF--AGENDRSSVLNIR--NYNVAFEESMFTD 1882
Cdd:cd05608    156 KDGQTKTKGYaGTPGFMAPELLLGEEYDYSVDYFTLGVTLYEMIAARGPFraRGEKVENKELKQRilNDSVTYSEKFSPA 235

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*
gi 1207186029 1883 lcheAKGFVIKLLVAD---RLRPDANEC--LR-HPWFKTLNKGKS 1921
Cdd:cd05608    236 ----SKSICEALLAKDpekRLGFRDGNCdgLRtHPFFRDINWRKL 276

Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK1 is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK) and is also called MAP3K9. MAP3Ks phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Little is known about the specific function of MLK1. It is capable of activating the c-Jun N-terminal kinase pathway. Mice lacking both MLK1 and MLK2 are viable, fertile, and have normal life spans. There could be redundancy in the function of MLKs. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The MLK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271047 [Multi-domain] Cd Length: 270 Bit Score: 72.77 E-value: 3.17e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYVKRVIQkaGKLEYAAKfiSAR-------AKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITELCHE 1740
Cdd:cd14145     14 IGIGGFGKVYRAIW--IGDEVAVK--AARhdpdediSQTIENVRQEAKLFAMLKHPNIIALRGVCLKEPNLCLVMEFARG 89

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1741 ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQ---LDILHLDIKPDNILM------ADHSSDQIRICDFGNAVKFMpDE 1811
Cdd:cd14145     90 GPLNRVLSGKRIPPDILVNWAVQIARGMNYLHCeaiVPVIHRDLKSSNILIlekvenGDLSNKILKITDFGLAREWH-RT 168

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*..
gi 1207186029 1812 AQYCKYGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAG 1858
Cdd:cd14145    169 TKMSAAGTYAWMAPEVIRSSMFSKGSDVWSYGVLLWELLTGEVPFRG 215

Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Activated Kinase-1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAK1 is also known as mitogen-activated protein kinase kinase kinase 7 (MAPKKK7 or MAP3K7), TAK, or MEKK7. As a MAPKKK, it is an important mediator of cellular responses to extracellular signals. It regulates both the c-Jun N-terminal kinase and p38 MAPK cascades by activating the MAPK kinases, MKK4 and MKK3/6. In addition, TAK1 plays diverse roles in immunity and development, in different biological contexts, through many signaling pathways including TGFbeta/BMP, Wnt/Fz, and NF-kB. It is also implicated in the activation of the tumor suppressor kinase, LKB1. The TAK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270960 [Multi-domain] Cd Length: 253 Bit Score: 72.47 E-value: 3.26e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYVKRVIQKAgkLEYAAKFISARAKRKAsALRELNILSHLDHERILYFHDAFEKKNAVIIITELCHE-ELLDRL 1746
Cdd:cd14058      1 VGRGSFGVVCKARWRN--QIVAVKIIESESEKKA-FEVEVRQLSRVDHPNIIKLYGACSNQKPVCLVMEYAEGgSLYNVL 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1747 TKKSTILE---SEIRSSVRQLLEGINYLHQLD---ILHLDIKPDNILMADHSSDqIRICDFGNAVKF---MPDEAqycky 1817
Cdd:cd14058     78 HGKEPKPIytaAHAMSWALQCAKGVAYLHSMKpkaLIHRDLKPPNLLLTNGGTV-LKICDFGTACDIsthMTNNK----- 151

                          170       180       190
                   ....*....|....*....|....*....|....*....
gi 1207186029 1818 GTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPF 1856
Cdd:cd14058    152 GSAAWMAPEVFEGSKYSEKCDVFSWGIILWEVITRRKPF 190

Catalytic domain of the Serine/Threonine Kinase, p38gamma Mitogen-Activated Protein Kinase (also called MAPK12); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38gamma/MAPK12 is predominantly expressed in skeletal muscle. Unlike p38alpha and p38beta, p38gamma is insensitive to pyridinylimidazoles. It displays an antagonizing function compared to p38alpha. p38gamma inhibits, while p38alpha stimulates, c-Jun phosphorylation and AP-1 mediated transcription. p38gamma also plays a role in the signaling between Ras and the estrogen receptor and has been implicated to increase cell invasion and breast cancer progression. In Xenopus, p38gamma is critical in the meiotic maturation of oocytes. p38 kinases are MAPKs, serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38gamma subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143385 [Multi-domain] Cd Length: 343 Bit Score: 74.22 E-value: 3.27e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1660 DYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAK-----FISAR-AKRkasALRELNILSHLDHERILYFHDAF------EK 1727
Cdd:cd07880     15 DRYRDLKQVGSGAYGTVCSALDRRTGAKVAIKklyrpFQSELfAKR---AYRELRLLKHMKHENVIGLLDVFtpdlslDR 91

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1728 KNAVIIITELCHEELlDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNilMADHSSDQIRICDFGNAVKF 1807
Cdd:cd07880     92 FHDFYLVMPFMGTDL-GKLMKHEKLSEDRIQFLVYQMLKGLKYIHAAGIIHRDLKPGN--LAVNEDCELKILDFGLARQT 168

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1808 MPDEAQYCKygTPEFVAPE-IVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNI------------------ 1868
Cdd:cd07880    169 DSEMTGYVV--TRWYRAPEvILNWMHYTQTVDIWSVGCIMAEMLTGKPLFKGHDHLDQLMEImkvtgtpskefvqklqse 246

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1207186029 1869 --RNYNVAFEE-------SMFTDLCHEAKGFVIKLLVAD-RLRPDANECLRHPWFKTL 1916
Cdd:cd07880    247 daKNYVKKLPRfrkkdfrSLLPNANPLAVNVLEKMLVLDaESRITAAEALAHPYFEEF 304

Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PIM gene locus was discovered as a result of the cloning of retroviral intergration sites in murine Moloney leukemia virus, leading to the identification of PIM kinases. They are constitutively active STKs with a broad range of cellular targets and are overexpressed in many haematopoietic malignancies and solid cancers. Vertebrates contain three distinct PIM kinase genes (PIM1-3). PIM3 can inhibit apoptosis and promote cell survival and protein translation, therefore, it can enhance the proliferation of normal and cancer cells. Mice deficient with PIM3 show minimal effects, suggesting that PIM3 msy not be essential. Since its expression is enhanced in several cancers, it may make a good molecular target for cancer drugs. The PIM3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271004 [Multi-domain] Cd Length: 253 Bit Score: 72.30 E-value: 3.56e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3379 KELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMN-VVKIIDFGSAQTFNPLFLKQFSppiG 3457
Cdd:cd14102     90 KDLFDFITEKGALDEDTARGFFRQVLEAVRHCYSCGVVHRDIKDENLLVDLRTgELKLIDFGSGALLKDTVYTDFD---G 166

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3458 TLDYMSPEMLKGDVV-GPPADIWSIGILTYIMLSGRLPFtENDPAETEARIQaakfdlskLYQNVSQSASLFIKKILCSY 3536
Cdd:cd14102    167 TRVYSPPEWIRYHRYhGRSATVWSLGVLLYDMVCGDIPF-EQDEEILRGRLY--------FRRRVSPECQQLIKWCLSLR 237

                          170
                   ....*....|....*.
gi 1207186029 3537 PWARPTIKDCFTNSWL 3552
Cdd:cd14102    238 PSDRPTLEQIFDHPWM 253

Catalytic domain of the Protein Tyrosine Kinase, Hematopoietic cell kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Hck is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Hck is present in myeloid and lymphoid cells that play a role in the development of cancer. It may be important in the oncogenic signaling of the protein Tel-Abl, which induces a chronic myelogenous leukemia (CML)-like disease. Hck also acts as a negative regulator of G-CSF-induced proliferation of granulocytic precursors, suggesting a possible role in the development of acute myeloid leukemia (AML). In addition, Hck is essential in regulating the degranulation of polymorphonuclear leukocytes. Genetic polymorphisms affect the expression level of Hck, which affects PMN mediator release and influences the development of chronic obstructive pulmonary disease (COPD). Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Hck subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270658 [Multi-domain] Cd Length: 265 Bit Score: 72.37 E-value: 4.82e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3337 SKQTVLQEYDILKSLHHEKIMALHeAYVTPRYLVLISECCSGKellhSLIDRFRYSEDD------VVAYIVQILQGLDYL 3410
Cdd:cd05073     49 SVEAFLAEANVMKTLQHDKLVKLH-AVVTKEPIYIITEFMAKG----SLLDFLKSDEGSkqplpkLIDFSAQIAEGMAFI 123

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3411 HSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPlflKQFSPPIGT---LDYMSPEMLKGDVVGPPADIWSIGI-LTY 3486
Cdd:cd05073    124 EQRNYIHRDLRAANILVSASLVCKIADFGLARVIED---NEYTAREGAkfpIKWTAPEAINFGSFTIKSDVWSFGIlLME 200

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3487 IMLSGRLPFtendPAETEARIQAAKFDLSKLYQNVSQSASLFIKKILC--SYPWARPTIKdcFTNSWLQD 3554
Cdd:cd05073    201 IVTYGRIPY----PGMSNPEVIRALERGYRMPRPENCPEELYNIMMRCwkNRPEERPTFE--YIQSVLDD 264

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 67.03 E-value: 5.48e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1123 PLFTRKLD-VLEVIEGRNARFDCKVSGTPPPQVIWSHFDRPLEENEDIRILKEGGrhsLIISHVSNEDEGLYTVAARNSH 1201
Cdd:cd20978      1 PKFIQKPEkNVVVKGGQDVTLPCQVTGVPQPKITWLHNGKPLQGPMERATVEDGT---LTIINVQPEDTGYYGCVATNEI 77

                           90
                   ....*....|.
gi 1207186029 1202 GEDECAAELYV 1212
Cdd:cd20978     78 GDIYTETLLHV 88

serine/threonine-protein kinase PknD;

Pssm-ID: 183880 [Multi-domain] Cd Length: 932 Bit Score: 75.58 E-value: 5.58e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3402 QILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNP-----LFLKQFSPPI------------GTLDYMSP 3464
Cdd:PRK13184   121 KICATIEYVHSKGVLHRDLKPDNILLGLFGEVVILDWGAAIFKKLeeedlLDIDVDERNIcyssmtipgkivGTPDYMAP 200

                           90       100       110
                   ....*....|....*....|....*....|.
gi 1207186029 3465 EMLKGDVVGPPADIWSIGILTYIMLSGRLPF 3495
Cdd:PRK13184   201 ERLLGVPASESTDIYALGVILYQMLTLSFPY 231

N-terminal Catalytic domain of the Serine/Threonine Kinase, Class IIIB myosin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Class IIIB myosin is expressed highly in retina. It is also present in the brain and testis. The human class IIIB myosin gene maps to a region that overlaps the locus for Bardet-Biedl syndrome, which is characterized by dysmorphic extremities, retinal dystrophy, obesity, male hypogenitalism, and renal abnormalities. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain. They may play an important role in maintaining the structural integrity of photoreceptor cell microvilli. They may also function as cargo carriers during light-dependent translocation, in photoreceptor cells, of proteins such as transducin and arrestin. The class III myosin subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270808 [Multi-domain] Cd Length: 291 Bit Score: 72.72 E-value: 5.66e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1659 TDYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASALRELNILSHL-DHERILYFHDAFEKKNAVI----- 1732
Cdd:cd06639     21 SDTWDIIETIGKGTYGKVYKVTNKKDGSLAAVKILDPISDVDEEIEAEYNILRSLpNHPNVVKFYGMFYKADQYVggqlw 100

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1733 IITELCH----EELLDRLTKKSTILESEIRSSV-RQLLEGINYLHQLDILHLDIKPDNILMADHSSdqIRICDFGNAVKF 1807
Cdd:cd06639    101 LVLELCNggsvTELVKGLLKCGQRLDEAMISYIlYGALLGLQHLHNNRIIHRDVKGNNILLTTEGG--VKLVDFGVSAQL 178

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1808 MPDEAQY-CKYGTPEFVAPEIV---NQTPVS--KATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNI-RNYNVAFEESmf 1880
Cdd:cd06639    179 TSARLRRnTSVGTPFWMAPEVIaceQQYDYSydARCDVWSLGITAIELADGDPPLFDMHPVKALFKIpRNPPPTLLNP-- 256

                          250       260       270
                   ....*....|....*....|....*....|....*
gi 1207186029 1881 TDLCHEAKGFVIKLLVAD-RLRPDANECLRHPWFK 1914
Cdd:cd06639    257 EKWCRGFSHFISQCLIKDfEKRPSVTHLLEHPFIK 291

Catalytic domain of the Serine/Threonine Kinase, p38beta Mitogen-Activated Protein Kinase (also called MAPK11); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38beta/MAPK11 is widely expressed in tissues and shows more similarity with p38alpha than with the other isoforms. Both are sensitive to pyridinylimidazoles and share some common substrates such as MAPK activated protein kinase 2 (MK2) and the transcription factors ATF2, c-Fos and, ELK-1. p38beta is involved in regulating the activation of the cyclooxygenase-2 promoter and the expression of TGFbeta-induced alpha-smooth muscle cell actin. p38 kinases are mitogen-activated protein kinases (MAPKs), serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38beta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143383 [Multi-domain] Cd Length: 343 Bit Score: 73.16 E-value: 5.76e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3343 QEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKEL----LHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHL 3418
Cdd:cd07878     63 RELRLLKHMKHENVIGLLDVFTPATSIENFNEVYLVTNLmgadLNNIVKCQKLSDEHVQFLIYQLLRGLKYIHSAGIIHR 142

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3419 DIKPENIIVTYMNVVKIIDFGSAQTFNplflKQFSPPIGTLDYMSPE-MLKGDVVGPPADIWSIGILTYIMLSGRLPFTE 3497
Cdd:cd07878    143 DLKPSNVAVNEDCELRILDFGLARQAD----DEMTGYVATRWYRAPEiMLNWMHYNQTVDIWSVGCIMAELLKGKALFPG 218

                          170
                   ....*....|
gi 1207186029 3498 NDPAETEARI 3507
Cdd:cd07878    219 NDYIDQLKRI 228

Catalytic domain of testis-specific serine/threonine kinase 3 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK3 has been reported to be expressed in the interstitial Leydig cells of adult testis. Its mRNA levels is low at birth, increases at puberty, and remains high throughout adulthood. The TSSK3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271065 [Multi-domain] Cd Length: 257 Bit Score: 71.95 E-value: 6.15e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3343 QEYDILKSLHHEKIMALHEAY-VTPRYLVLISECCSGKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIK 3421
Cdd:cd14163     49 RELQIVERLDHKNIIHVYEMLeSADGKIYLVMELAEDGDVFDCVLHGGPLPEHRAKALFRQLVEAIRYCHGCGVAHRDLK 128

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3422 PENIIVTYMNVvKIIDFGSAQTFnPLFLKQFSPPI-GTLDYMSPEMLKG---DvvGPPADIWSIGILTYIMLSGRLPFTE 3497
Cdd:cd14163    129 CENALLQGFTL-KLTDFGFAKQL-PKGGRELSQTFcGSTAYAAPEVLQGvphD--SRKGDIWSMGVVLYVMLCAQLPFDD 204

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1207186029 3498 NDPAETEARIQAAKFDLSKLyqNVSQSASLFIKKILCSYPWARPTIKDCFTNSWL 3552
Cdd:cd14163    205 TDIPKMLCQQQKGVSLPGHL--GVSRTCQDLLKRLLEPDMVLRPSIEEVSWHPWL 257

Catalytic domain of the Dual-specificity protein kinase, YAK1; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. This subfamily is composed of proteins with similarity to Saccharomyces cerevisiae YAK1 (or Yak1p), a dual-specificity kinase that autophosphorylates at tyrosine residues and phosphorylates substrates on S/T residues. YAK1 phosphorylates and activates the transcription factors Hsf1 and Msn2, which play important roles in cellular homeostasis during stress conditions including heat shock, oxidative stress, and nutrient deficiency. It also phosphorylates the protein POP2, a component of a complex that regulates transcription, under glucose-deprived conditions. It functions as a part of a glucose-sensing system that is involved in controlling growth in yeast. The YAK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271114 [Multi-domain] Cd Length: 330 Bit Score: 73.05 E-value: 6.46e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPESKQTVLQEYDILKSL---------HHekIMALHEAYVTPRYLV 3370
Cdd:cd14212      1 YLVLDLLGQGTFGQVVKCQDLKTNKLVAVKVLKNKPAYFRQAMLEIAILTLLntkydpedkHH--IVRLLDHFMHHGHLC 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3371 LISECCSGKelLHSLI--DRFR-YSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNV--VKIIDFGSA---- 3441
Cdd:cd14212     79 IVFELLGVN--LYELLkqNQFRgLSLQLIRKFLQQLLDALSVLKDARIIHCDLKPENILLVNLDSpeIKLIDFGSAcfen 156

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|.
gi 1207186029 3442 QTfnplfLKQFsppIGTLDYMSPEMLKGDVVGPPADIWSIG 3482
Cdd:cd14212    157 YT-----LYTY---IQSRFYRSPEVLLGLPYSTAIDMWSLG 189

Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LIMKs phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They act downstream of Rho GTPases and are expressed ubiquitously. As regulators of actin dynamics, they contribute to diverse cellular functions such as cell motility, morphogenesis, differentiation, apoptosis, meiosis, mitosis, and neurite extension. LIMKs contain the LIM (two repeats), PDZ, and catalytic kinase domains. Vertebrate have two members, LIMK1 and LIMK2. The LIMK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271056 [Multi-domain] Cd Length: 272 Bit Score: 72.16 E-value: 6.57e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGN-LYMAKIVPYEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSG---KELLH 3383
Cdd:cd14154      3 KGFFGQAIKVTHRETGEvMVMKELIRFDEEAQRNFLKEVKVMRSLDHPNVLKFIGVLYKDKKLNLITEYIPGgtlKDVLK 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3384 SLIDRFRYSEDdvVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSA--------QTFNPLF---LKQF 3452
Cdd:cd14154     83 DMARPLPWAQR--VRFAKDIASGMAYLHSMNIIHRDLNSHNCLVREDKTVVVADFGLArliveerlPSGNMSPsetLRHL 160

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|
gi 1207186029 3453 SPP--------IGTLDYMSPEMLKGDVVGPPADIWSIGIL 3484
Cdd:cd14154    161 KSPdrkkrytvVGNPYWMAPEMLNGRSYDEKVDIFSFGIV 200

Catalytic domain of the Serine/Threonine Kinase, A-Raf (Rapidly Accelerated Fibrosarcoma) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. A-Raf cooperates with C-Raf in regulating ERK transient phosphorylation that is associated with cyclin D expression and cell cycle progression. Mice deficient in A-Raf are born alive but show neurological and intestinal defects. A-Raf demonstrates low kinase activity to MEK, compared with B- and C-Raf, and may also have alternative functions other than in the ERK signaling cascade. It regulates the M2 type pyruvate kinase, a key glycolytic enzyme. It also plays a role in endocytic membrane trafficking. A-Raf is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. It functions in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. The A-Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271052 [Multi-domain] Cd Length: 265 Bit Score: 71.59 E-value: 7.25e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1666 KEIGRGAFSYVKRviqkaGKL--EYAAKF--ISARAKRKASALR-ELNILSHLDHERILYFHdAFEKKNAVIIITELCHE 1740
Cdd:cd14150      6 KRIGTGSFGTVFR-----GKWhgDVAVKIlkVTEPTPEQLQAFKnEMQVLRKTRHVNILLFM-GFMTRPNFAIITQWCEG 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1741 ELLDR-LTKKSTILESEIRSSV-RQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDFGNA-VKFMPDEAQYCKY 1817
Cdd:cd14150     80 SSLYRhLHVTETRFDTMQLIDVaRQTAQGMDYLHAKNIIHRDLKSNNIFL--HEGLTVKIGDFGLAtVKTRWSGSQQVEQ 157

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1207186029 1818 --GTPEFVAPEIV---NQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVL 1866
Cdd:cd14150    158 psGSILWMAPEVIrmqDTNPYSFQSDVYAYGVVLYELMSGTLPYSNINNRDQII 211

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C eta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-eta is predominantly expressed in squamous epithelia, where it plays a crucial role in the signaling of cell-type specific differentiation. It is also expressed in pro-B cells and early-stage thymocytes, and acts as a key regulator in early B-cell development. PKC-eta increases glioblastoma multiforme (GBM) proliferation and resistance to radiation, and is being developed as a therapeutic target for the management of GBM. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC-eta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270742 [Multi-domain] Cd Length: 323 Bit Score: 72.63 E-value: 7.34e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYVKRVIQKAGKLEYAAKFIsarakRKASALRELNILSHLDHERIL----------YFHDAFEKKNAVIIITEL 1737
Cdd:cd05590      3 LGKGSFGKVMLARLKESGRLYAVKVL-----KKDVILQDDDVECTMTEKRILslarnhpfltQLYCCFQTPDRLFFVMEF 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1738 CHE-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMaDHSSdQIRICDFGNAVKFMPD---EAQ 1813
Cdd:cd05590     78 VNGgDLMFHIQKSRRFDEARARFYAAEITSALMFLHDKGIIYRDLKLDNVLL-DHEG-HCKLADFGMCKEGIFNgktTST 155

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1814 YCkyGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDLCHEAKGFVIK 1893
Cdd:cd05590    156 FC--GTPDYIAPEILQEMLYGPSVDWWAMGVLLYEMLCGHAPFEAENEDDLFEAILNDEVVYPTWLSQDAVDILKAFMTK 233

                          250       260
                   ....*....|....*....|....*...
gi 1207186029 1894 lLVADRL--RPDANE--CLRHPWFKTLN 1917
Cdd:cd05590    234 -NPTMRLgsLTLGGEeaILRHPFFKELD 260

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 65.81 E-value: 8.24e-13

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1207186029 2878 VTLSCLPAGSPHPHISWMKDKKPLEIDPRMNMIScPDGRQLLMIMKTTKKDAGLYECVAANPLATVTSSCV 2948
Cdd:cd00096      1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRS-ELGNGTLTISNVTLEDSGTYTCVASNSAGGSASASV 70

N-terminal Catalytic domain of the Serine/Threonine Kinase, Class IIIA myosin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Class IIIA myosin is highly expressed in retina and in inner ear hair cells. It is localized to the distal ends of actin-bundled structures. Mutations in human myosin IIIA are responsible for progressive nonsyndromic hearing loss. Human myosin IIIA possesses ATPase and kinase activities, and the ability to move actin filaments in a motility assay. It may function as a cellular transporter capable of moving along actin bundles in sensory cells. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain. Class III myosins may play an important role in maintaining the structural integrity of photoreceptor cell microvilli. In photoreceptor cells, they may also function as cargo carriers during light-dependent translocation of proteins such as transducin and arrestin. The class III myosin subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 132969 [Multi-domain] Cd Length: 286 Bit Score: 71.97 E-value: 8.67e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1659 TDYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASALRELNILSHL-DHERILYFHDAFEKKNAVI----- 1732
Cdd:cd06638     17 SDTWEIIETIGKGTYGKVFKVLNKKNGSKAAVKILDPIHDIDEEIEAEYNILKALsDHPNVVKFYGMYYKKDVKNgdqlw 96

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1733 IITELCH----EELLDRLTKKSTILESEIRSSV-RQLLEGINYLHQLDILHLDIKPDNILMAdhSSDQIRICDFGNAVKF 1807
Cdd:cd06638     97 LVLELCNggsvTDLVKGFLKRGERMEEPIIAYIlHEALMGLQHLHVNKTIHRDVKGNNILLT--TEGGVKLVDFGVSAQL 174

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1808 MPDEAQY-CKYGTPEFVAPEIVN-----QTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNI-RNYNVAFEESMF 1880
Cdd:cd06638    175 TSTRLRRnTSVGTPFWMAPEVIAceqqlDSTYDARCDVWSLGITAIELGDGDPPLADLHPMRALFKIpRNPPPTLHQPEL 254

                          250       260       270
                   ....*....|....*....|....*....|.
gi 1207186029 1881 tdLCHEAKGFVIKLLVAD-RLRPDANECLRH 1910
Cdd:cd06638    255 --WSNEFNDFIRKCLTKDyEKRPTVSDLLQH 283

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 66.05 E-value: 8.71e-13

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1207186029 1257 DMDVVEGREAVLRCKVAGLPYPTITWFHNGKRIDSTEDRKMTQFRDVHSLVVRCVCHAHGGVYKCVISN 1325
Cdd:pfam13927   10 SVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

NIMA-related protein kinase; Provisional

Pssm-ID: 140293 [Multi-domain] Cd Length: 478 Bit Score: 73.90 E-value: 9.02e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1690 AKFISARAKRKASALR-ELNILSHLDHERILYFHDAFEKKNAVIIITEL-----CHEELLDRLTKKSTILESEIRSSVRQ 1763
Cdd:PTZ00267    98 AKFVMLNDERQAAYARsELHCLAACDHFGIVKHFDDFKSDDKLLLIMEYgsggdLNKQIKQRLKEHLPFQEYEVGLLFYQ 177

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1764 LLEGINYLHQLDILHLDIKPDNILMAdhSSDQIRICDFGNAVKF-----MPDEAQYCkyGTPEFVAPEIVNQTPVSKATD 1838
Cdd:PTZ00267   178 IVLALDEVHSRKMMHRDLKSANIFLM--PTGIIKLGDFGFSKQYsdsvsLDVASSFC--GTPYYLAPELWERKRYSKKAD 253

                          170       180
                   ....*....|....*....|....
gi 1207186029 1839 IWPIGVLTYLCLTGVSPFAGENDR 1862
Cdd:PTZ00267   254 MWSLGVILYELLTLHRPFKGPSQR 277

Catalytic domain of the Serine/Threonine Kinases, fungal Bck1-like Mitogen-Activated Protein Kinase Kinase Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include the MAPKKKs Saccharomyces cerevisiae Bck1 and Schizosaccharomyces pombe Mkh1, and related proteins. Budding yeast Bck1 is part of the cell integrity MAPK pathway, which is activated by stresses and aggressions to the cell wall. The MAPKKK Bck1, MAPKKs Mkk1 and Mkk2, and the MAPK Slt2 make up the cascade that is important in the maintenance of cell wall homeostasis. Fission yeast Mkh1 is involved in MAPK cascades regulating cell morphology, cell wall integrity, salt resistance, and filamentous growth in response to stress. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The Bck1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270799 [Multi-domain] Cd Length: 270 Bit Score: 71.64 E-value: 9.11e-13

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1696 RAKRKASALR-ELNILSHLDHERIL-YFhdAFEKKNAVI-IITELCHEELLDRLTKKSTILESE-IRSSVRQLLEGINYL 1771
Cdd:cd06629     47 RQKTVVDALKsEIDTLKDLDHPNIVqYL--GFEETEDYFsIFLEYVPGGSIGSCLRKYGKFEEDlVRFFTRQILDGLAYL 124

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1772 HQLDILHLDIKPDNILMaDHssDQI-RICDFGNAVK----FMPDEAQYCKyGTPEFVAPEIV--NQTPVSKATDIWPIGV 1844
Cdd:cd06629    125 HSKGILHRDLKADNILV-DL--EGIcKISDFGISKKsddiYGNNGATSMQ-GSVFWMAPEVIhsQGQGYSAKVDIWSLGC 200

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1207186029 1845 LTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDLCHEAKGFVIKLLVAD-RLRPDANECLRHPW 1912
Cdd:cd06629    201 VVLEMLAGRRPWSDDEAIAAMFKLGNKRSAPPVPEDVNLSPEALDFLNACFAIDpRDRPTAAELLSHPF 269

Catalytic domain of the Serine/Threonine Kinases, Fungal Mitogen-Activated Protein Kinases Sty1 and Hog1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the MAPKs Sty1 from Schizosaccharomyces pombe, Hog1 from Saccharomyces cerevisiae, and similar proteins. Sty1 and Hog1 are stress-activated MAPKs that partipate in transcriptional regulation in response to stress. Sty1 is activated in response to oxidative stress, osmotic stress, and UV radiation. It is regulated by the MAP2K Wis1, which is activated by the MAP3Ks Wis4 and Win1, which receive signals of the stress condition from membrane-spanning histidine kinases Mak1-3. Activated Sty1 stabilizes the Atf1 transcription factor and induces transcription of Atf1-dependent genes of the core environmetal stress response. Hog1 is the key element in the high osmolarity glycerol (HOG) pathway and is activated upon hyperosmotic stress. Activated Hog1 accumulates in the nucleus and regulates stress-induced transcription. The HOG pathway is mediated by two transmembrane osmosensors, Sln1 and Sho1. MAPKs are important mediators of cellular responses to extracellular signals. The Sty1/Hog1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270843 [Multi-domain] Cd Length: 328 Bit Score: 72.22 E-value: 1.04e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1658 LTDYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFI------SARAKRkasALRELNILSHLDHERILYFHDAF-EKKNA 1730
Cdd:cd07856      8 ITTRYSDLQPVGMGAFGLVCSARDQLTGQNVAVKKImkpfstPVLAKR---TYRELKLLKHLRHENIISLSDIFiSPLED 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1731 VIIITELCHEELlDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSdqIRICDFGNAVKFMPD 1810
Cdd:cd07856     85 IYFVTELLGTDL-HRLLTSRPLEKQFIQYFLYQILRGLKYVHSAGVIHRDLKPSNILVNENCD--LKICDFGLARIQDPQ 161

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1207186029 1811 EAQYCKygTPEFVAPEI-VNQTPVSKATDIWPIGVLTYLCLTGVSPFAGEN 1860
Cdd:cd07856    162 MTGYVS--TRYYRAPEImLTWQKYDVEVDIWSAGCIFAEMLEGKPLFPGKD 210

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 65.43 E-value: 1.10e-12

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1207186029 1140 ARFDCKVSGTPPPQVIWSHFDRPLEENEDIRILKEGGRHSLIISHVSNEDEGLYTVAARNSHGEDECA 1207
Cdd:cd00096      1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASA 68

Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNK4 shows a restricted expression pattern and is usually found in epithelial cells. It is expressed in nephrons and in extrarenal tissues including intestine, eye, mammary glands, and prostate. WNK4 regulates a variety of ion transport proteins including apical or basolateral ion transporters, ion channels in the transcellular pathway, and claudins in the paracellular pathway. Mutations in WNK4 cause PseudoHypoAldosteronism type II (PHAII), characterized by hypertension and hyperkalemia. WNK4 inhibits the activity of the thiazide-sensitive Na-Cl cotransporter (NCC), which is responsible for about 15% of NaCl reabsorption in the kidney. It also inhibits the renal outer medullary potassium channel (ROMK) and decreases its surface expression. Hypertension and hyperkalemia in PHAII patients with WNK4 mutations may be partly due to increased NaCl reabsorption through NCC and impaired renal potassium secretion by ROMK, respectively. The WNK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270935 [Multi-domain] Cd Length: 261 Bit Score: 70.80 E-value: 1.23e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1667 EIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASALR---ELNILSHLDHERILYFHDAFEK----KNAVIIITELCH 1739
Cdd:cd14033      8 EIGRGSFKTVYRGLDTETTVEVAWCELQTRKLSKGERQRfseEVEMLKGLQHPNIVRFYDSWKStvrgHKCIILVTELMT 87

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1740 EELLDRLTKKSTILESEI--RSSvRQLLEGINYLHQL--DILHLDIKPDNILMADHSSdQIRICDFGNAVKfmpDEAQYC 1815
Cdd:cd14033     88 SGTLKTYLKRFREMKLKLlqRWS-RQILKGLHFLHSRcpPILHRDLKCDNIFITGPTG-SVKIGDLGLATL---KRASFA 162

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....
gi 1207186029 1816 K--YGTPEFVAPEIVNQTpVSKATDIWPIGVLTYLCLTGVSPFA 1857
Cdd:cd14033    163 KsvIGTPEFMAPEMYEEK-YDEAVDVYAFGMCILEMATSEYPYS 205

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C delta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-delta plays a role in cell cycle regulation and programmed cell death in many cell types. It slows down cell proliferation, inducing cell cycle arrest and enhancing cell differentiation. PKC-delta is also involved in the regulation of transcription as well as immune and inflammatory responses. It plays a central role in the genotoxic stress response that leads to DNA damaged-induced apoptosis. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC-delta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173710 [Multi-domain] Cd Length: 316 Bit Score: 71.90 E-value: 1.23e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1666 KEIGRGAFSYVKrviqkAGKLEYAAKFISARAKRKASALRELNILSHLDHERIL----------YFHDAFEKKNAVIIIT 1735
Cdd:cd05620      1 KVLGKGSFGKVL-----LAELKGKGEYFAVKALKKDVVLIDDDVECTMVEKRVLalawenpfltHLYCTFQTKEHLFFVM 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1736 E-LCHEELLDRLTKK-------STILESEIrssvrqlLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDFGNAVKF 1807
Cdd:cd05620     76 EfLNGGDLMFHIQDKgrfdlyrATFYAAEI-------VCGLQFLHSKGIIYRDLKLDNVML--DRDGHIKIADFGMCKEN 146

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1808 MPDEAQYCKY-GTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESmftdLCHE 1886
Cdd:cd05620    147 VFGDNRASTFcGTPDYIAPEILQGLKYTFSVDWWSFGVLLYEMLIGQSPFHGDDEDELFESIRVDTPHYPRW----ITKE 222

                          250       260       270
                   ....*....|....*....|....*....|....
gi 1207186029 1887 AKGFVIKLLVAD---RLRPDANECLrHPWFKTLN 1917
Cdd:cd05620    223 SKDILEKLFERDptrRLGVVGNIRG-HPFFKTIN 255

Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain, and a C-terminal domain; IRAK-4 lacks the C-terminal domain. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK4 plays a critical role in NFkB activation by its interaction with MyD88, which acts as a scaffold that enables IRAK4 to phosphorylate and activate IRAK1 and/or IRAK2. It also plays an important role in type I IFN production induced by TLR7/8/9. The IRAK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271060 [Multi-domain] Cd Length: 288 Bit Score: 71.38 E-value: 1.33e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3309 GRFGVIRECRENATgNLYMAKIVPYE----PESKQTVLQEYDILKSLHHEKIMA-LHEAYVTPRYLVLISECCSGkellh 3383
Cdd:cd14158     26 GGFGVVFKGYINDK-NVAVKKLAAMVdistEDLTKQFEQEIQVMAKCQHENLVElLGYSCDGPQLCLVYTYMPNG----- 99

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3384 SLIDRFRySEDDVVAYIVQI--------LQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTfNPLFLK--QFS 3453
Cdd:cd14158    100 SLLDRLA-CLNDTPPLSWHMrckiaqgtANGINYLHENNHIHRDIKSANILLDETFVPKISDFGLARA-SEKFSQtiMTE 177

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*....
gi 1207186029 3454 PPIGTLDYMSPEMLKGDVVgPPADIWSIGILTYIMLSGRLPFTEN-DPA 3501
Cdd:cd14158    178 RIVGTTAYMAPEALRGEIT-PKSDIFSFGVVLLEIITGLPPVDENrDPQ 225

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 65.66 E-value: 1.40e-12

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1207186029 1123 PLFTRKLDVLEVIEGRNARFDCKVSGTPPPQVIWSHFDRPLEENEDIRILKEGGRHSLIISHVSNEDEGLYTVAARN 1199
Cdd:pfam13927    2 PVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

cAMP-dependent protein kinase catalytic subunit; Provisional

Pssm-ID: 173616 [Multi-domain] Cd Length: 340 Bit Score: 71.94 E-value: 1.42e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1641 KDDPMEDEASILRKMRrlTDYYDVHKEIGRGAFSYVKRVIQKAGKLEYAA-----KFISARAKRKASALRELNILSHLDH 1715
Cdd:PTZ00426    13 KDSDSTKEPKRKNKMK--YEDFNFIRTLGTGSFGRVILATYKNEDFPPVAikrfeKSKIIKQKQVDHVFSERKILNYINH 90

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1716 ERILYFHDAFEKKNAVIIITELCHEELLDRLTKKSTILESEIRS-SVRQLLEGINYLHQLDILHLDIKPDNILMadHSSD 1794
Cdd:PTZ00426    91 PFCVNLYGSFKDESYLYLVLEFVIGGEFFTFLRRNKRFPNDVGCfYAAQIVLIFEYLQSLNIVYRDLKPENLLL--DKDG 168

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1795 QIRICDFGNAVkfMPDEAQYCKYGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVA 1874
Cdd:PTZ00426   169 FIKMTDFGFAK--VVDTRTYTLCGTPEYIAPEILLNVGHGKAADWWTLGIFIYEILVGCPPFYANEPLLIYQKILEGIIY 246

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*....
gi 1207186029 1875 FEESMFTDLCHEAKgfviKLLVAD------RLRPDANECLRHPWFKTLN 1917
Cdd:PTZ00426   247 FPKFLDNNCKHLMK----KLLSHDltkrygNLKKGAQNVKEHPWFGNID 291

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK6 is regulated by D-type cyclins and INK4 inhibitors. It is active towards the retinoblastoma (pRb) protein, implicating it to function in regulating the early G1 phase of the cell cycle. It is expressed ubiquitously and is localized in the cytoplasm. It is also present in the ruffling edge of spreading fibroblasts and may play a role in cell spreading. It binds to the p21 inhibitor without any effect on its own activity and it is overexpressed in squamous cell carcinomas and neuroblastomas. CDK6 has also been shown to inhibit cell differentiation in many cell types. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270846 [Multi-domain] Cd Length: 290 Bit Score: 71.22 E-value: 1.44e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVkrviQKAGKLEYAAKFISARAKR--------KASALRELNILSHLDherilyfhdAFEKKNaVII 1733
Cdd:cd07862      3 YECVAEIGEGAYGKV----FKARDLKNGGRFVALKRVRvqtgeegmPLSTIREVAVLRHLE---------TFEHPN-VVR 68

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1734 ITELCHEELLDRLTKKSTILE--------------------SEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMAdhSS 1793
Cdd:cd07862     69 LFDVCTVSRTDRETKLTLVFEhvdqdlttyldkvpepgvptETIKDMMFQLLRGLDFLHSHRVVHRDLKPQNILVT--SS 146

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1207186029 1794 DQIRICDFGNAVKFMPDEAQYCKYGTPEFVAPEIVNQTPVSKATDIWPIGVL 1845
Cdd:cd07862    147 GQIKLADFGLARIYSFQMALTSVVVTLWYRAPEVLLQSSYATPVDLWSVGCI 198

Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. VEGFR1 (or Flt1) binds VEGFA, VEGFB, and placenta growth factor (PLGF). It regulates monocyte and macrophage migration, vascular permeability, haematopoiesis, and the recruitment of haematopietic progenitor cells from the bone marrow. VEGFR1 is a member of the VEGFR subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of VEGFRs to their ligands, the VEGFs, leads to receptor dimerization, activation, and intracellular signaling. The VEGFR1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271109 [Multi-domain] Cd Length: 340 Bit Score: 71.96 E-value: 1.52e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3394 DDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTF--NPLFLKQFSPPIgTLDYMSPEMLKGDV 3471
Cdd:cd14207    180 EDLISYSFQVARGMEFLSSRKCIHRDLAARNILLSENNVVKICDFGLARDIykNPDYVRKGDARL-PLKWMAPESIFDKI 258

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1207186029 3472 VGPPADIWSIGILTYIMLS-GRLPF----TEND---PAETEARIQAAKFDLSKLYQ 3519
Cdd:cd14207    259 YSTKSDVWSYGVLLWEIFSlGASPYpgvqIDEDfcsKLKEGIRMRAPEFATSEIYQ 314

Catalytic domain of the Serine/Threonine Kinases, Mixed Lineage Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Mammals have four MLKs (MLK1-4), mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The MLK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270963 [Multi-domain] Cd Length: 258 Bit Score: 70.50 E-value: 1.61e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYVKR-------VIQKAGKLEYAAKFisarAKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITELCHE 1740
Cdd:cd14061      2 IGVGGFGKVYRgiwrgeeVAVKAARQDPDEDI----SVTLENVRQEARLFWMLRHPNIIALRGVCLQPPNLCLVMEYARG 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1741 ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQ---LDILHLDIKPDNILMA-----DHSSDQI-RICDFGNAvKFMPDE 1811
Cdd:cd14061     78 GALNRVLAGRKIPPHVLVDWAIQIARGMNYLHNeapVPIIHRDLKSSNILILeaienEDLENKTlKITDFGLA-REWHKT 156

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*..
gi 1207186029 1812 AQYCKYGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAG 1858
Cdd:cd14061    157 TRMSAAGTYAWMAPEVIKSSTFSKASDVWSYGVLLWELLTGEVPYKG 203

Catalytic domain of the Serine/Threonine Kinases, Plant TEY Mitogen-Activated Protein Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Plant MAPKs are typed based on the conserved phosphorylation motif present in the activation loop, TEY and TDY. This subfamily represents the TEY subtype of plant MAPKs and is further subdivided into three groups (A, B, and C). Group A is represented by AtMPK3, AtMPK6, Nicotiana tabacum BTF4 (NtNTF4), among others. They are mostly involved in environmental and hormonal responses. AtMPK3 and AtMPK6 are also key regulators for stomatal development and patterning. Group B is represented by AtMPK4, AtMPK13, and NtNTF6, among others. They may be involved in both cell division and environmental stress response. AtMPK4 also participates in regulating innate immunity. Group C is represented by AtMPK1, AtMPK2, NtNTF3, Oryza sativa MAPK4 (OsMAPK4), among others. They may also be involved in stress responses. AtMPK1 and AtMPK2 are activated following mechanical injury and in the presence of stress chemicals such as jasmonic acid, hydrogen peroxide and abscisic acid. OsMAPK4 is also called OsMSRMK3 for Multiple Stress-Responsive MAPK3. In plants, MAPKs are associated with physiological, developmental, hormonal, and stress responses. Some plants show numerous gene duplications of MAPKs; Arabidopsis thaliana harbors at least 20 MAPKs, named AtMPK1-20. The TEY MAPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143363 [Multi-domain] Cd Length: 337 Bit Score: 71.63 E-value: 1.70e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3295 VPQKPYtfmdekARGRFGVIRECRENATGN-LYMAKIV-PYEP--ESKQTvLQEYDILKSLHHEKIMALHEAYVTPR--- 3367
Cdd:cd07858      8 VPIKPI------GRGAYGIVCSAKNSETNEkVAIKKIAnAFDNriDAKRT-LREIKLLRHLDHENVIAIKDIMPPPHrea 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3368 ----YLVLiseccsgkEL----LHSLIDRFRYSEDDVVAYIV-QILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDF 3438
Cdd:cd07858     81 fndvYIVY--------ELmdtdLHQIIRSSQTLSDDHCQYFLyQLLRGLKYIHSANVLHRDLKPSNLLLNANCDLKICDF 152

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3439 GSAQTFN--PLFLKQFsppIGTLDYMSPE-MLKGDVVGPPADIWSIG-ILTYIMlsGRLP-------------------- 3494
Cdd:cd07858    153 GLARTTSekGDFMTEY---VVTRWYRAPElLLNCSEYTTAIDVWSVGcIFAELL--GRKPlfpgkdyvhqlklitellgs 227

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1207186029 3495 -------FTENDPAETEARI--QAAKFDLSKLYQNVSQSASLFIKKILCSYPWARPTIKDCftnswLQDAYLMRL 3560
Cdd:cd07858    228 pseedlgFIRNEKARRYIRSlpYTPRQSFARLFPHANPLAIDLLEKMLVFDPSKRITVEEA-----LAHPYLASL 297

Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LRRK2 is one of two vertebrate LRRKs which show complementary expression in the brain. Mutations in LRRK2, found in the kinase, ROC-COR, and WD40 domains, are linked to both familial and sporadic forms of Parkinson's disease. The most prevalent mutation, G2019S located in the activation loop of the kinase domain, increases kinase activity. The R1441C/G mutations in the GTPase domain have also been reported to influence kinase activity. LRRKs are also classified as ROCO proteins because they contain a ROC (Ras of complex proteins)/GTPase domain followed by a COR (C-terminal of ROC) domain of unknown function. In addition, LRRKs contain a catalytic kinase domain and protein-protein interaction motifs including a WD40 domain, LRRs and ankyrin (ANK) repeats. LRRKs possess both GTPase and kinase activities, with the ROC domain acting as a molecular switch for the kinase domain, cycling between a GTP-bound state which drives kinase activity and a GDP-bound state which decreases the activity. The LRRK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270970 [Multi-domain] Cd Length: 252 Bit Score: 70.37 E-value: 1.71e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3343 QEYDILKSLHHEKIMALHEAYVTPRYLVLisECCSgKELLHSLIDRFRYSEDDVVAYIV--QILQGLDYLHSRRILHLDI 3420
Cdd:cd14068     36 QELVVLSHLHHPSLVALLAAGTAPRMLVM--ELAP-KGSLDALLQQDNASLTRTLQHRIalHVADGLRYLHSAMIIYRDL 112

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3421 KPENIIV--TYMN---VVKIIDFGSAQTFNPLFLKQFSppiGTLDYMSPEMLKGDVV-GPPADIWSIGILTYIMLS--GR 3492
Cdd:cd14068    113 KPHNVLLftLYPNcaiIAKIADYGIAQYCCRMGIKTSE---GTPGFRAPEVARGNVIyNQQADVYSFGLLLYDILTcgER 189

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1207186029 3493 LPFTENDPAE-TEARIQAAKFDLSKLYQNVS-QSASLFIKKILCSYPWARPT 3542
Cdd:cd14068    190 IVEGLKFPNEfDELAIQGKLPDPVKEYGCAPwPGVEALIKDCLKENPQCRPT 241

serine/threonine protein kinase; Provisional

Pssm-ID: 240344 [Multi-domain] Cd Length: 496 Bit Score: 72.98 E-value: 1.72e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3401 VQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGsaqtfnplFLKQFSPPI---------GTLDYMSPEMLKGDV 3471
Cdd:PTZ00283   150 IQVLLAVHHVHSKHMIHRDIKSANILLCSNGLVKLGDFG--------FSKMYAATVsddvgrtfcGTPYYVAPEIWRRKP 221

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1207186029 3472 VGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDlsKLYQNVSQSASLFIKKILCSYPWARPTIK 3544
Cdd:PTZ00283   222 YSKKADMFSLGVLLYELLTLKRPFDGENMEEVMHKTLAGRYD--PLPPSISPEMQEIVTALLSSDPKRRPSSS 292

Catalytic domain of the Serine/Threonine Kinase, Homeodomain-Interacting Protein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HIPK1 has been implicated in regulating eye size, lens formation, and retinal morphogenesis during late embryogenesis. It also contributes to the regulation of haematopoiesis and leukaemogenesis by phosphorylating and repressing the transcription factor c-Myb, which is crucial in T- and B-cell development. In glucose-deprived conditions, HIPK1 phosphorylates Daxx, leading to its relocalization from the nucleus to the cytoplasm, where it binds and stabilizes ASK1 (apoptosis signal-regulating kinase 1), a mitogen-activated protein kinase (MAPK) kinase kinase that activates the JNK and p38 MAPK pathways. HIPKs, originally identified by their ability to bind homeobox factors, are nuclear proteins containing catalytic kinase and homeobox-interacting domains as well as a PEST region overlapping with the speckle-retention signal (SRS). The HIPK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271130 [Multi-domain] Cd Length: 355 Bit Score: 72.04 E-value: 1.82e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1658 LTDYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASALRELNILSHLDHER-----ILYFHDAFEKKNAVI 1732
Cdd:cd14228     13 MTNSYEVLEFLGRGTFGQVAKCWKRSTKEIVAIKILKNHPSYARQGQIEVSILSRLSSENadeynFVRSYECFQHKNHTC 92

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1733 IITELCHEELLDRL--TKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMAD--HSSDQIRICDFGNAVKFm 1808
Cdd:cd14228     93 LVFEMLEQNLYDFLkqNKFSPLPLKYIRPILQQVATALMKLKSLGLIHADLKPENIMLVDpvRQPYRVKVIDFGSASHV- 171

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1207186029 1809 pDEAQYCKYGTPEFV-APEIVNQTPVSKATDIWPIGVLTYLCLTG--VSPFAGENDR 1862
Cdd:cd14228    172 -SKAVCSTYLQSRYYrAPEIILGLPFCEAIDMWSLGCVIAELFLGwpLYPGASEYDQ 227

Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAO1 is sometimes referred to as prostate-derived sterile 20-like kinase 2 (PSK2). TAO1 activates the p38 MAPK through direct interaction with and activation of MEK3. TAO1 is highly expressed in the brain and may play a role in neuronal apoptosis. TAO1 interacts with the checkpoint proteins BubR1 and Mad2, and plays an important role in regulating mitotic progression, which is required for both chromosome congression and checkpoint-induced anaphase delay. TAO1 may play a role in protecting genomic stability. TAO proteins possess MAPK kinase kinase activity. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. The TAO1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270805 [Multi-domain] Cd Length: 317 Bit Score: 71.23 E-value: 1.89e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1666 KEIGRGAFS--YVKRVIQKA-----GKLEYAAKfisARAKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITELC 1738
Cdd:cd06635     31 REIGHGSFGavYFARDVRTSevvaiKKMSYSGK---QSNEKWQDIIKEVKFLQRIKHPNSIEYKGCYLREHTAWLVMEYC 107

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1739 HEELLDRL-TKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADhsSDQIRICDFGNAVKFMPDEAqycKY 1817
Cdd:cd06635    108 LGSASDLLeVHKKPLQEIEIAAITHGALQGLAYLHSHNMIHRDIKAGNILLTE--PGQVKLADFGSASIASPANS---FV 182

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1818 GTPEFVAPEIV---NQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNI-RNYNVAFEESMFTDLCHEAKGFVIK 1893
Cdd:cd06635    183 GTPYWMAPEVIlamDEGQYDGKVDVWSLGITCIELAERKPPLFNMNAMSALYHIaQNESPTLQSNEWSDYFRNFVDSCLQ 262

                          250
                   ....*....|....*..
gi 1207186029 1894 LLVADrlRPDANECLRH 1910
Cdd:cd06635    263 KIPQD--RPTSEELLKH 277

Catalytic domain of the Dual-specificity protein kinase, YAK1; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. This subfamily is composed of proteins with similarity to Saccharomyces cerevisiae YAK1 (or Yak1p), a dual-specificity kinase that autophosphorylates at tyrosine residues and phosphorylates substrates on S/T residues. YAK1 phosphorylates and activates the transcription factors Hsf1 and Msn2, which play important roles in cellular homeostasis during stress conditions including heat shock, oxidative stress, and nutrient deficiency. It also phosphorylates the protein POP2, a component of a complex that regulates transcription, under glucose-deprived conditions. It functions as a part of a glucose-sensing system that is involved in controlling growth in yeast. The YAK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271114 [Multi-domain] Cd Length: 330 Bit Score: 71.51 E-value: 2.09e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASALRELNILSHL-------DHERILYFHDAFEKKNAVIII 1734
Cdd:cd14212      1 YLVLDLLGQGTFGQVVKCQDLKTNKLVAVKVLKNKPAYFRQAMLEIAILTLLntkydpeDKHHIVRLLDHFMHHGHLCIV 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1735 TELCHEELLDRLTKK-----STILeseIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSDQIRICDFGNAVkfMP 1809
Cdd:cd14212     81 FELLGVNLYELLKQNqfrglSLQL---IRKFLQQLLDALSVLKDARIIHCDLKPENILLVNLDSPEIKLIDFGSAC--FE 155

                          170       180       190
                   ....*....|....*....|....*....|....
gi 1207186029 1810 DEAQYCKYGTPEFVAPEIVNQTPVSKATDIWPIG 1843
Cdd:cd14212    156 NYTLYTYIQSRFYRSPEVLLGLPYSTAIDMWSLG 189

Catalytic domain of the Protein Tyrosine Kinases, Bruton's tyrosine kinase and Bone marrow kinase on the X chromosome; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Btk and Bmx (also named Etk) are members of the Tec-like subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, Btk contains the Tec homology (TH) domain with proline-rich and zinc-binding regions. Btk is expressed in B-cells, and a variety of myeloid cells including mast cells, platelets, neutrophils, and dendrictic cells. It interacts with a variety of partners, from cytosolic proteins to nuclear transcription factors, suggesting a diversity of functions. Stimulation of a diverse array of cell surface receptors, including antigen engagement of the B-cell receptor, leads to PH-mediated membrane translocation of Btk and subsequent phosphorylation by Src kinase and activation. Btk plays an important role in the life cycle of B-cells including their development, differentiation, proliferation, survival, and apoptosis. Mutations in Btk cause the primary immunodeficiency disease, X-linked agammaglobulinaemia (XLA) in humans. Bmx is primarily expressed in bone marrow and the arterial endothelium, and plays an important role in ischemia-induced angiogenesis. It facilitates arterial growth, capillary formation, vessel maturation, and bone marrow-derived endothelial progenitor cell mobilization. The Btk/Bmx subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173657 [Multi-domain] Cd Length: 256 Bit Score: 70.29 E-value: 2.10e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3298 KPYTFMDEKARGRFGVIRECRENATGNLYMaKIVPYEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCS 3377
Cdd:cd05113      4 KDLTFLKELGTGQFGVVKYGKWRGQYDVAI-KMIKEGSMSEDEFIEEAKVMMNLSHEKLVQLYGVCTKQRPIFIITEYMA 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3378 GKELLHSLID-RFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTfnpLFLKQFSPPI 3456
Cdd:cd05113     83 NGCLLNYLREmRKRFQTQQLLEMCKDVCEAMEYLESKQFLHRDLAARNCLVNDQGVVKVSDFGLSRY---VLDDEYTSSV 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3457 GT---LDYMSPEMLKGDVVGPPADIWSIGILTYIMLS-GRLPFTENDPAETEARIQAAKfdlsKLYQnvSQSASLFIKKI 3532
Cdd:cd05113    160 GSkfpVRWSPPEVLMYSKFSSKSDVWAFGVLMWEVYSlGKMPYERFTNSETVEHVSQGL----RLYR--PHLASEKVYTI 233

                          250       260
                   ....*....|....*....|.
gi 1207186029 3533 LCS----YPWARPTIKDCFTN 3549
Cdd:cd05113    234 MYScwheKADERPTFKILLSN 254

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin Superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.

Pssm-ID: 409420 [Multi-domain] Cd Length: 91 Bit Score: 65.33 E-value: 2.31e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1546 TFETIMEDLDVNVGETPRFAVVVEGKPVPDILWYKG---DTLLSESSHFTFVYDDNEcsLVVLNTQADDSGVYTCTAKNL 1622
Cdd:cd05763      1 SFTKTPHDITIRAGSTARLECAATGHPTPQIAWQKDggtDFPAARERRMHVMPEDDV--FFIVDVKIEDTGVYSCTAQNS 78

                           90
                   ....*....|..
gi 1207186029 1623 AGSVSCKAELTV 1634
Cdd:cd05763     79 AGSISANATLTV 90

Catalytic domain of the Dual-specificity protein kinases, CDC-like kinases; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. CLKs are involved in the phosphorylation and regulation of serine/arginine-rich (SR) proteins, which play a crucial role in pre-mRNA splicing by directing splice site selection. SR proteins are phosphorylated first by SR protein kinases (SRPKs) at the N-terminus, which leads to its assembly into nuclear speckles where splicing factors are stored. CLKs phosphorylate the C-terminal part of SR proteins, causing the nuclear speckles to dissolve and splicing factors to be recruited at sites of active transcription. Based on a conserved "EHLAMMERILG" signature motif which may be crucial for substrate specificity, CLKs are also referred to as LAMMER kinases. CLKs autophosphorylate at tyrosine residues and phosphorylate their substrates exclusively on S/T residues. In Drosophila, the CLK homolog DOA (Darkener of apricot) is essential for embryogenesis and its mutation leads to defects in sexual differentiation, eye formation, and neuronal development. In fission yeast, the CLK homolog Lkh1 is a negative regulator of filamentous growth and asexual flocculation, and is also involved in oxidative stress response. Vertebrates contain mutliple CLK proteins and mammals have four (CLK1-4). The CLK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271036 [Multi-domain] Cd Length: 332 Bit Score: 71.44 E-value: 2.38e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3283 IGKPGDSTLRQgvpqkpYTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPESKQTVLQEYDILKSLHHE------KI 3356
Cdd:cd14134      3 IYKPGDLLTNR------YKILRLLGEGTFGKVLECWDRKRKRYVAVKIIRNVEKYREAAKIEIDVLETLAEKdpngksHC 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3357 MALHEAYVTPRYLVLISECCsGKellhSLIDRFR------YSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENI----- 3425
Cdd:cd14134     77 VQLRDWFDYRGHMCIVFELL-GP----SLYDFLKknnygpFPLEHVQHIAKQLLEAVAFLHDLKLTHTDLKPENIllvds 151

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1207186029 3426 --IVTYMNV------------VKIIDFGSAqTFNplflKQF-SPPIGTLDYMSPEMLKGdvVG--PPADIWSIG-IL 3484
Cdd:cd14134    152 dyVKVYNPKkkrqirvpkstdIKLIDFGSA-TFD----DEYhSSIVSTRHYRAPEVILG--LGwsYPCDVWSIGcIL 221

serine/threonine kinase US3; Provisional

Pssm-ID: 177557 [Multi-domain] Cd Length: 357 Bit Score: 71.45 E-value: 2.41e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1699 RKASALRELNILSHLDHERILYFHDAFEKKNAVIIITELCHEELLDRLTKKSTILEseIRSS---VRQLLEGINYLHQLD 1775
Cdd:PHA03209   100 QKGTTLIEAMLLQNVNHPSVIRMKDTLVSGAITCMVLPHYSSDLYTYLTKRSRPLP--IDQAliiEKQILEGLRYLHAQR 177

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1207186029 1776 ILHLDIKPDNILMADhsSDQIRICDFGNAVKFMPDEAQYCKYGTPEFVAPEIVNQTPVSKATDIWPIGVLTY 1847
Cdd:PHA03209   178 IIHRDVKTENIFIND--VDQVCIGDLGAAQFPVVAPAFLGLAGTVETNAPEVLARDKYNSKADIWSAGIVLF 247

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409543 [Multi-domain] Cd Length: 94 Bit Score: 65.13 E-value: 2.61e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1249 PDFVKPLYDMDVVEGREAVLRCKVAGLPYPTITWFHNGKRID-STEDRKMTQFRD--VHSLVVRCVCHAHGGVYKCVISN 1325
Cdd:cd20951      1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIDpSSIPGKYKIESEygVHVLHIRRVTVEDSAVYSAVAKN 80

                           90
                   ....*....|...
gi 1207186029 1326 KVGKATCYSHLYV 1338
Cdd:cd20951     81 IHGEASSSASVVV 93

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C epsilon; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-epsilon has been shown to behave as an oncoprotein. Its overexpression contributes to neoplastic transformation depending on the cell type. It contributes to oncogenesis by inducing disordered cell growth and inhibiting cell death. It also plays a role in tumor invasion and metastasis. PKC-epsilon has also been found to confer cardioprotection against ischemia and reperfusion-mediated damage. Other cellular functions include the regulation of gene expression, cell adhesion, and cell motility. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC-epsilon subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270743 [Multi-domain] Cd Length: 321 Bit Score: 70.98 E-value: 2.80e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1666 KEIGRGAFSYVKRVIQKAGKLEYAAKFIsarakRKASALRELNILSHLDHERILYF----------HDAFEKKNAVIIIT 1735
Cdd:cd05591      1 KVLGKGSFGKVMLAERKGTDEVYAIKVL-----KKDVILQDDDVDCTMTEKRILALaakhpfltalHSCFQTKDRLFFVM 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1736 ELCHE-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDFGNAVKFMPDE--- 1811
Cdd:cd05591     76 EYVNGgDLMFQIQRARKFDEPRARFYAAEVTLALMFLHRHGVIYRDLKLDNILL--DAEGHCKLADFGMCKEGILNGktt 153

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1812 AQYCkyGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMFTDLCHEAKGFV 1891
Cdd:cd05591    154 TTFC--GTPDYIAPEILQELEYGPSVDWWALGVLMYEMMAGQPPFEADNEDDLFESILHDDVLYPVWLSKEAVSILKAFM 231

                          250       260       270
                   ....*....|....*....|....*....|.
gi 1207186029 1892 IKlLVADRL-----RPDANECLRHPWFKTLN 1917
Cdd:cd05591    232 TK-NPAKRLgcvasQGGEDAIRQHPFFREID 261

Catalytic domain of the protein kinase, Dual-specificity tYrosine-phosphorylated and -Regulated Kinase 1; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. Mammals contain two types of DYRK1 proteins, DYRK1A and DYRK1B. DYRK1A was previously called minibrain kinase homolog (MNBH) or dual-specificity YAK1-related kinase. It phosphorylates various substrates and is involved in many cellular events. It phosphorylates and inhibits the transcription factors, nuclear factor of activated T cells (NFAT) and forkhead in rhabdomyosarcoma (FKHR). It regulates neuronal differentiation by targetting CREB (cAMP response element-binding protein). It also targets many endocytic proteins including dynamin and amphiphysin and may play a role in the endocytic pathway. The gene encoding DYRK1A is located in the DSCR (Down syndrome critical region) of human chromosome 21 and DYRK1A has been implicated in the pathogenesis of DS. DYRK1B, also called minibrain-related kinase (MIRK), is highly expressed in muscle and plays a critical role in muscle differentiation by regulating transcription, cell motility, survival, and cell cycle progression. It is overexpressed in many solid tumors where it acts as a tumor survival factor. DYRKs autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. The DYRK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271128 [Multi-domain] Cd Length: 339 Bit Score: 70.81 E-value: 3.16e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1651 ILRKMRRLTDYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASALRELNILSHLDHE------RILYFHDA 1724
Cdd:cd14226      4 IVKNGEKWMDRYEIDSLIGKGSFGQVVKAYDHVEQEWVAIKIIKNKKAFLNQAQIEVRLLELMNKHdtenkyYIVRLKRH 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1725 FEKKNAVIIITELCHEELLD--RLTKKSTILESEIRSSVRQLLEGINYLHQ--LDILHLDIKPDNILMADHSSDQIRICD 1800
Cdd:cd14226     84 FMFRNHLCLVFELLSYNLYDllRNTNFRGVSLNLTRKFAQQLCTALLFLSTpeLSIIHCDLKPENILLCNPKRSAIKIID 163

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1207186029 1801 FGNAVKfmPDEAQYcKYGTPEFV-APEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNI 1868
Cdd:cd14226    164 FGSSCQ--LGQRIY-QYIQSRFYrSPEVLLGLPYDLAIDMWSLGCILVEMHTGEPLFSGANEVDQMNKI 229

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 64.72 E-value: 3.29e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029   55 PVFIRKMRNA--AVGTGcDIRLKVAVAGDPQPTLYWYHNDDLVNMDNQEY----GGLWIRDCKPSDAGLYTCIATNHLGE 128
Cdd:cd20978      1 PKFIQKPEKNvvVKGGQ-DVTLPCQVTGVPQPKITWLHNGKPLQGPMERAtvedGTLTIINVQPEDTGYYGCVATNEIGD 79


                   ....*....
gi 1207186029  129 ARSSAVLAV 137
Cdd:cd20978     80 IYTETLLHV 88

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409405 [Multi-domain] Cd Length: 91 Bit Score: 64.82 E-value: 3.64e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 2861 PVFHIKLRDHVLLEGDPVTLSCLPAGSPHPHISWMKDKKPLEIDPRMNMISCPDGRQLLMIMKTTKKDAGLYECVAANPL 2940
Cdd:cd05744      1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSAHKMLVRENGRHSLIIEPVTKRDAGIYTCIARNRA 80


                   ....*.
gi 1207186029 2941 ATVTSS 2946
Cdd:cd05744     81 GENSFN 86

Catalytic domain of the Serine/Threonine Kinase, Plant B-type Cyclin-Dependent protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The plant-specific B-type CDKs are expressed from the late S to the M phase of the cell cycle. They are characterized by the cyclin binding motif PPT[A/T]LRE. They play a role in controlling mitosis and integrating developmental pathways, such as stomata and leaf development. CdkB has been shown to associate with both cyclin B, which controls G2/M transition, and cyclin D, which acts as a mediator in linking extracellular signals to the cell cycle. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CdkB subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270830 [Multi-domain] Cd Length: 294 Bit Score: 70.25 E-value: 3.64e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPESK---QTVLQEYDILKSLHHE----KIMALHEAYVTPR-YLVL 3371
Cdd:cd07837      3 YEKLEKIGEGTYGKVYKARDKNTGKLVALKKTRLEMEEEgvpSTALREVSLLQMLSQSiyivRLLDVEHVEENGKpLLYL 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3372 ISECCSGKelLHSLIDRFRYSEDD------VVAYIVQILQGLDYLHSRRILHLDIKPENIIV-TYMNVVKIIDFGSAQTF 3444
Cdd:cd07837     83 VFEYLDTD--LKKFIDSYGRGPHNplpaktIQSFMYQLCKGVAHCHSHGVMHRDLKPQNLLVdKQKGLLKIADLGLGRAF 160

                          170       180       190
                   ....*....|....*....|....*....|....*....
gi 1207186029 3445 NpLFLKQFSPPIGTLDYMSPEMLKGDV-VGPPADIWSIG 3482
Cdd:cd07837    161 T-IPIKSYTHEIVTLWYRAPEVLLGSThYSTPVDMWSVG 198

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 1 from higher eukaryotes; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK1 is also called Cell division control protein 2 (Cdc2) or p34 protein kinase, and is regulated by cyclins A, B, and E. The CDK1/cyclin A complex controls G2 phase entry and progression. CDK1/cyclin A2 has also been implicated as an important regulator of S phase events. The CDK1/cyclin B complex is critical for G2 to M phase transition. It induces mitosis by activating nuclear enzymes that regulate chromatin condensation, nuclear membrane degradation, mitosis-specific microtubule and cytoskeletal reorganization. CDK1 also associates with cyclin E and plays a role in the entry into S phase. CDK1 transcription is stable throughout the cell cycle but is modulated in some pathological conditions. It may play a role in regulating apoptosis under these conditions. In breast cancer cells, HER2 can mediate apoptosis by inactivating CDK1. Activation of CDK1 may contribute to HIV-1 induced apoptosis as well as neuronal apoptosis in neurodegenerative diseases. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270845 [Multi-domain] Cd Length: 285 Bit Score: 70.14 E-value: 3.76e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1660 DYYDVHKeIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRK---ASALRELNILSHLDHERILYFHDAFEKKNAVIIITE 1736
Cdd:cd07861      1 DYTKIEK-IGEGTYGVVYKGRNKKTGQIVAMKKIRLESEEEgvpSTAIREISLLKELQHPNIVCLEDVLMQENRLYLVFE 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1737 LCHEEL---LDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDFGNAVKF-MPDEA 1812
Cdd:cd07861     80 FLSMDLkkyLDSLPKGKYMDAELVKSYLYQILQGILFCHSRRVLHRDLKPQNLLI--DNKGVIKLADFGLARAFgIPVRV 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1813 QYCKYGTPEFVAPEIVNQTP-VSKATDIWPIGVLTYLCLTGVSPFAG------------------ENDRSSVLNIRNYNV 1873
Cdd:cd07861    158 YTHEVVTLWYRAPEVLLGSPrYSTPVDIWSIGTIFAEMATKKPLFHGdseidqlfrifrilgtptEDIWPGVTSLPDYKN 237

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*...
gi 1207186029 1874 AFEE-------SMFTDLCHEAKGFVIKLLVAD-RLRPDANECLRHPWF 1913
Cdd:cd07861    238 TFPKwkkgslrTAVKNLDEDGLDLLEKMLIYDpAKRISAKKALVHPYF 285

Catalytic domain of the Serine/Threonine kinases, Interleukin-1 Receptor Associated Kinases and related STKs; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. Some IRAKs may also play roles in T- and B-cell signaling, and adaptive immunity. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK-1, -2, and -4 are ubiquitously expressed and are active kinases, while IRAK-M is only induced in monocytes and macrophages and is an inactive kinase. Variations in IRAK genes are linked to diverse diseases including infection, sepsis, cancer, and autoimmune diseases. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain (a pseudokinase domain in the case of IRAK3), and a C-terminal domain; IRAK-4 lacks the C-terminal domain. This subfamily includes plant receptor-like kinases (RLKs) including Arabidopsis thaliana BAK1 and CLAVATA1 (CLV1). BAK1 functions in BR (brassinosteroid)-regulated plant development and in pathways involved in plant resistance to pathogen infection and herbivore attack. CLV1, directly binds small signaling peptides, CLAVATA3 (CLV3) and CLAVATA3/EMBRYO SURROUNDING REGI0N (CLE), to restrict stem cell proliferation: the CLV3-CLV1-WUS (WUSCHEL) module influences stem cell maintenance in the shoot apical meristem, and the CLE40 (CLAVATA3/EMBRYO SURROUNDING REGION40) -ACR4 (CRINKLY4) -CLV1- WOX5 (WUSCHEL-RELATED HOMEOBOX5) module at the root apical meristem. The IRAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270968 [Multi-domain] Cd Length: 272 Bit Score: 69.61 E-value: 4.19e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYVKRVIQKAGKLeYAAKFI--SARAKRKASALRELNILSHLDHE---RILYFHDAFEKKnavIIITELCHE-E 1741
Cdd:cd14066      1 IGSGGFGTVYKGVLENGTV-VAVKRLneMNCAASKKEFLTELEMLGRLRHPnlvRLLGYCLESDEK---LLVYEYMPNgS 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1742 LLDRL--TKKSTILESEIRSSV-RQLLEGINYLHQ---LDILHLDIKPDNILMADHSsdQIRICDFGNAVKFMPDEAQYC 1815
Cdd:cd14066     77 LEDRLhcHKGSPPLPWPQRLKIaKGIARGLEYLHEecpPPIIHGDIKSSNILLDEDF--EPKLTDFGLARLIPPSESVSK 154

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1207186029 1816 K---YGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNY 1871
Cdd:cd14066    155 TsavKGTIGYLAPEYIRTGRVSTKSDVYSFGVVLLELLTGKPAVDENRENASRKDLVEW 213

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNK2 is expressed in every cell and tissue type. It is specifically translocated to the mitochondria during dopaminergic cell death. Specific substrates include the microtubule-associated proteins DCX and Tau, as well as TIF-IA which is involved in ribosomal RNA synthesis regulation. Mice deficient in Jnk2 show protection against arthritis, type 1 diabetes, atherosclerosis, abdominal aortic aneurysm, cardiac cell death, TNF-induced liver damage, and tumor growth, indicating that JNK2 may play roles in the pathogenesis of these diseases. Initially it was thought that JNK1 and JNK2 were functionally redundant as mice deficient in either genes could survive but disruption of both genes resulted in lethality. However, recent studies have shown that JNK1 and JNK2 perform distinct functions through specific binding partners and substrates. JNKs are mitogen-activated protein kinases (MAPKs) that are involved in many stress-activated responses including those during inflammation, neurodegeneration, apoptosis, and persistent pain sensitization, among others. The JNK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143381 [Multi-domain] Cd Length: 359 Bit Score: 70.83 E-value: 4.21e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3343 QEYDILKSLHHEKIMALHEAYvTPR---------YLVLISECCSGKELLHSLIDRFRYSeddvvAYIVQILQGLDYLHSR 3413
Cdd:cd07876     69 RELVLLKCVNHKNIISLLNVF-TPQksleefqdvYLVMELMDANLCQVIHMELDHERMS-----YLLYQMLCGIKHLHSA 142

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3414 RILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLkqFSPPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRL 3493
Cdd:cd07876    143 GIIHRDLKPSNIVVKSDCTLKILDFGLARTACTNFM--MTPYVVTRYYRAPEVILGMGYKENVDIWSVGCIMGELVKGSV 220


                   ....*.
gi 1207186029 3494 PFTEND 3499
Cdd:cd07876    221 IFQGTD 226

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 63.89 E-value: 4.82e-12

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1207186029 1567 VVEGKPVPDILWYKGDTLLSESSHFTFVYDDNECSLVVLNTQADDSGVYTCTAKNLAG 1624
Cdd:cd00096      6 SASGNPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAG 63

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 64.06 E-value: 5.43e-12

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  2868 RDHVLLEGDPVTLSCLPAGSPHPHISWMKDK-KPLEIDPRMNmISCPDGRQLLMIMKTTKKDAGLYECVAANPLATVTSS 2946
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGgKLLAESGRFS-VSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSG 80


                    ....
gi 1207186029  2947 CVVS 2950
Cdd:smart00410   81 TTLT 84

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 64.06 E-value: 5.64e-12

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  1034 RDVMVKAGETALFECHVIGPQDTDVDWLSDGKLIQPALLNCKMHFDGKRCRLLLNSVHEDDSGTYTCKLSTAKEELTSSA 1113
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGT 81


                    ....
gi 1207186029  1114 KLKV 1117
Cdd:smart00410   82 TLTV 85

Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409582 Cd Length: 91 Bit Score: 64.35 E-value: 5.74e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1123 PLFTRKLDVLEVIEGRNARFDCKVSGTPPPQVIWSHFDRPLEENEDIRIL-KEGGRHSLIISHVSNEDEGLYTVAARNSH 1201
Cdd:cd20990      1 PHFLQAPGDLTVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIRPDSAHKMLvRENGVHSLIIEPVTSRDAGIYTCIATNRA 80

                           90
                   ....*....|.
gi 1207186029 1202 GEDECAAELYV 1212
Cdd:cd20990     81 GQNSFNLELVV 91

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase 2; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MEK2 is a dual-specificity PK and a MAPK kinase (MAPKK or MKK) that phosphorylates and activates the downstream targets, ERK1 and ERK2, on specific threonine and tyrosine residues. The ERK cascade starts with extracellular signals including growth factors, hormones, and neurotransmitters, which act through receptors and ion channels to initiate intracellular signaling that leads to the activation at the MAPKKK (Raf-1 or MOS) level, which leads to the transmission of signals to MEK2, and finally to ERK1/2. The ERK cascade plays an important role in cell proliferation, differentiation, oncogenic transformation, and cell cycle control, as well as in apoptosis and cell survival under certain conditions. Gain-of-function mutations in genes encoding ERK cascade proteins, including MEK2, cause cardiofaciocutaneous (CFC) syndrome, a condition leading to multiple congenital anomalies and mental retardation in patients. The MEK subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 132980 [Multi-domain] Cd Length: 331 Bit Score: 70.08 E-value: 6.40e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1667 EIGRGAFSYVKRVIQKAGKLEYAAKFISARAKR--KASALRELNILSHLDHERILYFHDAFEKKNAVIIITELCHEELLD 1744
Cdd:cd06649     12 ELGAGNGGVVTKVQHKPSGLIMARKLIHLEIKPaiRNQIIRELQVLHECNSPYIVGFYGAFYSDGEISICMEHMDGGSLD 91

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1745 RLTKKSTILESEIRSSVR-QLLEGINYLHQL-DILHLDIKPDNILMadHSSDQIRICDFGNAVKFMpDEAQYCKYGTPEF 1822
Cdd:cd06649     92 QVLKEAKRIPEEILGKVSiAVLRGLAYLREKhQIMHRDVKPSNILV--NSRGEIKLCDFGVSGQLI-DSMANSFVGTRSY 168

                          170       180
                   ....*....|....*....|..
gi 1207186029 1823 VAPEIVNQTPVSKATDIWPIGV 1844
Cdd:cd06649    169 MSPERLQGTHYSVQSDIWSMGL 190

Catalytic domain of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Src subfamily members include Src, Lck, Hck, Blk, Lyn, Fgr, Fyn, Yrk, and Yes. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells and tumor vasculature, contributing to cancer progression and metastasis. Src kinases are overexpressed in a variety of human cancers, making them attractive targets for therapy. They are also implicated in acute inflammatory responses and osteoclast function. Src, Fyn, Yes, and Yrk are widely expressed, while Blk, Lck, Hck, Fgr, and Lyn show a limited expression pattern. The Src-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270630 [Multi-domain] Cd Length: 248 Bit Score: 68.46 E-value: 6.50e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3337 SKQTVLQEYDILKSLHHEKIMALHeAYVT---PRYLVliSECCSGKELLHSL-IDRFRYS-EDDVVAYIVQILQGLDYLH 3411
Cdd:cd05034     33 SPEAFLQEAQIMKKLRHDKLVQLY-AVCSdeePIYIV--TELMSKGSLLDYLrTGEGRALrLPQLIDMAAQIASGMAYLE 109

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3412 SRRILHLDIKPENIIVTYMNVVKIIDFGSAQ-----TFNPLFLKQFspPIgtlDYMSPEMLKGDVVGPPADIWSIGILTY 3486
Cdd:cd05034    110 SRNYIHRDLAARNILVGENNVCKVADFGLARlieddEYTAREGAKF--PI---KWTAPEAALYGRFTIKSDVWSFGILLY 184

                          170
                   ....*....|
gi 1207186029 3487 -IMLSGRLPF 3495
Cdd:cd05034    185 eIVTYGRVPY 194

Catalytic domain of the Protein Tyrosine Kinase, Lyn; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Lyn is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lyn is expressed in B lymphocytes and myeloid cells. It exhibits both positive and negative regulatory roles in B cell receptor (BCR) signaling. Lyn, as well as Fyn and Blk, promotes B cell activation by phosphorylating ITAMs (immunoreceptor tyr activation motifs) in CD19 and in Ig components of BCR. It negatively regulates signaling by its unique ability to phosphorylate ITIMs (immunoreceptor tyr inhibition motifs) in cell surface receptors like CD22 and CD5. Lyn also plays an important role in G-CSF receptor signaling by phosphorylating a variety of adaptor molecules. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Lyn subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270657 [Multi-domain] Cd Length: 272 Bit Score: 68.91 E-value: 6.50e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3295 VPQKPYTFMDEKARGRFGVIRECRENATGNLYMAKIVPyEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISE 3374
Cdd:cd05072      4 IPRESIKLVKKLGAGQFGEVWMGYYNNSTKVAVKTLKP-GTMSVQAFLEEANLMKTLQHDKLVRLYAVVTKEEPIYIITE 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3375 CCSGKellhSLIDRFRYSED------DVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPlf 3448
Cdd:cd05072     83 YMAKG----SLLDFLKSDEGgkvllpKLIDFSAQIAEGMAYIERKNYIHRDLRAANVLVSESLMCKIADFGLARVIED-- 156

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1207186029 3449 lKQFSPPIGT---LDYMSPEMLKGDVVGPPADIWSIGILTY-IMLSGRLPFtendPAETEARIQAA 3510
Cdd:cd05072    157 -NEYTAREGAkfpIKWTAPEAINFGSFTIKSDVWSFGILLYeIVTYGKIPY----PGMSNSDVMSA 217

Catalytic domain of the Protein Tyrosine Kinase, Wee1a; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of human Wee1a, Xenopus laevis Wee1b (XeWee1b) and similar vertebrate proteins. Members of this subfamily show a wide expression pattern. XeWee1b functions after the first zygotic cell divisions. It is expressed in all tissues and is also present after the gastrulation stage of embryos. Wee1 is a cell cycle checkpoint kinase that helps keep the cyclin-dependent kinase CDK1 in an inactive state through phosphorylation of an N-terminal tyr (Y15) residue. During the late G2 phase, CDK1 is activated and mitotic entry is promoted by the removal of this inhibitory phosphorylation by the phosphatase Cdc25. Although Wee1 is functionally a tyr kinase, it is more closely related to serine/threonine kinases (STKs). It contains a catalytic kinase domain sandwiched in between N- and C-terminal regulatory domains. It is regulated by phosphorylation and degradation, and its expression levels are also controlled by circadian clock proteins. The Wee1a subfamily is part of a larger superfamily that includes the catalytic domains of STKs, other PTKs, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271040 [Multi-domain] Cd Length: 276 Bit Score: 69.28 E-value: 6.58e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1656 RRLTDYYDVHKeIGRGAFSYVKRVIQKAGKLEYAAKfisaRAKR-------KASALRELNILSHL-DHERILYFHDAFEK 1727
Cdd:cd14138      2 RYATEFHELEK-IGSGEFGSVFKCVKRLDGCIYAIK----RSKKplagsvdEQNALREVYAHAVLgQHSHVVRYYSAWAE 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1728 KNAVIIITELCHE-ELLDRLTKKSTIL----ESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMA------------- 1789
Cdd:cd14138     77 DDHMLIQNEYCNGgSLADAISENYRIMsyftEPELKDLLLQVARGLKYIHSMSLVHMDIKPSNIFISrtsipnaaseegd 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1790 --DHSSDQI--RICDFGNAVKFMPDEAQyckYGTPEFVAPEIV--NQTPVSKAtDIWPIGvLTYLCLTGVSPFAGEND-- 1861
Cdd:cd14138    157 edEWASNKVifKIGDLGHVTRVSSPQVE---EGDSRFLANEVLqeNYTHLPKA-DIFALA-LTVVCAAGAEPLPTNGDqw 231

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1207186029 1862 ---RSSVLNiRNYNVAFEEsmFTDLcheakgfvIKLLV---ADRlRPDANECLRHP 1911
Cdd:cd14138    232 heiRQGKLP-RIPQVLSQE--FLDL--------LKVMIhpdPER-RPSAVALVKHS 275

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK6 may play a role in stress responses through its activation by the mitogen-activated protein kinase (MAPK) p38 and MAPK kinase 6 (MKK6) pathway. PAK6 is highly expressed in the brain. It is not required for viability, but together with PAK5, it is required for normal levels of locomotion and activity, and for learning and memory. Increased expression of PAK6 is found in primary and metastatic prostate cancer. PAK6 may play a role in the regulation of motility. PAK6 belongs to the group II PAKs, which contain a PBD (p21-binding domain) and a C-terminal catalytic domain, but do not harbor an AID (autoinhibitory domain) or SH3 binding sites. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270821 [Multi-domain] Cd Length: 297 Bit Score: 69.24 E-value: 7.36e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1661 YYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASAL-RELNILSHLDHERILYFHDAFEKKNAVIIITELCH 1739
Cdd:cd06659     22 LLENYVKIGEGSTGVVCIAREKHSGRQVAVKMMDLRKQQRRELLfNEVVIMRDYQHPNVVEMYKSYLVGEELWVLMEYLQ 101

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1740 EELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMAdhSSDQIRICDFGNAVKFMPD-EAQYCKYG 1818
Cdd:cd06659    102 GGALTDIVSQTRLNEEQIATVCEAVLQALAYLHSQGVIHRDIKSDSILLT--LDGRVKLSDFGFCAQISKDvPKRKSLVG 179

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1819 TPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNyNVAFEESMFTDLCHEAKGFVIKLLVAD 1898
Cdd:cd06659    180 TPYWMAPEVISRCPYGTEVDIWSLGIMVIEMVDGEPPYFSDSPVQAMKRLRD-SPPPKLKNSHKASPVLRDFLERMLVRD 258

                          250
                   ....*....|....*.
gi 1207186029 1899 RL-RPDANECLRHPWF 1913
Cdd:cd06659    259 PQeRATAQELLDHPFL 274

cyclin-dependent protein kinase; Provisional

Pssm-ID: 240233 [Multi-domain] Cd Length: 335 Bit Score: 69.79 E-value: 7.84e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1703 ALRELNILSHLDHERILYFHDAFEKKNAVIIITELCHEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIK 1782
Cdd:PTZ00024    67 TLRELKIMNEIKHENIMGLVDVYVEGDFINLVMDIMASDLKKVVDRKIRLTESQVKCILLQILNGLNVLHKWYFMHRDLS 146

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1783 PDNILMADHSsdQIRICDFGNAVKF----MPDEAQYCKYG------TPEFV-----APEIV-NQTPVSKATDIWPIGVLT 1846
Cdd:PTZ00024   147 PANIFINSKG--ICKIADFGLARRYgyppYSDTLSKDETMqrreemTSKVVtlwyrAPELLmGAEKYHFAVDMWSVGCIF 224

                          170
                   ....*....|....*
gi 1207186029 1847 YLCLTGVSPFAGEND 1861
Cdd:PTZ00024   225 AELLTGKPLFPGENE 239

Catalytic domain of the Protein Serine/Threonine Kinase, Large Tumor Suppressor 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LATS2 is an essential mitotic regulator responsible for coordinating accurate cytokinesis completion and governing the stabilization of other mitotic regulators. It is also critical in the maintenance of proper chromosome number, genomic stability, mitotic fidelity, and the integrity of centrosome duplication. Downregulation of LATS2 is associated with poor prognosis in acute lymphoblastic leukemia and breast cancer. The LATS2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173715 [Multi-domain] Cd Length: 381 Bit Score: 70.04 E-value: 8.00e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1666 KEIGRGAFSYVKRVIQKAGKLEYAAKFISAR----AKRKASALRELNILSHLDHERILYFHDAFE-KKNAVIIITELCHE 1740
Cdd:cd05626      7 KTLGIGAFGEVCLACKVDTHALYAMKTLRKKdvlnRNQVAHVKAERDILAEADNEWVVKLYYSFQdKDNLYFVMDYIPGG 86

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1741 ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMA------------------DHSS--------- 1793
Cdd:cd05626     87 DMMSLLIRMEVFPEVLARFYIAELTLAIESVHKMGFIHRDIKPDNILIDldghikltdfglctgfrwTHNSkyyqkgshi 166

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1794 -----------DQIRICDFGNAVKFMPDEA----QYCK----YGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVS 1854
Cdd:cd05626    167 rqdsmepsdlwDDVSNCRCGDRLKTLEQRAtkqhQRCLahslVGTPNYIAPEVLLRKGYTQLCDWWSVGVILFEMLVGQP 246

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1207186029 1855 PFAGENDRSSVLNIRNYNVAFEESMFTDLCHEAKGFVIKLLVA--DRL-RPDANECLRHPWFKTLNKGKSISTE 1925
Cdd:cd05626    247 PFLAPTPTETQLKVINWENTLHIPPQVKLSPEAVDLITKLCCSaeERLgRNGADDIKAHPFFSEVDFSSDIRTQ 320

Catalytic domain of the Serine/Threonine Kinase, Homeodomain-Interacting Protein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HIPK2, the most studied HIPK, is a coregulator of many transcription factors and cofactors including homeodomain proteins (Nkx and HOX families), Smad1-4, Pax6, c-Myb, AML1, the histone acetyltransferase p300, and the tumor repressor p53, among others. It regulates gene transcription during development and in DNA damage response (DDR), and mediates cell processes such as apoptosis, survival, differentiation, and proliferation. HIPK2 mediates apoptosis by phosphorylating and activating p53 during DDR, resulting in the activation of apoptotic genes. In the absence of p53, HIPK2 targets the anti-apoptotic corepressor C-terminal binding protein (CtBP), leading to CtBP's degradation and the promotion of apoptosis. HIPKs, originally identified by their ability to bind homeobox factors, are nuclear proteins containing catalytic kinase and homeobox-interacting domains as well as a PEST region overlapping with the speckle-retention signal (SRS). The HIPK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271129 [Multi-domain] Cd Length: 355 Bit Score: 70.12 E-value: 8.07e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1658 LTDYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASALRELNILSHLDHE-----RILYFHDAFEKKNAVI 1732
Cdd:cd14227     13 MTNTYEVLEFLGRGTFGQVVKCWKRGTNEIVAIKILKNHPSYARQGQIEVSILARLSTEsaddyNFVRAYECFQHKNHTC 92

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1733 IITELCHEELLDRL--TKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSD--QIRICDFGNAVKFm 1808
Cdd:cd14227     93 LVFEMLEQNLYDFLkqNKFSPLPLKYIRPILQQVATALMKLKSLGLIHADLKPENIMLVDPSRQpyRVKVIDFGSASHV- 171

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1207186029 1809 pDEAQYCKYGTPEFV-APEIVNQTPVSKATDIWPIGVLTYLCLTG--VSPFAGENDR 1862
Cdd:cd14227    172 -SKAVCSTYLQSRYYrAPEIILGLPFCEAIDMWSLGCVIAELFLGwpLYPGASEYDQ 227

Pseudokinase domain of Scy1-like proteins; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. This subfamily is composed of the catalytically inactive kinases with similarity to yeast Scy1. It includes four mammalian proteins called SCY1-like protein 1 (SCYL1), SCYL2, SCYL3, as well as Testis-EXpressed protein 14 (TEX14). SCYL1 binds to and co-localizes with the membrane trafficking coatomer I (COPI) complex, and regulates COPI-mediated vesicle trafficking. Null mutations in the SCYL1 gene are responsible for the pathology in mdf (muscle-deficient) mice which display progressive motor neuropathy. SCYL2, also called coated vesicle-associated kinase of 104 kDa (CVAK104), is involved in the trafficking of clathrin-coated vesicles. It also binds the HIV-1 accessory protein Vpu and acts as a regulatory factor that promotes the dephosphorylation of Vpu, facilitating the restriction of HIV-1 release. SCYL3, also called ezrin-binding protein PACE-1, may be involved in regulating cell adhesion and migration. TEX14 is required for spermatogenesis and male fertility. It localizes to kinetochores (KT) during mitosis and is a target of the mitotic kinase PLK1. It regulates the maturation of the outer KT and the KT-microtubule attachment. The SCY1-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270913 [Multi-domain] Cd Length: 287 Bit Score: 68.89 E-value: 8.09e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3392 SEDDVVAYIVQILQGLDYLHSR-RILHLDIKPENIIVTYMNVVKIIDFG---SAQTFNPLFLKQF-------SPPIGTLD 3460
Cdd:cd14011    112 YDVEIKYGLLQISEALSFLHNDvKLVHGNICPESVVINSNGEWKLAGFDfciSSEQATDQFPYFReydpnlpPLAQPNLN 191

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3461 YMSPEMLKGDVVGPPADIWSIGILTY-IMLSGRLPFT-ENDPAETEARIQAAKFDLSKLYQNVSQSASLFIKKILCSYPW 3538
Cdd:cd14011    192 YLAPEYILSKTCDPASDMFSLGVLIYaIYNKGKPLFDcVNNLLSYKKNSNQLRQLSLSLLEKVPEELRDHVKTLLNVTPE 271


                   ...
gi 1207186029 3539 ARP 3541
Cdd:cd14011    272 VRP 274

Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK4 is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The specific function of MLK4 is yet to be determined. Mutations in the kinase domain of MLK4 have been detected in colorectal cancers. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation.The MLK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271048 [Multi-domain] Cd Length: 268 Bit Score: 68.53 E-value: 8.29e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASA---LRELNILSHLDHERILYFHDAFEKKNAVIIITELCHEELLD 1744
Cdd:cd14146      2 IGVGGFGKVYRATWKGQEVAVKAARQDPDEDIKATAesvRQEAKLFSMLRHPNIIKLEGVCLEEPNLCLVMEFARGGTLN 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1745 RLTKKSTILESEIRSS----------VRQLLEGINYLHQ---LDILHLDIKPDNILMA------DHSSDQIRICDFGNAV 1805
Cdd:cd14146     82 RALAAANAAPGPRRARripphilvnwAVQIARGMLYLHEeavVPILHRDLKSSNILLLekiehdDICNKTLKITDFGLAR 161

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1207186029 1806 KFMpDEAQYCKYGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAG 1858
Cdd:cd14146    162 EWH-RTTKMSAAGTYAWMAPEVIKSSLFSKGSDIWSYGVLLWELLTGEVPYRG 213

Catalytic domain of the Protein Tyrosine Kinases, Src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristylation sites (Srm) and Breast tumor kinase (Brk); PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Srm and Brk (also called protein tyrosine kinase 6) are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Brk has been found to be overexpressed in a majority of breast tumors. Src kinases in general contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr; they are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). Srm and Brk however, lack the N-terminal myristylation sites. Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. The Srm/Brk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 133248 [Multi-domain] Cd Length: 261 Bit Score: 68.62 E-value: 8.30e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3296 PQKPYTFMDEKARGRFGVIRECRenATGNLYMA-KIVPYEPESKQTVLQ-EYDILKSLHHEKIMALHEAYVTPRYLVLIS 3373
Cdd:cd05148      4 PREEFTLERKLGSGYFGEVWEGL--WKNRVRVAiKILKSDDLLKQQDFQkEVQALKRLRHKHLISLFAVCSVGEPVYIIT 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3374 ECCSGKELLHSLidrfRYSEDDV--VAYIV----QILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPL 3447
Cdd:cd05148     82 ELMEKGSLLAFL----RSPEGQVlpVASLIdmacQVAEGMAYLEEQNSIHRDLAARNILVGEDLVCKVADFGLARLIKED 157

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*....
gi 1207186029 3448 FLKQFSPPIgTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLS-GRLPF 3495
Cdd:cd05148    158 VYLSSDKKI-PYKWTAPEAASHGTFSTKSDVWSFGILLYEMFTyGQVPY 205

Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jak3 is expressed only in hematopoietic cells. It binds the shared receptor subunit common gamma chain and thus, is essential in the signaling of cytokines that use it such as IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. Jak3 is important in lymphoid development and myeloid cell differentiation. Inactivating mutations in Jak3 have been reported in humans with severe combined immunodeficiency (SCID). Jak3 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal catalytic tyr kinase domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270665 [Multi-domain] Cd Length: 283 Bit Score: 68.77 E-value: 8.36e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECREN----ATGNLYMAKIVPYE-PESKQTVLQEYDILKSLHHEKIMALHEAYVTP--RYLVLISECCSGKE 3380
Cdd:cd05081     14 KGNFGSVELCRYDplgdNTGALVAVKQLQHSgPDQQRDFQREIQILKALHSDFIVKYRGVSYGPgrRSLRLVMEYLPSGC 93

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3381 LLHSLI-DRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFnPLFLKQF---SPPI 3456
Cdd:cd05081     94 LRDFLQrHRARLDASRLLLYSSQICKGMEYLGSRRCVHRDLAARNILVESEAHVKIADFGLAKLL-PLDKDYYvvrEPGQ 172

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3457 GTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLS----GRLPFTE-------NDPAETEARIQAAKFDLSKLYQNVSQSA 3525
Cdd:cd05081    173 SPIFWYAPESLSDNIFSRQSDVWSFGVVLYELFTycdkSCSPSAEflrmmgcERDVPALCRLLELLEEGQRLPAPPACPA 252

                          250       260
                   ....*....|....*....|..
gi 1207186029 3526 SLFIKKILC--SYPWARPTIKD 3545
Cdd:cd05081    253 EVHELMKLCwaPSPQDRPSFSA 274

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 63.35 E-value: 8.46e-12

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1207186029 1545 PTFETIMEDLDVNVGETPRFAVVVEGKPVPDILWYKGDTLLSESSHFTFVYDDNECSLVVLNTQADDSGVYTCTAKN 1621
Cdd:pfam13927    2 PVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. A splice variant of TLK1, called TLK1B, is expressed in the presence of double strand breaks (DSBs). It lacks the N-terminal part of TLK1, but is expected to phosphorylate the same substrates. TLK1/1B interacts with Rad9, which is critical in DNA damage-activated checkpoint response, and plays a role in the repair of linearized DNA with incompatible ends. TLKs play important functions during the cell cycle and are implicated in chromatin remodeling, DNA replication and repair, and mitosis. The TLK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270942 [Multi-domain] Cd Length: 299 Bit Score: 69.32 E-value: 8.54e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3343 QEYDILKSLHHEKIMALHEAY-VTPRYLVLISECCSGKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRR--ILHLD 3419
Cdd:cd14040     59 REYRIHKELDHPRIVKLYDYFsLDTDTFCTVLEYCEGNDLDFYLKQHKLMSEKEARSIVMQIVNALRYLNEIKppIIHYD 138

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3420 IKPENIIV---TYMNVVKIIDFGSAQ-----TFNPLFLKQFSPPIGTLDYMSPEMLkgdVVG--PP-----ADIWSIGIL 3484
Cdd:cd14040    139 LKPGNILLvdgTACGEIKITDFGLSKimdddSYGVDGMDLTSQGAGTYWYLPPECF---VVGkePPkisnkVDVWSVGVI 215

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1207186029 3485 TYIMLSGRLPFTENDPAE------TEARIQAAKFDLSKLyqnVSQSASLFIKKIL 3533
Cdd:cd14040    216 FFQCLYGRKPFGHNQSQQdilqenTILKATEVQFPVKPV---VSNEAKAFIRRCL 267

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK5 is unusual in that it is regulated by non-cyclin proteins, p35 and p39. It is highly expressed in the nervous system and is critical in normal neural development and function. It plays a role in neuronal migration and differentiation, and is also important in synaptic plasticity and learning. CDK5 also participates in protecting against cell death and promoting angiogenesis. Impaired CDK5 activity is implicated in Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, Huntington's disease and acute neuronal injury. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143344 [Multi-domain] Cd Length: 284 Bit Score: 69.00 E-value: 8.58e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1701 ASALRELNILSHLDHERILYFHDAFEKKNAVIIITELCHEEL---LDRLtkKSTILESEIRSSVRQLLEGINYLHQLDIL 1777
Cdd:cd07839     44 SSALREICLLKELKHKNIVRLYDVLHSDKKLTLVFEYCDQDLkkyFDSC--NGDIDPEIVKSFMFQLLKGLAFCHSHNVL 121

                           90       100       110
                   ....*....|....*....|....*....|
gi 1207186029 1778 HLDIKPDNILMADHSsdQIRICDFGNAVKF 1807
Cdd:cd07839    122 HRDLKPQNLLINKNG--ELKLADFGLARAF 149

Catalytic domain of With No Lysine (WNK) 2-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNK2 is widely expressed and has been shown to be epigenetically silenced in gliomas. It inhibits cell growth by acting as a negative regulator of MEK1-ERK1/2 signaling. WNK2 modulates growth factor-induced cancer cell proliferation, suggesting that it may be a tumor suppressor gene. WNKs comprise a subfamily of STKs with an unusual placement of the catalytic lysine relative to all other protein kinases. They are critical in regulating ion balance and are thus, important components in the control of blood pressure. The WNK2-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270934 [Multi-domain] Cd Length: 266 Bit Score: 68.57 E-value: 8.68e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1667 EIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASALR---ELNILSHLDHERILYFHDAFEK----KNAVIIITELCH 1739
Cdd:cd14032      8 ELGRGSFKTVYKGLDTETWVEVAWCELQDRKLTKVERQRfkeEAEMLKGLQHPNIVRFYDFWEScakgKRCIVLVTELMT 87

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1740 EELLDRLTKKSTILESEI-RSSVRQLLEGINYLHQLD--ILHLDIKPDNILMADhSSDQIRICDFGNAVKfmpDEAQYCK 1816
Cdd:cd14032     88 SGTLKTYLKRFKVMKPKVlRSWCRQILKGLLFLHTRTppIIHRDLKCDNIFITG-PTGSVKIGDLGLATL---KRASFAK 163

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|...
gi 1207186029 1817 --YGTPEFVAPEIVNQTpVSKATDIWPIGVLTYLCLTGVSPFA 1857
Cdd:cd14032    164 svIGTPEFMAPEMYEEH-YDESVDVYAFGMCMLEMATSEYPYS 205

Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TLKs play important functions during the cell cycle and are implicated in chromatin remodeling, DNA replication and repair, and mitosis. They phosphorylate and regulate Anti-silencing function 1 protein (Asf1), a histone H3/H4 chaperone that helps facilitate the assembly of chromatin following DNA replication during S phase. TLKs also phosphorylate the H3 histone tail and are essential in transcription. Vertebrates contain two subfamily members, TLK1 and TLK2. The TLK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).

Pssm-ID: 270943 [Multi-domain] Cd Length: 309 Bit Score: 69.32 E-value: 8.80e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3343 QEYDILKSLHHEKIMALHEAY-VTPRYLVLISECCSGKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRR--ILHLD 3419
Cdd:cd14041     59 REYRIHKELDHPRIVKLYDYFsLDTDSFCTVLEYCEGNDLDFYLKQHKLMSEKEARSIIMQIVNALKYLNEIKppIIHYD 138

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3420 IKPENIIV---TYMNVVKIIDFGSAQ-----TFNPL-FLKQFSPPIGTLDYMSPEMLkgdVVG--PP-----ADIWSIGI 3483
Cdd:cd14041    139 LKPGNILLvngTACGEIKITDFGLSKimdddSYNSVdGMELTSQGAGTYWYLPPECF---VVGkePPkisnkVDVWSVGV 215

                          170
                   ....*....|....*
gi 1207186029 3484 LTYIMLSGRLPFTEN 3498
Cdd:cd14041    216 IFYQCLYGRKPFGHN 230

Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C iota; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-iota is directly implicated in carcinogenesis. It is critical to oncogenic signaling mediated by Ras and Bcr-Abl. The PKC-iota gene is the target of tumor-specific gene amplification in many human cancers, and has been identified as a human oncogene. In addition to its role in transformed growth, PKC-iota also promotes invasion, chemoresistance, and tumor cell survival. Expression profiling of PKC-iota is a prognostic marker of poor clinical outcome in several human cancers. PKC-iota also plays a role in establishing cell polarity, and has critical embryonic functions. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. aPKCs only require phosphatidylserine (PS) for activation. The aPKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270769 [Multi-domain] Cd Length: 364 Bit Score: 69.68 E-value: 9.61e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASALRELNILSHL-----DHERILYFHDAFEKKNAVIIITE 1736
Cdd:cd05618     22 FDLLRVIGRGSYAKVLLVRLKKTERIYAMKVVKKELVNDDEDIDWVQTEKHVfeqasNHPFLVGLHSCFQTESRLFFVIE 101

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1737 LCHE-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDFGNAVKFM-PDEAQY 1814
Cdd:cd05618    102 YVNGgDLMFHMQRQRKLPEEHARFYSAEISLALNYLHERGIIYRDLKLDNVLL--DSEGHIKLTDYGMCKEGLrPGDTTS 179

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|..
gi 1207186029 1815 CKYGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPF 1856
Cdd:cd05618    180 TFCGTPNYIAPEILRGEDYGFSVDWWALGVLMFEMMAGRSPF 221

Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LIMK2 activation is induced by transforming growth factor-beta l (TGFb-l) and shares the same subcellular location as the cofilin family member twinfilin, which may be its biological substrate. LIMK2 plays a role in spermatogenesis, and may contribute to tumor progression and metastasis formation in some cancer cells. LIMKs phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They act downstream of Rho GTPases and are expressed ubiquitously. As regulators of actin dynamics, they contribute to diverse cellular functions such as cell motility, morphogenesis, differentiation, apoptosis, meiosis, mitosis, and neurite extension. LIMKs contain the LIM (two repeats), PDZ, and catalytic kinase domains. The LIMK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271124 [Multi-domain] Cd Length: 272 Bit Score: 68.43 E-value: 9.70e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGN-LYMAKIVPYEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLHSLI 3386
Cdd:cd14222      3 KGFFGQAIKVTHKATGKvMVMKELIRCDEETQKTFLTEVKVMRSLDHPNVLKFIGVLYKDKRLNLLTEFIEGGTLKDFLR 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3387 DRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFG-------------------SAQTFNPL 3447
Cdd:cd14222     83 ADDPFPWQQKVSFAKGIASGMAYLHSMSIIHRDLNSHNCLIKLDKTVVVADFGlsrliveekkkpppdkpttKKRTLRKN 162

                          170       180       190
                   ....*....|....*....|....*....|....*..
gi 1207186029 3448 FLKQFSPPIGTLDYMSPEMLKGDVVGPPADIWSIGIL 3484
Cdd:cd14222    163 DRKKRYTVVGNPYWMAPEMLNGKSYDEKVDIFSFGIV 199

Catalytic domain of the Serine/Threonine kinase, PDLIM1 interacting kinase 1 like; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PDIK1L is also called STK35 or CLIK-1. It is predominantly a nuclear protein which is capable of autophosphorylation. Through its interaction with the PDZ-LIM protein CLP-36, it is localized to actin stress fibers. The PDIK1L subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).

Pssm-ID: 270879 [Multi-domain] Cd Length: 322 Bit Score: 69.12 E-value: 9.74e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATG-NLYMAKIVPYEPESKQTVLQEYDILKSL--HHEKIMALHEA-------------- 3362
Cdd:cd13977      2 YSLIREVGRGSYGVVYEAVVRRTGaRVAVKKIRCNAPENVELALREFWALSSIqrQHPNVIQLEECvlqrdglaqrmshg 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3363 ----------------------YVTPRYLVLISECCSGKELLHSLIDRfRYSEDDVVAYIVQILQGLDYLHSRRILHLDI 3420
Cdd:cd13977     82 ssksdlylllvetslkgercfdPRSACYLWFVMEFCDGGDMNEYLLSR-RPDRQTNTSFMLQLSSALAFLHRNQIVHRDL 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3421 KPENIIVTYMN---VVKIIDFGSAQTFNPLFLKQ----------FSPPIGTLDYMSPEMLKGDVVGpPADIWSIGILTYI 3487
Cdd:cd13977    161 KPDNILISHKRgepILKVADFGLSKVCSGSGLNPeepanvnkhfLSSACGSDFYMAPEVWEGHYTA-KADIFALGIIIWA 239

                          250
                   ....*....|..
gi 1207186029 3488 MLSgRLPFTEND 3499
Cdd:cd13977    240 MVE-RITFRDGE 250

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 9; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK9, together with a cyclin partner (cyclin T1, T2a, T2b, or K), is the main component of distinct positive transcription elongation factors (P-TEFb), which function as Ser2 C-terminal domain kinases of RNA polymerase II. P-TEFb participates in multiple steps of gene expression including transcription elongation, mRNA synthesis, processing, export, and translation. It also plays a role in mediating cytokine induced transcription networks such as IL6-induced STAT3 signaling. In addition, the CDK9/cyclin T2a complex promotes muscle differentiation and enhances the function of some myogenic regulatory factors. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK9 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270848 [Multi-domain] Cd Length: 310 Bit Score: 68.93 E-value: 1.04e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKA---SALRELNILSHLDHERILYFHD-------AFEKKNAV 1731
Cdd:cd07865     14 YEKLAKIGQGTFGEVFKARHRKTGQIVALKKVLMENEKEGfpiTALREIKILQLLKHENVVNLIEicrtkatPYNRYKGS 93

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1732 I-IITELCHEELLDRLT-KKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSdqIRICDFGNAVKF-M 1808
Cdd:cd07865     94 IyLVFEFCEHDLAGLLSnKNVKFTLSEIKKVMKMLLNGLYYIHRNKILHRDMKAANILITKDGV--LKLADFGLARAFsL 171

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|
gi 1207186029 1809 PDEAQYCKYG----TPEFVAPEI-VNQTPVSKATDIWPIG 1843
Cdd:cd07865    172 AKNSQPNRYTnrvvTLWYRPPELlLGERDYGPPIDMWGAG 211

Catalytic (repeat 2) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak subfamily is composed of Jak1, Jak2, Jak3, TYK2, and similar proteins. They are PTKs, catalyzing the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jaks are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase catalytic domain. Most Jaks are expressed in a wide variety of tissues, except for Jak3, which is expressed only in hematopoietic cells. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). Jaks are also involved in regulating the surface expression of some cytokine receptors. The Jak-STAT pathway is involved in many biological processes including hematopoiesis, immunoregulation, host defense, fertility, lactation, growth, and embryogenesis. The Jak subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270634 [Multi-domain] Cd Length: 284 Bit Score: 68.56 E-value: 1.04e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3301 TFMDEKARGRFGVIRECR----ENATGNLYMAKI--VPYEPESKQTVLQEYDILKSLHHEKIMALHEAYVTP--RYLVLI 3372
Cdd:cd05038      7 KFIKQLGEGHFGSVELCRydplGDNTGEQVAVKSlqPSGEEQHMSDFKREIEILRTLDHEYIVKYKGVCESPgrRSLRLI 86

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3373 SECCSgkelLHSLIDRFRYSEDDV-----VAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFN-- 3445
Cdd:cd05038     87 MEYLP----SGSLRDYLQRHRDQIdlkrlLLFASQICKGMEYLGSQRYIHRDLAARNILVESEDLVKISDFGLAKVLPed 162

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1207186029 3446 ------------PLFlkqfsppigtldYMSPEMLKGDVVGPPADIWSIGILTYIMLS 3490
Cdd:cd05038    163 keyyyvkepgesPIF------------WYAPECLRESRFSSASDVWSFGVTLYELFT 207

Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 4; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Unlike other FGFRs, there is only one splice form of FGFR4. It binds FGF1, FGF2, FGF6, FGF19, and FGF23. FGF19 is a selective ligand for FGFR4. Although disruption of FGFR4 in mice causes no obvious phenotype, in vivo inhibition of FGFR4 in cultured skeletal muscle cells resulted in an arrest of muscle progenitor differentiation. FGF6 and FGFR4 are uniquely expressed in myofibers and satellite cells. FGF6/FGFR4 signaling appears to play a key role in the regulation of muscle regeneration. A polymorphism in FGFR4 is found in head and neck squamous cell carcinoma. FGFR4 is part of the FGFR subfamily, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. The FGFR4 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 133230 [Multi-domain] Cd Length: 314 Bit Score: 69.22 E-value: 1.05e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3395 DVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPL-FLKQFSPPIGTLDYMSPEMLKGDVVG 3473
Cdd:cd05099    135 DLVSCAYQVARGMEYLESRRCIHRDLAARNVLVTEDNVMKIADFGLARGVHDIdYYKKTSNGRLPVKWMAPEALFDRVYT 214

                           90       100
                   ....*....|....*....|...
gi 1207186029 3474 PPADIWSIGILTY-IMLSGRLPF 3495
Cdd:cd05099    215 HQSDVWSFGILMWeIFTLGGSPY 237

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.

Pssm-ID: 409406 [Multi-domain] Cd Length: 82 Bit Score: 62.99 E-value: 1.11e-11

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1207186029  795 GTEVLLKCIISGTPLPEVIWKKDNTEVKNSPthVVKIE--GERHSLLIKWTKPSDAGTYTVTAVNEVGEVssSATLFIK 871
Cdd:cd05748      7 GESLRLDIPIKGRPTPTVTWSKDGQPLKETG--RVQIEttASSTSLVIKNAKRSDSGKYTLTLKNSAGEK--SATINVK 81

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK4 partners with all three D-type cyclins (D1, D2, and D3) and is also regulated by INK4 inhibitors. It is active towards the retinoblastoma (pRb) protein and plays a role in regulating the early G1 phase of the cell cycle. It is expressed ubiquitously and is localized in the nucleus. CDK4 also shows kinase activity towards Smad3, a signal transducer of TGF-beta signaling which modulates transcription and plays a role in cell proliferation and apoptosis. CDK4 is inhibited by the p21 inhibitor and is specifically mutated in human melanoma. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143368 [Multi-domain] Cd Length: 288 Bit Score: 68.45 E-value: 1.15e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVkrviQKAGKLEyAAKFISARAKR--------KASALRELNILSHLDHerilyfhdaFEKKNaVII 1733
Cdd:cd07863      2 YEPVAEIGVGAYGTV----YKARDPH-SGHFVALKSVRvqtnedglPLSTVREVALLKRLEA---------FDHPN-IVR 66

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1734 ITELCHEELLDRLTKKSTILE--------------------SEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMAdhSS 1793
Cdd:cd07863     67 LMDVCATSRTDRETKVTLVFEhvdqdlrtyldkvpppglpaETIKDLMRQFLRGLDFLHANCIVHRDLKPENILVT--SG 144

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1207186029 1794 DQIRICDFGNAVKFMPDEAQYCKYGTPEFVAPEIVNQTPVSKATDIWPIGVL 1845
Cdd:cd07863    145 GQVKLADFGLARIYSCQMALTPVVVTLWYRAPEVLLQSTYATPVDMWSVGCI 196

Catalytic domain of PCTAIRE-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-like proteins show unusual expression patterns with high levels in post-mitotic tissues, suggesting that they may be involved in regulating post-mitotic cellular events. They share sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The association of PCTAIRE-like proteins with cyclins has not been widely studied, although PFTAIRE-1 has been shown to function as a CDK which is regulated by cyclin D3 as well as the membrane-associated cyclin Y. The PCTAIRE-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270835 [Multi-domain] Cd Length: 286 Bit Score: 68.56 E-value: 1.16e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1661 YYDVHKeIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKA--SALRELNILSHLDHERILYFHDAFEKKNAVIIITELC 1738
Cdd:cd07844      2 YKKLDK-LGEGSYATVYKGRSKLTGQLVALKEIRLEHEEGApfTAIREASLLKDLKHANIVTLHDIIHTKKTLTLVFEYL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1739 HEELLDRLTKKSTILE-SEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSsdQIRICDFGNA-VKFMPDEAQYCK 1816
Cdd:cd07844     81 DTDLKQYMDDCGGGLSmHNVRLFLFQLLRGLAYCHQRRVLHRDLKPQNLLISERG--ELKLADFGLArAKSVPSKTYSNE 158

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*.
gi 1207186029 1817 YGTPEFVAPEIV-NQTPVSKATDIWPIGVLTYLCLTGVSPFAGEND 1861
Cdd:cd07844    159 VVTLWYRPPDVLlGSTEYSTSLDMWGVGCIFYEMATGRPLFPGSTD 204

mitogen-activated protein kinase kinase; Provisional

Pssm-ID: 215036 [Multi-domain] Cd Length: 353 Bit Score: 69.47 E-value: 1.20e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYVKRVIQKAGKLEYAAKFISAR---AKRKaSALRELNILSHLDHERILYFHDAFEKKNAVIIITELcheelLD 1744
Cdd:PLN00034    82 IGSGAGGTVYKVIHRPTGRLYALKVIYGNhedTVRR-QICREIEILRDVNHPNVVKCHDMFDHNGEIQVLLEF-----MD 155

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1745 RLTKKSTIL--ESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDFGNAvKFMPDEAQYCK--YGTP 1820
Cdd:PLN00034   156 GGSLEGTHIadEQFLADVARQILSGIAYLHRRHIVHRDIKPSNLLI--NSAKNVKIADFGVS-RILAQTMDPCNssVGTI 232

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|...
gi 1207186029 1821 EFVAPEIVNqTPVSK------ATDIWPIGVLTYLCLTGVSPFA 1857
Cdd:PLN00034   233 AYMSPERIN-TDLNHgaydgyAGDIWSLGVSILEFYLGRFPFG 274

Catalytic domain of Fyn-related kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Frk and Srk are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Frk, also known as Rak, is specifically expressed in liver, lung, kidney, intestine, mammary glands, and the islets of Langerhans. Rodent homologs were previously referred to as GTK (gastrointestinal tyr kinase), BSK (beta-cell Src-like kinase), or IYK (intestinal tyr kinase). Studies in mice reveal that Frk is not essential for viability. It plays a role in the signaling that leads to cytokine-induced beta-cell death in Type I diabetes. It also regulates beta-cell number during embryogenesis and early in life. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Frk-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270653 [Multi-domain] Cd Length: 267 Bit Score: 68.20 E-value: 1.23e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1704 LRELNILSHLDHERILYFHDAFEKKNAVIIITEL-CHEELLDRLTKKSTILE-SEIRSSVRQLLEGINYLHQLDILHLDI 1781
Cdd:cd05068     51 LREAQIMKKLRHPKLIQLYAVCTLEEPIYIITELmKHGSLLEYLQGKGRSLQlPQLIDMAAQVASGMAYLESQNYIHRDL 130

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1782 KPDNILMADHSSdqIRICDFGNAVKFMPDEAQYCKYGTP---EFVAPEIVNQTPVSKATDIWPIGVLTYLCLT-GVSPFA 1857
Cdd:cd05068    131 AARNVLVGENNI--CKVADFGLARVIKVEDEYEAREGAKfpiKWTAPEAANYNRFSIKSDVWSFGILLTEIVTyGRIPYP 208


                   .
gi 1207186029 1858 G 1858
Cdd:cd05068    209 G 209

Catalytic domain of the Serine/Threonine Kinase, beta-adrenergic receptor kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The beta-ARK group is composed of GRK2, GRK3, and similar proteins. GRK2 and GRK3 are both widely expressed in many tissues, although GRK2 is present at higher levels. They contain an N-terminal RGS homology (RH) domain, a central catalytic domain, and C-terminal pleckstrin homology (PH) domain that mediates PIP2 and G protein betagamma-subunit translocation to the membrane. GRK2 (also called beta-ARK or beta-ARK1) is important in regulating several cardiac receptor responses. It plays a role in cardiac development and in hypertension. Deletion of GRK2 in mice results in embryonic lethality, caused by hypoplasia of the ventricular myocardium. GRK2 also plays important roles in the liver (as a regulator of portal blood pressure), in immune cells, and in the nervous system. Altered GRK2 expression has been reported in several disorders including major depression, schizophrenia, bipolar disorder, and Parkinsonism. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The beta-ARK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270757 [Multi-domain] Cd Length: 279 Bit Score: 68.23 E-value: 1.25e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYVKRViQKA--GKLeYAAKFIS-ARAKRKAS---ALRELNILS----HLDHERILYFHDAFEKKNAVIIITEL 1737
Cdd:cd05606      2 IGRGGFGEVYGC-RKAdtGKM-YAMKCLDkKRIKMKQGetlALNERIMLSlvstGGDCPFIVCMTYAFQTPDKLCFILDL 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1738 CHE-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSsdQIRICDFGNAVKFmPDEAQYCK 1816
Cdd:cd05606     80 MNGgDLHYHLSQHGVFSEAEMRFYAAEVILGLEHMHNRFIVYRDLKPANILLDEHG--HVRISDLGLACDF-SKKKPHAS 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1817 YGTPEFVAPEIVNQ-TPVSKATDIWPIGVLTYLCLTGVSPF-------AGENDRSSVlnirNYNVAFEESMFTDLcheaK 1888
Cdd:cd05606    157 VGTHGYMAPEVLQKgVAYDSSADWFSLGCMLYKLLKGHSPFrqhktkdKHEIDRMTL----TMNVELPDSFSPEL----K 228

                          250       260       270
                   ....*....|....*....|....*....|....*
gi 1207186029 1889 GFVIKLL---VADRLRPD---ANECLRHPWFKTLN 1917
Cdd:cd05606    229 SLLEGLLqrdVSKRLGCLgrgATEVKEHPFFKGVD 263

Catalytic domain of the Serine/Threonine Kinase, p38gamma Mitogen-Activated Protein Kinase (also called MAPK12); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38gamma/MAPK12 is predominantly expressed in skeletal muscle. Unlike p38alpha and p38beta, p38gamma is insensitive to pyridinylimidazoles. It displays an antagonizing function compared to p38alpha. p38gamma inhibits, while p38alpha stimulates, c-Jun phosphorylation and AP-1 mediated transcription. p38gamma also plays a role in the signaling between Ras and the estrogen receptor and has been implicated to increase cell invasion and breast cancer progression. In Xenopus, p38gamma is critical in the meiotic maturation of oocytes. p38 kinases are MAPKs, serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38gamma subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143385 [Multi-domain] Cd Length: 343 Bit Score: 69.21 E-value: 1.39e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3343 QEYDILKSLHHEKIMALHEAYvTPR---------YLVLISeccSGKELlHSLIDRFRYSEDDVVAYIVQILQGLDYLHSR 3413
Cdd:cd07880     63 RELRLLKHMKHENVIGLLDVF-TPDlsldrfhdfYLVMPF---MGTDL-GKLMKHEKLSEDRIQFLVYQMLKGLKYIHAA 137

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3414 RILHLDIKPENIIVTYMNVVKIIDFGSAQTFNplflKQFSPPIGTLDYMSPE-MLKGDVVGPPADIWSIGILTYIMLSGR 3492
Cdd:cd07880    138 GIIHRDLKPGNLAVNEDCELKILDFGLARQTD----SEMTGYVVTRWYRAPEvILNWMHYTQTVDIWSVGCIMAEMLTGK 213

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1207186029 3493 LPFTEND---------------PAETEARIQAA-------------KFDLSKLYQNVSQSASLFIKKILCSYPWARPT 3542
Cdd:cd07880    214 PLFKGHDhldqlmeimkvtgtpSKEFVQKLQSEdaknyvkklprfrKKDFRSLLPNANPLAVNVLEKMLVLDAESRIT 291

serine/threonine-protein kinase PknD;

Pssm-ID: 183880 [Multi-domain] Cd Length: 932 Bit Score: 70.95 E-value: 1.40e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFI----SARAKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITEL 1737
Cdd:PRK13184     4 YDIIRLIGKGGMGEVYLAYDPVCSRRVALKKIredlSENPLLKKRFLREAKIAADLIHPGIVPVYSICSDGDPVYYTMPY 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1738 CHEELLDRLTKKSTILES-----EIRSSVRQLL-------EGINYLHQLDILHLDIKPDNILMADHSsdQIRICDFGNAV 1805
Cdd:PRK13184    84 IEGYTLKSLLKSVWQKESlskelAEKTSVGAFLsifhkicATIEYVHSKGVLHRDLKPDNILLGLFG--EVVILDWGAAI 161

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1207186029 1806 -KFMPDEAQ-YCKY-----------------GTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDR 1862
Cdd:PRK13184   162 fKKLEEEDLlDIDVdernicyssmtipgkivGTPDYMAPERLLGVPASESTDIYALGVILYQMLTLSFPYRRKKGR 237

serine/threonine kinase US3; Provisional

Pssm-ID: 165473 [Multi-domain] Cd Length: 392 Bit Score: 69.49 E-value: 1.40e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3344 EYDILKSLHHEKIMALHEAY--------VTPRYlvliseccsgKELLHSLIDRFR-YSEDDVVAYIVQILQGLDYLHSRR 3414
Cdd:PHA03207   136 EIDILKTISHRAIINLIHAYrwkstvcmVMPKY----------KCDLFTYVDRSGpLPLEQAITIQRRLLEALAYLHGRG 205

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3415 ILHLDIKPENIIVTYMNVVKIIDFGSA-QTFNPLFLKQFSPPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRL 3493
Cdd:PHA03207   206 IIHRDVKTENIFLDEPENAVLGDFGAAcKLDAHPDTPQCYGWSGTLETNSPELLALDPYCAKTDIWSAGLVLFEMSVKNV 285


                   ..
gi 1207186029 3494 PF 3495
Cdd:PHA03207   286 TL 287

Pseudokinase domain of Tribbles Homolog proteins; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. Tribbles Homolog (TRB) proteins interact with many proteins involved in signaling pathways. They play scaffold-like regulatory functions and affect many cellular processes such as mitosis, apoptosis, differentiation, and gene expression. TRB proteins bind to the middle kinase in mitogen activated protein kinase (MAPK) signaling cascades, MAPK kinases. They regulate the activity of MAPK kinases, and thus, affect MAPK signaling. In Drosophila, Tribbles regulates String, the ortholog of mammalian Cdc25, during morphogenesis. String is implicated in the progression of mitosis during embryonic development. Vertebrates contain three TRB proteins encoded by three separate genes: Tribbles-1 (TRB1 or TRIB1), Tribbles-2 (TRB2 or TRIB2), and Tribbles-3 (TRB3 or TRIB3). The TRB subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270878 [Multi-domain] Cd Length: 242 Bit Score: 67.45 E-value: 1.41e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3322 TGNLYMAKIVPyEPESkQTVLQEYDILKSlhHEKIMALHEAYVTPRYLVLISECCSGKelLHSLI-DRFRYSEDDVVAYI 3400
Cdd:cd13976     17 TGEELVCKVVP-VPEC-HAVLRAYFRLPS--HPNISGVHEVIAGETKAYVFFERDHGD--LHSYVrSRKRLREPEAARLF 90

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3401 VQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKI---------IDFGSAQTFnplflkqfSPPIGTLDYMSPEMLK--G 3469
Cdd:cd13976     91 RQIASAVAHCHRNGIVLRDLKLRKFVFADEERTKLrlesledavILEGEDDSL--------SDKHGCPAYVSPEILNsgA 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3470 DVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLSklyQNVSQSASLFIKKILCSYPWARPTIKDCFTN 3549
Cdd:cd13976    163 TYSGKAADVWSLGVILYTMLVGRYPFHDSEPASLFAKIRRGQFAIP---ETLSPRARCLIRSLLRREPSERLTAEDILLH 239


                   ...
gi 1207186029 3550 SWL 3552
Cdd:cd13976    240 PWL 242

Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNK1 is widely expressed and is most abundant in the testis. In hyperosmotic or hypotonic low-chloride stress conditions, WNK1 is activated and it phosphorylates its substrates including SPAK and OSR1 kinases, which regulate the activity of cation-chloride cotransporters through direct interaction and phosphorylation. Mutations in WNK1 cause PseudoHypoAldosteronism type II (PHAII), characterized by hypertension and hyperkalemia. WNK1 negates WNK4-mediated inhibition of the sodium-chloride cotransporter NCC and activates the epithelial sodium channel ENaC by activating SGK1. WNK1 also decreases the surface expression of renal outer medullary potassium channel (ROMK) by stimulating their endocytosis. Hypertension and hyperkalemia in PHAII patients with WNK1 mutations may be due partly to increased activity of NCC and ENaC, and impaired renal potassium secretion by ROMK, respectively. In addition, WNK1 interacts with MEKK2/3 and acts as an activator of extracellular signal-regulated kinase (ERK) 5. It also negatively regulates TGFbeta signaling. WNKs comprise a subfamily of STKs with an unusual placement of the catalytic lysine relative to all other protein kinases. The WNK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270932 [Multi-domain] Cd Length: 289 Bit Score: 68.15 E-value: 1.64e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1667 EIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASALR---ELNILSHLDHERILYFHDAFEK----KNAVIIITELCH 1739
Cdd:cd14030     32 EIGRGSFKTVYKGLDTETTVEVAWCELQDRKLSKSERQRfkeEAGMLKGLQHPNIVRFYDSWEStvkgKKCIVLVTELMT 111

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1740 EELLDRLTKKSTILESEI-RSSVRQLLEGINYLHQLD--ILHLDIKPDNILMADhSSDQIRICDFGNAVKfmpDEAQYCK 1816
Cdd:cd14030    112 SGTLKTYLKRFKVMKIKVlRSWCRQILKGLQFLHTRTppIIHRDLKCDNIFITG-PTGSVKIGDLGLATL---KRASFAK 187

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|...
gi 1207186029 1817 --YGTPEFVAPEIVNQTpVSKATDIWPIGVLTYLCLTGVSPFA 1857
Cdd:cd14030    188 svIGTPEFMAPEMYEEK-YDESVDVYAFGMCMLEMATSEYPYS 229

Catalytic domain of the Protein Tyrosine Kinases, Tyrosine kinase expressed in hepatocellular carcinoma and Resting lymphocyte kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tec and Rlk (also named Txk) are members of the Tec-like subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. Instead of PH, Rlk contains an N-terminal cysteine-rich region. In addition to PH, Tec also contains the Tec homology (TH) domain with proline-rich and zinc-binding regions. Tec kinases are expressed mainly by haematopoietic cells. Tec is more widely-expressed than other Tec-like subfamily kinases. It is found in endothelial cells, both B- and T-cells, and a variety of myeloid cells including mast cells, erythroid cells, platelets, macrophages and neutrophils. Rlk is expressed in T-cells and mast cell lines. Tec and Rlk are both key components of T-cell receptor (TCR) signaling. They are important in TCR-stimulated proliferation, IL-2 production and phopholipase C-gamma1 activation. The Tec/Rlk subfamily is part of a larger superfamily, that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270685 [Multi-domain] Cd Length: 260 Bit Score: 67.58 E-value: 1.80e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3301 TFMDEKARGRFGVIRECRENATGNLYMAKIVPyEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKE 3380
Cdd:cd05114      7 TFMKELGSGLFGVVRLGKWRAQYKVAIKAIRE-GAMSEEDFIEEAKVMMKLTHPKLVQLYGVCTQQKPIYIVTEFMENGC 85

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3381 LLHSLIDRF-RYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTfnpLFLKQFSPPIGT- 3458
Cdd:cd05114     86 LLNYLRQRRgKLSRDMLLSMCQDVCEGMEYLERNNFIHRDLAARNCLVNDTGVVKVSDFGMTRY---VLDDQYTSSSGAk 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3459 --LDYMSPEMLKGDVVGPPADIWSIGILTY-IMLSGRLPFTENDPAETEARIQAAkfdlSKLYQNVSQSASLFIKKILCS 3535
Cdd:cd05114    163 fpVKWSPPEVFNYSKFSSKSDVWSFGVLMWeVFTEGKMPFESKSNYEVVEMVSRG----HRLYRPKLASKSVYEVMYSCW 238

                          250
                   ....*....|..
gi 1207186029 3536 Y--PWARPTIKD 3545
Cdd:cd05114    239 HekPEGRPTFAD 250

Catalytic domain of the Serine/Threonine Kinase, Homeodomain-Interacting Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HIPKs, originally identified by their ability to bind homeobox factors, are nuclear proteins containing catalytic kinase and homeobox-interacting domains as well as a PEST region overlapping with the speckle-retention signal (SRS). They show speckled localization in the nucleus, apart from the nucleoles. They play roles in the regulation of many nuclear pathways including gene transcription, cell survival, proliferation, differentiation, development, and DNA damage response. Vertebrates contain three HIPKs (HIPK1-3) and mammals harbor an additional family member HIPK4, which does not contain a homeobox-interacting domain and is localized in the cytoplasm. HIPK2, the most studied HIPK, is a coregulator of many transcription factors and cofactors and it regulates gene transcription during development and in DNA damage response. The HIPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271113 [Multi-domain] Cd Length: 329 Bit Score: 68.63 E-value: 1.82e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASALRELNILSHLDHE-----RILYFHDAFEKKNAVIIITE 1736
Cdd:cd14211      1 YEVLEFLGRGTFGQVVKCWKRGTNEIVAIKILKNHPSYARQGQIEVSILSRLSQEnadefNFVRAYECFQHKNHTCLVFE 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1737 LCHEELLDRL--TKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSD--QIRICDFGNAVKFmpDEA 1812
Cdd:cd14211     81 MLEQNLYDFLkqNKFSPLPLKYIRPILQQVLTALLKLKSLGLIHADLKPENIMLVDPVRQpyRVKVIDFGSASHV--SKA 158

                          170       180       190
                   ....*....|....*....|....*....|..
gi 1207186029 1813 QYCKYGTPEFV-APEIVNQTPVSKATDIWPIG 1843
Cdd:cd14211    159 VCSTYLQSRYYrAPEIILGLPFCEAIDMWSLG 190

Pseudokinase domain of Tribbles Homolog 1; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. TRB1 interacts directly with the mitogen activated protein kinase (MAPK) kinase MKK4, an activator of JNK. It regulates vascular smooth muscle cell proliferation and chemotaxis through the JNK signaling pathway. It is found to be down-regulated in human acute myeloid leukaemia (AML) and may play a role in the pathogenesis of the disease. It has also been identified as a potential biomarker for antibody-mediated allograft failure. TRB1 is one of three Tribbles Homolog (TRB) proteins present in vertebrates that are encoded by three separate genes. TRB proteins interact with many proteins involved in signalling pathways. They play scaffold-like regulatory functions and affect many cellular processes such as mitosis, apoptosis, and gene expression. The TRB1 subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270925 [Multi-domain] Cd Length: 242 Bit Score: 66.99 E-value: 1.86e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1754 ESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSDQIRICDFGNA-VKFMPDEAQYCKYGTPEFVAPEIVNQTP 1832
Cdd:cd14023     83 EEEAARLFKQIVSAVAHCHQSAIVLGDLKLRKFVFSDEERTQLRLESLEDThIMKGEDDALSDKHGCPAYVSPEILNTTG 162

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1833 V--SKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESmftdLCHEAKGFVIKLL---VADRLrpDANEC 1907
Cdd:cd14023    163 TysGKSADVWSLGVMLYTLLVGRYPFHDSDPSALFSKIRRGQFCIPDH----VSPKARCLIRSLLrrePSERL--TAPEI 236


                   ....*.
gi 1207186029 1908 LRHPWF 1913
Cdd:cd14023    237 LLHPWF 242

Pseudokinase domain, repeat 1, of eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or General Control Non-derepressible-2; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the overall downregulation of protein synthesis. eIF-2 phosphorylation is induced in response to cellular stresses including virus infection, heat shock, nutrient deficiency, and the accummulation of unfolded proteins, among others. There are four distinct kinases that phosphorylate eIF-2 and control protein synthesis under different stress conditions: GCN2, protein kinase regulated by RNA (PKR), heme-regulated inhibitor kinase (HRI), and PKR-like endoplasmic reticulum kinase (PERK). GCN2 is activated by amino acid or serum starvation and UV irradiation. It induces GCN4, a transcriptional activator of amino acid biosynthetic genes, leading to increased production of amino acids under amino acid-deficient conditions. In serum-starved cells, GCN2 activation induces translation of the stress-responsive transcription factor ATF4, while under UV stress, GCN2 triggers transcriptional rescue via NF-kappaB signaling. GCN2 contains an N-terminal RWD, a degenerate kinase-like (repeat 1), the catalytic kinase (repeat 2), a histidyl-tRNA synthetase (HisRS)-like, and a C-terminal ribosome-binding and dimerization (RB/DD) domains. The degenerate pseudokinase domain of GCN2 may function as a regulatory domain. The GCN2 subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270914 [Multi-domain] Cd Length: 254 Bit Score: 67.38 E-value: 1.92e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3382 LHSLIDRFRY-SEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIV---TYMNVVKIIDFGSAQTFNPLFLKQFSPPIG 3457
Cdd:cd14012     91 LSELLDSVGSvPLDTARRWTLQLLEALEYLHRNGVVHKSLHAGNVLLdrdAGTGIVKLTDYSLGKTLLDMCSRGSLDEFK 170

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3458 TLDYMSPEMLKGDV-VGPPADIWSIGILTYIMLSGRLPFtENDPAETEARIqaakfdlsklyqNVSQSASL--FIKKILC 3534
Cdd:cd14012    171 QTYWLPPELAQGSKsPTRKTDVWDLGLLFLQMLFGLDVL-EKYTSPNPVLV------------SLDLSASLqdFLSKCLS 237

                          170
                   ....*....|.
gi 1207186029 3535 SYPWARPTIKD 3545
Cdd:cd14012    238 LDPKKRPTALE 248

Catalytic domain of the Protein Tyrosine Kinases, Platelet Derived Growth Factor Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The PDGFR subfamily consists of PDGFR alpha, PDGFR beta, KIT, CSF-1R, the mammalian FLT3, and similar proteins. They are receptor PTKs (RTKs) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. PDGFR kinase domains are autoinhibited by their juxtamembrane regions containing tyr residues. The binding to their ligands leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. PDGFR subfamily receptors are important in the development of a variety of cells. PDGFRs are expressed in a many cells including fibroblasts, neurons, endometrial cells, mammary epithelial cells, and vascular smooth muscle cells. PDGFR signaling is critical in normal embryonic development, angiogenesis, and wound healing. Kit is important in the development of melanocytes, germ cells, mast cells, hematopoietic stem cells, the interstitial cells of Cajal, and the pacemaker cells of the GI tract. CSF-1R signaling is critical in the regulation of macrophages and osteoclasts. Mammalian FLT3 plays an important role in the survival, proliferation, and differentiation of stem cells. The PDGFR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase .

Pssm-ID: 133186 [Multi-domain] Cd Length: 302 Bit Score: 67.90 E-value: 1.96e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1666 KEIGRGAFSYVKR-----VIQKAGKLEYAAKFI--SARAKRKASALRELNILSHL-DHERILYFHDAFEKKNAVIIITEL 1737
Cdd:cd05055     41 KTLGAGAFGKVVEataygLSKSDAVMKVAVKMLkpTAHSSEREALMSELKIMSHLgNHENIVNLLGACTIGGPILVITEY 120

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1738 C-HEELLDRLTKKS-TILESE-IRSSVRQLLEGINYLHQLDILHLDIKPDNILMAdhSSDQIRICDFGNAVKFMPDeAQY 1814
Cdd:cd05055    121 CcYGDLLNFLRRKReSFLTLEdLLSFSYQVAKGMAFLASKNCIHRDLAARNVLLT--HGKIVKICDFGLARDIMND-SNY 197

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*....
gi 1207186029 1815 CKYGTP----EFVAPEIVNQTPVSKATDIWPIGVLTYLCLT-GVSPFAG 1858
Cdd:cd05055    198 VVKGNArlpvKWMAPESIFNCVYTFESDVWSYGILLWEIFSlGSNPYPG 246

Catalytic domain of Tec-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Tec-like subfamily is composed of Tec, Btk, Bmx (Etk), Itk (Tsk, Emt), Rlk (Txk), and similar proteins. They are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, some members contain the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. Tec kinases form the second largest subfamily of nonreceptor PTKs and are expressed mainly by haematopoietic cells, although Tec and Bmx are also found in endothelial cells. B-cells express Btk and Tec, while T-cells express Itk, Txk, and Tec. Collectively, Tec kinases are expressed in a variety of myeloid cells such as mast cells, platelets, macrophages, and dendritic cells. Each Tec kinase shows a distinct cell-type pattern of expression. Tec kinases play important roles in the development, differentiation, maturation, regulation, survival, and function of B-cells and T-cells. Mutations in Btk cause the severe B-cell immunodeficiency, X-linked agammaglobulinaemia (XLA). The Tec-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173637 [Multi-domain] Cd Length: 256 Bit Score: 67.09 E-value: 2.06e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1666 KEIGRGAFSYVKRVIQKaGKLEYAAKFISARAKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITE-LCHEELLD 1744
Cdd:cd05059     10 KELGSGQFGVVHLGKWR-GKIDVAIKMIKEGSMSEDDFIEEAKVMMKLSHPKLVQLYGVCTKQRPIFIVTEyMANGCLLN 88

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1745 RLTKKSTILESEIRSSV-RQLLEGINYLHQLDILHLDIKPDNILMADHSSdqIRICDFGNAvKFMPDEAQYCKYGTP--- 1820
Cdd:cd05059     89 YLRERRGKFQTEQLLEMcKDVCEAMEYLESNGFIHRDLAARNCLVGEQNV--VKVSDFGLA-RYVLDDEYTSSVGTKfpv 165

                          170       180       190
                   ....*....|....*....|....*....|....*....
gi 1207186029 1821 EFVAPEIVNQTPVSKATDIWPIGVLTYLCLT-GVSPFAG 1858
Cdd:cd05059    166 KWSPPEVFMYSKFSSKSDVWSFGVLMWEVFSeGKMPYER 204

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409565 [Multi-domain] Cd Length: 88 Bit Score: 62.59 E-value: 2.08e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1253 KPLYDMDVVEGREAVLRCKVAGLPYPTITWFHNGKRIdsTEDRKMTQFRD---VHSLVVRCVCHAHGGVYKCVISNKVGK 1329
Cdd:cd20973      2 QTLRDKEVVEGSAARFDCKVEGYPDPEVKWMKDDNPI--VESRRFQIDQDedgLCSLIISDVCGDDSGKYTCKAVNSLGE 79


                   ....*....
gi 1207186029 1330 ATCYSHLYV 1338
Cdd:cd20973     80 ATCSAELTV 88

Catalytic domain of the Protein Tyrosine Kinase, Activated Cdc42-associated kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily includes Ack1, thirty-eight-negative kinase 1 (Tnk1), and similar proteins. They are cytoplasmic (or nonreceptor) PTKs containing an N-terminal catalytic domain, an SH3 domain, a Cdc42-binding CRIB domain, and a proline-rich region. They are mainly expressed in brain and skeletal tissues and are involved in the regulation of cell adhesion and growth, receptor degradation, and axonal guidance. Ack1 is also associated with androgen-independent prostate cancer progression. Tnk1 regulates TNFalpha signaling and may play an important role in cell death. The Ack-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270636 [Multi-domain] Cd Length: 258 Bit Score: 67.37 E-value: 2.10e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1666 KEIGRGAFSYVKRVI--QKAGK-LEYAAKFISARAKRKASA----LRELNILSHLDHERI--LYfhdAFEKKNAVIIITE 1736
Cdd:cd05040      1 EKLGDGSFGVVRRGEwtTPSGKvIQVAVKCLKSDVLSQPNAmddfLKEVNAMHSLDHPNLirLY---GVVLSSPLMMVTE 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1737 LCH-EELLDRLTKKSTI-LESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMAdhSSDQIRICDFGnAVKFMPDEAQY 1814
Cdd:cd05040     78 LAPlGSLLDRLRKDQGHfLISTLCDYAVQIANGMAYLESKRFIHRDLAARNILLA--SKDKVKIGDFG-LMRALPQNEDH 154

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1207186029 1815 ckYGTPE-------FVAPEIVNQTPVSKATDIWPIGV-----LTYlcltGVSPFAGEN 1860
Cdd:cd05040    155 --YVMQEhrkvpfaWCAPESLKTRKFSHASDVWMFGVtlwemFTY----GEEPWLGLN 206

Catalytic domain of the Serine/Threonine protein kinase, Pten INduced Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PINK1 contains an N-terminal mitochondrial targeting sequence, a catalytic domain, and a C-terminal regulatory region. It plays an important role in maintaining mitochondrial homeostasis. It protects cells against oxidative stress-induced apoptosis by phosphorylating the chaperone TNFR-associated protein 1 (TRAP1), also called Hsp75. Phosphorylated TRAP1 prevents cytochrome c release and peroxide-induced apoptosis. PINK1 interacts with Omi/HtrA2, a serine protease, and Parkin, an E3 ubiquitin ligase, in different pathways to promote mitochondrial health. The parkin gene is the most commonly mutated gene in autosomal recessive familial parkinsonism. Mutations within the catalytic domain of PINK1 are also associated with Parkinson's disease. The PINK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270920 [Multi-domain] Cd Length: 313 Bit Score: 67.90 E-value: 2.18e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1763 QLLEGINYLHQLDILHLDIKPDNILMA--DHSSDQIRICDFGNAVK------FMPDEAQYC-KYGTPEFVAPEIVNQTP- 1832
Cdd:cd14018    146 QLLEGVDHLVRHGIAHRDLKSDNILLEldFDGCPWLVIADFGCCLAddsiglQLPFSSWYVdRGGNACLMAPEVSTAVPg 225

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1833 ------VSKAtDIWPIGVLTYLCLTGVSPFAGENDrsSVLNIRNYnvafEESMFTDLcHEAKGFVIKLLVADRLRPDANE 1906
Cdd:cd14018    226 pgvvinYSKA-DAWAVGAIAYEIFGLSNPFYGLGD--TMLESRSY----QESQLPAL-PSAVPPDVRQVVKDLLQRDPNK 297

Catalytic domain of the Serine/Threonine Kinase, Serine-aRginine Protein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SRPK1 binds with high affinity the alternative splicing factor, SRSF1 (serine/arginine-rich splicing factor 1), and regiospecifically phosphorylates 10-12 serines in its RS domain. It plays a role in the regulation of pre-mRNA splicing, chromatin structure, and germ cell development. SRPKs phosphorylate and regulate splicing factors from the SR protein family by specifically phosphorylating multiple serine residues residing in SR/RS dipeptide motifs (also known as RS domains). Phosphorylation of the RS domains enhances interaction with transportin SR and facilitates entry of the SR proteins into the nucleus. SRPKs contain a nonconserved insert domain, within the well-conserved catalytic kinase domain, that regulates their subcellular localization. The SRPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271118 [Multi-domain] Cd Length: 349 Bit Score: 68.52 E-value: 2.42e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3396 VVAYIVQILQGLDYLHSR-RILHLDIKPENIIVTYMNV------------------------------VKIIDFGSAQTF 3444
Cdd:cd14216    121 VKKIIRQVLQGLDYLHTKcRIIHTDIKPENILLSVNEQyirrlaaeatewqrnflvnplepknaeklkVKIADLGNACWV 200

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1207186029 3445 NplflKQFSPPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPF 3495
Cdd:cd14216    201 H----KHFTEDIQTRQYRSLEVLIGSGYNTPADIWSTACMAFELATGDYLF 247

Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNK4 shows a restricted expression pattern and is usually found in epithelial cells. It is expressed in nephrons and in extrarenal tissues including intestine, eye, mammary glands, and prostate. WNK4 regulates a variety of ion transport proteins including apical or basolateral ion transporters, ion channels in the transcellular pathway, and claudins in the paracellular pathway. Mutations in WNK4 cause PseudoHypoAldosteronism type II (PHAII), characterized by hypertension and hyperkalemia. WNK4 inhibits the activity of the thiazide-sensitive Na-Cl cotransporter (NCC), which is responsible for about 15% of NaCl reabsorption in the kidney. It also inhibits the renal outer medullary potassium channel (ROMK) and decreases its surface expression. Hypertension and hyperkalemia in PHAII patients with WNK4 mutations may be partly due to increased NaCl reabsorption through NCC and impaired renal potassium secretion by ROMK, respectively. The WNK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270935 [Multi-domain] Cd Length: 261 Bit Score: 66.95 E-value: 2.71e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3338 KQTVLQEYDILKSLHHEKIMALHEAYVTP----RYLVLISEC-CSGKelLHSLIDRFRYSEDDVVA-YIVQILQGLDYLH 3411
Cdd:cd14033     44 RQRFSEEVEMLKGLQHPNIVRFYDSWKSTvrghKCIILVTELmTSGT--LKTYLKRFREMKLKLLQrWSRQILKGLHFLH 121

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3412 SRR--ILHLDIKPENIIVT-YMNVVKIIDFGSAQTFNPLFLKQFsppIGTLDYMSPEMLKgDVVGPPADIWSIGILTYIM 3488
Cdd:cd14033    122 SRCppILHRDLKCDNIFITgPTGSVKIGDLGLATLKRASFAKSV---IGTPEFMAPEMYE-EKYDEAVDVYAFGMCILEM 197


                   ....*....
gi 1207186029 3489 LSGRLPFTE 3497
Cdd:cd14033    198 ATSEYPYSE 206

Catalytic domain of the Serine/Threonine Kinase, Homeodomain-Interacting Protein Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HIPK3 is a Fas-interacting protein that induces FADD (Fas-associated death domain) phosphorylation and mediates FasL-induced JNK activation. Overexpression of HIPK3 does not affect cell death, however its expression in prostate cancer cells contributes to increased resistance to Fas receptor-mediated apoptosis. HIPK3 also plays a role in regulating steroidogenic gene expression. In response to cAMP, HIPK3 activates the phosphorylation of JNK and c-Jun, leading to increased activity of the transcription factor SF-1 (Steroidogenic factor 1), a key regulator for steroid biosynthesis in the gonad and adrenal gland. HIPKs, originally identified by their ability to bind homeobox factors, are nuclear proteins containing catalytic kinase and homeobox-interacting domains as well as a PEST region overlapping with the speckle-retention signal (SRS). The HIPK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).

Pssm-ID: 271131 [Multi-domain] Cd Length: 330 Bit Score: 68.13 E-value: 2.78e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASALRELNILSHLDHERILYF-----HDAFEKKNAVIIITE 1736
Cdd:cd14229      2 YEVLDFLGRGTFGQVVKCWKRGTNEIVAVKILKNHPSYARQGQIEVGILARLSNENADEFnfvraYECFQHRNHTCLVFE 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1737 LCHEELLDRL--TKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMAD--HSSDQIRICDFGNA---VKFMP 1809
Cdd:cd14229     82 MLEQNLYDFLkqNKFSPLPLKVIRPILQQVATALKKLKSLGLIHADLKPENIMLVDpvRQPYRVKVIDFGSAshvSKTVC 161

                          170       180       190
                   ....*....|....*....|....*....|....
gi 1207186029 1810 DEAQYCKYgtpeFVAPEIVNQTPVSKATDIWPIG 1843
Cdd:cd14229    162 STYLQSRY----YRAPEIILGLPFCEAIDMWSLG 191

Catalytic domain of the Dual-specificity protein kinase, Lymphokine-activated killer T-cell-originated protein kinase; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TOPK, also called PDZ-binding kinase (PBK), is activated at the early stage of mitosis and plays a critical role in cytokinesis. It partly functions as a mitogen-activated protein kinase (MAPK) kinase and is capable of phosphorylating p38, JNK1, and ERK2. TOPK also plays a role in DNA damage sensing and repair through its phosphorylation of histone H2AX. It contributes to cancer development and progression by downregulating the function of tumor suppressor p53 and reducing cell-cycle regulatory proteins. TOPK is found highly expressed in breast and skin cancer cells. The TOPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270903 [Multi-domain] Cd Length: 292 Bit Score: 67.42 E-value: 2.85e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3344 EYDILKSLHHEKIM---ALHEAYVTPRYLVLisECCsGKELLhSLIDRFRYSEDD--VVAYI----VQILQGLDYLHS-R 3413
Cdd:cd14001     55 EAKILKSLNHPNIVgfrAFTKSEDGSLCLAM--EYG-GKSLN-DLIEERYEAGLGpfPAATIlkvaLSIARALEYLHNeK 130

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3414 RILHLDIKPENIIVTY-MNVVKIIDFGSAQTFNPLfLKQFSPP----IGTLDYMSPEMLKGD-VVGPPADIWSIGILTYI 3487
Cdd:cd14001    131 KILHGDIKSGNVLIKGdFESVKLCDFGVSLPLTEN-LEVDSDPkaqyVGTEPWKAKEALEEGgVITDKADIFAYGLVLWE 209

                          170
                   ....*....|....*..
gi 1207186029 3488 MLSGRLPFTENDPAETE 3504
Cdd:cd14001    210 MMTLSVPHLNLLDIEDD 226

Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PIM gene locus was discovered as a result of the cloning of retroviral intergration sites in murine Moloney leukemia virus, leading to the identification of PIM kinases. They are constitutively active STKs with a broad range of cellular targets and are overexpressed in many haematopoietic malignancies and solid cancers. Vertebrates contain three distinct PIM kinase genes (PIM1-3). PIM3 can inhibit apoptosis and promote cell survival and protein translation, therefore, it can enhance the proliferation of normal and cancer cells. Mice deficient with PIM3 show minimal effects, suggesting that PIM3 msy not be essential. Since its expression is enhanced in several cancers, it may make a good molecular target for cancer drugs. The PIM3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271004 [Multi-domain] Cd Length: 253 Bit Score: 66.90 E-value: 2.92e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1723 DAFEKKNAVIIITELCH--EELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMaDHSSDQIRICD 1800
Cdd:cd14102     71 DWYERPDGFLIVMERPEpvKDLFDFITEKGALDEDTARGFFRQVLEAVRHCYSCGVVHRDIKDENLLV-DLRTGELKLID 149

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1801 FGNAVkfMPDEAQYCKY-GTPEFVAPEIVN-QTPVSKATDIWPIGVLTYLCLTGVSPFagENDRsSVLNIRNYnvaFEES 1878
Cdd:cd14102    150 FGSGA--LLKDTVYTDFdGTRVYSPPEWIRyHRYHGRSATVWSLGVLLYDMVCGDIPF--EQDE-EILRGRLY---FRRR 221

                          170       180       190
                   ....*....|....*....|....*....|....
gi 1207186029 1879 MFTDlCHEAKGFVIKLLVADrlRPDANECLRHPW 1912
Cdd:cd14102    222 VSPE-CQQLIKWCLSLRPSD--RPTLEQIFDHPW 252

Catalytic domain of the protein kinases, Dual-specificity tYrosine-phosphorylated and -Regulated Kinases 2 and 3; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. This subfamily is composed of DYRK2 and DYRK3, and similar proteins. Drosophila DYRK2 interacts and phosphorylates the chromatin remodelling factor, SNR1 (Snf5-related 1), and also interacts with the essential chromatin component, trithorax. It may play a role in chromatin remodelling. Vertebrate DYRK2 phosphorylates and regulates the tumor suppressor p53 to induce apoptosis in response to DNA damage. It can also phosphorylate the transcription factor, nuclear factor of activated T cells (NFAT). DYRK2 is overexpressed in lung adenocarcinoma and esophageal carcinomas, and is a predictor for favorable prognosis in lung adenocarcinoma. DYRK3, also called regulatory erythroid kinase (REDK), is highly expressed in erythroid cells and the testis, and is also present in adult kidney and liver. It promotes cell survival by phosphorylating and activating SIRT1, an NAD(+)-dependent protein deacetylase, which promotes p53 deacetylation, resulting in the inhibition of apoptosis. DYRKs autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. The DYRK2/3 subfamily is part of a larger superfamily that includes the catalytic domains of other S/T kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271126 [Multi-domain] Cd Length: 380 Bit Score: 68.23 E-value: 2.98e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASALRELNILSHLDHE------RILYFHDAFEKKNAVIIIT 1735
Cdd:cd14224     67 YEVLKVIGKGSFGQVVKAYDHKTHQHVALKMVRNEKRFHRQAAEEIRILEHLKKQdkdntmNVIHMLESFTFRNHICMTF 146

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1736 ELCHEELLDrLTKK------STILESEIRSSVRQLLEGinyLHQLDILHLDIKPDNILMADHSSDQIRICDFGNAVkfMP 1809
Cdd:cd14224    147 ELLSMNLYE-LIKKnkfqgfSLQLVRKFAHSILQCLDA---LHRNKIIHCDLKPENILLKQQGRSGIKVIDFGSSC--YE 220

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1207186029 1810 DEAQYCKYGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGEND 1861
Cdd:cd14224    221 HQRIYTYIQSRFYRAPEVILGARYGMPIDMWSFGCILAELLTGYPLFPGEDE 272

Catalytic domain of the Serine/Threonine Kinases, Plant TDY Mitogen-Activated Protein Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Plant MAPKs are typed based on the conserved phosphorylation motif present in the activation loop, TEY and TDY. This subfamily represents the TDY subtype and is composed of Group D plant MAPKs including Arabidopsis thaliana MPK18 (AtMPK18), Oryza sativa Blast- and Wound-induced MAPK1 (OsBWMK1), OsWJUMK1 (Wound- and JA-Uninducible MAPK1), Zea mays MPK6, and the Medicago sativa TDY1 gene product. OsBWMK1 enhances resistance to pathogenic infections. It mediates stress-activated defense responses by activating a transcription factor that affects the expression of stress-related genes. AtMPK18 is involved in microtubule-related functions. In plants, MAPKs are associated with physiological, developmental, hormonal, and stress responses. Some plants show numerous gene duplications of MAPKs; Arabidopsis thaliana harbors at least 20 MAPKs, named AtMPK1-20 while Oryza sativa contains at least 17 MAPKs. Arabidopsis thaliana contains more TEY-type MAPKs than TDY-type, whereas the reverse is true for Oryza sativa. The TDY MAPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143364 [Multi-domain] Cd Length: 338 Bit Score: 67.88 E-value: 3.10e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASA---LRELNILSHLDH------ERILYFHDAFEKKNaVI 1732
Cdd:cd07859      2 YKIQEVIGKGSYGVVCSAIDTHTGEKVAIKKINDVFEHVSDAtriLREIKLLRLLRHpdiveiKHIMLPPSRREFKD-IY 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1733 IITELCHEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDFGNA-VKFM--P 1809
Cdd:cd07859     81 VVFELMESDLHQVIKANDDLTPEHHQFFLYQLLRALKYIHTANVFHRDLKPKNILA--NADCKLKICDFGLArVAFNdtP 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1810 DEAQYCKY-GTPEFVAPEIVNQ--TPVSKATDIWPIGVLTYLCLTGVSPFAGEN---------------DRSSVLNIRNY 1871
Cdd:cd07859    159 TAIFWTDYvATRWYRAPELCGSffSKYTPAIDIWSIGCIFAEVLTGKPLFPGKNvvhqldlitdllgtpSPETISRVRNE 238

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1207186029 1872 NV-AFEESM-------FTDLCHEAKGFVIKLLvaDRL-------RPDANECLRHPWFKTLNK 1918
Cdd:cd07859    239 KArRYLSSMrkkqpvpFSQKFPNADPLALRLL--ERLlafdpkdRPTAEEALADPYFKGLAK 298

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 62.14 E-value: 3.20e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  935 GDQSVIEGQEVTMSVLVTGQPKPMLYWLRDRVTIKTG-TRHIVQETeegNFEMIIKSAQRSDTGVYTCKIINE-YGTKQC 1012
Cdd:cd20970     10 FTVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEFnTRYIVREN---GTTLTIRNIRRSDMGIYLCIASNGvPGSVEK 86


                   ....*.
gi 1207186029 1013 EGKLEV 1018
Cdd:cd20970     87 RITLQV 92

Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. VEGFR2 (or Flk1) binds the ligands VEGFA, VEGFC, VEGFD and VEGFE. VEGFR2 signaling is implicated in all aspects of normal and pathological vascular endothelial cell biology. It induces a variety of cellular effects including migration, survival, and proliferation. It is critical in regulating embryonic vascular development and angiogenesis. VEGFR2 is the major signal transducer in pathological angiogenesis including cancer and diabetic retinopathy, and is a target for inhibition in cancer therapy. The carboxyl terminus of VEGFR2 plays an important role in its autophosphorylation and activation. VEGFR2 is a member of the VEGFR subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of VEGFRs to their ligands, the VEGFs, leads to receptor dimerization, activation, and intracellular signaling. The VEGFR2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270681 [Multi-domain] Cd Length: 343 Bit Score: 68.08 E-value: 3.38e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3394 DDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTF--NPLFLKQFSPPIgTLDYMSPEMLKGDV 3471
Cdd:cd05103    179 EDLICYSFQVAKGMEFLASRKCIHRDLAARNILLSENNVVKICDFGLARDIykDPDYVRKGDARL-PLKWMAPETIFDRV 257

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1207186029 3472 VGPPADIWSIGILTYIMLS-GRLPFTENDPAE-------TEARIQAAKFDLSKLYQNV 3521
Cdd:cd05103    258 YTIQSDVWSFGVLLWEIFSlGASPYPGVKIDEefcrrlkEGTRMRAPDYTTPEMYQTM 315

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 61.43 E-value: 3.45e-11

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1207186029  927 PPAFLAVIGDQSVIEGQEVTMSVLVTGQPKPMLYWLRDRVTIKTGtRHIVQETEEGNFEMIIKSAQRSDTGVYTCKIIN 1005
Cdd:pfam13927    1 KPVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSG-STRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

Catalytic domain of Fes-like Protein Tyrosine Kinases; Protein Tyrosine Kinase (PTK) family; Fes subfamily; catalytic (c) domain. Fes subfamily members include Fes (or Fps), Fer, and similar proteins. The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Fes subfamily proteins are cytoplasmic (or nonreceptor) tyr kinases containing an N-terminal region with FCH (Fes/Fer/CIP4 homology) and coiled-coil domains, followed by a SH2 domain, and a C-terminal catalytic domain. The genes for Fes (feline sarcoma) and Fps (Fujinami poultry sarcoma) were first isolated from tumor-causing retroviruses. The viral oncogenes encode chimeric Fes proteins consisting of Gag sequences at the N-termini, resulting in unregulated tyr kinase activity. Fes and Fer kinases play roles in haematopoiesis, inflammation and immunity, growth factor signaling, cytoskeletal regulation, cell migration and adhesion, and the regulation of cell-cell interactions. Fes and Fer show redundancy in their biological functions.

Pssm-ID: 270637 [Multi-domain] Cd Length: 251 Bit Score: 66.31 E-value: 3.65e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYVKRVIQKAGKLEYAAKfiSAR----AKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITELCHE-EL 1742
Cdd:cd05041      3 IGRGNFGDVYRGVLKPDNTEVAVK--TCRetlpPDLKRKFLQEARILKQYDHPNIVKLIGVCVQKQPIMIVMELVPGgSL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1743 LDRLTKKSTILeseirsSVRQLLE-------GINYLHQLDILHLDIKPDNILMADhsSDQIRICDFGnavkfMPDEAQYC 1815
Cdd:cd05041     81 LTFLRKKGARL------TVKQLLQmcldaaaGMEYLESKNCIHRDLAARNCLVGE--NNVLKISDFG-----MSREEEDG 147

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1207186029 1816 KY----GTPE----FVAPEIVNQTPVSKATDIWPIGVLTYLCLT-GVSPFAGENDR 1862
Cdd:cd05041    148 EYtvsdGLKQipikWTAPEALNYGRYTSESDVWSFGILLWEIFSlGATPYPGMSNQ 203

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 61.43 E-value: 3.66e-11

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1207186029   54 PPVFIRKMRNAAVGTGCDIRLKVAVAGDPQPTLYWYHND-------DLVNMDNQEYGGLWIRDCKPSDAGLYTCIATN 124
Cdd:pfam13927    1 KPVITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGepissgsTRSRSLSGSNSTLTISNVTRSDAGTYTCVASN 78

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 61.64 E-value: 3.73e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  786 PLQDTVASTGTEVLLKCIISGTPLPEVIWKKDNTEVKNSP--THVvkiegERHSLLIKWTKPSDAGTYTVTAVNEVGEVS 863
Cdd:cd20978      7 PEKNVVVKGGQDVTLPCQVTGVPQPKITWLHNGKPLQGPMerATV-----EDGTLTIINVQPEDTGYYGCVATNEIGDIY 81


                   ....*
gi 1207186029  864 SSATL 868
Cdd:cd20978     82 TETLL 86

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 61.75 E-value: 3.82e-11

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  1260 VVEGREAVLRCKVAGLPYPTITWFHNGKRIDSTEDR-KMTQFRDVHSLVVRCVCHAHGGVYKCVISNKVGKATCYSHLYV 1338
Cdd:smart00410    6 VKEGESVTLSCEASGSPPPEVTWYKQGGKLLAESGRfSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGTTLTV 85

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 61.76 E-value: 3.85e-11

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1207186029 1254 PLYDMDVVEGREAVLRCKVAGLPYPTITWFHNGKRID--STEDRKMTQFRDvhsLVVRCVCHAHGGVYKCVISNKVG 1328
Cdd:cd20970      8 PSFTVTAREGENATFMCRAEGSPEPEISWTRNGNLIIefNTRYIVRENGTT---LTIRNIRRSDMGIYLCIASNGVP 81

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 61.75 E-value: 3.85e-11

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029   788 QDTVASTGTEVLLKCIISGTPLPEVIWKKDNTE-VKNSPTHVVKIEGERHSLLIKWTKPSDAGTYTVTAVNEVGEVSSSA 866
Cdd:smart00410    2 PSVTVKEGESVTLSCEASGSPPPEVTWYKQGGKlLAESGRFSVSRSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGT 81


                    ....
gi 1207186029   867 TLFI 870
Cdd:smart00410   82 TLTV 85

Catalytic domain of the Serine/Threonine protein kinase, Casein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CK1 phosphorylates a variety of substrates including enzymes, transcription and splice factors, cytoskeletal proteins, viral oncogenes, receptors, and membrane-associated proteins. There are mutliple isoforms of CK1 and in mammals, seven isoforms (alpha, beta, gamma1-3, delta, and epsilon) have been characterized. These isoforms differ mainly in the length and structure of their C-terminal non-catalytic region. Some isoforms have several splice variants such as the long (L) and short (S) variants of CK1alpha. CK1 proteins are involved in the regulation of many cellular processes including membrane transport processes, circadian rhythm, cell division, apoptosis, and the development of cancer and neurodegenerative diseases. The CK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270918 [Multi-domain] Cd Length: 266 Bit Score: 66.71 E-value: 3.87e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1661 YYDVHKeIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKaSALRELNILSHL-DHERILYFHDAFEKKNAVIIITELCH 1739
Cdd:cd14016      2 YKLVKK-IGSGSFGEVYLGIDLKTGEEVAIKIEKKDSKHP-QLEYEAKVYKLLqGGPGIPRLYWFGQEGDYNVMVMDLLG 79

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1207186029 1740 EELLD-------RLTKKSTILESEirssvrQLLEGINYLHQLDILHLDIKPDNILM-ADHSSDQIRICDFGNAVKFM 1808
Cdd:cd14016     80 PSLEDlfnkcgrKFSLKTVLMLAD------QMISRLEYLHSKGYIHRDIKPENFLMgLGKNSNKVYLIDFGLAKKYR 150

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.

Pssm-ID: 409541 [Multi-domain] Cd Length: 89 Bit Score: 61.96 E-value: 3.87e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1125 FTRKLDVLEVIEGRNARFDCKVSGTPPPQVIWSHFDRPLEEN----EDIRILKEGgrhsLIISHVSNEDEGLYTVAARNS 1200
Cdd:cd20949      2 FTENAYVTTVKEGQSATILCEVKGEPQPNVTWHFNGQPISASvadmSKYRILADG----LLINKVTQDDTGEYTCRAYQV 77

                           90
                   ....*....|..
gi 1207186029 1201 HGEDECAAELYV 1212
Cdd:cd20949     78 NSIASDMQERTV 89

Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C zeta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-zeta plays a critical role in activating the glucose transport response. It is activated by glucose, insulin, and exercise through diverse pathways. PKC-zeta also plays a central role in maintaining cell polarity in yeast and mammalian cells. In addition, it affects actin remodeling in muscle cells. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. aPKCs only require phosphatidylserine (PS) for activation. The aPKC-zeta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270768 [Multi-domain] Cd Length: 357 Bit Score: 67.74 E-value: 3.95e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASALRELNILSHLDHER-----ILYFHDAFEKKNAVIIITE 1736
Cdd:cd05617     17 FDLIRVIGRGSYAKVLLVRLKKNDQIYAMKVVKKELVHDDEDIDWVQTEKHVFEQAssnpfLVGLHSCFQTTSRLFLVIE 96

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1737 LCHE-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDFGNAVKFM-PDEAQY 1814
Cdd:cd05617     97 YVNGgDLMFHMQRQRKLPEEHARFYAAEICIALNFLHERGIIYRDLKLDNVLL--DADGHIKLTDYGMCKEGLgPGDTTS 174

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|..
gi 1207186029 1815 CKYGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPF 1856
Cdd:cd05617    175 TFCGTPNYIAPEILRGEEYGFSVDWWALGVLMFEMMAGRSPF 216

Catalytic domain of the Protein Tyrosine Kinase, Lyn; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Lyn is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lyn is expressed in B lymphocytes and myeloid cells. It exhibits both positive and negative regulatory roles in B cell receptor (BCR) signaling. Lyn, as well as Fyn and Blk, promotes B cell activation by phosphorylating ITAMs (immunoreceptor tyr activation motifs) in CD19 and in Ig components of BCR. It negatively regulates signaling by its unique ability to phosphorylate ITIMs (immunoreceptor tyr inhibition motifs) in cell surface receptors like CD22 and CD5. Lyn also plays an important role in G-CSF receptor signaling by phosphorylating a variety of adaptor molecules. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Lyn subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270657 [Multi-domain] Cd Length: 272 Bit Score: 66.60 E-value: 4.17e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1704 LRELNILSHLDHERILYFHDAFEKKNAVIIITE-LCHEELLDRLTKK--STILESEIRSSVRQLLEGINYLHQLDILHLD 1780
Cdd:cd05072     50 LEEANLMKTLQHDKLVRLYAVVTKEEPIYIITEyMAKGSLLDFLKSDegGKVLLPKLIDFSAQIAEGMAYIERKNYIHRD 129

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1781 IKPDNILMADhsSDQIRICDFGNAvKFMPDEAQYCKYGTP---EFVAPEIVNQTPVSKATDIWPIGVLTYLCLT-GVSPF 1856
Cdd:cd05072    130 LRAANVLVSE--SLMCKIADFGLA-RVIEDNEYTAREGAKfpiKWTAPEAINFGSFTIKSDVWSFGILLYEIVTyGKIPY 206


                   ..
gi 1207186029 1857 AG 1858
Cdd:cd05072    207 PG 208

First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409566 [Multi-domain] Cd Length: 93 Bit Score: 61.99 E-value: 4.22e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  781 PVFEFPLQDTVASTGTEVLLKCIISGTPLPEVIWKKDNTEVKNSPTHVVKIE--GERHSLLIKWTKPSDAGTYTVTAVNE 858
Cdd:cd20974      1 PVFTQPLQSVVVLEGSTATFEAHVSGKPVPEVSWFRDGQVISTSTLPGVQISfsDGRAKLSIPAVTKANSGRYSLTATNG 80

                           90
                   ....*....|...
gi 1207186029  859 VGEVSSSATLFIK 871
Cdd:cd20974     81 SGQATSTAELLVL 93

Pseudokinase domain of Kinase Suppressor of Ras; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. KSR is a scaffold protein that functions downstream of Ras and upstream of Raf in the Extracellular signal-Regulated Kinase (ERK) pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. KSR proteins regulate the assembly and activation of the Raf/MEK/ERK module upon Ras activation at the membrane by direct association of its components. They are widely regarded as pseudokinases, but there is some debate in this designation as a few groups have reported detecting kinase catalytic activity for KSRs, specifically KSR1. Vertebrates contain two KSR proteins, KSR1 and KSR2. The KSR subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270965 [Multi-domain] Cd Length: 271 Bit Score: 66.60 E-value: 4.22e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1715 HERILYFHDAFEKKNAVIIITELC-HEELLDRL-TKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMadhS 1792
Cdd:cd14063     55 HDNLVLFMGACMDPPHLAIVTSLCkGRTLYSLIhERKEKFDFNKTVQIAQQICQGMGYLHAKGIIHKDLKSKNIFL---E 131

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1793 SDQIRICDFG--NAVKFMPDEAQYCKYGTPE----FVAPEIV----------NQTPVSKATDIWPIGVLTYLCLTGVSPF 1856
Cdd:cd14063    132 NGRVVITDFGlfSLSGLLQPGRREDTLVIPNgwlcYLAPEIIralspdldfeESLPFTKASDVYAFGTVWYELLAGRWPF 211


                   ....*....
gi 1207186029 1857 AGENDRSSV 1865
Cdd:cd14063    212 KEQPAESII 220

Catalytic domain of the dual-specificity Protein Kinases, Mitogen-activated protein Kinase Kinases 3 and 6; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK3 and MKK6 are dual-specificity PKs that phosphorylate and activate their downstream target, p38 MAPK, on specific threonine and tyrosine residues. MKK3/6 play roles in the regulation of cell cycle progression, cytokine- and stress-induced apoptosis, oncogenic transformation, and adult tissue regeneration. In addition, MKK6 plays a critical role in osteoclast survival in inflammatory disease while MKK3 is associated with tumor invasion, progression, and poor patient survival in glioma. The MKK3/6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173729 [Multi-domain] Cd Length: 283 Bit Score: 66.68 E-value: 4.23e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1667 EIGRGAFSYVKRVIQKAGKLEYAAKFISA--RAKRKASALRELNI-LSHLDHERILYFHDAFEKKNAVIIITELChEELL 1743
Cdd:cd06617      8 ELGRGAYGVVDKMRHVPTGTIMAVKRIRAtvNSQEQKRLLMDLDIsMRSVDCPYTVTFYGALFREGDVWICMEVM-DTSL 86

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1744 DRLTKKS-----TILESEIRSSVRQLLEGINYLH-QLDILHLDIKPDNILMADHSsdQIRICDFGNAVKFMPDEAQYCKY 1817
Cdd:cd06617     87 DKFYKKVydkglTIPEDILGKIAVSIVKALEYLHsKLSVIHRDVKPSNVLINRNG--QVKLCDFGISGYLVDSVAKTIDA 164

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1818 GTPEFVAPEIVNQTPVSKA----TDIWPIGVLTYLCLTGVSPFAgendrssvlnirNYNVAFE--------------ESM 1879
Cdd:cd06617    165 GCKPYMAPERINPELNQKGydvkSDVWSLGITMIELATGRFPYD------------SWKTPFQqlkqvveepspqlpAEK 232

                          250       260       270
                   ....*....|....*....|....*....|....*.
gi 1207186029 1880 FTDLCHEakgFVIKLLVAD-RLRPDANECLRHPWFK 1914
Cdd:cd06617    233 FSPEFQD---FVNKCLKKNyKERPNYPELLQHPFFE 265

serine/threonine kinase US3; Provisional

Pssm-ID: 165473 [Multi-domain] Cd Length: 392 Bit Score: 67.95 E-value: 4.24e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1705 RELNILSHLDHERILYFHDAFEKKNAVIIITELCHEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPD 1784
Cdd:PHA03207   135 REIDILKTISHRAIINLIHAYRWKSTVCMVMPKYKCDLFTYVDRSGPLPLEQAITIQRRLLEALAYLHGRGIIHRDVKTE 214

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1785 NILMADHssDQIRICDFGNAVKF--MPDEAQ-YCKYGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGEND 1861
Cdd:PHA03207   215 NIFLDEP--ENAVLGDFGAACKLdaHPDTPQcYGWSGTLETNSPELLALDPYCAKTDIWSAGLVLFEMSVKNVTLFGKQV 292

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|
gi 1207186029 1862 RSSVLNIRN-------YNVAFEESMFTDLCHEAKGFVIKL 1894
Cdd:PHA03207   293 KSSSSQLRSiircmqvHPLEFPQNGSTNLCKHFKQYAIVL 332

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 61.19 E-value: 4.30e-11

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1207186029 1266 AVLRCKVAGLPYPTITWFHNGKRIDSTEDRKMTQFRDVHSLVVRCVCHAHGGVYKCVISNKVGKAT 1331
Cdd:cd00096      1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSA 66

serine/threonine protein kinase; Provisional

Pssm-ID: 240344 [Multi-domain] Cd Length: 496 Bit Score: 68.36 E-value: 4.54e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1698 KRKASAlrELNILSHLDHERILYFHDAFEKKNA-----VIIITELC--------HEELLDRLTKKSTILESEIRSSVRQL 1764
Cdd:PTZ00283    75 KNRAQA--EVCCLLNCDFFSIVKCHEDFAKKDPrnpenVLMIALVLdyanagdlRQEIKSRAKTNRTFREHEAGLLFIQV 152

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1765 LEGINYLHQLDILHLDIKPDNILMAdhSSDQIRICDFGNAVKF---MPDEAQYCKYGTPEFVAPEIVNQTPVSKATDIWP 1841
Cdd:PTZ00283   153 LLAVHHVHSKHMIHRDIKSANILLC--SNGLVKLGDFGFSKMYaatVSDDVGRTFCGTPYYVAPEIWRRKPYSKKADMFS 230

                          170
                   ....*....|....*....
gi 1207186029 1842 IGVLTYLCLTGVSPFAGEN 1860
Cdd:PTZ00283   231 LGVLLYELLTLKRPFDGEN 249

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 7; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK7 is a dual-specificity PK that phosphorylates and activates its downstream target, c-Jun N-terminal kinase (JNK), on specific threonine and tyrosine residues. Although MKK7 is capable of dual phosphorylation, it prefers to phosphorylate the threonine residue of JNK. Thus, optimal activation of JNK requires both MKK4 and MKK7. MKK7 is primarily activated by cytokines. MKK7 is essential for liver formation during embryogenesis. It plays roles in G2/M cell cycle arrest and cell growth. In addition, it is involved in the control of programmed cell death, which is crucial in oncogenesis, cancer chemoresistance, and antagonism to TNFalpha-induced killing, through its inhibition by Gadd45beta and the subsequent suppression of the JNK cascade. The MKK7 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270791 [Multi-domain] Cd Length: 295 Bit Score: 66.63 E-value: 4.83e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1704 LRELNI--LSHlDHERILYFHDAFEKKNAVIIITEL---CHEELLDRLtkKSTILESEIRSSVRQLLEGINYL---HQld 1775
Cdd:cd06618     61 LMDLDVvlKSH-DCPYIVKCYGYFITDSDVFICMELmstCLDKLLKRI--QGPIPEDILGKMTVSIVKALHYLkekHG-- 135

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1776 ILHLDIKPDNILMADhsSDQIRICDFGNAVKFMPDEAQYCKYGTPEFVAPEIVNQTPVSK---ATDIWPIGVLTYLCLTG 1852
Cdd:cd06618    136 VIHRDVKPSNILLDE--SGNVKLCDFGISGRLVDSKAKTRSAGCAAYMAPERIDPPDNPKydiRADVWSLGISLVELATG 213

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1207186029 1853 VSPFAGENDRSSVLNI--------RNYNVAFEEsMFTDlcheakgFVIKLLVAD-RLRPDANECLRHPWFK 1914
Cdd:cd06618    214 QFPYRNCKTEFEVLTKilneeppsLPPNEGFSP-DFCS-------FVDLCLTKDhRYRPKYRELLQHPFIR 276

Catalytic domain of the Serine/Threonine Kinase, Serine-aRginine Protein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SRPK1 binds with high affinity the alternative splicing factor, SRSF1 (serine/arginine-rich splicing factor 1), and regiospecifically phosphorylates 10-12 serines in its RS domain. It plays a role in the regulation of pre-mRNA splicing, chromatin structure, and germ cell development. SRPKs phosphorylate and regulate splicing factors from the SR protein family by specifically phosphorylating multiple serine residues residing in SR/RS dipeptide motifs (also known as RS domains). Phosphorylation of the RS domains enhances interaction with transportin SR and facilitates entry of the SR proteins into the nucleus. SRPKs contain a nonconserved insert domain, within the well-conserved catalytic kinase domain, that regulates their subcellular localization. The SRPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271118 [Multi-domain] Cd Length: 349 Bit Score: 67.36 E-value: 5.09e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASALRELNILSHL--------DHERILYFHDAFEKKNA--- 1730
Cdd:cd14216     12 YHVIRKLGWGHFSTVWLSWDIQGKRFVAMKVVKSAEHYTETALDEIKLLKSVrnsdpndpNREMVVQLLDDFKISGVngt 91

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1731 -VIIITELCHEELLDRLTKKS--TILESEIRSSVRQLLEGINYLH-QLDILHLDIKPDNILM------------------ 1788
Cdd:cd14216     92 hICMVFEVLGHHLLKWIIKSNyqGLPLPCVKKIIRQVLQGLDYLHtKCRIIHTDIKPENILLsvneqyirrlaaeatewq 171

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1789 ------------ADHSsdQIRICDFGNAV---KFMPDEAQyckygTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTG- 1852
Cdd:cd14216    172 rnflvnplepknAEKL--KVKIADLGNACwvhKHFTEDIQ-----TRQYRSLEVLIGSGYNTPADIWSTACMAFELATGd 244

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1853 --VSPFAGEN---DRSSVLNI--------RNYNVA--FEESMFT---DLCH----------------------EAKGFVI 1892
Cdd:cd14216    245 ylFEPHSGEDysrDEDHIALIiellgkvpRKLIVAgkYSKEFFTkkgDLKHitklkpwglfevlvekyewsqeEAAGFTD 324

                          330       340
                   ....*....|....*....|....*
gi 1207186029 1893 KLLVADRLRPD----ANECLRHPWF 1913
Cdd:cd14216    325 FLLPMLELIPEkratAAECLRHPWL 349

Pseudokinase domain of membrane Guanylate Cyclase receptors; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs lack a critical aspartate involved in ATP binding and does not exhibit kinase activity. It functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270894 [Multi-domain] Cd Length: 268 Bit Score: 66.26 E-value: 5.20e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3323 GNLYMAKIVPYEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECC---SGKELL----HSLIDRFRYSedd 3395
Cdd:cd13992     25 GRTVAIKHITFSRTEKRTILQELNQLKELVHDNLNKFIGICINPPNIAVVTEYCtrgSLQDVLlnreIKMDWMFKSS--- 101

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3396 vvaYIVQILQGLDYLHSRRI-LHLDIKPENIIVTYMNVVKIIDFG-----SAQTFNPLflkQFSPPIGTLDYMSPEMLKG 3469
Cdd:cd13992    102 ---FIKDIVKGMNYLHSSSIgYHGRLKSSNCLVDSRWVVKLTDFGlrnllEEQTNHQL---DEDAQHKKLLWTAPELLRG 175

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|...
gi 1207186029 3470 DVVG----PPADIWSIGILTYIMLSGRLPFTENDPAETEARIQ 3508
Cdd:cd13992    176 SLLEvrgtQKGDVYSFAIILYEILFRSDPFALEREVAIVEKVI 218

Catalytic domain of the Protein Tyrosine Kinase, Csk homologous kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Chk is also referred to as megakaryocyte-associated tyrosine kinase (Matk). Chk inhibits Src kinases using a noncatalytic mechanism by simply binding to them. As a negative regulator of Src kinases, Chk may play important roles in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. Chk is expressed in brain and hematopoietic cells. Like Csk, it is a cytoplasmic (or nonreceptor) tyr kinase containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. To inhibit Src kinases that are anchored to the plasma membrane, Chk is translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. Studies in mice reveal that Chk is not functionally redundant with Csk and that it plays an important role as a regulator of immune responses. Chk also plays a role in neural differentiation in a manner independent of Src by enhancing Mapk activation via Ras-mediated signaling. The Chk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270666 [Multi-domain] Cd Length: 254 Bit Score: 66.05 E-value: 5.28e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3339 QTVLQEYDILKSLHHEKIMALHeAYVTPRYLVLISECCSGKELLHSLIDRFRY--SEDDVVAYIVQILQGLDYLHSRRIL 3416
Cdd:cd05083     44 QAFLEETAVMTKLQHKNLVRLL-GVILHNGLYIVMELMSKGNLVNFLRSRGRAlvPVIQLLQFSLDVAEGMEYLESKKLV 122

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3417 HLDIKPENIIVTYMNVVKIIDFGSAQTfNPLFLKQFSPPIgtlDYMSPEMLKGDVVGPPADIWSIGILTYIMLS-GRLPF 3495
Cdd:cd05083    123 HRDLAARNILVSEDGVAKISDFGLAKV-GSMGVDNSRLPV---KWTAPEALKNKKFSSKSDVWSYGVLLWEVFSyGRAPY 198

Catalytic domain of the Dual-specificity protein kinase, CDC-like kinase 3; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. CLK3 is predominantly expressed in mature spermatozoa, and might play a role in the fertilization process. CLKs are involved in the phosphorylation and regulation of serine/arginine-rich (SR) proteins, which play a crucial role in pre-mRNA splicing by directing splice site selection. SR proteins are phosphorylated first by SR protein kinases (SRPKs) at the N-terminus, which leads to its assembly into nuclear speckles where splicing factors are stored. CLKs phosphorylate the C-terminal part of SR proteins, causing the nuclear speckles to dissolve and splicing factors to be recruited at sites of active transcription. Based on a conserved "EHLAMMERILG" signature motif which may be crucial for substrate specificity, CLKs are also referred to as LAMMER kinases. CLKs autophosphorylate at tyrosine residues and phosphorylate their substrates exclusively on serine/threonine residues. The CLK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271116 [Multi-domain] Cd Length: 331 Bit Score: 66.96 E-value: 5.61e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1651 ILRKMRRLTDYYDVHKEIGRGAFSYVKRVIQKA-GKLEYAAKFISARAKRKASALRELNILSHL---DHER---ILYFHD 1723
Cdd:cd14214      4 VCRIGDWLQERYEIVGDLGEGTFGKVVECLDHArGKSQVALKIIRNVGKYREAARLEINVLKKIkekDKENkflCVLMSD 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1724 AFEKKNAVIIITELCHEELLDRLtKKSTILE---SEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSD------ 1794
Cdd:cd14214     84 WFNFHGHMCIAFELLGKNTFEFL-KENNFQPyplPHIRHMAYQLCHALKFLHENQLTHTDLKPENILFVNSEFDtlynes 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1795 -----------QIRICDFGNAVkfMPDEAQYCKYGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRS 1863
Cdd:cd14214    163 ksceeksvkntSIRVADFGSAT--FDHEHHTTIVATRHYRPPEVILELGWAQPCDVWSLGCILFEYYRGFTLFQTHENRE 240


                   ....*
gi 1207186029 1864 SVLNI 1868
Cdd:cd14214    241 HLVMM 245

Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. VEGFR3 (or Flt4) preferentially binds the ligands VEGFC and VEGFD. VEGFR3 is essential for lymphatic endothelial cell (EC) development and function. It has been shown to regulate adaptive immunity during corneal transplantation. VEGFR3 is upregulated on blood vascular ECs in pathological conditions such as vascular tumors and the periphery of solid tumors. It plays a role in cancer progression and lymph node metastasis. Missense mutations in the VEGFR3 gene are associated with primary human lymphedema. VEGFR3 is a member of the VEGFR subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and an intracellular catalytic domain. In VEGFR3, the fifth Ig-like domain is replaced by a disulfide bridge. The binding of VEGFRs to their ligands, the VEGFs, leads to receptor dimerization, activation, and intracellular signaling. The VEGFR3 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270680 [Multi-domain] Cd Length: 336 Bit Score: 66.93 E-value: 5.98e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3394 DDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTF--NPLFLKQFSPPIgTLDYMSPEMLKGDV 3471
Cdd:cd05102    172 EDLICYSFQVARGMEFLASRKCIHRDLAARNILLSENNVVKICDFGLARDIykDPDYVRKGSARL-PLKWMAPESIFDKV 250

                           90       100
                   ....*....|....*....|....*
gi 1207186029 3472 VGPPADIWSIGILTYIMLS-GRLPF 3495
Cdd:cd05102    251 YTTQSDVWSFGVLLWEIFSlGASPY 275

Catalytic domain of the Dual-specificity protein kinases, CDC-like kinases 1 and 4; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. CLK1 plays a role in neuronal differentiation. CLKs are involved in the phosphorylation and regulation of serine/arginine-rich (SR) proteins, which play a crucial role in pre-mRNA splicing by directing splice site selection. SR proteins are phosphorylated first by SR protein kinases (SRPKs) at the N-terminus, which leads to its assembly into nuclear speckles where splicing factors are stored. CLKs phosphorylate the C-terminal part of SR proteins, causing the nuclear speckles to dissolve and splicing factors to be recruited at sites of active transcription. Based on a conserved "EHLAMMERILG" signature motif which may be crucial for substrate specificity, CLKs are also referred to as LAMMER kinases. CLKs autophosphorylate at tyrosine residues and phosphorylate their substrates exclusively on serine/threonine residues. The CLK1/4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271115 [Multi-domain] Cd Length: 330 Bit Score: 66.80 E-value: 5.98e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1658 LTDYYDVHKEIGRGAFSYVKRVI-QKAGKLEYAAKFISARAKRKASALRELNILSHLDHE------RILYFHDAFEKKNA 1730
Cdd:cd14213     10 LRARYEIVDTLGEGAFGKVVECIdHKMGGMHVAVKIVKNVDRYREAARSEIQVLEHLNTTdpnstfRCVQMLEWFDHHGH 89

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1731 VIIITELCHEELLDRLtKKSTILE---SEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSD------------- 1794
Cdd:cd14213     90 VCIVFELLGLSTYDFI-KENSFLPfpiDHIRNMAYQICKSVNFLHHNKLTHTDLKPENILFVQSDYVvkynpkmkrdert 168

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1207186029 1795 ----QIRICDFGNAVkfMPDEAQYCKYGTPEFVAPEIVNQTPVSKATDIWPIGVLT---YLCLT 1851
Cdd:cd14213    169 lknpDIKVVDFGSAT--YDDEHHSTLVSTRHYRAPEVILALGWSQPCDVWSIGCILieyYLGFT 230

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409405 [Multi-domain] Cd Length: 91 Bit Score: 61.36 E-value: 6.03e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1545 PTFETIMEDLDVNVGETPRFAVVVEGKPVPDILWYKGDTLLSE-SSHFTFVYDDNECSLVVLNTQADDSGVYTCTAKNLA 1623
Cdd:cd05744      1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPdSAHKMLVRENGRHSLIIEPVTKRDAGIYTCIARNRA 80

                           90
                   ....*....|.
gi 1207186029 1624 GSVSCKAELTV 1634
Cdd:cd05744     81 GENSFNAELVV 91

Catalytic domain of the Serine/Threonine Kinase, Fungal Mitogen-Activated Protein Kinase MPK1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the MAPKs MPK1 from Saccharomyces cerevisiae, Pmk1 from Schizosaccharomyces pombe, and similar proteins. MPK1 (also called Slt2) and Pmk1 (also called Spm1) are stress-activated MAPKs that regulate the cell wall integrity pathway, and are therefore important in the maintainance of cell shape, cell wall construction, morphogenesis, and ion homeostasis. MPK1 is activated in response to cell wall stress including heat stimulation, osmotic shock, UV irradiation, and any agents that interfere with cell wall biogenesis such as chitin antagonists, caffeine, or zymolase. MPK1 is regulated by the MAP2Ks Mkk1/2, which are regulated by the MAP3K Bck1. Pmk1 is also activated by multiple stresses including elevated temperatures, hyper- or hypotonic stress, glucose deprivation, exposure to cell-wall damaging compounds, and oxidative stress. It is regulated by the MAP2K Pek1, which is regulated by the MAP3K Mkh1. MAPKs are important mediators of cellular responses to extracellular signals. The MPK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173750 [Multi-domain] Cd Length: 332 Bit Score: 67.04 E-value: 6.07e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3399 YIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLKQ---FSPPIGTLDYMSPE-MLKGDVVGP 3474
Cdd:cd07857    110 FIYQILCGLKYIHSANVLHRDLKPGNLLVNADCELKICDFGLARGFSENPGENagfMTEYVATRWYRAPEiMLSFQSYTK 189

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3475 PADIWSIGILTYIMLSGRLPFTEND---------------PAETEARIQAAK-------------FDLSKLYQNVSQSAS 3526
Cdd:cd07857    190 AIDVWSVGCILAELLGRKPVFKGKDyvdqlnqilqvlgtpDEETLSRIGSPKaqnyirslpnipkKPFESIFPNANPLAL 269

                          170       180
                   ....*....|....*....|....*.
gi 1207186029 3527 LFIKKILCSYPWARPTIKDCFTNSWL 3552
Cdd:cd07857    270 DLLEKLLAFDPTKRISVEEALEHPYL 295

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase 15 and similar MAPKs; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Human MAPK15 is also called Extracellular signal Regulated Kinase 8 (ERK8) while the rat protein is called ERK7. ERK7 and ERK8 display both similar and different biochemical properties. They autophosphorylate and activate themselves and do not require upstream activating kinases. ERK7 is constitutively active and is not affected by extracellular stimuli whereas ERK8 shows low basal activity and is activated by DNA-damaging agents. ERK7 and ERK8 also have different substrate profiles. Genome analysis shows that they are orthologs with similar gene structures. ERK7 and ERK 8 may be involved in the signaling of some nuclear receptor transcription factors. ERK7 regulates hormone-dependent degradation of estrogen receptor alpha while ERK8 down-regulates the transcriptional co-activation androgen and glucocorticoid receptors. MAPKs are important mediators of cellular responses to extracellular signals. The MAPK15 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270841 [Multi-domain] Cd Length: 337 Bit Score: 66.81 E-value: 6.75e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3382 LHSLIdRFRYSEDDVVAYIV-QILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFlKQFSPPIGTlD 3460
Cdd:cd07852     95 LHAVI-RANILEDIHKQYIMyQLLKALKYLHSGGVIHRDLKPSNILLNSDCRVKLADFGLARSLSQLE-EDDENPVLT-D 171

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3461 YM------SPEMLkgdvVGPPA-----DIWSIGILTYIMLSGR---------------LPFTENDPAETEARIQAA---- 3510
Cdd:cd07852    172 YVatrwyrAPEIL----LGSTRytkgvDMWSVGCILGEMLLGKplfpgtstlnqlekiIEVIGRPSAEDIESIQSPfaat 247

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1207186029 3511 ---------KFDLSKLYQNVSQSASLFIKKILCSYPWARPTIKDCFTNSWLQD 3554
Cdd:cd07852    248 mleslppsrPKSLDELFPKASPDALDLLKKLLVFNPNKRLTAEEALRHPYVAQ 300

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409565 [Multi-domain] Cd Length: 88 Bit Score: 61.05 E-value: 6.83e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  934 IGDQSVIEGQEVTMSVLVTGQPKPMLYWLRDRVTIKTGTRHIVQETEEGNFEMIIKSAQRSDTGVYTCKIINEYGTKQCE 1013
Cdd:cd20973      4 LRDKEVVEGSAARFDCKVEGYPDPEVKWMKDDNPIVESRRFQIDQDEDGLCSLIISDVCGDDSGKYTCKAVNSLGEATCS 83


                   ....*
gi 1207186029 1014 GKLEV 1018
Cdd:cd20973     84 AELTV 88

C-terminal immunoglobulin (Ig)-like domain of M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of M-protein (also known as myomesin-2). M-protein is a structural protein localized to the M-band, a transverse structure in the center of the sarcomere, and is a candidate for M-band bridges. M-protein is modular consisting mainly of repetitive IG-like and fibronectin type III (FnIII) domains and has a muscle-type specific expression pattern. M-protein is present in fast fibers.

Pssm-ID: 143299 Cd Length: 92 Bit Score: 61.08 E-value: 7.07e-11

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1207186029 1130 DVLEVIEGRNARFDCKVSGTPPPQVIWSHFDRPLEENEDIRILKEGGRH-SLIISHVSNEDEGLYTVAARNSHG 1202
Cdd:cd05891      9 DVVTIMEGKTLNLTCTVFGNPDPEVIWFKNDQDIELSEHYSVKLEQGKYaSLTIKGVTSEDSGKYSINVKNKYG 82

glycogen synthase kinase; Provisional

Pssm-ID: 173333 [Multi-domain] Cd Length: 440 Bit Score: 67.75 E-value: 7.53e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3296 PQKPYTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPESKQtvlQEYDILKSLHHEKIMALHEAYVTprylvlisEC 3375
Cdd:PTZ00036    64 PNKSYKLGNIIGNGSFGVVYEAICIDTSEKVAIKKVLQDPQYKN---RELLIMKNLNHINIIFLKDYYYT--------EC 132

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3376 C--SGKELLHSLIDRF----------RYSEDD-------VVAYIVQILQGLDYLHSRRILHLDIKPENIIVT-YMNVVKI 3435
Cdd:PTZ00036   133 FkkNEKNIFLNVVMEFipqtvhkymkHYARNNhalplflVKLYSYQLCRALAYIHSKFICHRDLKPQNLLIDpNTHTLKL 212

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1207186029 3436 IDFGSAQtfNPLFLKQFSPPIGTLDYMSPEMLKGDV-VGPPADIWSIG------ILTYIMLSGR 3492
Cdd:PTZ00036   213 CDFGSAK--NLLAGQRSVSYICSRFYRAPELMLGATnYTTHIDLWSLGciiaemILGYPIFSGQ 274

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MEK1 and MEK2 are MAPK kinases (MAPKKs or MKKs), and are dual-specificity PKs that phosphorylate and activate the downstream targets, ERK1 and ERK2, on specific threonine and tyrosine residues. The ERK cascade starts with extracellular signals including growth factors, hormones, and neurotransmitters, which act through receptors and ion channels to initiate intracellular signaling that leads to the activation at the MAPKKK (Raf-1 or MOS) level, which leads to the transmission of signals to MEK1/2, and finally to ERK1/2. The ERK cascade plays an important role in cell proliferation, differentiation, oncogenic transformation, and cell cycle control, as well as in apoptosis and cell survival under certain conditions. This cascade has also been implicated in synaptic plasticity, migration, morphological determination, and stress response immunological reactions. Gain-of-function mutations in genes encoding ERK cascade proteins, including MEK1/2, cause cardiofaciocutaneous (CFC) syndrome, a condition leading to multiple congenital anomalies and mental retardation in patients. The MEK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 132946 [Multi-domain] Cd Length: 308 Bit Score: 66.31 E-value: 7.55e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1666 KEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKR--KASALRELNILSHLDHERILYFHDAFEKKNAVIIITELCHEELL 1743
Cdd:cd06615      7 GELGAGNGGVVTKVLHRPSGLIMARKLIHLEIKPaiRNQIIRELKVLHECNSPYIVGFYGAFYSDGEISICMEHMDGGSL 86

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1744 DRLTKKSTILESEIRSSVR-QLLEGINYLHQ-LDILHLDIKPDNILMadHSSDQIRICDFGNAVKFMpDEAQYCKYGTPE 1821
Cdd:cd06615     87 DQVLKKAGRIPENILGKISiAVLRGLTYLREkHKIMHRDVKPSNILV--NSRGEIKLCDFGVSGQLI-DSMANSFVGTRS 163

                          170       180       190
                   ....*....|....*....|....*....|....*....
gi 1207186029 1822 FVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGEN 1860
Cdd:cd06615    164 YMSPERLQGTHYTVQSDIWSLGLSLVEMAIGRYPIPPPD 202

Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Human TAO2 is also known as prostate-derived Ste20-like kinase (PSK) and was identified in a screen for overexpressed RNAs in prostate cancer. TAO2 possesses mitogen-activated protein kinase (MAPK) kinase kinase activity and activates both p38 and c-Jun N-terminal kinase (JNK), by phosphorylating and activating their respective MAP/ERK kinases, MEK3/MEK6 and MKK4/MKK7. It contains a long C-terminal extension with autoinhibitory segments, and is activated by the release of this inhibition and the phosphorylation of its activation loop serine. TAO2 functions as a regulator of actin cytoskeletal and microtubule organization. In addition, it regulates the transforming growth factor-activated kinase 1 (TAK1), which is a MAPKKK that plays an essential role in the signaling pathways of tumor necrosis factor, interleukin 1, and Toll-like receptor. The TAO2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270804 [Multi-domain] Cd Length: 308 Bit Score: 66.20 E-value: 7.60e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1666 KEIGRGAFS--YVKRVIQKA-----GKLEYAAKfisARAKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITELC 1738
Cdd:cd06634     21 REIGHGSFGavYFARDVRNNevvaiKKMSYSGK---QSNEKWQDIIKEVKFLQKLRHPNTIEYRGCYLREHTAWLVMEYC 97

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1739 HEELLDRL-TKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADhsSDQIRICDFGNAVKFMPDEAqycKY 1817
Cdd:cd06634     98 LGSASDLLeVHKKPLQEVEIAAITHGALQGLAYLHSHNMIHRDVKAGNILLTE--PGLVKLGDFGSASIMAPANS---FV 172

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1818 GTPEFVAPEIV---NQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNI-RNYNVAFEESMFTDLCHEAKGFVIK 1893
Cdd:cd06634    173 GTPYWMAPEVIlamDEGQYDGKVDVWSLGITCIELAERKPPLFNMNAMSALYHIaQNESPALQSGHWSEYFRNFVDSCLQ 252

                          250
                   ....*....|....*..
gi 1207186029 1894 LLVADrlRPDANECLRH 1910
Cdd:cd06634    253 KIPQD--RPTSDVLLKH 267

Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LIMK1 activation is induced by bone morphogenic protein, vascular endothelial growth factor, and thrombin. It plays roles in microtubule disassembly and cell cycle progression, and is critical in the regulation of neurite outgrowth. LIMK1 knockout mice show abnormalities in dendritic spine morphology and synaptic function. LIMK1 is one of the genes deleted in patients with Williams Syndrome, which is characterized by distinct craniofacial features, cardiovascular problems, as well as behavioral and neurological abnormalities. LIMKs phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They act downstream of Rho GTPases and are expressed ubiquitously. As regulators of actin dynamics, they contribute to diverse cellular functions such as cell motility, morphogenesis, differentiation, apoptosis, meiosis, mitosis, and neurite extension. LIMKs contain the LIM (two repeats), PDZ, and catalytic kinase domains. The LIMK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271123 [Multi-domain] Cd Length: 267 Bit Score: 65.36 E-value: 8.99e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGN-LYMAKIVPYEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSG---KELLH 3383
Cdd:cd14221      3 KGCFGQAIKVTHRETGEvMVMKELIRFDEETQRTFLKEVKVMRCLEHPNVLKFIGVLYKDKRLNFITEYIKGgtlRGIIK 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3384 SLIDRFRYSEDdvVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSA-----QTFNPLFLKQFSPP--- 3455
Cdd:cd14221     83 SMDSHYPWSQR--VSFAKDIASGMAYLHSMNIIHRDLNSHNCLVRENKSVVVADFGLArlmvdEKTQPEGLRSLKKPdrk 160

                          170       180       190
                   ....*....|....*....|....*....|....
gi 1207186029 3456 -----IGTLDYMSPEMLKGDVVGPPADIWSIGIL 3484
Cdd:cd14221    161 krytvVGNPYWMAPEMINGRSYDEKVDVFSFGIV 194

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK3, also called beta-adrenergic receptor kinase 2 (beta-ARK2), is widely expressed in many tissues. It is involved in modulating the cholinergic response of airway smooth muscles, and also plays a role in dopamine receptor regulation. GRK3-deficient mice show a lack of olfactory receptor desensitization and altered regulation of the M2 muscarinic airway. GRK3 promoter polymorphisms may also be associated with bipolar disorder. GRK3 contains an N-terminal RGS homology (RH) domain, a central catalytic domain, and C-terminal pleckstrin homology (PH) domain that mediates PIP2 and G protein betagamma-subunit translocation to the membrane. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270781 [Multi-domain] Cd Length: 346 Bit Score: 66.62 E-value: 9.11e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFI-SARAKRKAS---ALRE---LNILSHLDHERILYFHDAFEKKNAVIII 1734
Cdd:cd05633      7 FSVHRIIGRGGFGEVYGCRKADTGKMYAMKCLdKKRIKMKQGetlALNErimLSLVSTGDCPFIVCMTYAFHTPDKLCFI 86

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1735 TELCHE-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSsdQIRICDFGNAVKFmPDEAQ 1813
Cdd:cd05633     87 LDLMNGgDLHYHLSQHGVFSEKEMRFYATEIILGLEHMHNRFVVYRDLKPANILLDEHG--HVRISDLGLACDF-SKKKP 163

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....
gi 1207186029 1814 YCKYGTPEFVAPEIVNQ-TPVSKATDIWPIGVLTYLCLTGVSPF 1856
Cdd:cd05633    164 HASVGTHGYMAPEVLQKgTAYDSSADWFSLGCMLFKLLRGHSPF 207

Catalytic domain of the Serine/Threonine Kinases, Raf (Rapidly Accelerated Fibrosarcoma) kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Raf kinases act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. They function in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. Aberrant expression or activation of components in this pathway are associated with tumor initiation, progression, and metastasis. Raf proteins contain a Ras binding domain, a zinc finger cysteine-rich domain, and a catalytic kinase domain. Vertebrates have three Raf isoforms (A-, B-, and C-Raf) with different expression profiles, modes of regulation, and abilities to function in the ERK cascade, depending on cellular context and stimuli. They have essential and non-overlapping roles during embryo- and organogenesis. Knockout of each isoform results in a lethal phenotype or abnormality in most mouse strains. The Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270964 [Multi-domain] Cd Length: 253 Bit Score: 65.11 E-value: 9.16e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1706 ELNILSHLDHERILYFHdAFEKKNAVIIITELC-------HEELLDRLTKKSTILESeirssVRQLLEGINYLHQLDILH 1778
Cdd:cd14062     39 EVAVLRKTRHVNILLFM-GYMTKPQLAIVTQWCegsslykHLHVLETKFEMLQLIDI-----ARQTAQGMDYLHAKNIIH 112

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1779 LDIKPDNILMadHSSDQIRICDFGNA-VKFMPDEAQYCKY--GTPEFVAPEIV---NQTPVSKATDIWPIGVLTYLCLTG 1852
Cdd:cd14062    113 RDLKSNNIFL--HEDLTVKIGDFGLAtVKTRWSGSQQFEQptGSILWMAPEVIrmqDENPYSFQSDVYAFGIVLYELLTG 190

                          170
                   ....*....|....
gi 1207186029 1853 VSPFAGENDRSSVL 1866
Cdd:cd14062    191 QLPYSHINNRDQIL 204

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409565 [Multi-domain] Cd Length: 88 Bit Score: 60.67 E-value: 9.61e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  786 PLQDTVASTGTEVLLKCIISGTPLPEVIWKKDNTEVKNSPTHVVKIEGERH-SLLIKWTKPSDAGTYTVTAVNEVGEVSS 864
Cdd:cd20973      3 TLRDKEVVEGSAARFDCKVEGYPDPEVKWMKDDNPIVESRRFQIDQDEDGLcSLIISDVCGDDSGKYTCKAVNSLGEATC 82


                   ....*.
gi 1207186029  865 SATLFI 870
Cdd:cd20973     83 SAELTV 88

Immunoglobulin (Ig)-like domain of myotilin, palladin, and myopalladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the immunoglobulin (Ig)-like domain in myotilin, palladin, and myopalladin. Myotilin, palladin, and myopalladin function as scaffolds that regulate actin organization. Myotilin and myopalladin are most abundant in skeletal and cardiac muscle; palladin is ubiquitously expressed in the organs of developing vertebrates and plays a key role in cellular morphogenesis. The three family members each interact with specific molecular partners with all three binding to alpha-actinin; In addition, palladin also binds to vasodilator-stimulated phosphoprotein (VASP) and ezrin, myotilin binds to filamin and actin, and myopalladin also binds to nebulin and cardiac ankyrin repeat protein (CARP). This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409405 [Multi-domain] Cd Length: 91 Bit Score: 60.59 E-value: 9.81e-11

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029   55 PVFIRKMRNAAVGTGCDIRLKVAVAGDPQPTLYWYHNDDLVNMDN------QEYG--GLWIRDCKPSDAGLYTCIATNHL 126
Cdd:cd05744      1 PHFLQAPGDLEVQEGRLCRFDCKVSGLPTPDLFWQLNGKPVRPDSahkmlvRENGrhSLIIEPVTKRDAGIYTCIARNRA 80

                           90
                   ....*....|.
gi 1207186029  127 GEARSSAVLAV 137
Cdd:cd05744     81 GENSFNAELVV 91

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 60.49 E-value: 1.00e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1553 DLDVNVGETPRFAVVVEGKPVPDILWYKGDTLLSESShfTFVYDDNecSLVVLNTQADDSGVYTCTAKNLAGSVSCKAEL 1632
Cdd:cd05725      6 NQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGELPKGR--YEILDDH--SLKIRKVTAGDMGSYTCVAENMVGKIEASATL 81


                   ..
gi 1207186029 1633 TV 1634
Cdd:cd05725     82 TV 83

Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNK3 shows a restricted expression pattern; it is found at high levels in the pituary glands and is also expressed in the kidney and brain. It has been shown to regulate many ion transporters including members of the SLC12A family of cation-chloride cotransporters such as NCC and NKCC2, the renal potassium channel ROMK, and the epithelial calcium channels TRPV5 and TRPV6. WNK3 appears to sense low-chloride hypotonic stress and under these conditions, it activates SPAK, which directly interacts and phosphorylates cation-chloride cotransporters. WNK3 has also been shown to promote cell survival, possibly through interaction with procaspase-3 and HSP70. WNKs comprise a subfamily of STKs with an unusual placement of the catalytic lysine relative to all other protein kinases. The WNK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270933 [Multi-domain] Cd Length: 275 Bit Score: 65.51 E-value: 1.02e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3338 KQTVLQEYDILKSLHHEKIMALHEAYVT----PRYLVLISECCSGKELlHSLIDRFRYSEDDVV-AYIVQILQGLDYLHS 3412
Cdd:cd14031     53 QQRFKEEAEMLKGLQHPNIVRFYDSWESvlkgKKCIVLVTELMTSGTL-KTYLKRFKVMKPKVLrSWCRQILKGLQFLHT 131

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3413 RR--ILHLDIKPENIIVT-YMNVVKIIDFGSAQTFNPLFLKQFsppIGTLDYMSPEMLKgDVVGPPADIWSIGILTYIML 3489
Cdd:cd14031    132 RTppIIHRDLKCDNIFITgPTGSVKIGDLGLATLMRTSFAKSV---IGTPEFMAPEMYE-EHYDESVDVYAFGMCMLEMA 207


                   ....*...
gi 1207186029 3490 SGRLPFTE 3497
Cdd:cd14031    208 TSEYPYSE 215

Catalytic domain of the Dual-specificity protein kinase, Lymphokine-activated killer T-cell-originated protein kinase; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TOPK, also called PDZ-binding kinase (PBK), is activated at the early stage of mitosis and plays a critical role in cytokinesis. It partly functions as a mitogen-activated protein kinase (MAPK) kinase and is capable of phosphorylating p38, JNK1, and ERK2. TOPK also plays a role in DNA damage sensing and repair through its phosphorylation of histone H2AX. It contributes to cancer development and progression by downregulating the function of tumor suppressor p53 and reducing cell-cycle regulatory proteins. TOPK is found highly expressed in breast and skin cancer cells. The TOPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270903 [Multi-domain] Cd Length: 292 Bit Score: 65.50 E-value: 1.06e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1676 VKRVIQKAGKlEYAAKFISaRAKRKASALRELNilshldHERILYFHdAFEKKNA--VIIITELCHEELLDRLTKKSTIL 1753
Cdd:cd14001     33 VKKINSKCDK-GQRSLYQE-RLKEEAKILKSLN------HPNIVGFR-AFTKSEDgsLCLAMEYGGKSLNDLIEERYEAG 103

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1754 E-----SEIRSSVRQLLEGINYLHQ-LDILHLDIKPDNILM-ADHSSdqIRICDFGNAVKFMPD-------EAQYCkyGT 1819
Cdd:cd14001    104 LgpfpaATILKVALSIARALEYLHNeKKILHGDIKSGNVLIkGDFES--VKLCDFGVSLPLTENlevdsdpKAQYV--GT 179

                          170       180       190
                   ....*....|....*....|....*....|....*..
gi 1207186029 1820 PEFVAPEIVNQ-TPVSKATDIWPIGVLTYLCLTGVSP 1855
Cdd:cd14001    180 EPWKAKEALEEgGVITDKADIFAYGLVLWEMMTLSVP 216

Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tyk2 is widely expressed in many tissues. It is involved in signaling via the cytokine receptors IFN-alphabeta, IL-6, IL-10, IL-12, IL-13, and IL-23. It mediates cell surface urokinase receptor (uPAR) signaling and plays a role in modulating vascular smooth muscle cell (VSMC) functional behavior in response to injury. Tyk2 is also important in dendritic cell function and T helper (Th)1 cell differentiation. A homozygous mutation of Tyk2 was found in a patient with hyper-IgE syndrome (HIES), a primary immunodeficiency characterized by recurrent skin abscesses, pneumonia, and elevated serum IgE. This suggests that Tyk2 may play important roles in multiple cytokine signaling involved in innate and adaptive immunity. Tyk2 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase catalytic domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The Tyk2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270664 [Multi-domain] Cd Length: 283 Bit Score: 65.31 E-value: 1.16e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3309 GRFG-VIRECRE---NATGNLYMAKIVPYE--PESKQTVLQEYDILKSLHHEKImalheayvtprylVLISECCS---GK 3379
Cdd:cd05080     15 GHFGkVSLYCYDptnDGTGEMVAVKALKADcgPQHRSGWKQEIDILKTLYHENI-------------VKYKGCCSeqgGK 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3380 EL--------LHSLID---RFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTF---- 3444
Cdd:cd05080     82 SLqlimeyvpLGSLRDylpKHSIGLAQLLLFAQQICEGMAYLHSQHYIHRDLAARNVLLDNDRLVKIGDFGLAKAVpegh 161

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1207186029 3445 ----------NPLFlkqfsppigtldYMSPEMLKGDVVGPPADIWSIGILTYIMLS 3490
Cdd:cd05080    162 eyyrvredgdSPVF------------WYAPECLKEYKFYYASDVWSFGVTLYELLT 205

Pseudokinase domain of Tribbles Homolog proteins; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. Tribbles Homolog (TRB) proteins interact with many proteins involved in signaling pathways. They play scaffold-like regulatory functions and affect many cellular processes such as mitosis, apoptosis, differentiation, and gene expression. TRB proteins bind to the middle kinase in mitogen activated protein kinase (MAPK) signaling cascades, MAPK kinases. They regulate the activity of MAPK kinases, and thus, affect MAPK signaling. In Drosophila, Tribbles regulates String, the ortholog of mammalian Cdc25, during morphogenesis. String is implicated in the progression of mitosis during embryonic development. Vertebrates contain three TRB proteins encoded by three separate genes: Tribbles-1 (TRB1 or TRIB1), Tribbles-2 (TRB2 or TRIB2), and Tribbles-3 (TRB3 or TRIB3). The TRB subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270878 [Multi-domain] Cd Length: 242 Bit Score: 64.76 E-value: 1.16e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1754 ESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSDQIRICDFGNAVKFM-PDEAQYCKYGTPEFVAPEIVN--Q 1830
Cdd:cd13976     83 EPEAARLFRQIASAVAHCHRNGIVLRDLKLRKFVFADEERTKLRLESLEDAVILEgEDDSLSDKHGCPAYVSPEILNsgA 162

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1831 TPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESmftdLCHEAKGFVIKLLVAD-RLRPDANECLR 1909
Cdd:cd13976    163 TYSGKAADVWSLGVILYTMLVGRYPFHDSEPASLFAKIRRGQFAIPET----LSPRARCLIRSLLRREpSERLTAEDILL 238


                   ....
gi 1207186029 1910 HPWF 1913
Cdd:cd13976    239 HPWL 242

Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409548 [Multi-domain] Cd Length: 96 Bit Score: 60.65 E-value: 1.25e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  780 APVFEFPLQDTVASTGTEVLLKCIISGTPLPEVIWKKDNTEVKNSP----THVVKIEGERHSLL-IKWTKPSDAGTYTVT 854
Cdd:cd20956      1 APVLLETFSEQTLQPGPSVSLKCVASGNPLPQITWTLDGFPIPESPrfrvGDYVTSDGDVVSYVnISSVRVEDGGEYTCT 80

                           90
                   ....*....|....
gi 1207186029  855 AVNEVGEVSSSATL 868
Cdd:cd20956     81 ATNDVGSVSHSARI 94

N-terminal Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 and 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. MAP4K4 is also called Nck Interacting kinase (NIK). It facilitates the activation of the MAPKs, extracellular signal-regulated kinase (ERK) 1, ERK2, and c-Jun N-terminal kinase (JNK), by phosphorylating and activating MEKK1. MAP4K4 plays a role in tumor necrosis factor (TNF) alpha-induced insulin resistance. MAP4K4 silencing in skeletal muscle cells from type II diabetic patients restores insulin-mediated glucose uptake. MAP4K4, through JNK, also plays a broad role in cell motility, which impacts inflammation, homeostasis, as well as the invasion and spread of cancer. MAP4K4 is found to be highly expressed in most tumor cell lines relative to normal tissue. MAP4K6 (also called MINK for Misshapen/NIKs-related kinase) is activated after Ras induction and mediates activation of p38 MAPK. MAP4K6 plays a role in cell cycle arrest, cytoskeleton organization, cell adhesion, and cell motility. The MAP4K4/6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270806 [Multi-domain] Cd Length: 282 Bit Score: 65.41 E-value: 1.26e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1652 LRKMRRLTDYYDVHKEIGRGAFSYV-KRVIQKAGKLEyAAKFISARAKRKASALRELNILSHLDHER-ILYFHDAFEKK- 1728
Cdd:cd06636      8 LSALRDPAGIFELVEVVGNGTYGQVyKGRHVKTGQLA-AIKVMDVTEDEEEEIKLEINMLKKYSHHRnIATYYGAFIKKs 86

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1729 -----NAVIIITELCHEELLDRL---TKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSsdQIRICD 1800
Cdd:cd06636     87 ppghdDQLWLVMEFCGAGSVTDLvknTKGNALKEDWIAYICREILRGLAHLHAHKVIHRDIKGQNVLLTENA--EVKLVD 164

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1801 FGNAVKFMPDEAQYCKY-GTPEFVAPEIV--NQTPVSK---ATDIWPIGVLTYLCLTGVSPFAGEND-RSSVLNIRNYNV 1873
Cdd:cd06636    165 FGVSAQLDRTVGRRNTFiGTPYWMAPEVIacDENPDATydyRSDIWSLGITAIEMAEGAPPLCDMHPmRALFLIPRNPPP 244

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|
gi 1207186029 1874 AFEESMFTdlcHEAKGFVIKLLVADRL-RPDANECLRHPW 1912
Cdd:cd06636    245 KLKSKKWS---KKFIDFIEGCLVKNYLsRPSTEQLLKHPF 281

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 60.20 E-value: 1.27e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029   63 NAAVGTGCDIRLKVAVAGDPQPTLYWYHNDDLVNMDN-----QEYGGLWIRDCKPSDAGLYTCIATNHLGEARSSAVLAV 137
Cdd:cd20952      8 NQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLLGKDerittLENGSLQIKGAEKSDTGEYTCVALNLSGEATWSAVLDV 87

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNK3 is expressed primarily in the brain, and to a lesser extent in the heart and testis. Mice deficient in JNK3 are protected against kainic acid-induced seizures, stroke, sciatic axotomy neural death, and neuronal death due to NGF deprivation, oxidative stress, or exposure to beta-amyloid peptide. This suggests that JNK3 may play roles in the pathogenesis of these diseases. JNKs are mitogen-activated protein kinases (MAPKs) that are involved in many stress-activated responses including those during inflammation, neurodegeneration, apoptosis, and persistent pain sensitization, among others. The JNK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143379 [Multi-domain] Cd Length: 355 Bit Score: 66.27 E-value: 1.36e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3332 PYEPESK-QTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLHSLIDRFRYSEDD--VVAYIV-QILQGL 3407
Cdd:cd07874     53 PFQNQTHaKRAYRELVLMKCVNHKNIISLLNVFTPQKSLEEFQDVYLVMELMDANLCQVIQMELDheRMSYLLyQMLCGI 132

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3408 DYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLkqFSPPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYI 3487
Cdd:cd07874    133 KHLHSAGIIHRDLKPSNIVVKSDCTLKILDFGLARTAGTSFM--MTPYVVTRYYRAPEVILGMGYKENVDIWSVGCIMGE 210

                          170
                   ....*....|..
gi 1207186029 3488 MLSGRLPFTEND 3499
Cdd:cd07874    211 MVRHKILFPGRD 222

Catalytic domain of the dual-specificity Protein Kinases, Mitogen-activated protein Kinase Kinases 3 and 6; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK3 and MKK6 are dual-specificity PKs that phosphorylate and activate their downstream target, p38 MAPK, on specific threonine and tyrosine residues. MKK3/6 play roles in the regulation of cell cycle progression, cytokine- and stress-induced apoptosis, oncogenic transformation, and adult tissue regeneration. In addition, MKK6 plays a critical role in osteoclast survival in inflammatory disease while MKK3 is associated with tumor invasion, progression, and poor patient survival in glioma. The MKK3/6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173729 [Multi-domain] Cd Length: 283 Bit Score: 65.14 E-value: 1.41e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3301 TFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPESKQ--TVLQEYDI-LKSLHHekimalheAYVTPRYLVLISE--- 3374
Cdd:cd06617      4 EVIEELGRGAYGVVDKMRHVPTGTIMAVKRIRATVNSQEqkRLLMDLDIsMRSVDC--------PYTVTFYGALFREgdv 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3375 --CcsgKELLHSLIDRF--------RYSEDDVVAYI-VQILQGLDYLHSR-RILHLDIKPENIIVTYMNVVKIIDFG-SA 3441
Cdd:cd06617     76 wiC---MEVMDTSLDKFykkvydkgLTIPEDILGKIaVSIVKALEYLHSKlSVIHRDVKPSNVLINRNGQVKLCDFGiSG 152

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1207186029 3442 QTFNPLFLKQfspPIGTLDYMSPEMLKGDVVGP----PADIWSIGILTYIMLSGRLPFT 3496
Cdd:cd06617    153 YLVDSVAKTI---DAGCKPYMAPERINPELNQKgydvKSDVWSLGITMIELATGRFPYD 208

Catalytic domain of the Serine/Threonine Kinase, Microtubule-associated serine/threonine-like kinase (also called greatwall kinase); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The MASTL kinases in this group carry only a catalytic domain, which contains a long insertion relative to MAST kinases. MASTL, also called greatwall kinase (Gwl), is involved in the regulation of mitotic entry, which is controlled by the coordinated activities of protein kinases and opposing protein phosphatases (PPs). The cyclin B/CDK1 complex induces entry into M-phase while PP2A-B55 shows anti-mitotic activity. MASTL/Gwl is activated downstream of cyclin B/CDK1 and indirectly inhibits PP2A-B55 by phosphorylating the small protein alpha-endosulfine (Ensa) or the cAMP-regulated phosphoprotein 19 (Arpp19), resulting in M-phase progression. Gwl kinase may also play roles in mRNA stabilization and DNA checkpoint recovery. The human MASTL gene has also been named FLJ14813; a missense mutation in FLJ14813 is associated with autosomal dominant thrombocytopenia. The MASTL kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270761 [Multi-domain] Cd Length: 349 Bit Score: 66.06 E-value: 1.54e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1666 KEIGRGAFSYVKRVIQKAGKLEYAAKFI------------SARAKRKASALRELNILSHLdherilyFHDAFEKKNAVII 1733
Cdd:cd05610     10 KPISRGAFGKVYLGRKKNNSKLYAVKVVkkadminknmvhQVQAERDALALSKSPFIVHL-------YYSLQSANNVYLV 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1734 ITELCHEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMAdhSSDQIRICDFG----------- 1802
Cdd:cd05610     83 MEYLIGGDVKSLLHIYGYFDEEMAVKYISEVALALDYLHRHGIIHRDLKPDNMLIS--NEGHIKLTDFGlskvtlnreln 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1803 -----NAVKFMPDEAQYCK--------------------------------------YGTPEFVAPEIVNQTPVSKATDI 1839
Cdd:cd05610    161 mmdilTTPSMAKPKNDYSRtpgqvlslisslgfntptpyrtpksvrrgaarvegeriLGTPDYLAPELLLGKPHGPAVDW 240

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1207186029 1840 WPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESMfTDLCHEAKGFVIKLLVADRL-RPDANECLRHPWF 1913
Cdd:cd05610    241 WALGVCLFEFLTGIPPFNDETPQQVFQNILNRDIPWPEGE-EELSVNAQNAIEILLTMDPTkRAGLKELKQHPLF 314

Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jak2 is widely expressed in many tissues and is essential for the signaling of hormone-like cytokines such as growth hormone, erythropoietin, thrombopoietin, and prolactin, as well as some IFNs and cytokines that signal through the IL-3 and gp130 receptors. Disruption of Jak2 in mice results in an embryonic lethal phenotype with multiple defects including erythropoietic and cardiac abnormalities. It is the only Jak gene that results in a lethal phenotype when disrupted in mice. A mutation in the pseudokinase domain of Jak2, V617F, is present in many myeloproliferative diseases, including almost all patients with polycythemia vera, and 50% of patients with essential thrombocytosis and myelofibrosis. Jak2 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal catalytic tyr kinase domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271107 [Multi-domain] Cd Length: 284 Bit Score: 65.04 E-value: 1.54e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1705 RELNILSHLDHERILYFHD---AFEKKNAVIIITELCHEELLDRLTK-KSTILESEIRSSVRQLLEGINYLHQLDILHLD 1780
Cdd:cd14205     54 REIEILKSLQHDNIVKYKGvcySAGRRNLRLIMEYLPYGSLRDYLQKhKERIDHIKLLQYTSQICKGMEYLGTKRYIHRD 133

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1207186029 1781 IKPDNILMadHSSDQIRICDFGnAVKFMPDEAQYCKYGTPE-----FVAPEIVNQTPVSKATDIWPIGVLTYLCLT 1851
Cdd:cd14205    134 LATRNILV--ENENRVKIGDFG-LTKVLPQDKEYYKVKEPGespifWYAPESLTESKFSVASDVWSFGVVLYELFT 206

C5 immunoglobulin (Ig) domain of cardiac myosin binding protein C (MyBP-C); The members here are composed of the C5 immunoglobulin (Ig) domain of cardiac myosin binding protein C (MyBP-C). MyBP-C consists of repeated domains, Ig and fibronectin type 3, and various linkers. Three isoforms of MYBP-C exist: slow-skeletal (ssMyBP-C), fast-skeletal (fsMyBP-C), and cardiac (cMyBP-C). cMYBP-C has insertions between and inside domains and an additional cardiac-specific Ig domain at the N-terminus. For cMYBP_C an interaction has been demonstrated between this C5 domain and the Ig C8 domain.

Pssm-ID: 409475 Cd Length: 86 Bit Score: 59.85 E-value: 1.57e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1130 DVLEVIEGRNARFDCKVSGTPPPQVIWSHFDRPLEENED-IRILKEGGRHSLIISHVSNEDEGLYTVAARNSHGEDEcaA 1208
Cdd:cd05894      3 NTIVVVAGNKLRLDVPISGEPAPTVTWSRGDKAFTATEGrVRVESYKDLSSFVIEGAEREDEGVYTITVTNPVGEDH--A 80


                   ....*
gi 1207186029 1209 ELYVQ 1213
Cdd:cd05894     81 SLFVK 85

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNK1 is expressed in every cell and tissue type. It specifically binds with JAMP (JNK1-associated membrane protein), which regulates the duration of JNK1 activity in response to stimuli. Specific JNK1 substrates include Itch and SG10, which are implicated in Th2 responses and airway inflammation, and microtubule dynamics and axodendritic length, respectively. Mice deficient in JNK1 are protected against arthritis, obesity, type 2 diabetes, cardiac cell death, and non-alcoholic liver disease, suggesting that JNK1 may play roles in the pathogenesis of these diseases. Initially, it was thought that JNK1 and JNK2 were functionally redundant as mice deficient in either genes could survive but disruption of both genes resulted in lethality. However, recent studies have shown that JNK1 and JNK2 perform distinct functions through specific binding partners and substrates. JNKs are mitogen-activated protein kinases that are involved in many stress-activated responses including those during inflammation, neurodegeneration, apoptosis, and persistent pain sensitization, among others. The JNK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143380 [Multi-domain] Cd Length: 364 Bit Score: 65.84 E-value: 1.69e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3343 QEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLHSLIDRFRYSEDD--VVAYIV-QILQGLDYLHSRRILHLD 3419
Cdd:cd07875     72 RELVLMKCVNHKNIIGLLNVFTPQKSLEEFQDVYIVMELMDANLCQVIQMELDheRMSYLLyQMLCGIKHLHSAGIIHRD 151

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3420 IKPENIIVTYMNVVKIIDFGSAQTFNPLFLkqFSPPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTEND 3499
Cdd:cd07875    152 LKPSNIVVKSDCTLKILDFGLARTAGTSFM--MTPYVVTRYYRAPEVILGMGYKENVDIWSVGCIMGEMIKGGVLFPGTD 229

Catalytic domain of the Serine/Threonine Kinase, p38delta Mitogen-Activated Protein Kinase (also called MAPK13); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38delta/MAPK13 is found in skeletal muscle, heart, lung, testis, pancreas, and small intestine. It regulates microtubule function by phosphorylating Tau. It activates the c-jun promoter and plays a role in G2 cell cycle arrest. It also controls the degration of c-Myb, which is associated with myeloid leukemia and poor prognosis in colorectal cancer. p38delta is the main isoform involved in regulating the differentiation and apoptosis of keratinocytes. p38 kinases are MAPKs, serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38delta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143384 [Multi-domain] Cd Length: 342 Bit Score: 65.69 E-value: 1.72e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISAR------AKRkasALRELNILSHLDHERILYFHDAFEKKNAVIIIT 1735
Cdd:cd07879     17 YTSLKQVGSGAYGSVCSAIDKRTGEKVAIKKLSRPfqseifAKR---AYRELTLLKHMQHENVIGLLDVFTSAVSGDEFQ 93

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1736 E--LCHEELLDRLTK--KSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNilMADHSSDQIRICDFGNAVKFMPDE 1811
Cdd:cd07879     94 DfyLVMPYMQTDLQKimGHPLSEDKVQYLVYQMLCGLKYIHSAGIIHRDLKPGN--LAVNEDCELKILDFGLARHADAEM 171

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1812 AQYCKygTPEFVAPE-IVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGEN 1860
Cdd:cd07879    172 TGYVV--TRWYRAPEvILNWMHYNQTVDIWSVGCIMAEMLTGKTLFKGKD 219

Catalytic domain of the Protein Tyrosine Kinase, Spleen tyrosine kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Syk is a cytoplasmic (or nonreceptor) PTK containing two Src homology 2 (SH2) domains N-terminal to the catalytic tyr kinase domain. Syk was first cloned from the spleen, and its function in hematopoietic cells is well-established. It is involved in the signaling downstream of activated receptors (including B-cell and Fc receptors) that contain ITAMs (immunoreceptor tyr activation motifs), leading to processes such as cell proliferation, differentiation, survival, adhesion, migration, and phagocytosis. More recently, Syk expression has been detected in other cell types (including epithelial cells, vascular endothelial cells, neurons, hepatocytes, and melanocytes), suggesting a variety of biological functions in non-immune cells. Syk plays a critical role in maintaining vascular integrity and in wound healing during embryogenesis. It also regulates Vav3, which is important in osteoclast function including bone development. In breast epithelial cells, where Syk acts as a negative regulator for EGFR signaling, loss of Syk expression is associated with abnormal proliferation during cancer development suggesting a potential role as a tumor suppressor. In mice, Syk has been shown to inhibit malignant transformation of mammary epithelial cells induced with murine mammary tumor virus (MMTV). The Syk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 133247 [Multi-domain] Cd Length: 257 Bit Score: 64.60 E-value: 1.78e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1666 KEIGRGAFSYVKRVIQKAGKLE--YAAKFI---SARAKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIItELCHE 1740
Cdd:cd05116      1 GELGSGNFGTVKKGYYQMKKVVktVAVKILkneANDPALKDELLREANVMQQLDNPYIVRMIGICEAESWMLVM-EMAEL 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1741 ELLDR-LTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMAdhSSDQIRICDFGNAVKFMPDEAQYCKYGT 1819
Cdd:cd05116     80 GPLNKfLQKNRHVTEKNITELVHQVSMGMKYLEESNFVHRDLAARNVLLV--TQHYAKISDFGLSKALRADENYYKAQTH 157

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....
gi 1207186029 1820 ---P-EFVAPEIVNQTPVSKATDIWPIGVLTYLCLT-GVSPFAG 1858
Cdd:cd05116    158 gkwPvKWYAPECMNYYKFSSKSDVWSFGVLMWEAFSyGQKPYKG 201

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

Pssm-ID: 238020 [Multi-domain] Cd Length: 93 Bit Score: 59.82 E-value: 1.99e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1343 PDPPDGaPVVESITGKTITLSWKKPKRLDPSIDpsslMYAIQQQALGSIQWTIIAS-CLKQTTYTISNLSKGVRYAFRVL 1421
Cdd:cd00063      1 PSPPTN-LRVTDVTSTSVTLSWTPPEDDGGPIT----GYVVEYREKGSGDWKEVEVtPGSETSYTLTGLKPGTEYEFRVR 75

                           90
                   ....*....|....*
gi 1207186029 1422 SITSKAFSKPSPATE 1436
Cdd:cd00063     76 AVNGGGESPPSESVT 90

Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. There are many splice variants of FGFR2 which show differential expression and binding to FGF ligands. Disruption of either FGFR2 or FGFR2b is lethal in mice, due to defects in the placenta or severe impairment of tissue development including lung, limb, and thyroid, respectively. Disruption of FGFR2c in mice results in defective bone and skull development. Genetic alterations of FGFR2 are associated with many human skeletal disorders including Apert syndrome, Crouzon syndrome, Jackson-Weiss syndrome, and Pfeiffer syndrome. FGFR2 is part of the FGFR subfamily, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. The FGFR2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270679 [Multi-domain] Cd Length: 313 Bit Score: 65.04 E-value: 2.04e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3395 DVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPL-FLKQFSPPIGTLDYMSPEMLKGDVVG 3473
Cdd:cd05101    147 DLVSCTYQLARGMEYLASQKCIHRDLAARNVLVTENNVMKIADFGLARDINNIdYYKKTTNGRLPVKWMAPEALFDRVYT 226

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1207186029 3474 PPADIWSIGILTY-IMLSGRLPFTeNDPAETEARIQAAKFDLSKLyQNVSQSASLFIKKILCSYPWARPTIK 3544
Cdd:cd05101    227 HQSDVWSFGVLMWeIFTLGGSPYP-GIPVEELFKLLKEGHRMDKP-ANCTNELYMMMRDCWHAVPSQRPTFK 296

Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK2 is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK) and is also called MAP3K10. MAP3Ks phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLK2 is abundant in brain, skeletal muscle, and testis. It functions upstream of the MAPK, c-Jun N-terminal kinase. It binds hippocalcin, a calcium-sensor protein that protects neurons against calcium-induced cell death. Both MLK2 and hippocalcin may be associated with the pathogenesis of Parkinson's disease. MLK2 also binds to normal huntingtin (Htt), which is important in neuronal transcription, development, and survival. MLK2 does not bind to the polyglutamine-expanded Htt, which is implicated in the pathogeneis of Huntington's disease, leading to neuronal toxicity. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The MLK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).

Pssm-ID: 271050 [Multi-domain] Cd Length: 258 Bit Score: 64.24 E-value: 2.14e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYVKRVIQKAGKLEYAA------KFISARAKrkaSALRELNILSHLDHERILYFHDAFEKKNAVIIITELCHEE 1741
Cdd:cd14148      2 IGVGGFGKVYKGLWRGEEVAVKAarqdpdEDIAVTAE---NVRQEARLFWMLQHPNIIALRGVCLNPPHLCLVMEYARGG 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1742 LLDRLTKKSTILESEIRSSVRQLLEGINYLHQ---LDILHLDIKPDNILMA------DHSSDQIRICDFGNAVKFMpDEA 1812
Cdd:cd14148     79 ALNRALAGKKVPPHVLVNWAVQIARGMNYLHNeaiVPIIHRDLKSSNILILepiendDLSGKTLKITDFGLAREWH-KTT 157

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....
gi 1207186029 1813 QYCKYGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPF 1856
Cdd:cd14148    158 KMSAAGTYAWMAPEVIRLSLFSKSSDVWSFGVLLWELLTGEVPY 201

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 5; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK5 (also called MEK5) is a dual-specificity PK that phosphorylates its downstream target, extracellular signal-regulated kinase 5 (ERK5), on specific threonine and tyrosine residues. MKK5 is activated by MEKK2 and MEKK3 in response to mitogenic and stress stimuli. The ERK5 cascade promotes cell proliferation, differentiation, neuronal survival, and neuroprotection. This cascade plays an essential role in heart development. Mice deficient in either ERK5 or MKK5 die around embryonic day 10 due to cardiovascular defects including underdevelopment of the myocardium. In addition, MKK5 is associated with metastasis and unfavorable prognosis in prostate cancer. The MKK5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 132950 [Multi-domain] Cd Length: 279 Bit Score: 64.51 E-value: 2.35e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1704 LRELNILSHLDHERILYFHDAFEKKNAVIIITELCHEELLDRLTKKSTILESEIRSSVrqlLEGINYLHQLDILHLDIKP 1783
Cdd:cd06619     47 MSELEILYKCDSPYIIGFYGAFFVENRISICTEFMDGGSLDVYRKIPEHVLGRIAVAV---VKGLTYLWSLKILHRDVKP 123

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1207186029 1784 DNILMadHSSDQIRICDFGNAVKFMPDEAQyCKYGTPEFVAPEIVNQTPVSKATDIWPIGV 1844
Cdd:cd06619    124 SNMLV--NTRGQVKLCDFGVSTQLVNSIAK-TYVGTNAYMAPERISGEQYGIHSDVWSLGI 181

Catalytic domain of the Serine/Threonine Kinase, B-Raf (Rapidly Accelerated Fibrosarcoma) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. B-Raf activates ERK with the strongest magnitude, compared with other Raf kinases. Mice embryos deficient in B-Raf die around midgestation due to vascular hemorrhage caused by apoptotic endothelial cells. Mutations in B-Raf have been implicated in initiating tumorigenesis and tumor progression, and are found in malignant cutaneous melanoma, papillary thyroid cancer, as well as in ovarian and colorectal carcinomas. Most oncogenic B-Raf mutations are located at the activation loop of the kinase and surrounding regions; the V600E mutation accounts for around 90% of oncogenic mutations. The V600E mutant constitutively activates MEK, resulting in sustained activation of ERK. B-Raf is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. They function in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. The B-Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271053 [Multi-domain] Cd Length: 274 Bit Score: 64.31 E-value: 2.39e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1664 VHKEIGRGAFSYVKRViQKAGKLEYAAKFISARAKRKASALR-ELNILSHLDHERILYFHdAFEKKNAVIIITELCH-EE 1741
Cdd:cd14151     12 VGQRIGSGSFGTVYKG-KWHGDVAVKMLNVTAPTPQQLQAFKnEVGVLRKTRHVNILLFM-GYSTKPQLAIVTQWCEgSS 89

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1742 LLDRLTKKSTILE-SEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDFGNAV--KFMPDEAQYCKY- 1817
Cdd:cd14151     90 LYHHLHIIETKFEmIKLIDIARQTAQGMDYLHAKSIIHRDLKSNNIFL--HEDLTVKIGDFGLATvkSRWSGSHQFEQLs 167

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1207186029 1818 GTPEFVAPEIV---NQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVL 1866
Cdd:cd14151    168 GSILWMAPEVIrmqDKNPYSFQSDVYAFGIVLYELMTGQLPYSNINNRDQII 219

Catalytic domain of the Protein Tyrosine Kinase, Wee1b; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of human Wee1b (also called Wee2), Xenopus laevis Wee1a (XeWee1a) and similar vertebrate proteins. XeWee1a accumulates after exiting the metaphase II stage in oocytes and in early mitotic cells. It functions during the first zygotic cell division and not during subsequent divisions. Mammalian Wee2/Wee1b is an oocyte-specific inhibitor of meiosis that functions downstream of cAMP. Wee1 is a cell cycle checkpoint kinase that helps keep the cyclin-dependent kinase CDK1 in an inactive state through phosphorylation of an N-terminal tyr (Y15) residue. During the late G2 phase, CDK1 is activated and mitotic entry is promoted by the removal of this inhibitory phosphorylation by the phosphatase Cdc25. Although Wee1 is functionally a tyr kinase, it is more closely related to serine/threonine kinases (STKs). It contains a catalytic kinase domain sandwiched in between N- and C-terminal regulatory domains. It is regulated by phosphorylation and degradation, and its expression levels are also controlled by circadian clock proteins. The Wee1b subfamily is part of a larger superfamily that includes the catalytic domains of STKs, other PTKs, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271041 [Multi-domain] Cd Length: 274 Bit Score: 64.18 E-value: 2.41e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3309 GRFGVIRECRENATGNLYMAK--IVPY-EPESKQTVLQEYDILKSL-HHEKIMALHEAYVTPRYLVLISECCSGKELLHS 3384
Cdd:cd14139     11 GEFGSVYKCIKRLDGCVYAIKrsMRPFaGSSNEQLALHEVYAHAVLgHHPHVVRYYSAWAEDDHMIIQNEYCNGGSLQDA 90

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3385 LIDRFR----YSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYM---------------------NVV-KIIDF 3438
Cdd:cd14139     91 ISENTKsgnhFEEPELKDILLQVSMGLKYIHNSGLVHLDIKPSNIFICHKmqsssgvgeevsneedeflsaNVVyKIGDL 170

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3439 GSAQTFNplflkqfSPPI--GTLDYMSPEMLKGDVVG-PPADIWSIGiLTYIMLSGRLPFTENDPAETEARiqaaKFDLS 3515
Cdd:cd14139    171 GHVTSIN-------KPQVeeGDSRFLANEILQEDYRHlPKADIFALG-LTVALAAGAEPLPTNGAAWHHIR----KGNFP 238

                          250       260
                   ....*....|....*....|....*..
gi 1207186029 3516 KLYQNVSQSASLFIKKILCSYPWARPT 3542
Cdd:cd14139    239 DVPQELPESFSSLLKNMIQPDPEQRPS 265

Catalytic domain of Cyclin-Dependent protein Kinase 1-like Serine/Threonine Kinases and of Plant B-type Cyclin-Dependent protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDK, CDK2, and CDK3. CDK1 is also called Cell division control protein 2 (Cdc2) or p34 protein kinase, and is regulated by cyclins A, B, and E. The CDK1/cyclin A complex controls G2 phase entry and progression while the CDK1/cyclin B complex is critical for G2 to M phase transition. CDK2 is regulated by cyclin E or cyclin A. Upon activation by cyclin E, it phosphorylates the retinoblastoma (pRb) protein which activates E2F mediated transcription and allows cells to move into S phase. The CDK2/cyclin A complex plays a role in regulating DNA replication. Studies in knockout mice revealed that CDK1 can compensate for the loss of the cdk2 gene as it can also bind cyclin E and drive G1 to S phase transition. CDK3 is regulated by cyclin C and it phosphorylates pRB specifically during the G0/G1 transition. This phosphorylation is required for cells to exit G0 efficiently and enter the G1 phase. The plant-specific B-type CDKs are expressed from the late S to the M phase of the cell cycle. They are characterized by the cyclin binding motif PPT[A/T]LRE. They play a role in controlling mitosis and integrating developmental pathways, such as stomata and leaf development. CdkB has been shown to associate with both cyclin B, which controls G2/M transition, and cyclin D, which acts as a mediator in linking extracellular signals to the cell cycle. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270829 [Multi-domain] Cd Length: 283 Bit Score: 64.23 E-value: 2.49e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1702 SALRELNILSHLDHERILYFHDAFEKKNAVIIITELCHEEL---LDRLTKKStILESEIRSSVRQLLEGINYLHQLDILH 1778
Cdd:cd07835     44 TAIREISLLKELNHPNIVRLLDVVHSENKLYLVFEFLDLDLkkyMDSSPLTG-LDPPLIKSYLYQLLQGIAFCHSHRVLH 122

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1207186029 1779 LDIKPDNILMadHSSDQIRICDFGNAVKFMPDEAQYckygTPEFV-----APEI-VNQTPVSKATDIWPIG 1843
Cdd:cd07835    123 RDLKPQNLLI--DTEGALKLADFGLARAFGVPVRTY----THEVVtlwyrAPEIlLGSKHYSTPVDIWSVG 187

Catalytic domain of the Serine/Threonine protein kinase, Casein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CK1 phosphorylates a variety of substrates including enzymes, transcription and splice factors, cytoskeletal proteins, viral oncogenes, receptors, and membrane-associated proteins. There are mutliple isoforms of CK1 and in mammals, seven isoforms (alpha, beta, gamma1-3, delta, and epsilon) have been characterized. These isoforms differ mainly in the length and structure of their C-terminal non-catalytic region. Some isoforms have several splice variants such as the long (L) and short (S) variants of CK1alpha. CK1 proteins are involved in the regulation of many cellular processes including membrane transport processes, circadian rhythm, cell division, apoptosis, and the development of cancer and neurodegenerative diseases. The CK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270918 [Multi-domain] Cd Length: 266 Bit Score: 64.02 E-value: 2.50e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3309 GRFGVIRECRENATGNLYMAKIVPYEPESKQtVLQEYDILKSLHHE----KIMAL--HEAYvtpRYLVLiseccsgkELL 3382
Cdd:cd14016     11 GSFGEVYLGIDLKTGEEVAIKIEKKDSKHPQ-LEYEAKVYKLLQGGpgipRLYWFgqEGDY---NVMVM--------DLL 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3383 -HSLIDRFRY-----SEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIV---TYMNVVKIIDFGSAqtfnplflKQFS 3453
Cdd:cd14016     79 gPSLEDLFNKcgrkfSLKTVLMLADQMISRLEYLHSKGYIHRDIKPENFLMglgKNSNKVYLIDFGLA--------KKYR 150

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1207186029 3454 PP--------------IGTLDYMSPEMLKG------DvvgppaDIWSIG-ILTYiMLSGRLP 3494
Cdd:cd14016    151 DPrtgkhipyregkslTGTARYASINAHLGieqsrrD------DLESLGyVLIY-FLKGSLP 205

Catalytic domain of the Dual-specificity protein kinase, CDC-like kinase 2; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. CLK2 plays a role in hepatic insulin signaling and glucose metabolism. It is induced by the insulin/Akt pathway as part of the hepatic refeeding reponse, and it directly phosphorylates the SR domain of PGC-1alpha, which results in decreased gluconeogenic gene expression and glucose output. CLKs are involved in the phosphorylation and regulation of serine/arginine-rich (SR) proteins, which play a crucial role in pre-mRNA splicing by directing splice site selection. SR proteins are phosphorylated first by SR protein kinases (SRPKs) at the N-terminus, which leads to its assembly into nuclear speckles where splicing factors are stored. CLKs phosphorylate the C-terminal part of SR proteins, causing the nuclear speckles to dissolve and splicing factors to be recruited at sites of active transcription. Based on a conserved "EHLAMMERILG" signature motif which may be crucial for substrate specificity, CLKs are also referred to as LAMMER kinases. CLKs autophosphorylate at tyrosine residues and phosphorylate their substrates exclusively on serine/threonine residues. The CLK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271117 [Multi-domain] Cd Length: 330 Bit Score: 65.04 E-value: 2.56e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1658 LTDYYDVHKEIGRGAFSYVKRVI-QKAGKLEYAAKFISARAKRKASALRELNILSHLDHER------ILYFHDAFEKKNA 1730
Cdd:cd14215     10 LQERYEIVSTLGEGTFGRVVQCIdHRRGGARVALKIIKNVEKYKEAARLEINVLEKINEKDpenknlCVQMFDWFDYHGH 89

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1731 VIIITELCHEELLDRLTKKSTILES--EIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADH----------------- 1791
Cdd:cd14215     90 MCISFELLGLSTFDFLKENNYLPYPihQVRHMAFQVCQAVKFLHDNKLTHTDLKPENILFVNSdyeltynlekkrdersv 169

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1207186029 1792 SSDQIRICDFGNAVkfMPDEAQYCKYGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDR 1862
Cdd:cd14215    170 KSTAIRVVDFGSAT--FDHEHHSTIVSTRHYRAPEVILELGWSQPCDVWSIGCIIFEYYVGFTLFQTHDNR 238

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.

Pssm-ID: 409367 [Multi-domain] Cd Length: 89 Bit Score: 59.38 E-value: 2.86e-10

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1207186029 1257 DMDVVEGREAVLRCKVAGLPYPTITWFHNGKRID-STEDRKMTQFRDvhSLVVRCVCHAHGGVYKCVISNKVG 1328
Cdd:cd04978      8 SLVLSPGETGELICEAEGNPQPTITWRLNGVPIEpAPEDMRRTVDGR--TLIFSNLQPNDTAVYQCNASNVHG 78

Catalytic domain of Serine/Threonine Kinase 16; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK16 is associated with many names including Myristylated and Palmitylated Serine/threonine Kinase 1 (MPSK1), Kinase related to cerevisiae and thaliana (Krct), and Protein Kinase expressed in day 12 fetal liver (PKL12). It is widely expressed in mammals with highest levels found in liver, testis, and kidney. It is localized in the Golgi but is translocated to the nucleus upon disorganization of the Golgi. STK16 is constitutively active and is capable of phosphorylating itself and other substrates. It may be involved in regulating stromal-epithelial interactions during mammary gland ductal morphogenesis. It may also function as a transcriptional co-activator of type-C natriuretic peptide and VEGF. The STK16 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270888 [Multi-domain] Cd Length: 282 Bit Score: 64.24 E-value: 2.92e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLY-MAKIVPYEPESKQTVLQEYDILKSLHHEKIMAL------------HEAY-VT 3365
Cdd:cd13986      2 YRIQRLLGEGGFSFVYLVEDLSTGRLYaLKKILCHSKEDVKEAMREIENYRLFNHPNILRLldsqivkeaggkKEVYlLL 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3366 PRYLvliseccsgKELLHSLIDRFR-----YSEDDVVAYIVQILQGLDYLHS---RRILHLDIKPENIIVTYMNVVKIID 3437
Cdd:cd13986     82 PYYK---------RGSLQDEIERRLvkgtfFPEDRILHIFLGICRGLKAMHEpelVPYAHRDIKPGNVLLSEDDEPILMD 152

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3438 FGSAqtfNP-----------LFLKQFSPPIGTLDYMSPEMLK---GDVVGPPADIWSIGILTYIMLSGRLPFtendpaet 3503
Cdd:cd13986    153 LGSM---NParieiegrreaLALQDWAAEHCTMPYRAPELFDvksHCTIDEKTDIWSLGCTLYALMYGESPF-------- 221

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1207186029 3504 EARIQ-------AAKFDLSKLYQNVSQSASL--FIKKILCSYPWARPTIKD 3545
Cdd:cd13986    222 ERIFQkgdslalAVLSGNYSFPDNSRYSEELhqLVKSMLVVNPAERPSIDD 272

Pseudokinase domain, repeat 1, of eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or General Control Non-derepressible-2; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the overall downregulation of protein synthesis. eIF-2 phosphorylation is induced in response to cellular stresses including virus infection, heat shock, nutrient deficiency, and the accummulation of unfolded proteins, among others. There are four distinct kinases that phosphorylate eIF-2 and control protein synthesis under different stress conditions: GCN2, protein kinase regulated by RNA (PKR), heme-regulated inhibitor kinase (HRI), and PKR-like endoplasmic reticulum kinase (PERK). GCN2 is activated by amino acid or serum starvation and UV irradiation. It induces GCN4, a transcriptional activator of amino acid biosynthetic genes, leading to increased production of amino acids under amino acid-deficient conditions. In serum-starved cells, GCN2 activation induces translation of the stress-responsive transcription factor ATF4, while under UV stress, GCN2 triggers transcriptional rescue via NF-kappaB signaling. GCN2 contains an N-terminal RWD, a degenerate kinase-like (repeat 1), the catalytic kinase (repeat 2), a histidyl-tRNA synthetase (HisRS)-like, and a C-terminal ribosome-binding and dimerization (RB/DD) domains. The degenerate pseudokinase domain of GCN2 may function as a regulatory domain. The GCN2 subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270914 [Multi-domain] Cd Length: 254 Bit Score: 63.92 E-value: 2.93e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1675 YVKRVIQKAGKLEYaakFISARAKRKASAL-RELNILSHLDHERIL-YFHDAFEKKNA-----VIIITEL----CHEELL 1743
Cdd:cd14012     19 NSKKPGKFLTSQEY---FKTSNGKKQIQLLeKELESLKKLRHPNLVsYLAFSIERRGRsdgwkVYLLTEYapggSLSELL 95

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1744 DRLTKKSTileSEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSDQI-RICDFGnavkFMPDEAQYCKYGT--- 1819
Cdd:cd14012     96 DSVGSVPL---DTARRWTLQLLEALEYLHRNGVVHKSLHAGNVLLDRDAGTGIvKLTDYS----LGKTLLDMCSRGSlde 168

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1820 ---PEFVAPEIVNQ-TPVSKATDIWPIGVLTYLCLTGVSPFagendrssvlniRNYNVAFEESMFTDLCHEAKGFVIKLL 1895
Cdd:cd14012    169 fkqTYWLPPELAQGsKSPTRKTDVWDLGLLFLQMLFGLDVL------------EKYTSPNPVLVSLDLSASLQDFLSKCL 236

                          250
                   ....*....|....*..
gi 1207186029 1896 VAD-RLRPDANECLRHP 1911
Cdd:cd14012    237 SLDpKKRPTALELLPHE 253

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.

Pssm-ID: 409490 [Multi-domain] Cd Length: 99 Bit Score: 59.49 E-value: 3.09e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 2869 DHVLLEGDPVTLSCLPAGSPHPHISWMKDKKPLEID---PRMNMISCPDGRQLLMIM---KTTKKDAGLYECVAANPLAT 2942
Cdd:cd07693      9 DLIVSKGDPATLNCKAEGRPTPTIQWLKNGQPLETDkddPRSHRIVLPSGSLFFLRVvhgRKGRSDEGVYVCVAHNSLGE 88


                   ...
gi 1207186029 2943 VTS 2945
Cdd:cd07693     89 AVS 91

Fibronectin type 3 domain; One of three types of internal repeats found in the plasma protein fibronectin. Its tenth fibronectin type III repeat contains an RGD cell recognition sequence in a flexible loop between 2 strands. Approximately 2% of all animal proteins contain the FN3 repeat; including extracellular and intracellular proteins, membrane spanning cytokine receptors, growth hormone receptors, tyrosine phosphatase receptors, and adhesion molecules. FN3-like domains are also found in bacterial glycosyl hydrolases.

Pssm-ID: 238020 [Multi-domain] Cd Length: 93 Bit Score: 59.43 E-value: 3.15e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 2955 PNSPGTPEVPQKYKNTALVVW-RPSDTTAPCT-YSLERKTEGENNWLIVATGVAD-CYYNVLDLPAGASYRFRVACVNKA 3031
Cdd:cd00063      1 PSPPTNLRVTDVTSTSVTLSWtPPEDDGGPITgYVVEYREKGSGDWKEVEVTPGSeTSYTLTGLKPGTEYEFRVRAVNGG 80

                           90
                   ....*....|...
gi 1207186029 3032 GQGPYSSLSEVVV 3044
Cdd:cd00063     81 GESPPSESVTVTT 93

Pseudokinase domain of Tribbles Homolog 2; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. TRB2 binds and negatively regulates the mitogen activated protein kinase (MAPK) kinases, MKK7 and MEK1, which are activators of the MAPKs, ERK and JNK. It controls the activation of inflammatory monocytes, which is essential in innate immune responses and the pathogenesis of inflammatory diseases such as atherosclerosis. TRB2 expression is down-regulated in human acute myeloid leukaemia (AML), which may lead to enhanced cell survival and pathogenesis of the disease. TRB2 is one of three Tribbles Homolog (TRB) proteins present in vertebrates that are encoded by three separate genes. TRB proteins interact with many proteins involved in signalling pathways. They play scaffold-like regulatory functions and affect many cellular processes such as mitosis, apoptosis, and gene expression. The TRB2 subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270924 [Multi-domain] Cd Length: 242 Bit Score: 63.52 E-value: 3.24e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3461 YMSPEMLK--GDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLSklyQNVSQSASLFIKKILCSYPW 3538
Cdd:cd14022    152 YVSPEILNtsGSYSGKAADVWSLGVMLYTMLVGRYPFHDIEPSSLFSKIRRGQFNIP---ETLSPKAKCLIRSILRREPS 228

                           90
                   ....*....|....
gi 1207186029 3539 ARPTIKDCFTNSWL 3552
Cdd:cd14022    229 ERLTSQEILDHPWF 242

Catalytic domain of the Protein Tyrosine Kinase, Wee1a; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of human Wee1a, Xenopus laevis Wee1b (XeWee1b) and similar vertebrate proteins. Members of this subfamily show a wide expression pattern. XeWee1b functions after the first zygotic cell divisions. It is expressed in all tissues and is also present after the gastrulation stage of embryos. Wee1 is a cell cycle checkpoint kinase that helps keep the cyclin-dependent kinase CDK1 in an inactive state through phosphorylation of an N-terminal tyr (Y15) residue. During the late G2 phase, CDK1 is activated and mitotic entry is promoted by the removal of this inhibitory phosphorylation by the phosphatase Cdc25. Although Wee1 is functionally a tyr kinase, it is more closely related to serine/threonine kinases (STKs). It contains a catalytic kinase domain sandwiched in between N- and C-terminal regulatory domains. It is regulated by phosphorylation and degradation, and its expression levels are also controlled by circadian clock proteins. The Wee1a subfamily is part of a larger superfamily that includes the catalytic domains of STKs, other PTKs, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271040 [Multi-domain] Cd Length: 276 Bit Score: 63.89 E-value: 3.28e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3309 GRFGVIRECRENATGNLYMAKivpyepESKQTV---LQEYDILKSLH-------HEKIMALHEAYVTPRYLVLISECCSG 3378
Cdd:cd14138     16 GEFGSVFKCVKRLDGCIYAIK------RSKKPLagsVDEQNALREVYahavlgqHSHVVRYYSAWAEDDHMLIQNEYCNG 89

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3379 KELLHSLIDRFR----YSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMN-------------------VVKI 3435
Cdd:cd14138     90 GSLADAISENYRimsyFTEPELKDLLLQVARGLKYIHSMSLVHMDIKPSNIFISRTSipnaaseegdedewasnkvIFKI 169

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3436 IDFGSAQTFNplflkqfSPPI--GTLDYMSPEMLKGDVVG-PPADIWSIGiLTYIMLSGRLPFTENDPAETEARiqaaKF 3512
Cdd:cd14138    170 GDLGHVTRVS-------SPQVeeGDSRFLANEVLQENYTHlPKADIFALA-LTVVCAAGAEPLPTNGDQWHEIR----QG 237

                          250       260       270
                   ....*....|....*....|....*....|
gi 1207186029 3513 DLSKLYQNVSQSASLFIKKILCSYPWARPT 3542
Cdd:cd14138    238 KLPRIPQVLSQEFLDLLKVMIHPDPERRPS 267

Catalytic domain of the Serine/Threonine Kinase, C-Raf (Rapidly Accelerated Fibrosarcoma) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. C-Raf, also known as Raf-1 or c-Raf-1, is ubiquitously expressed and was the first Raf identified. It was characterized as the acquired oncogene from an acutely transforming murine sarcoma virus (3611-MSV) and the transforming agent from the avian retrovirus MH2. C-Raf-deficient mice embryos die around midgestation with increased apoptosis of embryonic tissues, especially in the fetal liver. One of the main functions of C-Raf is restricting caspase activation to promote survival in response to specific stimuli such as Fas stimulation, macrophage apoptosis, and erythroid differentiation. C-Raf is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. It functions in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. The C-Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271051 [Multi-domain] Cd Length: 283 Bit Score: 63.90 E-value: 3.35e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1706 ELNILSHLDHERILYFHDAFEKKNaVIIITELCHEElldRLTKKSTILESEIR-----SSVRQLLEGINYLHQLDILHLD 1780
Cdd:cd14149     58 EVAVLRKTRHVNILLFMGYMTKDN-LAIVTQWCEGS---SLYKHLHVQETKFQmfqliDIARQTAQGMDYLHAKNIIHRD 133

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1781 IKPDNILMadHSSDQIRICDFGNA-VKFMPDEAQYCKY--GTPEFVAPEIV---NQTPVSKATDIWPIGVLTYLCLTGVS 1854
Cdd:cd14149    134 MKSNNIFL--HEGLTVKIGDFGLAtVKSRWSGSQQVEQptGSILWMAPEVIrmqDNNPFSFQSDVYSYGIVLYELMTGEL 211

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1207186029 1855 PFAGENDRSSVLNI--RNYNVAFEESMFTDlCHEAkgfvIKLLVADRLRPDANEclrHPWFKTLNKGKSISTESLKK 1929
Cdd:cd14149    212 PYSHINNRDQIIFMvgRGYASPDLSKLYKN-CPKA----MKRLVADCIKKVKEE---RPLFPQILSSIELLQHSLPK 280

Catalytic domain of the Protein Kinase superfamily; The PK superfamily contains the large family of typical PKs that includes serine/threonine kinases (STKs), protein tyrosine kinases (PTKs), and dual-specificity PKs that phosphorylate both serine/threonine and tyrosine residues of target proteins, as well as pseudokinases that lack crucial residues for catalytic activity and/or ATP binding. It also includes phosphoinositide 3-kinases (PI3Ks), aminoglycoside 3'-phosphotransferases (APHs), choline kinase (ChoK), Actin-Fragmin Kinase (AFK), and the atypical RIO and Abc1p-like protein kinases. These proteins catalyze the transfer of the gamma-phosphoryl group from ATP to their target substrates; these include serine/threonine/tyrosine residues in proteins for typical or atypical PKs, the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives for PI3Ks, the 4-hydroxyl of PtdIns for PI4Ks, and other small molecule substrates for APH/ChoK and similar proteins such as aminoglycosides, macrolides, choline, ethanolamine, and homoserine.

Pssm-ID: 270870 [Multi-domain] Cd Length: 136 Bit Score: 60.53 E-value: 3.44e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASALRE--LNILSHLDHER-ILYFHDAFEKKNAVIIITELCHEELLD 1744
Cdd:cd13968      1 MGEGASAKVFWAEGECTTIGVAVKIGDDVNNEEGEDLESemDILRRLKGLELnIPKVLVTEDVDGPNILLMELVKGGTLI 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1207186029 1745 RLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSdqIRICDFG 1802
Cdd:cd13968     81 AYTQEEELDEKDVESIMYQLAECMRLLHSFHLIHRDLNNDNILLSEDGN--VKLIDFG 136

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409564 [Multi-domain] Cd Length: 91 Bit Score: 59.13 E-value: 3.45e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029   54 PPVFIRKMRNAAVGTGCDIRLKVAVAGDPQPTLYWY------HND-DLVNMDNQEYGGLWIRDCKPSDAGLYTCIATNHL 126
Cdd:cd20972      1 PPQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFcegkelQNSpDIQIHQEGDLHSLIIAEAFEEDTGRYSCLATNSV 80

                           90
                   ....*....|.
gi 1207186029  127 GEARSSAVLAV 137
Cdd:cd20972     81 GSDTTSAEIFV 91

Catalytic domain of the Serine/Threonine protein kinase, Tau-Tubulin Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TTBK is a neuron-specific kinase that phosphorylates the microtubule-associated protein tau and promotes its aggregation. Higher vertebrates contain two TTBK proteins, TTBK1 and TTBK2, both of which have been implicated in neurodegeneration. TTBK1 has been linked to Alzheimer's disease (AD) while TTBK2 is associated with spinocerebellar ataxia type 11 (SCA11). Both AD and SCA11 patients show the presence of neurofibrillary tangles in the brain. The Drosophila TTBK homolog, Asator, is an essential protein that localizes to the mitotic spindle during mitosis and may be involved in regulating microtubule dynamics and function. The TTBK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270919 [Multi-domain] Cd Length: 263 Bit Score: 63.43 E-value: 3.61e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKR-----KASALRELNILSHldherILYFHDAFEKKNAVIIITE 1736
Cdd:cd14017      2 WKVVKKIGGGGFGEIYKVRDVVDGEEVAMKVESKSQPKqvlkmEVAVLKKLQGKPH-----FCRLIGCGRTERYNYIVMT 76

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1207186029 1737 LCHEEL--LDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSD--QIRICDFGNAVKFM 1808
Cdd:cd14017     77 LLGPNLaeLRRSQPRGKFSVSTTLRLGIQILKAIEDIHEVGFLHRDVKPSNFAIGRGPSDerTVYILDFGLARQYT 152

Catalytic domain of the Serine/Threonine kinase, Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase 8; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP3K8 is also called Tumor progression locus 2 (Tpl2) or Cancer Osaka thyroid (Cot), and was first identified as a proto-oncogene in T-cell lymphoma induced by MoMuL virus and in breast carcinoma induced by MMTV. Activated MAP3K8 induces various MAPK pathways including Extracellular Regulated Kinase (ERK) 1/2, c-Jun N-terminal kinase (JNK), and p38. It plays a pivotal role in innate immunity, linking Toll-like receptors to the production of TNF and the activation of ERK in macrophages. It is also required in interleukin-1beta production and is critical in host defense against Gram-positive bacteria. MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The MAP3K8 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270897 [Multi-domain] Cd Length: 256 Bit Score: 63.49 E-value: 3.84e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKAsalrELNILSHLDHERILYFHDAFEKKNAVIIITELCHE-ELLDRL 1746
Cdd:cd13995     12 IPRGAFGKVYLAQDTKTKKRMACKLIPVEQFKPS----DVEIQACFRHENIAELYGALLWEETVHLFMEAGEGgSVLEKL 87

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1747 TKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMAdhsSDQIRICDFGNAVKfMPDEAQYCK--YGTPEFVA 1824
Cdd:cd13995     88 ESCGPMREFEIIWVTKHVLKGLDFLHSKNIIHHDIKPSNIVFM---STKAVLVDFGLSVQ-MTEDVYVPKdlRGTEIYMS 163

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|
gi 1207186029 1825 PEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSS 1864
Cdd:cd13995    164 PEVILCRGHNTKADIYSLGATIIHMQTGSPPWVRRYPRSA 203

First C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409474 Cd Length: 92 Bit Score: 58.96 E-value: 3.88e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 2861 PVFHIKLRDHVLLEGDPVTLSCLPAGSPHPHISWMKDKKplEIDPRMNMISCP---DGRQLLMIMKTTKKDAGLYECVAA 2937
Cdd:cd05893      1 PFFEMKLKHYKIFEGMPVTFTCRVAGNPKPKIYWFKDGK--QISPKSDHYTIQrdlDGTCSLHTTASTLDDDGNYTIMAA 78


                   ....*....
gi 1207186029 2938 NPLATVTSS 2946
Cdd:cd05893     79 NPQGRISCT 87

Catalytic domain of the Serine/Threonine Kinase, Protein Kinase N; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKN has a C-terminal catalytic domain that is highly homologous to PKCs. Its unique N-terminal regulatory region contains antiparallel coiled-coil (ACC) domains. In mammals, there are three PKN isoforms from different genes (designated PKN-alpha, beta, and gamma), which show different enzymatic properties, tissue distribution, and varied functions. PKN can be activated by the small GTPase Rho, and by fatty acids such as arachidonic and linoleic acids. It is involved in many biological processes including cytokeletal regulation, cell adhesion, vesicle transport, glucose transport, regulation of meiotic maturation and embryonic cell cycles, signaling to the nucleus, and tumorigenesis. The PKN subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270741 [Multi-domain] Cd Length: 326 Bit Score: 64.24 E-value: 4.07e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAK-------IVPYEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKE 3380
Cdd:cd05589      9 RGHFGKVLLAEYKPTGELFAIKalkkgdiIARDEVESLMCEKRIFETVNSARHPFLVNLFACFQTPEHVCFVMEYAAGGD 88

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3381 L-LHSLIDRFrySEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTfNPLFLKQFSPPIGTL 3459
Cdd:cd05589     89 LmMHIHEDVF--SEPRAVFYAACVVLGLQFLHEHKIVYRDLKLDNLLLDTEGYVKIADFGLCKE-GMGFGDRTSTFCGTP 165

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|...
gi 1207186029 3460 DYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAE 3502
Cdd:cd05589    166 EFLAPEVLTDTSYTRAVDWWGLGVLIYEMLVGESPFPGDDEEE 208

Catalytic domain of the Protein Tyrosine Kinases, Lymphocyte-specific kinase and Blk; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Lck and Blk are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lck is expressed in T-cells and natural killer cells. It plays a critical role in T-cell maturation, activation, and T-cell receptor (TCR) signaling. Lck phosphorylates ITAM (immunoreceptor tyr activation motif) sequences on several subunits of TCRs, leading to the activation of different second messenger cascades. Phosphorylated ITAMs serve as binding sites for other signaling factor such as Syk and ZAP-70, leading to their activation and propagation of downstream events. In addition, Lck regulates drug-induced apoptosis by interfering with the mitochondrial death pathway. The apototic role of Lck is independent of its primary function in T-cell signaling. Blk is expressed specifically in B-cells. It is involved in pre-BCR (B-cell receptor) signaling. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Lck/Blk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270652 [Multi-domain] Cd Length: 264 Bit Score: 63.37 E-value: 4.09e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3337 SKQTVLQEYDILKSLHHEKIMALHeAYVTPRYLVLISECCSGKellhSLIDRFRYSE------DDVVAYIVQILQGLDYL 3410
Cdd:cd05067     45 SPDAFLAEANLMKQLQHQRLVRLY-AVVTQEPIYIITEYMENG----SLVDFLKTPSgikltiNKLLDMAAQIAEGMAFI 119

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3411 HSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPlflKQFSPPIGT---LDYMSPEMLKGDVVGPPADIWSIGI-LTY 3486
Cdd:cd05067    120 EERNYIHRDLRAANILVSDTLSCKIADFGLARLIED---NEYTAREGAkfpIKWTAPEAINYGTFTIKSDVWSFGIlLTE 196


                   ....*....
gi 1207186029 3487 IMLSGRLPF 3495
Cdd:cd05067    197 IVTHGRIPY 205

Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase kinase kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP4K5, also called germinal center kinase-related enzyme (GCKR), has been shown to activate the MAPK c-Jun N-terminal kinase (JNK). MAP4K5 also facilitates Wnt signaling in B cells, and may therefore be implicated in the control of cell fate, proliferation, and polarity. MAP4Ks are involved in some MAPK signaling pathways by activating a MAPK kinase kinase. Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Members of this subfamily contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. The MAP4K5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270813 [Multi-domain] Cd Length: 268 Bit Score: 63.51 E-value: 4.12e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFS--YVKRVIQkAGKLEyAAKFISARAKRKASALR-ELNILSHLDHERILYFHDAFEKKNAVIIITELC 1738
Cdd:cd06646     11 YELIQRVGSGTYGdvYKARNLH-TGELA-AVKIIKLEPGDDFSLIQqEIFMVKECKHCNIVAYFGSYLSREKLWICMEYC 88

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1739 HE-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSdqIRICDFGNAVKFMPDEAQYCKY 1817
Cdd:cd06646     89 GGgSLQDIYHVTGPLSELQIAYVCRETLQGLAYLHSKGKMHRDIKGANILLTDNGD--VKLADFGVAAKITATIAKRKSF 166

                          170       180       190
                   ....*....|....*....|....*....|.
gi 1207186029 1818 -GTPEFVAPEIV---NQTPVSKATDIWPIGV 1844
Cdd:cd06646    167 iGTPYWMAPEVAaveKNGGYNQLCDIWAVGI 197

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK2, also called beta-adrenergic receptor kinase (beta-ARK) or beta-ARK1, is important in regulating several cardiac receptor responses. It plays a role in cardiac development and in hypertension. Deletion of GRK2 in mice results in embryonic lethality, caused by hypoplasia of the ventricular myocardium. GRK2 also plays important roles in the liver (as a regulator of portal blood pressure), in immune cells, and in the nervous system. Altered GRK2 expression has been reported in several disorders including major depression, schizophrenia, bipolar disorder, and Parkinsonism. GRK2 contains an N-terminal RGS homology (RH) domain, a central catalytic domain, and C-terminal pleckstrin homology (PH) domain that mediates PIP2 and G protein betagamma-subunit translocation to the membrane. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. TheGRK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271125 [Multi-domain] Cd Length: 321 Bit Score: 64.30 E-value: 4.16e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFI-SARAKRKAS---ALRE---LNILSHLDHERILYFHDAFEKKNAVIII 1734
Cdd:cd14223      2 FSVHRIIGRGGFGEVYGCRKADTGKMYAMKCLdKKRIKMKQGetlALNErimLSLVSTGDCPFIVCMSYAFHTPDKLSFI 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1735 TELCHE-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSsdQIRICDFGNAVKFmPDEAQ 1813
Cdd:cd14223     82 LDLMNGgDLHYHLSQHGVFSEAEMRFYAAEIILGLEHMHSRFVVYRDLKPANILLDEFG--HVRISDLGLACDF-SKKKP 158

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....
gi 1207186029 1814 YCKYGTPEFVAPEIVNQ-TPVSKATDIWPIGVLTYLCLTGVSPF 1856
Cdd:cd14223    159 HASVGTHGYMAPEVLQKgVAYDSSADWFSLGCMLFKLLRGHSPF 202

Catalytic domain of With No Lysine (WNK) 2-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNK2 is widely expressed and has been shown to be epigenetically silenced in gliomas. It inhibits cell growth by acting as a negative regulator of MEK1-ERK1/2 signaling. WNK2 modulates growth factor-induced cancer cell proliferation, suggesting that it may be a tumor suppressor gene. WNKs comprise a subfamily of STKs with an unusual placement of the catalytic lysine relative to all other protein kinases. They are critical in regulating ion balance and are thus, important components in the control of blood pressure. The WNK2-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270934 [Multi-domain] Cd Length: 266 Bit Score: 63.56 E-value: 4.18e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3338 KQTVLQEYDILKSLHHEKIMALHEAYVTP----RYLVLISECCSGKELlHSLIDRFRYSEDDVV-AYIVQILQGLDYLHS 3412
Cdd:cd14032     44 RQRFKEEAEMLKGLQHPNIVRFYDFWESCakgkRCIVLVTELMTSGTL-KTYLKRFKVMKPKVLrSWCRQILKGLLFLHT 122

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3413 RR--ILHLDIKPENIIVT-YMNVVKIIDFGSAQTFNPLFLKQFsppIGTLDYMSPEMLKgDVVGPPADIWSIGILTYIML 3489
Cdd:cd14032    123 RTppIIHRDLKCDNIFITgPTGSVKIGDLGLATLKRASFAKSV---IGTPEFMAPEMYE-EHYDESVDVYAFGMCMLEMA 198

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1207186029 3490 SGRLPFTENDPAETEARIQAAKFDLSKLYQNVSQSASLFIKKILCSYPWARPTIKDCFTNSWLQD 3554
Cdd:cd14032    199 TSEYPYSECQNAAQIYRKVTCGIKPASFEKVTDPEIKEIIGECICKNKEERYEIKDLLSHAFFAE 263

Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PIM gene locus was discovered as a result of the cloning of retroviral intergration sites in murine Moloney leukemia virus, leading to the identification of PIM kinases. They are constitutively active STKs with a broad range of cellular targets and are overexpressed in many haematopoietic malignancies and solid cancers. Vertebrates contain three distinct PIM kinase genes (PIM1-3); each gene may result in mutliple protein isoforms. There are three PIM2 isoforms resulting from alternative translation initiation sites. PIM2 is highly expressed in leukemia and lymphomas and has been shown to promote the survival and proliferation of tumor cells. The PIM2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271003 [Multi-domain] Cd Length: 257 Bit Score: 63.33 E-value: 4.60e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1715 HERILYFHDAFEKKNAVIIITE--LCHEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMaDHS 1792
Cdd:cd14101     66 HRGVIRLLDWFEIPEGFLLVLErpQHCQDLFDYITERGALDESLARRFFKQVVEAVQHCHSKGVVHRDIKDENILV-DLR 144

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1793 SDQIRICDFGNAVkFMPDEAQYCKYGTPEFVAPEIV--NQTPVSKATdIWPIGVLTYLCLTGVSPFAGENDrssvlnIRN 1870
Cdd:cd14101    145 TGDIKLIDFGSGA-TLKDSMYTDFDGTRVYSPPEWIlyHQYHALPAT-VWSLGILLYDMVCGDIPFERDTD------ILK 216

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*.
gi 1207186029 1871 YNVAFEESMFTDLCHeakgfVIKLLVADR--LRPDANECLRHPWFK 1914
Cdd:cd14101    217 AKPSFNKRVSNDCRS-----LIRSCLAYNpsDRPSLEQILLHPWMM 257

Catalytic domain of the Protein Tyrosine Kinase, Activated Cdc42-associated kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily includes Ack1, thirty-eight-negative kinase 1 (Tnk1), and similar proteins. They are cytoplasmic (or nonreceptor) PTKs containing an N-terminal catalytic domain, an SH3 domain, a Cdc42-binding CRIB domain, and a proline-rich region. They are mainly expressed in brain and skeletal tissues and are involved in the regulation of cell adhesion and growth, receptor degradation, and axonal guidance. Ack1 is also associated with androgen-independent prostate cancer progression. Tnk1 regulates TNFalpha signaling and may play an important role in cell death. The Ack-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270636 [Multi-domain] Cd Length: 258 Bit Score: 63.13 E-value: 4.62e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3309 GRFGVIRECRENATGN--LYMA-----KIVPYEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRyLVLISECCSgkel 3381
Cdd:cd05040      6 GSFGVVRRGEWTTPSGkvIQVAvkclkSDVLSQPNAMDDFLKEVNAMHSLDHPNLIRLYGVVLSSP-LMMVTELAP---- 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1207186029 3382 LHSLIDRFRYSEDDVVA-----YIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFG 3439
Cdd:cd05040     81 LGSLLDRLRKDQGHFLIstlcdYAVQIANGMAYLESKRFIHRDLAARNILLASKDKVKIGDFG 143

Pseudokinase domain of Ryk (Receptor related to tyrosine kinase); Ryk is a receptor tyr kinase (RTK) containing an extracellular region with two leucine-rich motifs, a transmembrane segment, and an intracellular inactive pseudokinase domain, which shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. The extracellular region of Ryk shows homology to the N-terminal domain of Wnt inhibitory factor-1 (WIF) and serves as the ligand (Wnt) binding domain of Ryk. Ryk is expressed in many different tissues both during development and in adults, suggesting a widespread function. It acts as a chemorepulsive axon guidance receptor of Wnt glycoproteins and is responsible for the establishment of axon tracts during the development of the central nervous system. In addition, studies in mice reveal that Ryk is essential in skeletal, craniofacial, and cardiac development. Thus, it appears Ryk is involved in signal transduction despite its lack of kinase activity. Ryk may function as an accessory protein that modulates the signals coming from catalytically active partner RTKs such as the Eph receptors. The Ryk subfamily is part of a larger superfamily that includes other pseudokinases and the catalytic domains of active kinases including PTKs, protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270639 [Multi-domain] Cd Length: 279 Bit Score: 63.62 E-value: 5.08e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3342 LQEYDILKSLHHEKIMA-LH---EAYVTPryLVLISEccSGKELLHSLIDRFRYSED---------DVVAYIVQILQGLD 3408
Cdd:cd05043     55 LQESSLLYGLSHQNLLPiLHvciEDGEKP--MVLYPY--MNWGNLKLFLQQCRLSEAnnpqalstqQLVHMALQIACGMS 130

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3409 YLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNP-----LFLKQFSPpigtLDYMSPEMLKGDVVGPPADIWSIGI 3483
Cdd:cd05043    131 YLHRRGVIHKDIAARNCVIDDELQVKITDNALSRDLFPmdyhcLGDNENRP----IKWMSLESLVNKEYSSASDVWSFGV 206

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1207186029 3484 LTYIMLS-GRLPFTENDPAETEARIQAAKfdlsKLYQNVSQSASLFIKKILCsypWA-----RPT 3542
Cdd:cd05043    207 LLWELMTlGQTPYVEIDPFEMAAYLKDGY----RLAQPINCPDELFAVMACC---WAldpeeRPS 264

serine/threonine kinase US3; Provisional

Pssm-ID: 165476 [Multi-domain] Cd Length: 501 Bit Score: 65.10 E-value: 5.12e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3347 ILKSLHHEKIMALHEAYVTPRYLVLISEccSGKELLHSlidrFRYSED----------DVVAYIVQILQGLDYLHSRRIL 3416
Cdd:PHA03210   216 ALGRLNHENILKIEEILRSEANTYMITQ--KYDFDLYS----FMYDEAfdwkdrpllkQTRAIMKQLLCAVEYIHDKKLI 289

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1207186029 3417 HLDIKPENIIVTYMNVVKIIDFGSAQTF-NPLFLKQFSpPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLS 3490
Cdd:PHA03210   290 HRDIKLENIFLNCDGKIVLGDFGTAMPFeKEREAFDYG-WVGTVATNSPEILAGDGYCEITDIWSCGLILLDMLS 363

Catalytic domain of the Serine/Threonine Kinase, PCTAIRE-2 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-2 is specifically expressed in neurons in the central nervous system, mainly in terminally differentiated neurons. It associates with Trap (Tudor repeat associator with PCTAIRE-2) and could play a role in regulating mitochondrial function in neurons. PCTAIRE-2 shares sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The PCTAIRE-2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143377 [Multi-domain] Cd Length: 309 Bit Score: 63.86 E-value: 5.72e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1657 RLTDYYDVHKeIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKA--SALRELNILSHLDHERILYFHDAFEKKNAVIII 1734
Cdd:cd07872      4 KMETYIKLEK-LGEGTYATVFKGRSKLTENLVALKEIRLEHEEGApcTAIREVSLLKDLKHANIVTLHDIVHTDKSLTLV 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1735 TELCHEELLDRLTKKSTILE-SEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSsdQIRICDFGNA-VKFMPDEA 1812
Cdd:cd07872     83 FEYLDKDLKQYMDDCGNIMSmHNVKIFLYQILRGLAYCHRRKVLHRDLKPQNLLINERG--ELKLADFGLArAKSVPTKT 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1813 QYCKYGTPEFVAPEI-VNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDR---------------------SSVLNIRN 1870
Cdd:cd07872    161 YSNEVVTLWYRPPDVlLGSSEYSTQIDMWGVGCIFFEMASGRPLFPGSTVEdelhlifrllgtpteetwpgiSSNDEFKN 240

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1207186029 1871 YNV-AFEESMFTDLCHEAKGFVIKLLVA-----DRLRPDANECLRHPWFKTLNKG-----KSISTESLK 1928
Cdd:cd07872    241 YNFpKYKPQPLINHAPRLDTEGIELLTKflqyeSKKRISAEEAMKHAYFRSLGTRihslpESISIFSLK 309

Catalytic domain of the Protein Tyrosine Kinase, Interleukin-2-inducible T-cell Kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Itk, also known as Tsk or Emt, is a member of the Tec-like subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, Itk contains the Tec homology (TH) domain containing one proline-rich region and a zinc-binding region. Itk is expressed in T-cells and mast cells, and is important in their development and differentiation. Of the three Tec kinases expressed in T-cells, Itk plays the predominant role in T-cell receptor (TCR) signaling. It is activated by phosphorylation upon TCR crosslinking and is involved in the pathway resulting in phospholipase C-gamma1 activation and actin polymerization. It also plays a role in the downstream signaling of the T-cell costimulatory receptor CD28, the T-cell surface receptor CD2, and the chemokine receptor CXCR4. In addition, Itk is crucial for the development of T-helper(Th)2 effector responses. The Itk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 133243 [Multi-domain] Cd Length: 256 Bit Score: 63.05 E-value: 5.74e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3301 TFMDEKARGRFGVI-----RECRENATgnlymaKIVPYEPESKQTVLQEYDILKSLHHEKIMALHEAYV--TPRYLV--- 3370
Cdd:cd05112      7 TFVQEIGSGQFGLVhlgywLNKDKVAI------KTIREGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLeqAPICLVfef 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3371 LISECCSgkELLHSliDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTfnpLFLK 3450
Cdd:cd05112     81 MEHGCLS--DYLRT--QRGLFSAETLLGMCLDVCEGMAYLEEASVIHRDLAARNCLVGENQVVKVSDFGMTRF---VLDD 153

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1207186029 3451 QFSPPIGT---LDYMSPEMLKGDVVGPPADIWSIGILTYIMLS-GRLPFTENDPAETEARIQA 3509
Cdd:cd05112    154 QYTSSTGTkfpVKWSSPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIPYENRSNSEVVEDINA 216

Pseudokinase domain of STE20-related kinase adapter protein; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. STRAD forms a complex with the scaffolding protein MO25, and the serine/threonine kinase (STK), LKB1, resulting in the activation of the kinase. In the complex, LKB1 phosphorylates and activates adenosine monophosphate-activated protein kinases (AMPKs), which regulate cell energy metabolism and cell polarity. LKB1 is a tumor suppressor linked to the rare inherited disease, Peutz-Jeghers syndrome, which is characterized by a predisposition to benign polyps and hyperpigmentation of the buccal mucosa. There are two forms of STRAD, alpha and beta, that complex with LKB1 and MO25. The structure of STRAD-alpha is available and shows that this protein binds ATP, has an ordered activation loop, and adopts a closed conformation typical of fully active protein kinases. It does not possess activity due to nonconservative substitutions of essential catalytic residues. ATP binding enhances the affinity of STRAD for MO25. The conformation of STRAD-alpha stabilized through ATP and MO25 may be needed to activate LKB1. The STRAD subfamily is part of a larger superfamily that includes the catalytic domains of STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270856 [Multi-domain] Cd Length: 315 Bit Score: 63.85 E-value: 6.15e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3318 RENATGNLYMAKIVPYEPESKQTV---LQEYDILKSLHHEKIMALHEAYVTPRYLVLISE-CCSGKELLhsLIDRFrYSE 3393
Cdd:cd08216     20 KHKPTNTLVAVKKINLESDSKEDLkflQQEILTSRQLQHPNILPYVTSFVVDNDLYVVTPlMAYGSCRD--LLKTH-FPE 96

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3394 ---DDVVAYIVQ-ILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTfnplFLKQ-------FSPPIGT---L 3459
Cdd:cd08216     97 glpELAIAFILRdVLNALEYIHSKGYIHRSVKASHILISGDGKVVLSGLRYAYS----MVKHgkrqrvvHDFPKSSeknL 172

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|...
gi 1207186029 3460 DYMSPEMLKGDVVG--PPADIWSIGILTYIMLSGRLPFTENDP 3500
Cdd:cd08216    173 PWLSPEVLQQNLLGynEKSDIYSVGITACELANGVVPFSDMPA 215

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409543 [Multi-domain] Cd Length: 94 Bit Score: 58.59 E-value: 6.62e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 2861 PVFHIKLRDHVLLEGDPVTLSCLPAGSPHPHISWMKDKKPLE--IDPRMNMISCPDGRQLLMIMKTTKKDAGLYECVAAN 2938
Cdd:cd20951      1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIDpsSIPGKYKIESEYGVHVLHIRRVTVEDSAVYSAVAKN 80

                           90
                   ....*....|.
gi 1207186029 2939 PLATVTSSCVV 2949
Cdd:cd20951     81 IHGEASSSASV 91

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409568 [Multi-domain] Cd Length: 90 Bit Score: 58.42 E-value: 6.65e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1544 APTFETIMEDLDVNVGETPRFAVVVEGKPVPDILWYK-GDTLLSESSHFTFvyDDNECSLVVLNTQADDSGVYTCTAKNL 1622
Cdd:cd20976      1 APSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRnAQPLQYAADRSTC--EAGVGELHIQDVLPEDHGTYTCLAKNA 78

                           90
                   ....*....|..
gi 1207186029 1623 AGSVSCKAELTV 1634
Cdd:cd20976     79 AGQVSCSAWVTV 90

Catalytic domain of the Protein Tyrosine Kinases, Fibroblast Growth Factor Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The FGFR subfamily consists of FGFR1, FGFR2, FGFR3, FGFR4, and similar proteins. They are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, and to heparin/heparan sulfate (HS) results in the formation of a ternary complex, which leads to receptor dimerization and activation, and intracellular signaling. There are at least 23 FGFs and four types of FGFRs. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. FGF/FGFR signaling is important in the regulation of embryonic development, homeostasis, and regenerative processes. Depending on the cell type and stage, FGFR signaling produces diverse cellular responses including proliferation, growth arrest, differentiation, and apoptosis. Aberrant signaling leads to many human diseases such as skeletal, olfactory, and metabolic disorders, as well as cancer. The FGFR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase .

Pssm-ID: 270646 [Multi-domain] Cd Length: 294 Bit Score: 63.21 E-value: 6.73e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3395 DVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPL-FLKQFSPpiGTLDY--MSPEMLKGDV 3471
Cdd:cd05053    134 DLVSFAYQVARGMEYLASKKCIHRDLAARNVLVTEDNVMKIADFGLARDIHHIdYYRKTTN--GRLPVkwMAPEALFDRV 211

                           90       100
                   ....*....|....*....|....*
gi 1207186029 3472 VGPPADIWSIGILTY-IMLSGRLPF 3495
Cdd:cd05053    212 YTHQSDVWSFGVLLWeIFTLGGSPY 236

Catalytic domain of the Serine/Threonine Kinase, Serine-aRginine Protein Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SRPK3 is highly expressed in the heart and skeletal muscles, and is controlled by a muscle-specific enhancer that is regulated by MEF2. It may play an important role in muscle development. SRPKs phosphorylate and regulate splicing factors from the SR protein family by specifically phosphorylating multiple serine residues residing in SR/RS dipeptide motifs (also known as RS domains). Phosphorylation of the RS domains enhances interaction with transportin SR and facilitates entry of the SR proteins into the nucleus. SRPKs contain a nonconserved insert domain, within the well-conserved catalytic kinase domain, that regulates their subcellular localization. The SRPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271120 [Multi-domain] Cd Length: 365 Bit Score: 63.88 E-value: 7.21e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3396 VVAYIVQILQGLDYLHSR-RILHLDIKPENIIVTYMNVV---------------------KIIDFGSAQTF-NPL----- 3447
Cdd:cd14218    121 VKSILRQVLQGLDYLHTKcKIIHTDIKPENILMCVDEGYvrrlaaeatiwqqagapppsgSSVSFGASDFLvNPLepqna 200

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1207186029 3448 ---------------FLKQFSPPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPF 3495
Cdd:cd14218    201 dkirvkiadlgnacwVHKHFTEDIQTRQYRALEVLIGAEYGTPADIWSTACMAFELATGDYLF 263

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409564 [Multi-domain] Cd Length: 91 Bit Score: 58.36 E-value: 7.45e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 2860 PPVFHIKLRDHVLLEGDPVTLSCLPAGSPHPHISWMKDKKPLEIDPRMNmISCPDGRQLLMIMKTTKKDAGLYECVAANP 2939
Cdd:cd20972      1 PPQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKELQNSPDIQ-IHQEGDLHSLIIAEAFEEDTGRYSCLATNS 79


                   ....*..
gi 1207186029 2940 LATVTSS 2946
Cdd:cd20972     80 VGSDTTS 86

Catalytic domain of the LIM domain kinase-like protein kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. Members of this subfamily include LIMK, Testicular or testis-specific protein kinase (TESK), and similar proteins. LIMKs are characterized as serine/threonine kinases (STKs) while TESKs are dual-specificity protein kinases. Both LIMK and TESK phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They are implicated in many cellular functions including cell spreading, motility, morphogenesis, meiosis, mitosis, and spermatogenesis. The LIMK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270967 [Multi-domain] Cd Length: 252 Bit Score: 62.51 E-value: 8.05e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYVKRVIQKAGKLEYAAKfISARAKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITEL----CHEELL 1743
Cdd:cd14065      1 LGKGFFGEVYKVTHRETGKVMVMK-ELKRFDEQRSFLKEVKLMRRLSHPNILRFIGVCVKDNKLNFITEYvnggTLEELL 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1744 DRLtkKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNIL--MADHSSDQIrICDFGNAVKfMPDE--------AQ 1813
Cdd:cd14065     80 KSM--DEQLPWSQRVSLAKDIASGMAYLHSKNIIHRDLNSKNCLvrEANRGRNAV-VADFGLARE-MPDEktkkpdrkKR 155

                          170       180       190
                   ....*....|....*....|....*....|....*.
gi 1207186029 1814 YCKYGTPEFVAPEIVNQTPVSKATDIWPIGVLtyLC 1849
Cdd:cd14065    156 LTVVGSPYWMAPEMLRGESYDEKVDVFSFGIV--LC 189

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.

Pssm-ID: 409406 [Multi-domain] Cd Length: 82 Bit Score: 57.60 E-value: 8.74e-10

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1207186029 1556 VNVGETPRFAVVVEGKPVPDILWYKGDTLLSESSHFTFVYDDNECSLVVLNTQADDSGVYTCTAKNLAGSVSckAELTV 1634
Cdd:cd05748      4 VRAGESLRLDIPIKGRPTPTVTWSKDGQPLKETGRVQIETTASSTSLVIKNAKRSDSGKYTLTLKNSAGEKS--ATINV 80

Catalytic domain of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Src subfamily members include Src, Lck, Hck, Blk, Lyn, Fgr, Fyn, Yrk, and Yes. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells and tumor vasculature, contributing to cancer progression and metastasis. Src kinases are overexpressed in a variety of human cancers, making them attractive targets for therapy. They are also implicated in acute inflammatory responses and osteoclast function. Src, Fyn, Yes, and Yrk are widely expressed, while Blk, Lck, Hck, Fgr, and Lyn show a limited expression pattern. The Src-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270630 [Multi-domain] Cd Length: 248 Bit Score: 62.30 E-value: 8.88e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1666 KEIGRGAFSYVKRVIQKaGKLEYAAKFISARAKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITEL-CHEELLD 1744
Cdd:cd05034      1 KKLGAGQFGEVWMGVWN-GTTKVAVKTLKPGTMSPEAFLQEAQIMKKLRHDKLVQLYAVCSDEEPIYIVTELmSKGSLLD 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1745 RLTKK--STILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSdqIRICDFGNAVKFMPDEaqYCKYGTPEF 1822
Cdd:cd05034     80 YLRTGegRALRLPQLIDMAAQIASGMAYLESRNYIHRDLAARNILVGENNV--CKVADFGLARLIEDDE--YTAREGAKF 155

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1207186029 1823 ----VAPEIVNQTPVSKATDIWPIGVLTYLCLT-GVSPFAGENDRSSVLNI-RNY 1871
Cdd:cd05034    156 pikwTAPEAALYGRFTIKSDVWSFGILLYEIVTyGRVPYPGMTNREVLEQVeRGY 210

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 57.89 E-value: 9.04e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 2869 DHVLLEGDPVTLSCLPAGSPHPHISWMKDKKPLEI-DPRMNMIscPDGRqlLMIMKTTKKDAGLYECVAANPLATVTSSC 2947
Cdd:cd20952      8 NQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLLGkDERITTL--ENGS--LQIKGAEKSDTGEYTCVALNLSGEATWSA 83


                   ..
gi 1207186029 2948 VV 2949
Cdd:cd20952     84 VL 85

Catalytic domain of the Protein Tyrosine Kinases, Platelet Derived Growth Factor Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The PDGFR subfamily consists of PDGFR alpha, PDGFR beta, KIT, CSF-1R, the mammalian FLT3, and similar proteins. They are receptor PTKs (RTKs) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. PDGFR kinase domains are autoinhibited by their juxtamembrane regions containing tyr residues. The binding to their ligands leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. PDGFR subfamily receptors are important in the development of a variety of cells. PDGFRs are expressed in a many cells including fibroblasts, neurons, endometrial cells, mammary epithelial cells, and vascular smooth muscle cells. PDGFR signaling is critical in normal embryonic development, angiogenesis, and wound healing. Kit is important in the development of melanocytes, germ cells, mast cells, hematopoietic stem cells, the interstitial cells of Cajal, and the pacemaker cells of the GI tract. CSF-1R signaling is critical in the regulation of macrophages and osteoclasts. Mammalian FLT3 plays an important role in the survival, proliferation, and differentiation of stem cells. The PDGFR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase .

Pssm-ID: 133186 [Multi-domain] Cd Length: 302 Bit Score: 62.89 E-value: 9.23e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3338 KQTVLQEYDILKSL-HHEKIMALHEAYVTPRYLVLISE-CCSGKEL--LHSLIDRFrYSEDDVVAYIVQILQGLDYLHSR 3413
Cdd:cd05055     82 REALMSELKIMSHLgNHENIVNLLGACTIGGPILVITEyCCYGDLLnfLRRKRESF-LTLEDLLSFSYQVAKGMAFLASK 160

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3414 RILHLDIKPENIIVTYMNVVKIIDFGSAQTF---NPLFLK--QFSPpigtLDYMSPEMLKGDVVGPPADIWSIGILTYIM 3488
Cdd:cd05055    161 NCIHRDLAARNVLLTHGKIVKICDFGLARDImndSNYVVKgnARLP----VKWMAPESIFNCVYTFESDVWSYGILLWEI 236


                   ..
gi 1207186029 3489 LS 3490
Cdd:cd05055    237 FS 238

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409568 [Multi-domain] Cd Length: 90 Bit Score: 58.03 E-value: 9.27e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1123 PLFTRKLDVLEVIEGRNARFDCKVSGTPPPQVIWSHFDRPLEENEDiRILKEGGRHSLIISHVSNEDEGLYTVAARNSHG 1202
Cdd:cd20976      2 PSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPLQYAAD-RSTCEAGVGELHIQDVLPEDHGTYTCLAKNAAG 80

                           90
                   ....*....|
gi 1207186029 1203 EDECAAELYV 1212
Cdd:cd20976     81 QVSCSAWVTV 90

cyclin-dependent kinase A; Provisional

Pssm-ID: 177649 [Multi-domain] Cd Length: 294 Bit Score: 62.91 E-value: 9.77e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1660 DYYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRK---ASALRELNILSHLDHERILYFHDAFEKKNAVIIITE 1736
Cdd:PLN00009     2 DQYEKVEKIGEGTYGVVYKARDRVTNETIALKKIRLEQEDEgvpSTAIREISLLKEMQHGNIVRLQDVVHSEKRLYLVFE 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1737 LCHEELLDRLTKKSTILESE--IRSSVRQLLEGINYLHQLDILHLDIKPDNILMaDHSSDQIRICDFGNAVKF-MPDEAQ 1813
Cdd:PLN00009    82 YLDLDLKKHMDSSPDFAKNPrlIKTYLYQILRGIAYCHSHRVLHRDLKPQNLLI-DRRTNALKLADFGLARAFgIPVRTF 160

                          170       180       190
                   ....*....|....*....|....*....|....*
gi 1207186029 1814 YCKYGTPEFVAPEIV-----NQTPVskatDIWPIG 1843
Cdd:PLN00009   161 THEVVTLWYRAPEILlgsrhYSTPV----DIWSVG 191

Catalytic domain of the Protein Tyrosine Kinase, Focal Adhesion Kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. FAK is a cytoplasmic (or nonreceptor) PTK that contains an autophosphorylation site and a FERM domain at the N-terminus, a central tyr kinase domain, proline-rich regions, and a C-terminal FAT (focal adhesion targeting) domain. FAK activity is dependent on integrin-mediated cell adhesion, which facilitates N-terminal autophosphorylation. Full activation is achieved by the phosphorylation of its two adjacent A-loop tyrosines. FAK is important in mediating signaling initiated at sites of cell adhesions and at growth factor receptors. Through diverse molecular interactions, FAK functions as a biosensor or integrator to control cell motility. It is a key regulator of cell survival, proliferation, migration and invasion, and thus plays an important role in the development and progression of cancer. Src binds to autophosphorylated FAK forming the FAK-Src dual kinase complex, which is activated in a wide variety of tumor cells and generates signals promoting growth and metastasis. FAK is being developed as a target for cancer therapy. The FAK subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 133187 [Multi-domain] Cd Length: 270 Bit Score: 62.44 E-value: 9.80e-10

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYVKRVI---QKAGKLEYAAKF--ISARAKRKASALRELNILSHLDHERILYFHDAFEKkNAVIIITELC-HEE 1741
Cdd:cd05056     14 IGEGQFGDVYQGVymsPENEKIAVAVKTckNCTSPSVREKFLQEAYIMRQFDHPHIVKLIGVITE-NPVWIVMELApLGE 92

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1742 LLDRLTKKSTILESEIRSS-VRQLLEGINYLHQLDILHLDIKPDNILMAdhSSDQIRICDFGNAvKFMPDEAQY--CKYG 1818
Cdd:cd05056     93 LRSYLQVNKYSLDLASLILyAYQLSTALAYLESKRFVHRDIAARNVLVS--SPDCVKLGDFGLS-RYMEDESYYkaSKGK 169

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1207186029 1819 TP-EFVAPEIVNQTPVSKATDIWPIGVLTYLCLT-GVSPFAGENDRSSVLNIRN 1870
Cdd:cd05056    170 LPiKWMAPESINFRRFTSASDVWMFGVCMWEILMlGVKPFQGVKNNDVIGRIEN 223

Immunoglobulin-like domain of human Aortic Preferentially Expressed Protein-1 (APEG-1) and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin I-set (IgI) domain of the Human Aortic Preferentially Expressed Protein-1 (APEG-1) and similar proteins. APEG-1 is a novel specific smooth muscle differentiation marker predicted to play a role in the growth and differentiation of arterial smooth muscle cells (SMCs). The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the human APEG-1 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409567 Cd Length: 91 Bit Score: 57.87 E-value: 1.09e-09

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1207186029 2861 PVFHIKLRDHVLLEGDPVTLSCLPAGSPHPHISWMKDKKPLEIDPRMNMISCPDGRQLLMIMKTTKKDAGLYECVAAN 2938
Cdd:cd20975      1 PTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEAEGGLCRLRILAAERGDAGFYTCKAVN 78

Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LRRK2 is one of two vertebrate LRRKs which show complementary expression in the brain. Mutations in LRRK2, found in the kinase, ROC-COR, and WD40 domains, are linked to both familial and sporadic forms of Parkinson's disease. The most prevalent mutation, G2019S located in the activation loop of the kinase domain, increases kinase activity. The R1441C/G mutations in the GTPase domain have also been reported to influence kinase activity. LRRKs are also classified as ROCO proteins because they contain a ROC (Ras of complex proteins)/GTPase domain followed by a COR (C-terminal of ROC) domain of unknown function. In addition, LRRKs contain a catalytic kinase domain and protein-protein interaction motifs including a WD40 domain, LRRs and ankyrin (ANK) repeats. LRRKs possess both GTPase and kinase activities, with the ROC domain acting as a molecular switch for the kinase domain, cycling between a GTP-bound state which drives kinase activity and a GDP-bound state which decreases the activity. The LRRK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270970 [Multi-domain] Cd Length: 252 Bit Score: 61.89 E-value: 1.11e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYVKRVIQKagKLEYAAKFISARAKRKAsaLR-ELNILSHLDHERILYFHDAFEKKNAVIIitELCHEELLDRL 1746
Cdd:cd14068      2 LGDGGFGSVYRAVYR--GEDVAVKIFNKHTSFRL--LRqELVVLSHLHHPSLVALLAAGTAPRMLVM--ELAPKGSLDAL 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1747 TKK-STILESEIRSSVR-QLLEGINYLHQLDILHLDIKPDNILMADHSSDQ---IRICDFGnavkfmpdEAQYC------ 1815
Cdd:cd14068     76 LQQdNASLTRTLQHRIAlHVADGLRYLHSAMIIYRDLKPHNVLLFTLYPNCaiiAKIADYG--------IAQYCcrmgik 147

                          170       180       190
                   ....*....|....*....|....*....|....*....
gi 1207186029 1816 -KYGTPEFVAPEIVNQTPV-SKATDIWPIGVLTYLCLTG 1852
Cdd:cd14068    148 tSEGTPGFRAPEVARGNVIyNQQADVYSFGLLLYDILTC 186

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409543 [Multi-domain] Cd Length: 94 Bit Score: 57.82 E-value: 1.11e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1545 PTFETIMEDLDVNVGETPRFAVVVEGKPVPDILWYKGDTLLSESSH---FTFVYDDNECSLVVLNTQADDSGVYTCTAKN 1621
Cdd:cd20951      1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIDPSSIpgkYKIESEYGVHVLHIRRVTVEDSAVYSAVAKN 80

                           90
                   ....*....|...
gi 1207186029 1622 LAGSVSCKAELTV 1634
Cdd:cd20951     81 IHGEASSSASVVV 93

C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein (also known as myomesin-2). Myomesin and M-protein are both structural proteins localized to the M-band, a transverse structure in the center of the sarcomere, and are candidates for M-band bridges. Both proteins are modular, consisting mainly of repetitive Ig-like and fibronectin type III (FnIII) domains. Myomesin is expressed in all types of vertebrate striated muscle; M-protein has a muscle-type specific expression pattern. Myomesin is present in both slow and fast fibers; M-protein is present only in fast fibers. It has been suggested that myomesin acts as a molecular spring with alternative splicing as a means of modifying its elasticity.

Pssm-ID: 319300 Cd Length: 92 Bit Score: 57.99 E-value: 1.11e-09

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1207186029 1130 DVLEVIEGRNARFDCKVSGTPPPQVIWSHFDRPLEENEDIRILKEGGRH-SLIISHVSNEDEGLYTVAARNSHG 1202
Cdd:cd05737      9 DVVTIMEGKTLNLTCNVWGDPPPEVSWLKNDQALAFLDHCNLKVEAGRTvYFTINGVSSEDSGKYGLVVKNKYG 82

Pseudokinase domain of Tribbles Homolog 1; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. TRB1 interacts directly with the mitogen activated protein kinase (MAPK) kinase MKK4, an activator of JNK. It regulates vascular smooth muscle cell proliferation and chemotaxis through the JNK signaling pathway. It is found to be down-regulated in human acute myeloid leukaemia (AML) and may play a role in the pathogenesis of the disease. It has also been identified as a potential biomarker for antibody-mediated allograft failure. TRB1 is one of three Tribbles Homolog (TRB) proteins present in vertebrates that are encoded by three separate genes. TRB proteins interact with many proteins involved in signalling pathways. They play scaffold-like regulatory functions and affect many cellular processes such as mitosis, apoptosis, and gene expression. The TRB1 subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270925 [Multi-domain] Cd Length: 242 Bit Score: 61.60 E-value: 1.15e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3461 YMSPEMLK--GDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLSklyQNVSQSASLFIKKILCSYPW 3538
Cdd:cd14023    152 YVSPEILNttGTYSGKSADVWSLGVMLYTLLVGRYPFHDSDPSALFSKIRRGQFCIP---DHVSPKARCLIRSLLRREPS 228

                           90
                   ....*....|....
gi 1207186029 3539 ARPTIKDCFTNSWL 3552
Cdd:cd14023    229 ERLTAPEILLHPWF 242

Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Alternative splicing of FGFR1 transcripts produces a variety of isoforms, which are differentially expressed in cells. FGFR1 binds the ligands, FGF1 and FGF2, with high affinity and has also been reported to bind FGF4, FGF6, and FGF9. FGFR1 signaling is critical in the control of cell migration during embryo development. It promotes cell proliferation in fibroblasts. Nuclear FGFR1 plays a role in the regulation of transcription. Mutations, insertions or deletions of FGFR1 have been identified in patients with Kallman's syndrome (KS), an inherited disorder characterized by hypogonadotropic hypogonadism and loss of olfaction. Aberrant FGFR1 expression has been found in some human cancers including 8P11 myeloproliferative syndrome (EMS), breast cancer, and pancreatic adenocarcinoma. FGFR1 is part of the FGFR subfamily, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. The FGFR1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270678 [Multi-domain] Cd Length: 302 Bit Score: 62.72 E-value: 1.20e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3392 SEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPL-FLKQFSPPIGTLDYMSPEMLKGD 3470
Cdd:cd05098    133 SSKDLVSCAYQVARGMEYLASKKCIHRDLAARNVLVTEDNVMKIADFGLARDIHHIdYYKKTTNGRLPVKWMAPEALFDR 212

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1207186029 3471 VVGPPADIWSIGILTY-IMLSGRLPFTeNDPAETEARIQAAKFDLSKLyQNVSQSASLFIKKILCSYPWARPTIK 3544
Cdd:cd05098    213 IYTHQSDVWSFGVLLWeIFTLGGSPYP-GVPVEELFKLLKEGHRMDKP-SNCTNELYMMMRDCWHAVPSQRPTFK 285

Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409582 Cd Length: 91 Bit Score: 57.80 E-value: 1.21e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1249 PDFVKPLYDMDVVEGREAVLRCKVAGLPYPTITWFHNGKRIDSTEDRKM-TQFRDVHSLVVRCVCHAHGGVYKCVISNKV 1327
Cdd:cd20990      1 PHFLQAPGDLTVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIRPDSAHKMlVRENGVHSLIIEPVTSRDAGIYTCIATNRA 80


                   ..
gi 1207186029 1328 GK 1329
Cdd:cd20990     81 GQ 82

Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LIMK1 activation is induced by bone morphogenic protein, vascular endothelial growth factor, and thrombin. It plays roles in microtubule disassembly and cell cycle progression, and is critical in the regulation of neurite outgrowth. LIMK1 knockout mice show abnormalities in dendritic spine morphology and synaptic function. LIMK1 is one of the genes deleted in patients with Williams Syndrome, which is characterized by distinct craniofacial features, cardiovascular problems, as well as behavioral and neurological abnormalities. LIMKs phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They act downstream of Rho GTPases and are expressed ubiquitously. As regulators of actin dynamics, they contribute to diverse cellular functions such as cell motility, morphogenesis, differentiation, apoptosis, meiosis, mitosis, and neurite extension. LIMKs contain the LIM (two repeats), PDZ, and catalytic kinase domains. The LIMK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271123 [Multi-domain] Cd Length: 267 Bit Score: 62.28 E-value: 1.24e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYVKRVIQK-AGKLEYAAKFISARAKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITELCHEELLDRL 1746
Cdd:cd14221      1 LGKGCFGQAIKVTHReTGEVMVMKELIRFDEETQRTFLKEVKVMRCLEHPNVLKFIGVLYKDKRLNFITEYIKGGTLRGI 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1747 TKK--STILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSdqIRICDFGNAvKFMPDEA------------ 1812
Cdd:cd14221     81 IKSmdSHYPWSQRVSFAKDIASGMAYLHSMNIIHRDLNSHNCLVRENKS--VVVADFGLA-RLMVDEKtqpeglrslkkp 157

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|.
gi 1207186029 1813 ----QYCKYGTPEFVAPEIVNQTPVSKATDIWPIGVLtyLC 1849
Cdd:cd14221    158 drkkRYTVVGNPYWMAPEMINGRSYDEKVDVFSFGIV--LC 196

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409565 [Multi-domain] Cd Length: 88 Bit Score: 57.58 E-value: 1.27e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029   58 IRKMRNAAVGTGCDIRLKVAVAGDPQPTLYWYHNDDLVNMDNQ---EYGG-----LWIRDCKPSDAGLYTCIATNHLGEA 129
Cdd:cd20973      1 IQTLRDKEVVEGSAARFDCKVEGYPDPEVKWMKDDNPIVESRRfqiDQDEdglcsLIISDVCGDDSGKYTCKAVNSLGEA 80


                   ....*...
gi 1207186029  130 RSSAVLAV 137
Cdd:cd20973     81 TCSAELTV 88

Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The VEGFR subfamily consists of VEGFR1 (Flt1), VEGFR2 (Flk1), VEGFR3 (Flt4), and similar proteins. VEGFR subfamily members are receptor PTKss (RTKs) containing an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and an intracellular catalytic domain. In VEGFR3, the fifth Ig-like domain is replaced by a disulfide bridge. The binding of VEGFRs to their ligands, the VEGFs, leads to receptor dimerization, activation, and intracellular signaling. There are five VEGF ligands in mammals, which bind, in an overlapping pattern to the three VEGFRs, which can form homo or heterodimers. VEGFRs regulate the cardiovascular system. They are critical for vascular development during embryogenesis and blood vessel formation in adults. They induce cellular functions common to other growth factor receptors such as cell migration, survival, and proliferation. The VEGFR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270647 [Multi-domain] Cd Length: 298 Bit Score: 62.51 E-value: 1.28e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3394 DDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTF--NPLFLKQFSPPIgTLDYMSPEMLKGDV 3471
Cdd:cd05054    138 EDLICYSFQVARGMEFLASRKCIHRDLAARNILLSENNVVKICDFGLARDIykDPDYVRKGDARL-PLKWMAPESIFDKV 216

                           90
                   ....*....|....*....
gi 1207186029 3472 VGPPADIWSIGILTYIMLS 3490
Cdd:cd05054    217 YTTQSDVWSFGVLLWEIFS 235

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 56.95 E-value: 1.30e-09

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1207186029  945 VTMSVLVTGQPKPMLYWLRDRVTIKTGTRHIVqETEEGNFEMIIKSAQRSDTGVYTCKIINEYGTKQ 1011
Cdd:cd00096      1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSR-RSELGNGTLTISNVTLEDSGTYTCVASNSAGGSA 66

First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409566 [Multi-domain] Cd Length: 93 Bit Score: 57.36 E-value: 1.44e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 2861 PVFHIKLRDHVLLEGDPVTLSCLPAGSPHPHISWMKDKKPLEID--PRMNmISCPDGRQLLMIMKTTKKDAGLYECVAAN 2938
Cdd:cd20974      1 PVFTQPLQSVVVLEGSTATFEAHVSGKPVPEVSWFRDGQVISTStlPGVQ-ISFSDGRAKLSIPAVTKANSGRYSLTATN 79

                           90
                   ....*....|.
gi 1207186029 2939 PLATVTSSCVV 2949
Cdd:cd20974     80 GSGQATSTAEL 90

serine/threonine kinase US3; Provisional

Pssm-ID: 165478 [Multi-domain] Cd Length: 391 Bit Score: 63.09 E-value: 1.45e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1696 RAKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITELCHEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLD 1775
Cdd:PHA03212   123 KAGQRGGTATEAHILRAINHPSIIQLKGTFTYNKFTCLILPRYKTDLYCYLAAKRNIAICDILAIERSVLRAIQYLHENR 202

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1776 ILHLDIKPDNILMaDHSSDqirIC--DFGNAVkfMPDEAQYCKY----GTPEFVAPEIVNQTPVSKATDIWPIGVLTYLC 1849
Cdd:PHA03212   203 IIHRDIKAENIFI-NHPGD---VClgDFGAAC--FPVDINANKYygwaGTIATNAPELLARDPYGPAVDIWSAGIVLFEM 276


                   ...
gi 1207186029 1850 LTG 1852
Cdd:PHA03212   277 ATC 279

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409568 [Multi-domain] Cd Length: 90 Bit Score: 57.26 E-value: 1.52e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  780 APVFEFPLQDTVASTGTEVLLKCIISGTPLPEVIWKKDNTEVKNSPTHvVKIEGERHSLLIKWTKPSDAGTYTVTAVNEV 859
Cdd:cd20976      1 APSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPLQYAADR-STCEAGVGELHIQDVLPEDHGTYTCLAKNAA 79


                   ....*....
gi 1207186029  860 GEVSSSATL 868
Cdd:cd20976     80 GQVSCSAWV 88

Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNK1 is widely expressed and is most abundant in the testis. In hyperosmotic or hypotonic low-chloride stress conditions, WNK1 is activated and it phosphorylates its substrates including SPAK and OSR1 kinases, which regulate the activity of cation-chloride cotransporters through direct interaction and phosphorylation. Mutations in WNK1 cause PseudoHypoAldosteronism type II (PHAII), characterized by hypertension and hyperkalemia. WNK1 negates WNK4-mediated inhibition of the sodium-chloride cotransporter NCC and activates the epithelial sodium channel ENaC by activating SGK1. WNK1 also decreases the surface expression of renal outer medullary potassium channel (ROMK) by stimulating their endocytosis. Hypertension and hyperkalemia in PHAII patients with WNK1 mutations may be due partly to increased activity of NCC and ENaC, and impaired renal potassium secretion by ROMK, respectively. In addition, WNK1 interacts with MEKK2/3 and acts as an activator of extracellular signal-regulated kinase (ERK) 5. It also negatively regulates TGFbeta signaling. WNKs comprise a subfamily of STKs with an unusual placement of the catalytic lysine relative to all other protein kinases. The WNK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270932 [Multi-domain] Cd Length: 289 Bit Score: 61.99 E-value: 1.56e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3338 KQTVLQEYDILKSLHHEKIMALHEAYVTP----RYLVLISECCSGKELlHSLIDRFRYSEDDVV-AYIVQILQGLDYLHS 3412
Cdd:cd14030     68 RQRFKEEAGMLKGLQHPNIVRFYDSWESTvkgkKCIVLVTELMTSGTL-KTYLKRFKVMKIKVLrSWCRQILKGLQFLHT 146

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3413 RR--ILHLDIKPENIIVT-YMNVVKIIDFGSAQTFNPLFLKQFsppIGTLDYMSPEMLKgDVVGPPADIWSIGILTYIML 3489
Cdd:cd14030    147 RTppIIHRDLKCDNIFITgPTGSVKIGDLGLATLKRASFAKSV---IGTPEFMAPEMYE-EKYDESVDVYAFGMCMLEMA 222

                          170       180
                   ....*....|....*....|....*....
gi 1207186029 3490 SGRLPFTE-NDPAETEAR----IQAAKFD 3513
Cdd:cd14030    223 TSEYPYSEcQNAAQIYRRvtsgVKPASFD 251

Catalytic domain of the protein kinase, Dual-specificity tYrosine-phosphorylated and -Regulated Kinase 4; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. DYRK4 is a testis-specific kinase with restricted expression to postmeiotic spermatids. It may function during spermiogenesis, however, it is not required for male fertility. DYRK4 has also been detected in a human teratocarcinoma cell line induced to produce postmitotic neurons. It may have a role in neuronal differentiation. DYRKs autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. They play important roles in cell proliferation, differentiation, survival, and development. The DYRK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271127 [Multi-domain] Cd Length: 341 Bit Score: 62.80 E-value: 1.59e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGK 3379
Cdd:cd14225     45 YEILEVIGKGSFGQVVKALDHKTNEHVAIKIIRNKKRFHHQALVEVKILDALRRKDRDNSHNVIHMKEYFYFRNHLCITF 124

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3380 EL----LHSLIDR--FR-YSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTY--MNVVKIIDFGSAQTFNplflK 3450
Cdd:cd14225    125 ELlgmnLYELIKKnnFQgFSLSLIRRFAISLLQCLRLLYRERIIHCDLKPENILLRQrgQSSIKVIDFGSSCYEH----Q 200

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1207186029 3451 QFSPPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFtendPAETEA 3505
Cdd:cd14225    201 RVYTYIQSRFYRSPEVILGLPYSMAIDMWSLGCILAELYTGYPLF----PGENEV 251

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 57.03 E-value: 1.73e-09

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1207186029 2868 RDHVLLEGDPVTLSCLPA-GSPHPHISWMKDKKPLEID-PRMNMIScpDGRqlLMIMKTTKKDAGLYECVAAN 2938
Cdd:cd05724      5 SDTQVAVGEMAVLECSPPrGHPEPTVSWRKDGQPLNLDnERVRIVD--DGN--LLIAEARKSDEGTYKCVATN 73

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 57.02 E-value: 1.85e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  938 SVIEGQEVTMSVLVTGQPKPMLYWLR--DRVTIKTGTRHIVQETeegnfeMIIKSAQRSDTGVYTCKIINEYGTKQCEGK 1015
Cdd:cd20978     12 VVKGGQDVTLPCQVTGVPQPKITWLHngKPLQGPMERATVEDGT------LTIINVQPEDTGYYGCVATNEIGDIYTETL 85


                   ...
gi 1207186029 1016 LEV 1018
Cdd:cd20978     86 LHV 88

Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jak1 is widely expressed in many tissues. Many cytokines are dependent on Jak1 for signaling, including those that use the shared receptor subunits common gamma chain (IL-2, IL-4, IL-7, IL-9, IL-15, IL-21) and gp130 (IL-6, IL-11, oncostatin M, G-CSF, and IFNs, among others). The many varied interactions of Jak1 and its ubiquitous expression suggest many biological roles. Jak1 is important in neurological development, as well as in lymphoid development and function. It also plays a role in the pathophysiology of cardiac hypertrophy and heart failure. A mutation in the ATP-binding site of Jak1 was identified in a human uterine leiomyosarcoma cell line, resulting in defective cytokine induction and antigen presentation, thus allowing the tumor to evade the immune system. Jak1 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The Jak1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173644 [Multi-domain] Cd Length: 284 Bit Score: 61.48 E-value: 2.16e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3309 GRFGVIRECRENA----TGNLYMAKIVpyEPESKQT----VLQEYDILKSLHHEKIMAlHEAYVTP---RYLVLISE--- 3374
Cdd:cd05079     15 GHFGKVELCRYDPegdnTGEQVAVKSL--KPESGGNhiadLKKEIEILRNLYHENIVK-YKGICTEdggNGIKLIMEflp 91

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3375 CCSGKELLHSLIDRFRYSEddVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPlfLKQFSP 3454
Cdd:cd05079     92 SGSLKEYLPRNKNKINLKQ--QLKYAVQICKGMDYLGSRQYVHRDLAARNVLVESEHQVKIGDFGLTKAIET--DKEYYT 167

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|
gi 1207186029 3455 PIGTLD----YMSPEMLKGDVVGPPADIWSIGILTYIMLS 3490
Cdd:cd05079    168 VKDDLDspvfWYAPECLIQSKFYIASDVWSFGVTLYELLT 207

Catalytic domain of the Protein Tyrosine Kinase, Wee1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Wee1 is a nuclear cell cycle checkpoint kinase that helps keep the cyclin-dependent kinase CDK1 in an inactive state through phosphorylation of an N-terminal tyr (Y15) residue. During the late G2 phase, CDK1 is activated and mitotic entry is promoted by the removal of this inhibitory phosphorylation by the phosphatase Cdc25. Although Wee1 is functionally a tyr kinase, it is more closely related to serine/threonine kinases (STKs). It contains a catalytic kinase domain sandwiched in between N- and C-terminal regulatory domains. It is regulated by phosphorylation and degradation, and its expression levels are also controlled by circadian clock proteins. There are two distinct Wee1 proteins in vertebrates showing different expression patterns, called Wee1a and Wee1b. They are functionally dstinct and are implicated in different steps of egg maturation and embryo development. The Wee1 subfamily is part of a larger superfamily that includes the catalytic domains of STKs, other PTKs, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270953 [Multi-domain] Cd Length: 275 Bit Score: 61.27 E-value: 2.23e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3309 GRFGVIRECRENATGNLYMAKivpyepESKQTVLQEYDilkslhhEKiMALHEAYV---------TPRY---------LV 3370
Cdd:cd14051     11 GEFGSVYKCINRLDGCVYAIK------KSKKPVAGSVD-------EQ-NALNEVYAhavlgkhphVVRYysawaeddhMI 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3371 LISECCSGKellhSLIDRF--------RYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVT-------------- 3428
Cdd:cd14051     77 IQNEYCNGG----SLADAIsenekageRFSEAELKDLLLQVAQGLKYIHSQNLVHMDIKPGNIFISrtpnpvsseeeeed 152

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3429 ----------YMNVVKIIDFGSAQTFNplflkqfSPPI--GTLDYMSPEMLKGDVVG-PPADIWSIGiLTYIMLSGRLPF 3495
Cdd:cd14051    153 fegeednpesNEVTYKIGDLGHVTSIS-------NPQVeeGDCRFLANEILQENYSHlPKADIFALA-LTVYEAAGGGPL 224

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*..
gi 1207186029 3496 TENDPAETEARiqaaKFDLSKLyQNVSQSASLFIKKILCSYPWARPT 3542
Cdd:cd14051    225 PKNGDEWHEIR----QGNLPPL-PQCSPEFNELLRSMIHPDPEKRPS 266

NIMA-related protein kinase; Provisional

Pssm-ID: 173502 [Multi-domain] Cd Length: 1021 Bit Score: 63.60 E-value: 2.45e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVPY----EPESKQTVLqEYDILKSLHHEKIMALHEAYVTP--RYLVLIS 3373
Cdd:PTZ00266    15 YEVIKKIGNGRFGEVFLVKHKRTQEFFCWKAISYrglkEREKSQLVI-EVNVMRELKHKNIVRYIDRFLNKanQKLYILM 93

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3374 ECCSGKELLHSLIDRFRY----SEDDVVAYIVQILQGLDYLHS-------RRILHLDIKPENIIVTY------------- 3429
Cdd:PTZ00266    94 EFCDAGDLSRNIQKCYKMfgkiEEHAIVDITRQLLHALAYCHNlkdgpngERVLHRDLKPQNIFLSTgirhigkitaqan 173

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3430 -MN---VVKIIDFGSAQTFNPLFLKQFSppIGTLDYMSPEMLKGDV--VGPPADIWSIGILTYIMLSGRLPFTE-NDPAE 3502
Cdd:PTZ00266   174 nLNgrpIAKIGDFGLSKNIGIESMAHSC--VGTPYYWSPELLLHETksYDDKSDMWALGCIIYELCSGKTPFHKaNNFSQ 251

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*
gi 1207186029 3503 TEARIQAAKfDLSklYQNVSQSASLFIKKILCSYPWARPTIKDCF 3547
Cdd:PTZ00266   252 LISELKRGP-DLP--IKGKSKELNILIKNLLNLSAKERPSALQCL 293

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409568 [Multi-domain] Cd Length: 90 Bit Score: 56.87 E-value: 2.46e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 2860 PPVFHIKLRDHVLLEGDPVTLSCLPAGSPHPHISWMKDKKPLEIDPrmNMISCPDGRQLLMIMKTTKKDAGLYECVAANP 2939
Cdd:cd20976      1 APSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPLQYAA--DRSTCEAGVGELHIQDVLPEDHGTYTCLAKNA 78

                           90
                   ....*....|..
gi 1207186029 2940 LATVTSSCVVSL 2951
Cdd:cd20976     79 AGQVSCSAWVTV 90

Catalytic domain of the Serine/Threonine Kinase, Pre-mRNA-Processing factor 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PRP4 phosphorylates a number of factors involved in the formation of active spliceosomes, which catalyze pre-mRNA splicing. It phosphorylates PRP6 and PRP31, components of the U4/U6-U5 tri-small nuclear ribonucleoprotein (snRNP), during spliceosomal complex formation. In fission yeast, PRP4 phosphorylates the splicing factor PRP1 (U5-102 kD in mammals). Thus, PRP4 plays a key role in regulating spliceosome assembly and pre-mRNA splicing. It also plays an important role in mitosis by acting as a spindle assembly checkpoint kinase that is required for chromosome alignment and the recruitment of the checkpoint proteins MPS1, MAD1, and MAD2 at kinetochores. The PRP4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271037 [Multi-domain] Cd Length: 318 Bit Score: 61.85 E-value: 2.55e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMA-KIVPYEPESKQTVLQEYDILKSLH--------HekIMALHEAYVTPRYLV 3370
Cdd:cd14135      2 YRVYGYLGKGVFSNVVRARDLARGNQEVAiKIIRNNELMHKAGLKELEILKKLNdadpddkkH--CIRLLRHFEHKNHLC 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3371 LISECCSGKelLHSLIDRFR----YSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTY-MNVVKIIDFGSAQTFN 3445
Cdd:cd14135     80 LVFESLSMN--LREVLKKYGknvgLNIKAVRSYAQQLFLALKHLKKCNILHADIKPDNILVNEkKNTLKLCDFGSASDIG 157

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1207186029 3446 -----PLFLKQFsppigtldYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPF---TEND 3499
Cdd:cd14135    158 eneitPYLVSRF--------YRAPEIILGLPYDYPIDMWSVGCTLYELYTGKILFpgkTNNH 211

Catalytic domain of the Protein Tyrosine Kinase, Fes; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Fes (or Fps) is a cytoplasmic (or nonreceptor) PTK containing an N-terminal region with FCH (Fes/Fer/CIP4 homology) and coiled-coil domains, followed by a SH2 domain, and a C-terminal catalytic domain. The genes for Fes (feline sarcoma) and Fps (Fujinami poultry sarcoma) were first isolated from tumor-causing retroviruses. The viral oncogenes encode chimeric Fes proteins consisting of Gag sequences at the N-termini, resulting in unregulated PTK activity. Fes kinase is expressed in myeloid, vascular endothelial, epithelial, and neuronal cells. It plays important roles in cell growth and differentiation, angiogenesis, inflammation and immunity, and cytoskeletal regulation. A recent study implicates Fes kinase as a tumor suppressor in colorectal cancer. The Fes subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270667 [Multi-domain] Cd Length: 252 Bit Score: 60.71 E-value: 2.56e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAK----IVPyePESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLH 3383
Cdd:cd05084      6 RGNFGEVFSGRLRADNTPVAVKscreTLP--PDLKAKFLQEARILKQYSHPNIVRLIGVCTQKQPIYIVMELVQGGDFLT 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3384 SLID---RFRYSEddVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFG-SAQTFNPLF-----LKQFsp 3454
Cdd:cd05084     84 FLRTegpRLKVKE--LIRMVENAAAGMEYLESKHCIHRDLAARNCLVTEKNVLKISDFGmSREEEDGVYaatggMKQI-- 159

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1207186029 3455 PIgtlDYMSPEMLKGDVVGPPADIWSIGILTYIMLS-GRLPFTENDPAETEARIQ 3508
Cdd:cd05084    160 PV---KWTAPEALNYGRYSSESDVWSFGILLWETFSlGAVPYANLSNQQTREAVE 211

Catalytic domain of the Dual-specificity Protein Kinase, Dusty; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. Dusty protein kinase is also called Receptor-interacting protein kinase 5 (RIPK5 or RIP5) or RIP-homologous kinase. It is widely distributed in the central nervous system, and may be involved in inducing both caspase-dependent and caspase-independent cell death. The Dusty subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270877 [Multi-domain] Cd Length: 262 Bit Score: 60.97 E-value: 2.68e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3305 EKARGRFGVIRECRE-NATGNLYMAKIVPYEPESKQTVLQEYDILKSL-HHEKIMALHEAYVTPRY-------LVLISEC 3375
Cdd:cd13975      7 ELGRGQYGVVYACDSwGGHFPCALKSVVPPDDKHWNDLALEFHYTRSLpKHERIVSLHGSVIDYSYgggssiaVLLIMER 86

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3376 CSGKelLHSLIdRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGsaqtfnplflkqFSPP 3455
Cdd:cd13975     87 LHRD--LYTGI-KAGLSLEERLQIALDVVEGIRFLHSQGLVHRDIKLKNVLLDKKNRAKITDLG------------FCKP 151

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1207186029 3456 --------IGTLDYMSPEMLKGDvVGPPADIWSIGILTYIMLSG--RLPFT 3496
Cdd:cd13975    152 eammsgsiVGTPIHMAPELFSGK-YDNSVDVYAFGILFWYLCAGhvKLPEA 201

Catalytic domain of the Serine/Threonine Kinase, Large Tumor Suppressor 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LATS1 functions as a tumor suppressor and is implicated in cell cycle regulation. Inactivation of LATS1 in mice results in the development of various tumors, including sarcomas and ovarian cancer. Promoter methylation, loss of heterozygosity, and missense mutations targeting the LATS1 gene have also been found in human sarcomas and ovarian cancers. In addition, decreased expression of LATS1 is associated with an aggressive phenotype and poor prognosis. LATS1 induces G2 arrest and promotes cytokinesis. It may be a component of the mitotic exit network in higher eukaryotes. The LATS1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270775 [Multi-domain] Cd Length: 382 Bit Score: 62.37 E-value: 2.73e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3309 GRFGVIRECRENATGNLYMAKIVpyepESKQTVLQ--------EYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKE 3380
Cdd:cd05625     12 GAFGEVCLARKVDTKALYATKTL----RKKDVLLRnqvahvkaERDILAEADNEWVVRLYYSFQDKDNLYFVMDYIPGGD 87

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3381 LLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPL------------- 3447
Cdd:cd05625     88 MMSLLIRMGVFPEDLARFYIAELTCAVESVHKMGFIHRDIKPDNILIDRDGHIKLTDFGLCTGFRWThdskyyqsgdhlr 167

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3448 -----FLKQFSPP----------------------------IGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLP 3494
Cdd:cd05625    168 qdsmdFSNEWGDPencrcgdrlkplerraarqhqrclahslVGTPNYIAPEVLLRTGYTQLCDWWSVGVILFEMLVGQPP 247

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*..
gi 1207186029 3495 FTENDPAETEARIQAAKFDLSKLYQ-NVSQSASLFIKKiLCSYPWAR 3540
Cdd:cd05625    248 FLAQTPLETQMKVINWQTSLHIPPQaKLSPEASDLIIK-LCRGPEDR 293

Pseudokinase domain of Tribbles Homolog 3; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. TRB3 binds and regulates ATF4, p65/RelA, and PKB (or Akt). It negatively regulates ATF4-mediated gene expression including that of CHOP (C/EBP homologous protein) and HO-1, which are both involved in modulating apoptosis. It also inhibits insulin-mediated phosphorylation of PKB and is a possible determinant of insulin resistance and related disorders. In osteoarthritic chondrocytes where it inhibits insulin-like growth factor 1-mediated cell survival, TRB3 is overexpressed, resulting in increased cell death. TRB3 is one of three Tribbles Homolog (TRB) proteins present in vertebrates that are encoded by three separate genes. TRB proteins interact with many proteins involved in signalling pathways. They play scaffold-like regulatory functions and affect many cellular processes such as mitosis, apoptosis, and gene expression. The TRB3 subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270926 [Multi-domain] Cd Length: 242 Bit Score: 60.66 E-value: 2.74e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3322 TGNLYMAKIVPYEpeSKQTVLQEYDILksLHHEKIMALHEAYVTPRYLVLISECCSGKelLHSLI-DRFRYSEDDVVAYI 3400
Cdd:cd14024     17 TEKEYTCKVLSLR--SYQECLAPYDRL--GPHEGVCSVLEVVIGQDRAYAFFSRHYGD--MHSHVrRRRRLSEDEARGLF 90

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3401 VQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTF------NPLFLKQFSPPigtldYMSPEML--KGDVV 3472
Cdd:cd14024     91 TQMARAVAHCHQHGVILRDLKLRRFVFTDELRTKLVLVNLEDSCplngddDSLTDKHGCPA-----YVGPEILssRRSYS 165

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3473 GPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKFDLSklyQNVSQSASLFIKKILCSYPWARPTIKDCFTNSWL 3552
Cdd:cd14024    166 GKAADVWSLGVCLYTMLLGRYPFQDTEPAALFAKIRRGAFSLP---AWLSPGARCLVSCMLRRSPAERLKASEILLHPWL 242

104 kDa microneme/rhoptry antigen; Provisional

Pssm-ID: 185628 [Multi-domain] Cd Length: 943 Bit Score: 63.17 E-value: 3.12e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  228 EALALGSRAPGPQSARSP--SDDVLRDSPPQVLPPPSPKFGRSTASPllsrsgsGPATPLAPRKkvvVPTEyqdTVPGEF 305
Cdd:PTZ00449   515 EASGLPPKAPGDKEGEEGehEDSKESDEPKEGGKPGETKEGEVGKKP-------GPAKEHKPSK---IPTL---SKKPEF 581

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  306 EEKIKQPKSSGMSQSSAQDSRPQTPVSeysrkeltlRPSPKLTRaSSKIfekvrvfeerRRSIDNPEGSISGRSWAGFNR 385
Cdd:PTZ00449   582 PKDPKHPKDPEEPKKPKRPRSAQRPTR---------PKSPKLPE-LLDI----------PKSPKRPESPKSPKRPPPPQR 641

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  386 ASSIDSDEGGSrlgiSRESSKEDLREALKADaaqrrtmfkqraasledrPRYTQKVQDienKFTEELQRIKKLVGKPHMK 465
Cdd:PTZ00449   642 PSSPERPEGPK----IIKSPKPPKSPKPPFD------------------PKFKEKFYD---DYLDAAAKSKETKTTVVLD 696

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  466 KSFSTEQLSTCHRSR-QPVRKLEPIPPqvlQKLQDRERAQLAQLEQEMRERDQAKERSPPKSPSRRRKDHLAQQPPERAE 544
Cdd:PTZ00449   697 ESFESILKETLPETPgTPFTTPRPLPP---KLPRDEEFPFEPIGDPDAEQPDDIEFFTPPEEERTFFHETPADTPLPDIL 773

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  545 TKVVST---TGLEPSPPEAMSLSDLPGQRSPRFRGPSPSRDSTR-RSPTVEISAMAEERPRGR-AESPSRNVLEMT---- 615
Cdd:PTZ00449   774 AEEFKEediHAETGEPDEAMKRPDSPSEHEDKPPGDHPSLPKKRhRLDGLALSTTDLESDAGRiAKDASGKIVKLKrsks 853

                          410       420       430       440       450       460       470
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1207186029  616 ---LRKVEPRP-ASPLVKRVVRVQEVPQANDQPMHrkTPIEVSLRKLERRPesplvqgetvaiqdfPVQAPPKPPR 687
Cdd:PTZ00449   854 fddLTTVEEAEeMGAEARKIVVDDDGTEADDEDTH--PPEEKHKSEVRRRR---------------PPKKPSKPKK 912

Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The EphA2 receptor is overexpressed in tumor cells and tumor blood vessels in a variety of cancers including breast, prostate, lung, and colon. As a result, it is an attractive target for drug design since its inhibition could affect several aspects of tumor progression. EphRs comprise the largest subfamily of receptor PTKs (RTKs). Class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. EphRs contain an ephrin binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). Ephrin/EphR interaction mainly results in cell-cell repulsion or adhesion, making it important in neural development and plasticity, cell morphogenesis, cell-fate determination, embryonic development, tissue patterning, and angiogenesis. The EphA2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K).

Pssm-ID: 133194 [Multi-domain] Cd Length: 268 Bit Score: 60.76 E-value: 3.21e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1665 HKEIGRGAFSYVKRVIQK-AGKLEYAAKFISARA----KRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITELCH 1739
Cdd:cd05063     10 QKVIGAGEFGEVFRGILKmPGRKEVAVAIKTLKPgyteKQRQDFLSEASIMGQFSHHNIIRLEGVVTKFKPAMIITEYME 89

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1740 EELLDRLTKKSTILESEIR--SSVRQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDFGNAVKFMPD-EAQYCK 1816
Cdd:cd05063     90 NGALDKYLRDHDGEFSSYQlvGMLRGIAAGMKYLSDMNYVHRDLAARNILV--NSNLECKVSDFGLSRVLEDDpEGTYTT 167

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....
gi 1207186029 1817 YGTP---EFVAPEIVNQTPVSKATDIWPIGVLTYLCLT-GVSPF 1856
Cdd:cd05063    168 SGGKipiRWTAPEAIAYRKFTSASDVWSFGIVMWEVMSfGERPY 211

Catalytic domain of the LIM domain kinase-like protein kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. Members of this subfamily include LIMK, Testicular or testis-specific protein kinase (TESK), and similar proteins. LIMKs are characterized as serine/threonine kinases (STKs) while TESKs are dual-specificity protein kinases. Both LIMK and TESK phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They are implicated in many cellular functions including cell spreading, motility, morphogenesis, meiosis, mitosis, and spermatogenesis. The LIMK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270967 [Multi-domain] Cd Length: 252 Bit Score: 60.58 E-value: 3.29e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3307 ARGRFGVIRECRENATGNLYMAKIVPYePESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSG---KELLH 3383
Cdd:cd14065      2 GKGFFGEVYKVTHRETGKVMVMKELKR-FDEQRSFLKEVKLMRRLSHPNILRFIGVCVKDNKLNFITEYVNGgtlEELLK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3384 SLIDRFRYSEDdvVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVK---IIDFGSAQTFNPLFL-----KQFSPP 3455
Cdd:cd14065     81 SMDEQLPWSQR--VSLAKDIASGMAYLHSKNIIHRDLNSKNCLVREANRGRnavVADFGLAREMPDEKTkkpdrKKRLTV 158

                          170       180       190
                   ....*....|....*....|....*....|....*....
gi 1207186029 3456 IGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLsGRLP 3494
Cdd:cd14065    159 VGSPYWMAPEMLRGESYDEKVDVFSFGIVLCEII-GRVP 196

Catalytic domain of Spleen Tyrosine Kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Syk-like subfamily is composed of Syk, ZAP-70, Shark, and similar proteins. They are cytoplasmic (or nonreceptor) PTKs containing two Src homology 2 (SH2) domains N-terminal to the catalytic tyr kinase domain. They are involved in the signaling downstream of activated receptors (including B-cell, T-cell, and Fc receptors) that contain ITAMs (immunoreceptor tyr activation motifs), leading to processes such as cell proliferation, differentiation, survival, adhesion, migration, and phagocytosis. Syk is important in B-cell receptor signaling, while Zap-70 is primarily expressed in T-cells and NK cells, and is a crucial component in T-cell receptor signaling. Syk also plays a central role in Fc receptor-mediated phagocytosis in the adaptive immune system. Shark is exclusively expressed in ectodermally derived epithelia, and is localized preferentially to the apical surface of the epithelial cells, it may play a role in a signaling pathway for epithelial cell polarity. The Syk-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270650 [Multi-domain] Cd Length: 257 Bit Score: 60.44 E-value: 3.56e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1666 KEIGRGAFSYVKRVI--QKAGK-LEYAAKFISAR--AKRKASALRELNILSHLDHERILYFHdAFEKKNAVIIITELCHE 1740
Cdd:cd05060      1 KELGHGNFGSVRKGVylMKSGKeVEVAVKTLKQEheKAGKKEFLREASVMAQLDHPCIVRLI-GVCKGEPLMLVMELAPL 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1741 -ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHssDQIRICDFG--NAVKFMPDEAQYCKY 1817
Cdd:cd05060     80 gPLLKYLKKRREIPVSDLKELAHQVAMGMAYLESKHFVHRDLAARNVLLVNR--HQAKISDFGmsRALGAGSDYYRATTA 157

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....
gi 1207186029 1818 GT-P-EFVAPEIVNQTPVSKATDIWPIGVLTYLCLT-GVSPFAG 1858
Cdd:cd05060    158 GRwPlKWYAPECINYGKFSSKSDVWSYGVTLWEAFSyGAKPYGE 201

Catalytic domain of the Dual-specificity protein kinase, CDC-like kinase 2; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. CLK2 plays a role in hepatic insulin signaling and glucose metabolism. It is induced by the insulin/Akt pathway as part of the hepatic refeeding reponse, and it directly phosphorylates the SR domain of PGC-1alpha, which results in decreased gluconeogenic gene expression and glucose output. CLKs are involved in the phosphorylation and regulation of serine/arginine-rich (SR) proteins, which play a crucial role in pre-mRNA splicing by directing splice site selection. SR proteins are phosphorylated first by SR protein kinases (SRPKs) at the N-terminus, which leads to its assembly into nuclear speckles where splicing factors are stored. CLKs phosphorylate the C-terminal part of SR proteins, causing the nuclear speckles to dissolve and splicing factors to be recruited at sites of active transcription. Based on a conserved "EHLAMMERILG" signature motif which may be crucial for substrate specificity, CLKs are also referred to as LAMMER kinases. CLKs autophosphorylate at tyrosine residues and phosphorylate their substrates exclusively on serine/threonine residues. The CLK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271117 [Multi-domain] Cd Length: 330 Bit Score: 61.57 E-value: 3.58e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3297 QKPYTFMDEKARGRFGVIRECRENATGNLYMA-KIVPYEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISEC 3375
Cdd:cd14215     11 QERYEIVSTLGEGTFGRVVQCIDHRRGGARVAlKIIKNVEKYKEAARLEINVLEKINEKDPENKNLCVQMFDWFDYHGHM 90

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3376 CSGKELLH-SLID------RFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENII-------VTY------------ 3429
Cdd:cd14215     91 CISFELLGlSTFDflkennYLPYPIHQVRHMAFQVCQAVKFLHDNKLTHTDLKPENILfvnsdyeLTYnlekkrdersvk 170

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1207186029 3430 MNVVKIIDFGSAqTFNPlflKQFSPPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAETEARIQ 3508
Cdd:cd14215    171 STAIRVVDFGSA-TFDH---EHHSTIVSTRHYRAPEVILELGWSQPCDVWSIGCIIFEYYVGFTLFQTHDNREHLAMME 245

Third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein), and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein) and similar proteins. WFIKKN is a secreted protein that consists of multiple types of protease inhibitory modules, including two tandem Kunitz-type protease inhibitor-domains. The Ig superfamily is a heterogenous group of proteins built on a common fold comprised of a sandwich of two beta sheets. Members of the Ig superfamily are components of immunoglobulin, neuroglia, cell surface glycoproteins, such as T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409422 [Multi-domain] Cd Length: 95 Bit Score: 56.40 E-value: 3.85e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1556 VNVGETPRFAVVVEGKPVPDILWYKG----DTLLSESSH-FTFVYDDNECSLVVLNTQADDSGVYTCTAKNLAGSVSCKA 1630
Cdd:cd05765     12 VKVGETASFHCDVTGRPQPEITWEKQvpgkENLIMRPNHvRGNVVVTNIGQLVIYNAQPQDAGLYTCTARNSGGLLRANF 91


                   ....
gi 1207186029 1631 ELTV 1634
Cdd:cd05765     92 PLSV 95

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar domains; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three Ig-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans. This group also contains fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

Pssm-ID: 409393 [Multi-domain] Cd Length: 95 Bit Score: 56.07 E-value: 4.21e-09

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1207186029  795 GTEVLLKCIISGTPLPEVIWKKDNTEVKnsPTHVV---KIEGERHSLLIKWTKPSDAGTYTVTAVNEVGEVSSS 865
Cdd:cd05729     19 ANKVRLECGAGGNPMPNITWLKDGKEFK--KEHRIggtKVEEKGWSLIIERAIPRDKGKYTCIVENEYGSINHT 90

Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Many FGFR3 splice variants have been reported with the IIIb and IIIc isoforms being the predominant forms. FGFR3 IIIc is the isoform expressed in chondrocytes, the cells affected in dwarfism, while IIIb is expressed in epithelial cells. FGFR3 ligands include FGF1, FGF2, FGF4, FGF8, FGF9, and FGF23. It is a negative regulator of long bone growth. In the cochlear duct and in the lens, FGFR3 is involved in differentiation while it appears to have a role in cell proliferation in epithelial cells. Germline mutations in FGFR3 are associated with skeletal disorders including several forms of dwarfism. Some missense mutations are associated with multiple myeloma and carcinomas of the bladder and cervix. Overexpression of FGFR3 is found in thyroid carcinoma. FGFR3 is part of the FGFR subfamily, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. The FGFR3 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173652 [Multi-domain] Cd Length: 334 Bit Score: 61.19 E-value: 4.43e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3395 DVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPL-FLKQFSPPIGTLDYMSPEMLKGDVVG 3473
Cdd:cd05100    135 DLVSCAYQVARGMEYLASQKCIHRDLAARNVLVTEDNVMKIADFGLARDVHNIdYYKKTTNGRLPVKWMAPEALFDRVYT 214

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1207186029 3474 PPADIWSIGILTY-IMLSGRLPFTeNDPAETEARIQAAKFDLSKLyQNVSQSASLFIKKILCSYPWARPTIK 3544
Cdd:cd05100    215 HQSDVWSFGVLLWeIFTLGGSPYP-GIPVEELFKLLKEGHRMDKP-ANCTHELYMIMRECWHAVPSQRPTFK 284

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409565 [Multi-domain] Cd Length: 88 Bit Score: 56.04 E-value: 4.45e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1030 IRPVRDVMVKAGETALFECHVIGPQDTDVDWLSDGKLIQPALlNCKMHFDGK-RCRLLLNSVHEDDSGTYTCKLSTAKEE 1108
Cdd:cd20973      1 IQTLRDKEVVEGSAARFDCKVEGYPDPEVKWMKDDNPIVESR-RFQIDQDEDgLCSLIISDVCGDDSGKYTCKAVNSLGE 79


                   ....*....
gi 1207186029 1109 LTSSAKLKV 1117
Cdd:cd20973     80 ATCSAELTV 88

First C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409474 Cd Length: 92 Bit Score: 55.87 E-value: 4.80e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1545 PTFETIMEDLDVNVGETPRFAVVVEGKPVPDILWYK-GDTLLSESSHFTFVYD-DNECSLVVLNTQADDSGVYTCTAKNL 1622
Cdd:cd05893      1 PFFEMKLKHYKIFEGMPVTFTCRVAGNPKPKIYWFKdGKQISPKSDHYTIQRDlDGTCSLHTTASTLDDDGNYTIMAANP 80

                           90
                   ....*....|..
gi 1207186029 1623 AGSVSCKAELTV 1634
Cdd:cd05893     81 QGRISCTGRLMV 92

Catalytic domain of the Protein Serine/Threonine Kinase, Large Tumor Suppressor 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LATS2 is an essential mitotic regulator responsible for coordinating accurate cytokinesis completion and governing the stabilization of other mitotic regulators. It is also critical in the maintenance of proper chromosome number, genomic stability, mitotic fidelity, and the integrity of centrosome duplication. Downregulation of LATS2 is associated with poor prognosis in acute lymphoblastic leukemia and breast cancer. The LATS2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173715 [Multi-domain] Cd Length: 381 Bit Score: 61.57 E-value: 4.88e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3309 GRFGVIRECRENATGNLYMAKIVpyepeSKQTVLQ---------EYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGK 3379
Cdd:cd05626     12 GAFGEVCLACKVDTHALYAMKTL-----RKKDVLNrnqvahvkaERDILAEADNEWVVKLYYSFQDKDNLYFVMDYIPGG 86

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3380 ELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTF----NPLFLKQFS-- 3453
Cdd:cd05626     87 DMMSLLIRMEVFPEVLARFYIAELTLAIESVHKMGFIHRDIKPDNILIDLDGHIKLTDFGLCTGFrwthNSKYYQKGShi 166

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3454 ------PP----------------------------------IGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRL 3493
Cdd:cd05626    167 rqdsmePSdlwddvsncrcgdrlktleqratkqhqrclahslVGTPNYIAPEVLLRKGYTQLCDWWSVGVILFEMLVGQP 246

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|...
gi 1207186029 3494 PFTENDPAETEARIQAAKFDLSKLYQ-NVSQSASLFIKKILCS 3535
Cdd:cd05626    247 PFLAPTPTETQLKVINWENTLHIPPQvKLSPEAVDLITKLCCS 289

Catalytic domain of the Protein Tyrosine Kinase, Wee1b; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of human Wee1b (also called Wee2), Xenopus laevis Wee1a (XeWee1a) and similar vertebrate proteins. XeWee1a accumulates after exiting the metaphase II stage in oocytes and in early mitotic cells. It functions during the first zygotic cell division and not during subsequent divisions. Mammalian Wee2/Wee1b is an oocyte-specific inhibitor of meiosis that functions downstream of cAMP. Wee1 is a cell cycle checkpoint kinase that helps keep the cyclin-dependent kinase CDK1 in an inactive state through phosphorylation of an N-terminal tyr (Y15) residue. During the late G2 phase, CDK1 is activated and mitotic entry is promoted by the removal of this inhibitory phosphorylation by the phosphatase Cdc25. Although Wee1 is functionally a tyr kinase, it is more closely related to serine/threonine kinases (STKs). It contains a catalytic kinase domain sandwiched in between N- and C-terminal regulatory domains. It is regulated by phosphorylation and degradation, and its expression levels are also controlled by circadian clock proteins. The Wee1b subfamily is part of a larger superfamily that includes the catalytic domains of STKs, other PTKs, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271041 [Multi-domain] Cd Length: 274 Bit Score: 60.33 E-value: 4.97e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYVKRVIQKAGKLEYAAKfisaRAKR-------KASALREL---NILSHldHERILYFHDAFEKKNAVIIITEL 1737
Cdd:cd14139      8 IGVGEFGSVYKCIKRLDGCVYAIK----RSMRpfagssnEQLALHEVyahAVLGH--HPHVVRYYSAWAEDDHMIIQNEY 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1738 C-----HEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILM-----------------AD--HSS 1793
Cdd:cd14139     82 CnggslQDAISENTKSGNHFEEPELKDILLQVSMGLKYIHNSGLVHLDIKPSNIFIchkmqsssgvgeevsneEDefLSA 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1794 DQI-RICDFGNAVKFMPDEAQyckYGTPEFVAPEIVNQ--TPVSKAtDIWPIGvLTYLCLTGVSPFAGENDRSSvlNIRN 1870
Cdd:cd14139    162 NVVyKIGDLGHVTSINKPQVE---EGDSRFLANEILQEdyRHLPKA-DIFALG-LTVALAAGAEPLPTNGAAWH--HIRK 234

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|..
gi 1207186029 1871 YNVAfeeSMFTDLCHEAKGFVIKLLVAD-RLRPDANECLRHP 1911
Cdd:cd14139    235 GNFP---DVPQELPESFSSLLKNMIQPDpEQRPSATALARHT 273

glycogen synthase kinase; Provisional

Pssm-ID: 173333 [Multi-domain] Cd Length: 440 Bit Score: 61.59 E-value: 5.12e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1646 EDEASILRKMRRLTD-YYDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKAsalRELNILSHLDHERILYFHDA 1724
Cdd:PTZ00036    51 DEEKMIDNDINRSPNkSYKLGNIIGNGSFGVVYEAICIDTSEKVAIKKVLQDPQYKN---RELLIMKNLNHINIIFLKDY 127

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1725 FE----KKNAVII--------ITELCHEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMaDHS 1792
Cdd:PTZ00036   128 YYtecfKKNEKNIflnvvmefIPQTVHKYMKHYARNNHALPLFLVKLYSYQLCRALAYIHSKFICHRDLKPQNLLI-DPN 206

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1207186029 1793 SDQIRICDFGNAVKFMPDEAQYCKYGTPEFVAPEI-VNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNI 1868
Cdd:PTZ00036   207 THTLKLCDFGSAKNLLAGQRSVSYICSRFYRAPELmLGATNYTTHIDLWSLGCIIAEMILGYPIFSGQSSVDQLVRI 283

Catalytic domain of Fes-like Protein Tyrosine Kinases; Protein Tyrosine Kinase (PTK) family; Fes subfamily; catalytic (c) domain. Fes subfamily members include Fes (or Fps), Fer, and similar proteins. The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Fes subfamily proteins are cytoplasmic (or nonreceptor) tyr kinases containing an N-terminal region with FCH (Fes/Fer/CIP4 homology) and coiled-coil domains, followed by a SH2 domain, and a C-terminal catalytic domain. The genes for Fes (feline sarcoma) and Fps (Fujinami poultry sarcoma) were first isolated from tumor-causing retroviruses. The viral oncogenes encode chimeric Fes proteins consisting of Gag sequences at the N-termini, resulting in unregulated tyr kinase activity. Fes and Fer kinases play roles in haematopoiesis, inflammation and immunity, growth factor signaling, cytoskeletal regulation, cell migration and adhesion, and the regulation of cell-cell interactions. Fes and Fer show redundancy in their biological functions.

Pssm-ID: 270637 [Multi-domain] Cd Length: 251 Bit Score: 59.77 E-value: 5.52e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIRECRENATGNLYMAKI--VPYEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLHSL 3385
Cdd:cd05041      5 RGNFGDVYRGVLKPDNTEVAVKTcrETLPPDLKRKFLQEARILKQYDHPNIVKLIGVCVQKQPIMIVMELVPGGSLLTFL 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3386 idrfRYSEDDVVayIVQILQ-------GLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFG-SAQTFNPLF-----LKQF 3452
Cdd:cd05041     85 ----RKKGARLT--VKQLLQmcldaaaGMEYLESKNCIHRDLAARNCLVGENNVLKISDFGmSREEEDGEYtvsdgLKQI 158

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1207186029 3453 spPIgtlDYMSPEMLKGDVVGPPADIWSIGILTY-IMLSGRLPFTENDPAETEARIQ 3508
Cdd:cd05041    159 --PI---KWTAPEALNYGRYTSESDVWSFGILLWeIFSLGATPYPGMSNQQTREQIE 210

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.

Pssm-ID: 143205 [Multi-domain] Cd Length: 85 Bit Score: 55.68 E-value: 5.55e-09

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1207186029 1137 GRNARFDCKVSGTPPPQVIWSHFDRPLEENEDIRIlkEGGrhSLIISHVSNEDEGLYTVAARNSHGEDECAAELYV 1212
Cdd:cd05728     14 GSSLRWECKASGNPRPAYRWLKNGQPLASENRIEV--EAG--DLRITKLSLSDSGMYQCVAENKHGTIYASAELAV 85

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 55.58 E-value: 5.61e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1556 VNVGETPRFAVVVEGKPVPDILWYK-GDTLLSESSHFTFVyddNECSLVVLNTQADDSGVYTCTAKNLAGSVSCKAELTV 1634
Cdd:cd20952     11 VAVGGTVVLNCQATGEPVPTISWLKdGVPLLGKDERITTL---ENGSLQIKGAEKSDTGEYTCVALNLSGEATWSAVLDV 87

Catalytic domain of Fyn-related kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Frk and Srk are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Frk, also known as Rak, is specifically expressed in liver, lung, kidney, intestine, mammary glands, and the islets of Langerhans. Rodent homologs were previously referred to as GTK (gastrointestinal tyr kinase), BSK (beta-cell Src-like kinase), or IYK (intestinal tyr kinase). Studies in mice reveal that Frk is not essential for viability. It plays a role in the signaling that leads to cytokine-induced beta-cell death in Type I diabetes. It also regulates beta-cell number during embryogenesis and early in life. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Frk-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270653 [Multi-domain] Cd Length: 267 Bit Score: 60.11 E-value: 5.68e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3295 VPQKPYTFMDEKARGRFGVIRECRENATGNLYMAKIVPyEPESKQTVLQEYDILKSLHHEKIMALHeAYVT---PRYLvl 3371
Cdd:cd05068      5 IDRKSLKLLRKLGSGQFGEVWEGLWNNTTPVAVKTLKP-GTMDPEDFLREAQIMKKLRHPKLIQLY-AVCTleePIYI-- 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3372 ISECCSGKELLHSLIDRFRYSE-DDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPlfLK 3450
Cdd:cd05068     81 ITELMKHGSLLEYLQGKGRSLQlPQLIDMAAQVASGMAYLESQNYIHRDLAARNVLVGENNICKVADFGLARVIKV--ED 158

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*....
gi 1207186029 3451 QFSPPIGT---LDYMSPEMLKGDVVGPPADIWSIGIL-TYIMLSGRLPF 3495
Cdd:cd05068    159 EYEAREGAkfpIKWTAPEAANYNRFSIKSDVWSFGILlTEIVTYGRIPY 207

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 55.58 E-value: 5.77e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  786 PLQDTVASTGTeVLLKCIISGTPLPEVIWKKDNTEVKNSPTHVVKIegERHSLLIKWTKPSDAGTYTVTAVNEVGEVSSS 865
Cdd:cd20952      6 PQNQTVAVGGT-VVLNCQATGEPVPTISWLKDGVPLLGKDERITTL--ENGSLQIKGAEKSDTGEYTCVALNLSGEATWS 82


                   ...
gi 1207186029  866 ATL 868
Cdd:cd20952     83 AVL 85

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409568 [Multi-domain] Cd Length: 90 Bit Score: 55.72 E-value: 6.33e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1249 PDFVKPLYDMDVVEGREAVLRCKVAGLPYPTITWFHNGKRIDSTEDRKMTQFRdVHSLVVRCVCHAHGGVYKCVISNKVG 1328
Cdd:cd20976      2 PSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPLQYAADRSTCEAG-VGELHIQDVLPEDHGTYTCLAKNAAG 80

                           90
                   ....*....|
gi 1207186029 1329 KATCYSHLYV 1338
Cdd:cd20976     81 QVSCSAWVTV 90

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409543 [Multi-domain] Cd Length: 94 Bit Score: 55.50 E-value: 6.74e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  928 PAFLAVIGDQSVIEGQEVTMSVLVTGQPKPMLYWLRDRVTI---KTGTRHIVqETEEGNFEMIIKSAQRSDTGVYTCKII 1004
Cdd:cd20951      1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIdpsSIPGKYKI-ESEYGVHVLHIRRVTVEDSAVYSAVAK 79

                           90
                   ....*....|....*
gi 1207186029 1005 NEYGTKQCEGKLEVK 1019
Cdd:cd20951     80 NIHGEASSSASVVVE 94

Catalytic domain of C-terminal Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of Csk, Chk, and similar proteins. They are cytoplasmic (or nonreceptor) PTKs containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. They negatively regulate the activity of Src kinases that are anchored to the plasma membrane. To inhibit Src kinases, Csk and Chk are translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. Csk catalyzes the tyr phosphorylation of the regulatory C-terminal tail of Src kinases, resulting in their inactivation. Chk inhibit Src kinases using a noncatalytic mechanism by simply binding to them. As negative regulators of Src kinases, Csk and Chk play important roles in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. The Csk-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270635 [Multi-domain] Cd Length: 256 Bit Score: 59.67 E-value: 7.21e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3338 KQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKellhSLIDRFRYSEDDVVAYIVQIL------QGLDYLH 3411
Cdd:cd05039     44 AQAFLAEASVMTTLRHPNLVQLLGVVLEGNGLYIVTEYMAKG----SLVDYLRSRGRAVITRKDQLGfaldvcEGMEYLE 119

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3412 SRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNplfLKQFSP--PIgtlDYMSPEMLKGDVVGPPADIWSIGILTYIML 3489
Cdd:cd05039    120 SKKFVHRDLAARNVLVSEDNVAKVSDFGLAKEAS---SNQDGGklPI---KWTAPEALREKKFSTKSDVWSFGILLWEIY 193


                   ....*..
gi 1207186029 3490 S-GRLPF 3495
Cdd:cd05039    194 SfGRVPY 200

Catalytic domain of the Serine/Threonine Kinase, p38delta Mitogen-Activated Protein Kinase (also called MAPK13); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38delta/MAPK13 is found in skeletal muscle, heart, lung, testis, pancreas, and small intestine. It regulates microtubule function by phosphorylating Tau. It activates the c-jun promoter and plays a role in G2 cell cycle arrest. It also controls the degration of c-Myb, which is associated with myeloid leukemia and poor prognosis in colorectal cancer. p38delta is the main isoform involved in regulating the differentiation and apoptosis of keratinocytes. p38 kinases are MAPKs, serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38delta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143384 [Multi-domain] Cd Length: 342 Bit Score: 60.69 E-value: 7.25e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3343 QEYDILKSLHHEKIMALHEAYVTPR--------YLVLiseccsgkELLHSLIDRFR---YSEDDVVAYIVQILQGLDYLH 3411
Cdd:cd07879     63 RELTLLKHMQHENVIGLLDVFTSAVsgdefqdfYLVM--------PYMQTDLQKIMghpLSEDKVQYLVYQMLCGLKYIH 134

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3412 SRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNplflKQFSPPIGTLDYMSPE-MLKGDVVGPPADIWSIGILTYIMLS 3490
Cdd:cd07879    135 SAGIIHRDLKPGNLAVNEDCELKILDFGLARHAD----AEMTGYVVTRWYRAPEvILNWMHYNQTVDIWSVGCIMAEMLT 210


                   ....*....
gi 1207186029 3491 GRLPFTEND 3499
Cdd:cd07879    211 GKTLFKGKD 219

Catalytic domain of the Serine/Threonine Kinases, Plant TDY Mitogen-Activated Protein Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Plant MAPKs are typed based on the conserved phosphorylation motif present in the activation loop, TEY and TDY. This subfamily represents the TDY subtype and is composed of Group D plant MAPKs including Arabidopsis thaliana MPK18 (AtMPK18), Oryza sativa Blast- and Wound-induced MAPK1 (OsBWMK1), OsWJUMK1 (Wound- and JA-Uninducible MAPK1), Zea mays MPK6, and the Medicago sativa TDY1 gene product. OsBWMK1 enhances resistance to pathogenic infections. It mediates stress-activated defense responses by activating a transcription factor that affects the expression of stress-related genes. AtMPK18 is involved in microtubule-related functions. In plants, MAPKs are associated with physiological, developmental, hormonal, and stress responses. Some plants show numerous gene duplications of MAPKs; Arabidopsis thaliana harbors at least 20 MAPKs, named AtMPK1-20 while Oryza sativa contains at least 17 MAPKs. Arabidopsis thaliana contains more TEY-type MAPKs than TDY-type, whereas the reverse is true for Oryza sativa. The TDY MAPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143364 [Multi-domain] Cd Length: 338 Bit Score: 60.57 E-value: 7.55e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVP--YEPESKQT-VLQEYDILKSLHHEKIMALHEAYVTPR-------YL 3369
Cdd:cd07859      2 YKIQEVIGKGSYGVVCSAIDTHTGEKVAIKKINdvFEHVSDATrILREIKLLRLLRHPDIVEIKHIMLPPSrrefkdiYV 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3370 VLiseccsgkELLHSLIDRFRYSEDDVVA-----YIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQ-T 3443
Cdd:cd07859     82 VF--------ELMESDLHQVIKANDDLTPehhqfFLYQLLRALKYIHTANVFHRDLKPKNILANADCKLKICDFGLARvA 153

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1207186029 3444 FN----PLFLKQFsppIGTLDYMSPEmLKGDVVG---PPADIWSIGILTYIMLSGRLPF 3495
Cdd:cd07859    154 FNdtptAIFWTDY---VATRWYRAPE-LCGSFFSkytPAIDIWSIGCIFAEVLTGKPLF 208

Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK3 is a mitogen-activated protein kinase kinase kinases (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLK3 activates multiple MAPK pathways and plays a role in apoptosis, proliferation, migration, and differentiation, depending on the cellular context. It is highly expressed in breast cancer cells and its signaling through c-Jun N-terminal kinase has been implicated in the migration, invasion, and malignancy of cancer cells. MLK3 also functions as a negative regulator of Inhibitor of Nuclear Factor-KappaB Kinase (IKK) and consequently, it also impacts inflammation and immunity. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation.The MLK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271049 [Multi-domain] Cd Length: 267 Bit Score: 59.66 E-value: 7.56e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYVKR-------VIQKAGKLEyAAKFISARAKrkaSALRELNILSHLDHERILYFHDAFEKKNAVIIITELCHE 1740
Cdd:cd14147     11 IGIGGFGKVYRgswrgelVAVKAARQD-PDEDISVTAE---SVRQEARLFAMLAHPNIIALKAVCLEEPNLCLVMEYAAG 86

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1741 ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQ---LDILHLDIKPDNILMA------DHSSDQIRICDFGNAVKFMpDE 1811
Cdd:cd14147     87 GPLSRALAGRRVPPHVLVNWAVQIARGMHYLHCealVPVIHRDLKSNNILLLqpiendDMEHKTLKITDFGLAREWH-KT 165

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*..
gi 1207186029 1812 AQYCKYGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAG 1858
Cdd:cd14147    166 TQMSAAGTYAWMAPEVIKASTFSKGSDVWSFGVLLWELLTGEVPYRG 212

Catalytic domain of the Protein Tyrosine Kinases, Lymphocyte-specific kinase and Blk; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Lck and Blk are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lck is expressed in T-cells and natural killer cells. It plays a critical role in T-cell maturation, activation, and T-cell receptor (TCR) signaling. Lck phosphorylates ITAM (immunoreceptor tyr activation motif) sequences on several subunits of TCRs, leading to the activation of different second messenger cascades. Phosphorylated ITAMs serve as binding sites for other signaling factor such as Syk and ZAP-70, leading to their activation and propagation of downstream events. In addition, Lck regulates drug-induced apoptosis by interfering with the mitochondrial death pathway. The apototic role of Lck is independent of its primary function in T-cell signaling. Blk is expressed specifically in B-cells. It is involved in pre-BCR (B-cell receptor) signaling. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Lck/Blk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270652 [Multi-domain] Cd Length: 264 Bit Score: 59.52 E-value: 7.77e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1666 KEIGRGAFSYVKRVIQKaGKLEYAAKFISARAKRKASALRELNILSHLDHERILYFHdAFEKKNAVIIITE-LCHEELLD 1744
Cdd:cd05067     13 ERLGAGQFGEVWMGYYN-GHTKVAIKSLKQGSMSPDAFLAEANLMKQLQHQRLVRLY-AVVTQEPIYIITEyMENGSLVD 90

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1745 RLT----KKSTIleSEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADhsSDQIRICDFGNAvKFMPDEAQYCKYGTP 1820
Cdd:cd05067     91 FLKtpsgIKLTI--NKLLDMAAQIAEGMAFIEERNYIHRDLRAANILVSD--TLSCKIADFGLA-RLIEDNEYTAREGAK 165

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1207186029 1821 ---EFVAPEIVNQTPVSKATDIWPIGV-LTYLCLTGVSPFAGENDRSSVLNI-RNY 1871
Cdd:cd05067    166 fpiKWTAPEAINYGTFTIKSDVWSFGIlLTEIVTHGRIPYPGMTNPEVIQNLeRGY 221

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 54.64 E-value: 8.03e-09

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029   72 IRLKVAVAGDPQPTLYWYHNDDLVNMDNQEY-------GGLWIRDCKPSDAGLYTCIATNHLGEARSSAV 134
Cdd:cd00096      1 VTLTCSASGNPPPTITWYKNGKPLPPSSRDSrrselgnGTLTISNVTLEDSGTYTCVASNSAGGSASASV 70

Catalytic domain of Serine/Threonine Kinase, Cell Division Cycle 2-like 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDC2L6 is also called CDK8-like and was previously referred to as CDK11. However, this is a confusing nomenclature as CDC2L6 is distinct from CDC2L1, which is represented by the two protein products from its gene, called CDK11(p110) and CDK11(p58), as well as the caspase-processed CDK11(p46). CDK11(p110), CDK11(p58), and CDK11(p46)do not belong to this subfamily. CDC2L6 is an associated protein of Mediator, a multiprotein complex that provides a platform to connect transcriptional and chromatin regulators and cofactors, in order to activate and mediate RNA polymerase II transcription. CDC2L6 is localized mainly in the nucleus amd exerts an opposing effect to CDK8 in VP16-dependent transcriptional activation by being a negative regulator. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDC2L6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270850 [Multi-domain] Cd Length: 318 Bit Score: 60.08 E-value: 8.52e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1667 EIGRGAFSYVKRVIQKAGK--LEYAAKFISARAKrKASALRELNILSHLDHERILYFHDAF--EKKNAVIIITELCHEEL 1742
Cdd:cd07867      9 KVGRGTYGHVYKAKRKDGKdeKEYALKQIEGTGI-SMSACREIALLRELKHPNVIALQKVFlsHSDRKVWLLFDYAEHDL 87

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1743 --------LDRLTKKSTIL-ESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSD--QIRICDFGNAVKFMPDE 1811
Cdd:cd07867     88 whiikfhrASKANKKPMQLpRSMVKSLLYQILDGIHYLHANWVLHRDLKPANILVMGEGPErgRVKIADMGFARLFNSPL 167

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*
gi 1207186029 1812 AQYCKYG----TPEFVAPE-IVNQTPVSKATDIWPIGVLTYLCLT 1851
Cdd:cd07867    168 KPLADLDpvvvTFWYRAPElLLGARHYTKAIDIWAIGCIFAELLT 212

Catalytic domain of the Protein Tyrosine Kinase, Fer; Protein Tyrosine Kinase (PTK) family; Fer kinase; catalytic (c) domain. The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Fer kinase is a member of the Fes subfamily of proteins which are cytoplasmic (or nonreceptor) tyr kinases containing an N-terminal region with FCH (Fes/Fer/CIP4 homology) and coiled-coil domains, followed by a SH2 domain, and a C-terminal catalytic domain. Fer kinase is expressed in a wide variety of tissues, and is found to reside in both the cytoplasm and the nucleus. It plays important roles in neuronal polarization and neurite development, cytoskeletal reorganization, cell migration, growth factor signaling, and the regulation of cell-cell interactions mediated by adherens junctions and focal adhesions. Fer kinase also regulates cell cycle progression in malignant cells.

Pssm-ID: 270668 [Multi-domain] Cd Length: 251 Bit Score: 59.25 E-value: 8.75e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3336 ESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLHSLidrfRYSEDDV-----VAYIVQILQGLDYL 3410
Cdd:cd05085     35 ELKIKFLSEARILKQYDHPNIVKLIGVCTQRQPIYIVMELVPGGDFLSFL----RKKKDELktkqlVKFSLDAAAGMAYL 110

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3411 HSRRILHLDIKPENIIVTYMNVVKIIDFGSAQ-----TFNPLFLKQFspPIgtlDYMSPEMLKGDVVGPPADIWSIGILT 3485
Cdd:cd05085    111 ESKNCIHRDLAARNCLVGENNALKISDFGMSRqeddgVYSSSGLKQI--PI---KWTAPEALNYGRYSSESDVWSFGILL 185

                          170       180
                   ....*....|....*....|....*....
gi 1207186029 3486 YIMLS-GRLPFtendPAET--EARIQAAK 3511
Cdd:cd05085    186 WETFSlGVCPY----PGMTnqQAREQVEK 210

Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409550 [Multi-domain] Cd Length: 89 Bit Score: 55.27 E-value: 8.86e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1249 PDFVKPLYDMDVVEGREAVLRCKVAGLPYPTITWFHNGKRIdsTEDRKMTQFRDvHSLVVRCVCHAH-GGVYKCVISNKV 1327
Cdd:cd20958      1 PPFIRPMGNLTAVAGQTLRLHCPVAGYPISSITWEKDGRRL--PLNHRQRVFPN-GTLVIENVQRSSdEGEYTCTARNQQ 77


                   .
gi 1207186029 1328 G 1328
Cdd:cd20958     78 G 78

Catalytic domain of Tec-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Tec-like subfamily is composed of Tec, Btk, Bmx (Etk), Itk (Tsk, Emt), Rlk (Txk), and similar proteins. They are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, some members contain the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. Tec kinases form the second largest subfamily of nonreceptor PTKs and are expressed mainly by haematopoietic cells, although Tec and Bmx are also found in endothelial cells. B-cells express Btk and Tec, while T-cells express Itk, Txk, and Tec. Collectively, Tec kinases are expressed in a variety of myeloid cells such as mast cells, platelets, macrophages, and dendritic cells. Each Tec kinase shows a distinct cell-type pattern of expression. Tec kinases play important roles in the development, differentiation, maturation, regulation, survival, and function of B-cells and T-cells. Mutations in Btk cause the severe B-cell immunodeficiency, X-linked agammaglobulinaemia (XLA). The Tec-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173637 [Multi-domain] Cd Length: 256 Bit Score: 59.38 E-value: 9.04e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3301 TFMDEKARGRFGVIRecRENATGNLYMA-KIVPYEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGK 3379
Cdd:cd05059      7 TFLKELGSGQFGVVH--LGKWRGKIDVAiKMIKEGSMSEDDFIEEAKVMMKLSHPKLVQLYGVCTKQRPIFIVTEYMANG 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3380 ELLHSLIDR-FRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTfnpLFLKQFSPPIGT 3458
Cdd:cd05059     85 CLLNYLRERrGKFQTEQLLEMCKDVCEAMEYLESNGFIHRDLAARNCLVGEQNVVKVSDFGLARY---VLDDEYTSSVGT 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3459 ---LDYMSPEMLKGDVVGPPADIWSIGILTYIMLS-GRLPFTENDPAETEARIQAAkfdlSKLYQnvSQSASLFIKKILC 3534
Cdd:cd05059    162 kfpVKWSPPEVFMYSKFSSKSDVWSFGVLMWEVFSeGKMPYERFSNSEVVEHISQG----YRLYR--PHLAPTEVYTIMY 235

                          250
                   ....*....|....
gi 1207186029 3535 S----YPWARPTIK 3544
Cdd:cd05059    236 ScwheKPEERPTFK 249

Catalytic domain of a subset of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily includes a subset of Src-like PTKs including Src, Fyn, Yrk, and Yes, which are all widely expressed. Yrk has been detected only in chickens. It is primarily found in neuronal and epithelial cells and in macrophages. It may play a role in inflammation and in response to injury. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells and tumor vasculature, contributing to cancer progression and metastasis. They are also implicated in acute inflammatory responses and osteoclast function. The Src/Fyn-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271105 [Multi-domain] Cd Length: 248 Bit Score: 59.16 E-value: 9.30e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3309 GRFGVIRECRENATGNLYMAKIVP--YEPESkqtVLQEYDILKSLHHEKIMALHeAYVTPRYLVLISECCSGKELLHSLI 3386
Cdd:cd14203      6 GCFGEVWMGTWNGTTKVAIKTLKPgtMSPEA---FLEEAQIMKKLRHDKLVQLY-AVVSEEPIYIVTEFMSKGSLLDFLK 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3387 D-RFRYSE-DDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPlflKQFSPPIGT---LDY 3461
Cdd:cd14203     82 DgEGKYLKlPQLVDMAAQIASGMAYIERMNYIHRDLRAANILVGDNLVCKIADFGLARLIED---NEYTARQGAkfpIKW 158

                          170       180       190
                   ....*....|....*....|....*....|....*
gi 1207186029 3462 MSPEMLKGDVVGPPADIWSIGIL-TYIMLSGRLPF 3495
Cdd:cd14203    159 TAPEAALYGRFTIKSDVWSFGILlTELVTKGRVPY 193

Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409548 [Multi-domain] Cd Length: 96 Bit Score: 55.26 E-value: 9.86e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 2860 PPVFHIKLRDHVLLEGDPVTLSCLPAGSPHPHISWMKDKKPLEIDPRMNM---IScPDGRQL--LMIMKTTKKDAGLYEC 2934
Cdd:cd20956      1 APVLLETFSEQTLQPGPSVSLKCVASGNPLPQITWTLDGFPIPESPRFRVgdyVT-SDGDVVsyVNISSVRVEDGGEYTC 79

                           90
                   ....*....|..
gi 1207186029 2935 VAANPLATVTSS 2946
Cdd:cd20956     80 TATNDVGSVSHS 91

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 55.16 E-value: 9.99e-09

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  781 PVFE--FPLQDTVASTGTEVLLKCIISGTPLPEVIWKKDNTEVKNSPTHVVKIEGerhSLLIKWTKPSDAGTYTVTAVNE 858
Cdd:cd04969      1 PDFElnPVKKKILAAKGGDVIIECKPKASPKPTISWSKGTELLTNSSRICILPDG---SLKIKNVTKSDEGKYTCFAVNF 77

                           90
                   ....*....|
gi 1207186029  859 VGEVSSSATL 868
Cdd:cd04969     78 FGKANSTGSL 87

Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tyk2 is widely expressed in many tissues. It is involved in signaling via the cytokine receptors IFN-alphabeta, IL-6, IL-10, IL-12, IL-13, and IL-23. It mediates cell surface urokinase receptor (uPAR) signaling and plays a role in modulating vascular smooth muscle cell (VSMC) functional behavior in response to injury. Tyk2 is also important in dendritic cell function and T helper (Th)1 cell differentiation. A homozygous mutation of Tyk2 was found in a patient with hyper-IgE syndrome (HIES), a primary immunodeficiency characterized by recurrent skin abscesses, pneumonia, and elevated serum IgE. This suggests that Tyk2 may play important roles in multiple cytokine signaling involved in innate and adaptive immunity. Tyk2 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase catalytic domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The Tyk2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270664 [Multi-domain] Cd Length: 283 Bit Score: 59.53 E-value: 1.16e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1705 RELNILSHLDHERILYFHDAFEK---KNAVIIITELCHEELLDRLTKKSTILeSEIRSSVRQLLEGINYLHQLDILHLDI 1781
Cdd:cd05080     55 QEIDILKTLYHENIVKYKGCCSEqggKSLQLIMEYVPLGSLRDYLPKHSIGL-AQLLLFAQQICEGMAYLHSQHYIHRDL 133

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1782 KPDNILMadHSSDQIRICDFGNAvKFMPDEAQYCKYG----TPEF-VAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPF 1856
Cdd:cd05080    134 AARNVLL--DNDRLVKIGDFGLA-KAVPEGHEYYRVRedgdSPVFwYAPECLKEYKFYYASDVWSFGVTLYELLTHCDSS 210

Catalytic domain of the Protein Tyrosine Kinases, Tyrosine kinase expressed in hepatocellular carcinoma and Resting lymphocyte kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tec and Rlk (also named Txk) are members of the Tec-like subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. Instead of PH, Rlk contains an N-terminal cysteine-rich region. In addition to PH, Tec also contains the Tec homology (TH) domain with proline-rich and zinc-binding regions. Tec kinases are expressed mainly by haematopoietic cells. Tec is more widely-expressed than other Tec-like subfamily kinases. It is found in endothelial cells, both B- and T-cells, and a variety of myeloid cells including mast cells, erythroid cells, platelets, macrophages and neutrophils. Rlk is expressed in T-cells and mast cell lines. Tec and Rlk are both key components of T-cell receptor (TCR) signaling. They are important in TCR-stimulated proliferation, IL-2 production and phopholipase C-gamma1 activation. The Tec/Rlk subfamily is part of a larger superfamily, that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270685 [Multi-domain] Cd Length: 260 Bit Score: 59.10 E-value: 1.17e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1666 KEIGRGAFSYVkRVIQKAGKLEYAAKFISARAKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITE-LCHEELLD 1744
Cdd:cd05114     10 KELGSGLFGVV-RLGKWRAQYKVAIKAIREGAMSEEDFIEEAKVMMKLTHPKLVQLYGVCTQQKPIYIVTEfMENGCLLN 88

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1745 RLTKKSTILESEIRSSVRQ-LLEGINYLHQLDILHLDIKPDNILMADHSSdqIRICDFGNAVKFMPDeaQYCKYGTPEF- 1822
Cdd:cd05114     89 YLRQRRGKLSRDMLLSMCQdVCEGMEYLERNNFIHRDLAARNCLVNDTGV--VKVSDFGMTRYVLDD--QYTSSSGAKFp 164

                          170       180       190
                   ....*....|....*....|....*....|....*...
gi 1207186029 1823 ---VAPEIVNQTPVSKATDIWPIGVLTYLCLT-GVSPF 1856
Cdd:cd05114    165 vkwSPPEVFNYSKFSSKSDVWSFGVLMWEVFTeGKMPF 202

Catalytic domain of the Serine/Threonine kinase, Vacuolar protein sorting-associated protein 15; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Vps15 is a large protein consisting of an N-terminal kinase domain, a C-terminal WD-repeat containing domain, and an intermediate bridge domain that contain HEAT repeats. The kinase domain is necessary for the signaling functions of Vps15. Human Vps15 was previously called p150. It associates and regulates Vps34, also called Class III phosphoinositide 3-kinase (PI3K), which catalyzes the phosphorylation of D-myo-phosphatidylinositol (PtdIns). Vps34 is the only PI3K present in yeast. It plays an important role in the regulation of protein and vesicular trafficking and sorting, autophagy, trimeric G-protein signaling, and phagocytosis. The Vps15 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and PI3K.

Pssm-ID: 270882 [Multi-domain] Cd Length: 278 Bit Score: 59.19 E-value: 1.20e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1698 KRKASALRE-LNILSHldherILYFHDAFEKKNAVIIITELCHEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDI 1776
Cdd:cd13980     44 KQRLEEIRDrLLELPN-----VLPFQKVIETDKAAYLIRQYVKYNLYDRISTRPFLNLIEKKWIAFQLLHALNQCHKRGV 118

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1777 LHLDIKPDNILMAdhSSDQIRICDFGnAVK--FMPDE--AQY-----------CkYGTPE-------FVAPEIVNQTPVS 1834
Cdd:cd13980    119 CHGDIKTENVLVT--SWNWVYLTDFA-SFKptYLPEDnpADFsyffdtsrrrtC-YIAPErfvdaltLDAESERRDGELT 194

                          170       180       190
                   ....*....|....*....|....*....|....*..
gi 1207186029 1835 KATDIWPIG-VLTYLCLTGVSPFagenDRSSVLNIRN 1870
Cdd:cd13980    195 PAMDIFSLGcVIAELFTEGRPLF----DLSQLLAYRK 227

Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LRRK1 is one of two vertebrate LRRKs which show complementary expression in the brain. It can form heterodimers with LRRK2, and may influence the age of onset of LRRK2-associated Parkinson's disease. LRRKs are also classified as ROCO proteins because they contain a ROC (Ras of complex proteins)/GTPase domain followed by a COR (C-terminal of ROC) domain of unknown function. In addition, LRRKs contain a catalytic kinase domain and protein-protein interaction motifs including a WD40 domain, LRRs and ankyrin (ANK) repeats. LRRKs possess both GTPase and kinase activities, with the ROC domain acting as a molecular switch for the kinase domain, cycling between a GTP-bound state which drives kinase activity and a GDP-bound state which decreases the activity. The LRRK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270969 [Multi-domain] Cd Length: 276 Bit Score: 59.21 E-value: 1.21e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3343 QEYDILKSLHHEKIMALHEAYVTPRYLVL-----------ISECCSGKELL---HSLIDRfryseddvVAYivQILQGLD 3408
Cdd:cd14067     59 QEASMLHSLQHPCIVYLIGISIHPLCFALelaplgslntvLEENHKGSSFMplgHMLTFK--------IAY--QIAAGLA 128

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3409 YLHSRRILHLDIKPENIIVTYMNV-----VKIIDFG-SAQTFNPLFLKQfsppIGTLDYMSPEMLKGDVVGPPADIWSIG 3482
Cdd:cd14067    129 YLHKKNIIFCDLKSDNILVWSLDVqehinIKLSDYGiSRQSFHEGALGV----EGTPGYQAPEIRPRIVYDEKVDMFSYG 204

                          170
                   ....*....|..
gi 1207186029 3483 ILTYIMLSGRLP 3494
Cdd:cd14067    205 MVLYELLSGQRP 216

immunoglobulin-like domain of telokin and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin (Ig) domain in telokin, the C-terminal domain of myosin light chain kinase which is identical to telokin, and similar proteins. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the telokin Ig domain lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409565 [Multi-domain] Cd Length: 88 Bit Score: 54.89 E-value: 1.21e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 2867 LRDHVLLEGDPVTLSCLPAGSPHPHISWMKDKKPLEIDPRMNMISCPDGRQLLMIMKTTKKDAGLYECVAANPLATVTSS 2946
Cdd:cd20973      4 LRDKEVVEGSAARFDCKVEGYPDPEVKWMKDDNPIVESRRFQIDQDEDGLCSLIISDVCGDDSGKYTCKAVNSLGEATCS 83


                   ...
gi 1207186029 2947 CVV 2949
Cdd:cd20973     84 AEL 86

Catalytic domain of the Serine/Threonine Kinase, Cell Division Cycle 7 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Cdc7 kinase (or Hsk1 in fission yeast) is a critical regulator in the initiation of DNA replication. It forms a complex with a Dbf4-related regulatory subunit, a cyclin-like molecule that activates the kinase in late G1 phase, and is also referred to as Dbf4-dependent kinase (DDK). Its main targets are mini-chromosome maintenance (MCM) proteins. Cdc7 kinase may also have additional roles in meiosis, checkpoint responses, the maintenance and repair of chromosome structures, and cancer progression. The Cdc7 kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270921 [Multi-domain] Cd Length: 252 Bit Score: 58.77 E-value: 1.22e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3298 KPYTFMDEKARGRFGV------IRECRENATGNLYMAKIVPYEPESKQTVLQEYDILKSLH-HEKIMAL--------HEA 3362
Cdd:cd14019      1 NKYRIIEKIGEGTFSSvykaedKLHDLYDRNKGRLVALKHIYPTSSPSRILNELECLERLGgSNNVSGLitafrnedQVV 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3363 YVTPRYlvlisECCSGKELLHSLidrfrySEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMN-VVKIIDFGSA 3441
Cdd:cd14019     81 AVLPYI-----EHDDFRDFYRKM------SLTDIRIYLRNLFKALKHVHSFGIIHRDVKPGNFLYNRETgKGVLVDFGLA 149

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1207186029 3442 QTFNPLFLKQfSPPIGTLDYMSPEML-KGDVVGPPADIWSIGILTYIMLSGRLPF 3495
Cdd:cd14019    150 QREEDRPEQR-APRAGTRGFRAPEVLfKCPHQTTAIDIWSAGVILLSILSGRFPF 203

Immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain from the C-terminus of human titin x and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is gigantic; depending on isoform composition it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone and appears to function similar to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 143224 [Multi-domain] Cd Length: 92 Bit Score: 54.67 E-value: 1.24e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1207186029 1132 LEVIEGRNARFDCKVSGTPPPQVIWSHFDRPLEENEDIRILKEGGRHSLIISHVSNEDEGLYTVAARNSHGEDE 1205
Cdd:cd05747     13 LTVSEGESARFSCDVDGEPAPTVTWMREGQIIVSSQRHQITSTEYKSTFEISKVQMSDEGNYTVVVENSEGKQE 86

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 54.43 E-value: 1.32e-08

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1207186029    69 GCDIRLKVAVAGDPQPTLYWYHNDDLVNMDNQEYGG--------LWIRDCKPSDAGLYTCIATNHLGEARSSAVLAV 137
Cdd:smart00410    9 GESVTLSCEASGSPPPEVTWYKQGGKLLAESGRFSVsrsgststLTISNVTPEDSGTYTCAATNSSGSASSGTTLTV 85

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 4; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK4 is a dual-specificity PK that phosphorylates and activates the downstream targets, c-Jun N-terminal kinase (JNK) and p38 MAPK, on specific threonine and tyrosine residues. JNK and p38 are collectively known as stress-activated MAPKs, as they are activated in response to a variety of environmental stresses and pro-inflammatory cytokines. Their activation is associated with the induction of cell death. Mice deficient in MKK4 die during embryogenesis and display anemia, severe liver hemorrhage, and abnormal hepatogenesis. MKK4 may also play roles in the immune system and in cardiac hypertrophy. It plays a major role in cancer as a tumor and metastasis suppressor. Under certain conditions, MKK4 is pro-oncogenic. The MKK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270790 [Multi-domain] Cd Length: 291 Bit Score: 59.30 E-value: 1.39e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTF-------MDEKARGRFGVIRECRENATGNlYMA----KIVPYEPESKQtVLQEYDILKSlhhekimALHEAYVTPRY 3368
Cdd:cd06616      1 YEFtaedlkdLGEIGRGAFGTVNKMLHKPSGT-IMAvkriRSTVDEKEQKR-LLMDLDVVMR-------SSDCPYIVKFY 71

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3369 LVLISE--CCSGKELLHSLIDRF---------RYSEDDVVAYI-VQILQGLDYLHSR-RILHLDIKPENIIVTYMNVVKI 3435
Cdd:cd06616     72 GALFREgdCWICMELMDISLDKFykyvyevldSVIPEEILGKIaVATVKALNYLKEElKIIHRDVKPSNILLDRNGNIKL 151

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3436 IDFG-SAQTFNPLFLKQfspPIGTLDYMSPEMLKGDVVGPP----ADIWSIGILTYIMLSGRLPFTENDP 3500
Cdd:cd06616    152 CDFGiSGQLVDSIAKTR---DAGCRPYMAPERIDPSASRDGydvrSDVWSLGITLYEVATGKFPYPKWNS 218

Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. aPKCs only require phosphatidylserine (PS) for activation. They contain a C2-like region, instead of a calcium-binding (C2) region found in classical PKCs, in their regulatory domain. There are two aPKC isoforms, zeta and iota. aPKCs are involved in many cellular functions including proliferation, migration, apoptosis, polarity maintenance and cytoskeletal regulation. They also play a critical role in the regulation of glucose metabolism and in the pathogenesis of type 2 diabetes. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. The aPKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270740 [Multi-domain] Cd Length: 328 Bit Score: 59.74 E-value: 1.41e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASALRELNILSHL-----DHERILYFHDAFEKKNAVIIITELCHE-E 1741
Cdd:cd05588      3 IGRGSYAKVLMVELKKTKRIYAMKVIKKELVNDDEDIDWVQTEKHVfetasNHPFLVGLHSCFQTESRLFFVIEFVNGgD 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1742 LLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMaDHSSdQIRICDFGnavkfMPDE--------AQ 1813
Cdd:cd05588     83 LMFHMQRQRRLPEEHARFYSAEISLALNFLHEKGIIYRDLKLDNVLL-DSEG-HIKLTDYG-----MCKEglrpgdttST 155

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|...
gi 1207186029 1814 YCkyGTPEFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPF 1856
Cdd:cd05588    156 FC--GTPNYIAPEILRGEDYGFSVDWWALGVLMFEMLAGRSPF 196

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.

Pssm-ID: 409406 [Multi-domain] Cd Length: 82 Bit Score: 54.13 E-value: 1.48e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1207186029  939 VIEGQEVTMSVLVTGQPKPMLYWLRDRVTIKTGTRHIVQETEEgNFEMIIKSAQRSDTGVYTCKIINEYGTKQ 1011
Cdd:cd05748      4 VRAGESLRLDIPIKGRPTPTVTWSKDGQPLKETGRVQIETTAS-STSLVIKNAKRSDSGKYTLTLKNSAGEKS 75

serine/threonine kinase US3; Provisional

Pssm-ID: 223009 [Multi-domain] Cd Length: 461 Bit Score: 60.29 E-value: 1.54e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3396 VVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSAqtfnpLFLK-QFSPPI-----GTLDYMSPEMLKG 3469
Cdd:PHA03211   262 VTAVARQLLSAIDYIHGEGIIHRDIKTENVLVNGPEDICLGDFGAA-----CFARgSWSTPFhygiaGTVDTNAPEVLAG 336

                           90
                   ....*....|....*..
gi 1207186029 3470 DVVGPPADIWSIGILTY 3486
Cdd:PHA03211   337 DPYTPSVDIWSAGLVIF 353

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 54.32 E-value: 1.64e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1545 PTFETIMED-LDVNVGETPRFAVVVEGKPVPDILW-YKGDTLlsESSHFTFVYDDNecSLVVLNTQADDSGVYTCTAKNL 1622
Cdd:cd20978      1 PKFIQKPEKnVVVKGGQDVTLPCQVTGVPQPKITWlHNGKPL--QGPMERATVEDG--TLTIINVQPEDTGYYGCVATNE 76

                           90
                   ....*....|..
gi 1207186029 1623 AGSVSCKAELTV 1634
Cdd:cd20978     77 IGDIYTETLLHV 88

Catalytic domain of the Serine/Threonine kinase, Leucine-Rich Repeat Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LRRKs are also classified as ROCO proteins because they contain a ROC (Ras of complex proteins)/GTPase domain followed by a COR (C-terminal of ROC) domain of unknown function. In addition, LRRKs contain a catalytic kinase domain and protein-protein interaction motifs including a WD40 domain, LRRs and ankyrin (ANK) repeats. LRRKs possess both GTPase and kinase activities, with the ROC domain acting as a molecular switch for the kinase domain, cycling between a GTP-bound state which drives kinase activity and a GDP-bound state which decreases the activity. Vertebrates contain two members, LRRK1 and LRRK2, which show complementary expression in the brain. Mutations in LRRK2 are linked to both familial and sporadic forms of Parkinson's disease. The normal roles of LRRKs are not clearly defined. They may be involved in mitogen-activated protein kinase (MAPK) pathways, protein translation control, programmed cell death pathways, and cytoskeletal dynamics. The LRRK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270902 [Multi-domain] Cd Length: 275 Bit Score: 58.78 E-value: 1.65e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1698 KRKASALRELNILSHLDHERILYFhdafekknAVIIITELCHEELLDRLTKKSTILESEIRSS-----------VRQLLE 1766
Cdd:cd14000     52 KNFRLLRQELTVLSHLHHPSIVYL--------LGIGIHPLMLVLELAPLGSLDHLLQQDSRSFaslgrtlqqriALQVAD 123

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1767 GINYLHQLDILHLDIKPDNIL---MADHSSDQIRICDFGNAVKFMPDEAQYCKyGTPEFVAPEIVNQTPV-SKATDIWPI 1842
Cdd:cd14000    124 GLRYLHSAMIIYRDLKSHNVLvwtLYPNSAIIIKIADYGISRQCCRMGAKGSE-GTPGFRAPEIARGNVIyNEKVDVFSF 202

                          170
                   ....*....|....*.
gi 1207186029 1843 GVLTYLCLTGVSPFAG 1858
Cdd:cd14000    203 GMLLYEILSGGAPMVG 218

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.

Pssm-ID: 409367 [Multi-domain] Cd Length: 89 Bit Score: 54.38 E-value: 1.66e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1207186029 2868 RDHVLLEGDPVTLSCLPAGSPHPHISWMKDKKPLEI---DPRMNmiscpDGRQLLMIMKTTKKDAGLYECVAANPLATV 2943
Cdd:cd04978      7 PSLVLSPGETGELICEAEGNPQPTITWRLNGVPIEPapeDMRRT-----VDGRTLIFSNLQPNDTAVYQCNASNVHGYL 80

Catalytic domain of the Protein Tyrosine Kinase, C-terminal Src kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Csk catalyzes the tyr phosphorylation of the regulatory C-terminal tail of Src kinases, resulting in their inactivation. Csk is expressed in a wide variety of tissues. As a negative regulator of Src, Csk plays a role in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. Csk is a cytoplasmic (or nonreceptor) PTK containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. To inhibit Src kinases, Csk is translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. In addition, Csk also shows Src-independent functions. It is a critical component in G-protein signaling, and plays a role in cytoskeletal reorganization and cell migration. The Csk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 133213 [Multi-domain] Cd Length: 256 Bit Score: 58.45 E-value: 1.80e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3337 SKQTVLQEYDILKSLHHEKIMALHEAYVTPR-YLVLISECCSGKELLHSLIDRFR--YSEDDVVAYIVQILQGLDYLHSR 3413
Cdd:cd05082     42 TAQAFLAEASVMTQLRHSNLVQLLGVIVEEKgGLYIVTEYMAKGSLVDYLRSRGRsvLGGDCLLKFSLDVCEAMEYLEGN 121

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3414 RILHLDIKPENIIVTYMNVVKIIDFG------SAQTFNPLFLKqfsppigtldYMSPEMLKGDVVGPPADIWSIGILTYI 3487
Cdd:cd05082    122 NFVHRDLAARNVLVSEDNVAKVSDFGltkeasSTQDTGKLPVK----------WTAPEALREKKFSTKSDVWSFGILLWE 191


                   ....*....
gi 1207186029 3488 MLS-GRLPF 3495
Cdd:cd05082    192 IYSfGRVPY 200

Catalytic domain of the protein kinase, Dual-specificity tYrosine-phosphorylated and -Regulated Kinase 1; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. Mammals contain two types of DYRK1 proteins, DYRK1A and DYRK1B. DYRK1A was previously called minibrain kinase homolog (MNBH) or dual-specificity YAK1-related kinase. It phosphorylates various substrates and is involved in many cellular events. It phosphorylates and inhibits the transcription factors, nuclear factor of activated T cells (NFAT) and forkhead in rhabdomyosarcoma (FKHR). It regulates neuronal differentiation by targetting CREB (cAMP response element-binding protein). It also targets many endocytic proteins including dynamin and amphiphysin and may play a role in the endocytic pathway. The gene encoding DYRK1A is located in the DSCR (Down syndrome critical region) of human chromosome 21 and DYRK1A has been implicated in the pathogenesis of DS. DYRK1B, also called minibrain-related kinase (MIRK), is highly expressed in muscle and plays a critical role in muscle differentiation by regulating transcription, cell motility, survival, and cell cycle progression. It is overexpressed in many solid tumors where it acts as a tumor survival factor. DYRKs autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. The DYRK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271128 [Multi-domain] Cd Length: 339 Bit Score: 59.25 E-value: 2.04e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3402 QILQGLDYLHSR--RILHLDIKPENIIVTYMN--VVKIIDFGSAQTFNplflKQFSPPIGTLDYMSPEMLKGDVVGPPAD 3477
Cdd:cd14226    124 QLCTALLFLSTPelSIIHCDLKPENILLCNPKrsAIKIIDFGSSCQLG----QRIYQYIQSRFYRSPEVLLGLPYDLAID 199

                           90
                   ....*....|....
gi 1207186029 3478 IWSIGILTYIMLSG 3491
Cdd:cd14226    200 MWSLGCILVEMHTG 213

Catalytic domain of the Serine/Threonine kinases, Spindle assembly checkpoint proteins Bub1 and BubR1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Bub1 (Budding uninhibited by benzimidazoles 1), BubR1, and similar proteins. They contain an N-terminal Bub1/Mad3 homology domain essential for Cdc20 binding and a C-terminal kinase domain. Bub1 and BubR1 are involved in SAC, a surveillance system that delays metaphase to anaphase transition by blocking the activity of APC/C (the anaphase promoting complex) until all chromosomes achieve proper attachments to the mitotic spindle, to avoid chromosome missegregation. Impaired SAC leads to genomic instabilities and tumor development. Bub1 and BubR1 facilitate the localization of SAC proteins to kinetochores and regulate kinetochore-microtubule (K-MT) attachments. Repression studies of Bub1 and BubR1 show that they exert an additive effect in misalignment phenotypes and may function cooperatively or in parallel pathways in regulating K-MT attachments. The Bub1/BubR1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270883 [Multi-domain] Cd Length: 298 Bit Score: 58.91 E-value: 2.13e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYaaKFISARAKRKASALrELNILSHLdHER---------ILYFHDAFEKKNAVI 1732
Cdd:cd13981      2 YVISKELGEGGYASVYLAKDDDEQSDG--SLVALKVEKPPSIW-EFYICDQL-HSRlknsrlresISGAHSAHLFQDESI 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1733 IITELCHE-ELLD-----RLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILM-------------ADHSS 1793
Cdd:cd13981     78 LVMDYSSQgTLLDvvnkmKNKTGGGMDEPLAMFFTIELLKVVEALHEVGIIHGDIKPDNFLLrleicadwpgegeNGWLS 157

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1207186029 1794 DQIRICDFGNAV--KFMPDEAQYCKYGTP-EFVAPEIVNQTPVSKATDIWPIGVLTYLCLTG 1852
Cdd:cd13981    158 KGLKLIDFGRSIdmSLFPKNQSFKADWHTdSFDCIEMREGRPWTYQIDYFGIAATIHVMLFG 219

serine/threonine kinase US3; Provisional

Pssm-ID: 223009 [Multi-domain] Cd Length: 461 Bit Score: 59.91 E-value: 2.23e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1675 YVKRVIQKAGKLeyaakfisarakrkASALRELNILSHLDHERILYFHDAFEKKNAVIIITELCHEELLDRLTKKSTILE 1754
Cdd:PHA03211   193 YPQRVVVKAGWY--------------ASSVHEARLLRRLSHPAVLALLDVRVVGGLTCLVLPKYRSDLYTYLGARLRPLG 258

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1755 -SEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDFGNAVkFM----PDEAQYCKYGTPEFVAPEIVN 1829
Cdd:PHA03211   259 lAQVTAVARQLLSAIDYIHGEGIIHRDIKTENVLV--NGPEDICLGDFGAAC-FArgswSTPFHYGIAGTVDTNAPEVLA 335

                          170
                   ....*....|....*...
gi 1207186029 1830 QTPVSKATDIWPIGVLTY 1847
Cdd:PHA03211   336 GDPYTPSVDIWSAGLVIF 353

Catalytic domain of the protein kinases, Dual-specificity tYrosine-phosphorylated and -Regulated Kinases 2 and 3; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. This subfamily is composed of DYRK2 and DYRK3, and similar proteins. Drosophila DYRK2 interacts and phosphorylates the chromatin remodelling factor, SNR1 (Snf5-related 1), and also interacts with the essential chromatin component, trithorax. It may play a role in chromatin remodelling. Vertebrate DYRK2 phosphorylates and regulates the tumor suppressor p53 to induce apoptosis in response to DNA damage. It can also phosphorylate the transcription factor, nuclear factor of activated T cells (NFAT). DYRK2 is overexpressed in lung adenocarcinoma and esophageal carcinomas, and is a predictor for favorable prognosis in lung adenocarcinoma. DYRK3, also called regulatory erythroid kinase (REDK), is highly expressed in erythroid cells and the testis, and is also present in adult kidney and liver. It promotes cell survival by phosphorylating and activating SIRT1, an NAD(+)-dependent protein deacetylase, which promotes p53 deacetylation, resulting in the inhibition of apoptosis. DYRKs autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. The DYRK2/3 subfamily is part of a larger superfamily that includes the catalytic domains of other S/T kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271126 [Multi-domain] Cd Length: 380 Bit Score: 59.37 E-value: 2.26e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3403 ILQGLDYLHSRRILHLDIKPENIIVTYM--NVVKIIDFGSAqtfnpLFLKQ-FSPPIGTLDYMSPEMLKGDVVGPPADIW 3479
Cdd:cd14224    177 ILQCLDALHRNKIIHCDLKPENILLKQQgrSGIKVIDFGSS-----CYEHQrIYTYIQSRFYRAPEVILGARYGMPIDMW 251

                           90       100
                   ....*....|....*....|....*
gi 1207186029 3480 SIGILTYIMLSGRLPFtendPAETE 3504
Cdd:cd14224    252 SFGCILAELLTGYPLF----PGEDE 272

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 54.05 E-value: 2.29e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1552 EDLDVNVGETPRFAVVVEGKPVPDILWYKGDTLLSESSHfTFVYDDNECSLVVLNTQADDSGVYTCTAKNLA-GSVSCKA 1630
Cdd:cd20970     10 FTVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEFNT-RYIVRENGTTLTIRNIRRSDMGIYLCIASNGVpGSVEKRI 88


                   ....
gi 1207186029 1631 ELTV 1634
Cdd:cd20970     89 TLQV 92

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409543 [Multi-domain] Cd Length: 94 Bit Score: 53.96 E-value: 2.35e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  781 PVFEFPLQDTVASTGTEVLLKCIISGTPLPEVIWKKDNTEVKNS---PTHVVKIEGERHSLLIKWTKPSDAGTYTVTAVN 857
Cdd:cd20951      1 PEFIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIDPSsipGKYKIESEYGVHVLHIRRVTVEDSAVYSAVAKN 80

                           90
                   ....*....|....
gi 1207186029  858 EVGEVSSSATLFIK 871
Cdd:cd20951     81 IHGEASSSASVVVE 94

Catalytic domain of Epidermal Growth Factor Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EGFR (HER, ErbB) subfamily members include EGFR (HER1, ErbB1), HER2 (ErbB2), HER3 (ErbB3), HER4 (ErbB4), and similar proteins. They are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, resulting in the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. Collectively, they can recognize a variety of ligands including EGF, TGFalpha, and neuregulins, among others. All four subfamily members can form homo- or heterodimers. HER3 contains an impaired kinase domain and depends on its heterodimerization partner for activation. EGFR subfamily members are involved in signaling pathways leading to a broad range of cellular responses including cell proliferation, differentiation, migration, growth inhibition, and apoptosis. Gain of function alterations, through their overexpression, deletions, or point mutations in their kinase domains, have been implicated in various cancers. These receptors are targets of many small molecule inhibitors and monoclonal antibodies used in cancer therapy. The EGFR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270648 [Multi-domain] Cd Length: 279 Bit Score: 58.20 E-value: 2.40e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3335 PESKQTVLQEYDILKSLHHEKIMALHEAYVTPRyLVLISECCSgkelLHSLIDRFRYSEDDVVAYI-----VQILQGLDY 3409
Cdd:cd05057     50 PKANEEILDEAYVMASVDHPHLVRLLGICLSSQ-VQLITQLMP----LGCLLDYVRNHRDNIGSQLllnwcVQIAKGMSY 124

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3410 LHSRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNP----LFLKQFSPPIgtlDYMSPEMLKGDVVGPPADIWSIGILT 3485
Cdd:cd05057    125 LEEKRLVHRDLAARNVLVKTPNHVKITDFGLAKLLDVdekeYHAEGGKVPI---KWMALESIQYRIYTHKSDVWSYGVTV 201

                          170
                   ....*....|....*..
gi 1207186029 3486 Y-IMLSGRLPFtENDPA 3501
Cdd:cd05057    202 WeLMTFGAKPY-EGIPA 217

Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Type II Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TGFbR2 belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, bone morphogenetic proteins, activins, growth and differentiation factors, and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane region, and a cytoplasmic catalytic kinase domain. Type II receptors, such as TGFbR2, are high-affinity receptors which bind ligands, autophosphorylate, as well as trans-phosphorylate and activate low-affinity type I receptors. TGFbR2 acts as the receptor for TGFbeta, which is crucial in growth control and homeostasis in many different tissues. It plays roles in regulating apoptosis and in maintaining the balance between self renewal and cell loss. It also plays a key role in maintaining vascular integrity and in regulating responses to genotoxic stress. Mutations in TGFbR2 can cause aortic aneurysm disorders such as Loeys-Dietz and Marfan syndromes. The TGFbR2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270957 [Multi-domain] Cd Length: 295 Bit Score: 58.54 E-value: 2.71e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1666 KEIGRGAFSYV---KRVIQKAGKLEYAAKFIsARAKRKASALRELNILS--HLDHERILYFHDAFEKKNAV----IIITE 1736
Cdd:cd14055      1 KLVGKGRFAEVwkaKLKQNASGQYETVAVKI-FPYEEYASWKNEKDIFTdaSLKHENILQFLTAEERGVGLdrqyWLITA 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1737 LCHEELLDRLTKKSTILESEIRSSVRQLLEGINYLH---------QLDILHLDIKPDNILMADHSSdqIRICDFGNAVKF 1807
Cdd:cd14055     80 YHENGSLQDYLTRHILSWEDLCKMAGSLARGLAHLHsdrtpcgrpKIPIAHRDLKSSNILVKNDGT--CVLADFGLALRL 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1808 MP-----DEAQYCKYGTPEFVAPEI----VNQTPVS--KATDIWPIGVLTYLCLTgvspfagendRSSVL-NIRNYNVAF 1875
Cdd:cd14055    158 DPslsvdELANSGQVGTARYMAPEAlesrVNLEDLEsfKQIDVYSMALVLWEMAS----------RCEASgEVKPYELPF 227

                          250       260       270
                   ....*....|....*....|....*....|....*...
gi 1207186029 1876 EESMFTDLCHEA-KGFVIKllvaDRLRPD-ANECLRHP 1911
Cdd:cd14055    228 GSKVRERPCVESmKDLVLR----DRGRPEiPDSWLTHQ 261

Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase kinase kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP4K3 plays a role in the nutrient-responsive pathway of mTOR (mammalian target of rapamycin) signaling. MAP4K3 is required in the activation of S6 kinase by amino acids and for the phosphorylation of the mTOR-regulated inhibitor of eukaryotic initiation factor 4E. mTOR regulates ribosome biogenesis and protein translation, and is frequently deregulated in cancer. MAP4Ks are involved in MAPK signaling pathways by activating a MAPK kinase kinase. Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Members of this subfamily contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. The MAP4K3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270812 [Multi-domain] Cd Length: 272 Bit Score: 58.13 E-value: 2.95e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1705 RELNILSHLDHERILYFHDAFEKKNAVIIITELCHE-ELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKP 1783
Cdd:cd06645     57 QEIIMMKDCKHSNIVAYFGSYLRRDKLWICMEFCGGgSLQDIYHVTGPLSESQIAYVSRETLQGLYYLHSKGKMHRDIKG 136

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1784 DNILMADHSsdQIRICDFGNAVKFMPDEAQYCKY-GTPEFVAPEIV---NQTPVSKATDIWPIGVlTYLCLTGVSP--FA 1857
Cdd:cd06645    137 ANILLTDNG--HVKLADFGVSAQITATIAKRKSFiGTPYWMAPEVAaveRKGGYNQLCDIWAVGI-TAIELAELQPpmFD 213

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1207186029 1858 GENDRSSVLNIRNynvAFEESMFTDLCHEAKGF--VIKLLVAD--RLRPDANECLRHPW 1912
Cdd:cd06645    214 LHPMRALFLMTKS---NFQPPKLKDKMKWSNSFhhFVKMALTKnpKKRPTAEKLLQHPF 269

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 53.62 E-value: 3.07e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029   57 FIRKMRNAAVGTGCDIRLKVAvaGDPQPTLYWYHNDDLVN-------MDNqeyGGLWIRDCKPSDAGLYTCIATNHLGEA 129
Cdd:cd04969      7 PVKKKILAAKGGDVIIECKPK--ASPKPTISWSKGTELLTnssriciLPD---GSLKIKNVTKSDEGKYTCFAVNFFGKA 81


                   ....*...
gi 1207186029  130 RSSAVLAV 137
Cdd:cd04969     82 NSTGSLSV 89

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409568 [Multi-domain] Cd Length: 90 Bit Score: 53.79 E-value: 3.17e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  927 PPAFLAVIGDQSVIEGQEVTMSVLVTGQPKPMLYWLRDRVTIKTGTRHIVQETEEGnfEMIIKSAQRSDTGVYTCKIINE 1006
Cdd:cd20976      1 APSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPLQYAADRSTCEAGVG--ELHIQDVLPEDHGTYTCLAKNA 78

                           90
                   ....*....|..
gi 1207186029 1007 YGTKQCEGKLEV 1018
Cdd:cd20976     79 AGQVSCSAWVTV 90

Pseudokinase domain of Scy1-like proteins; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. This subfamily is composed of the catalytically inactive kinases with similarity to yeast Scy1. It includes four mammalian proteins called SCY1-like protein 1 (SCYL1), SCYL2, SCYL3, as well as Testis-EXpressed protein 14 (TEX14). SCYL1 binds to and co-localizes with the membrane trafficking coatomer I (COPI) complex, and regulates COPI-mediated vesicle trafficking. Null mutations in the SCYL1 gene are responsible for the pathology in mdf (muscle-deficient) mice which display progressive motor neuropathy. SCYL2, also called coated vesicle-associated kinase of 104 kDa (CVAK104), is involved in the trafficking of clathrin-coated vesicles. It also binds the HIV-1 accessory protein Vpu and acts as a regulatory factor that promotes the dephosphorylation of Vpu, facilitating the restriction of HIV-1 release. SCYL3, also called ezrin-binding protein PACE-1, may be involved in regulating cell adhesion and migration. TEX14 is required for spermatogenesis and male fertility. It localizes to kinetochores (KT) during mitosis and is a target of the mitotic kinase PLK1. It regulates the maturation of the outer KT and the KT-microtubule attachment. The SCY1-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270913 [Multi-domain] Cd Length: 287 Bit Score: 57.72 E-value: 3.63e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1754 ESEIRSSVRQLLEGINYLHQ-LDILHLDIKPDNILMadHSSDQIRICDFGNAVK---FMPDEAQYCKYG---------TP 1820
Cdd:cd14011    113 DVEIKYGLLQISEALSFLHNdVKLVHGNICPESVVI--NSNGEWKLAGFDFCISseqATDQFPYFREYDpnlpplaqpNL 190

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1821 EFVAPEIVNQTPVSKATDIWPIGVLTY-LCLTGVSPFAGEND------RSSVLNIRNYNvafeesMFTDLCHEAKGFVIK 1893
Cdd:cd14011    191 NYLAPEYILSKTCDPASDMFSLGVLIYaIYNKGKPLFDCVNNllsykkNSNQLRQLSLS------LLEKVPEELRDHVKT 264

                          170       180
                   ....*....|....*....|.
gi 1207186029 1894 LL-VADRLRPDANECLRHPWF 1913
Cdd:cd14011    265 LLnVTPEVRPDAEQLSKIPFF 285

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 53.17 E-value: 3.69e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1207186029 1134 VIEGRNARFDCKVSGTPPPQVIWSHFDRPLEENEdIRILKEggrHSLIISHVSNEDEGLYTVAARNSHGEDECAAELYV 1212
Cdd:cd05725      9 VLVDDSAEFQCEVGGDPVPTVRWRKEDGELPKGR-YEILDD---HSLKIRKVTAGDMGSYTCVAENMVGKIEASATLTV 83

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 7; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK7 is a dual-specificity PK that phosphorylates and activates its downstream target, c-Jun N-terminal kinase (JNK), on specific threonine and tyrosine residues. Although MKK7 is capable of dual phosphorylation, it prefers to phosphorylate the threonine residue of JNK. Thus, optimal activation of JNK requires both MKK4 and MKK7. MKK7 is primarily activated by cytokines. MKK7 is essential for liver formation during embryogenesis. It plays roles in G2/M cell cycle arrest and cell growth. In addition, it is involved in the control of programmed cell death, which is crucial in oncogenesis, cancer chemoresistance, and antagonism to TNFalpha-induced killing, through its inhibition by Gadd45beta and the subsequent suppression of the JNK cascade. The MKK7 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270791 [Multi-domain] Cd Length: 295 Bit Score: 57.77 E-value: 3.79e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3401 VQILQGLDYLHSRR-ILHLDIKPENIIVTYMNVVKIIDFGSAQtfnplFL---KQFSPPIGTLDYMSPEML------KGD 3470
Cdd:cd06618    121 VSIVKALHYLKEKHgVIHRDVKPSNILLDESGNVKLCDFGISG-----RLvdsKAKTRSAGCAAYMAPERIdppdnpKYD 195

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3471 VvgpPADIWSIGILTYIMLSGRLPFTENDpAETEARIQAAKFDLSKL--YQNVSQSASLFIKKILCSYPWARPTIKDCFT 3548
Cdd:cd06618    196 I---RADVWSLGISLVELATGQFPYRNCK-TEFEVLTKILNEEPPSLppNEGFSPDFCSFVDLCLTKDHRYRPKYRELLQ 271


                   ....*.
gi 1207186029 3549 NSWLQD 3554
Cdd:cd06618    272 HPFIRR 277

Catalytic domain of the Protein Tyrosine Kinase, Wee1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Wee1 is a nuclear cell cycle checkpoint kinase that helps keep the cyclin-dependent kinase CDK1 in an inactive state through phosphorylation of an N-terminal tyr (Y15) residue. During the late G2 phase, CDK1 is activated and mitotic entry is promoted by the removal of this inhibitory phosphorylation by the phosphatase Cdc25. Although Wee1 is functionally a tyr kinase, it is more closely related to serine/threonine kinases (STKs). It contains a catalytic kinase domain sandwiched in between N- and C-terminal regulatory domains. It is regulated by phosphorylation and degradation, and its expression levels are also controlled by circadian clock proteins. There are two distinct Wee1 proteins in vertebrates showing different expression patterns, called Wee1a and Wee1b. They are functionally dstinct and are implicated in different steps of egg maturation and embryo development. The Wee1 subfamily is part of a larger superfamily that includes the catalytic domains of STKs, other PTKs, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270953 [Multi-domain] Cd Length: 275 Bit Score: 57.41 E-value: 4.12e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYVKRVIQKAGKLEYAAKfisaRAKR-------KASALREL---NILSHLDHerILYFHDAFEKKNAVIIITEL 1737
Cdd:cd14051      8 IGSGEFGSVYKCINRLDGCVYAIK----KSKKpvagsvdEQNALNEVyahAVLGKHPH--VVRYYSAWAEDDHMIIQNEY 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1738 CHE-ELLDRLT--KKSTIL--ESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILM-----ADHSSDQIRICDfGNAVKF 1807
Cdd:cd14051     82 CNGgSLADAISenEKAGERfsEAELKDLLLQVAQGLKYIHSQNLVHMDIKPGNIFIsrtpnPVSSEEEEEDFE-GEEDNP 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1808 MPDEAQYcKYG---------TPE-------FVAPEIV--NQTPVSKAtDIWPIGvLTYLCLTGVSPFAGENDRSSvlNIR 1869
Cdd:cd14051    161 ESNEVTY-KIGdlghvtsisNPQveegdcrFLANEILqeNYSHLPKA-DIFALA-LTVYEAAGGGPLPKNGDEWH--EIR 235

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*.
gi 1207186029 1870 NYNvafeesmFTDLCHEAKGFVIKLLV----ADRLRPDANECLRHP 1911
Cdd:cd14051    236 QGN-------LPPLPQCSPEFNELLRSmihpDPEKRPSAAALLQHP 274

Third immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 143259 Cd Length: 88 Bit Score: 53.10 E-value: 4.41e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1207186029 2860 PPVFHIKLRDHVLLEGDPVTLSCLPAGSPHPHISWMKDKKPLEIDPRMNMISCpdgrqLLMIMKTTKKDAGLYECVAAN 2938
Cdd:cd05851      1 PADINVKFKDTYALKGQNVTLECFALGNPVPVIRWRKILEPMPATAEISMSGA-----VLKIFNIQPEDEGTYECEAEN 74

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 52.95 E-value: 4.44e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1207186029 1029 IIRPVRDVMVKAGETALFECHVIGPQDTDVDWLSDGKLIQPALLNcKMHFDGKRCRLLLNSVHEDDSGTYTCKLS 1103
Cdd:pfam13927    4 ITVSPSSVTVREGETVTLTCEATGSPPPTITWYKNGEPISSGSTR-SRSLSGSNSTLTISNVTRSDAGTYTCVAS 77

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 53.23 E-value: 4.76e-08

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1207186029 1569 EGKPVPDILWYKGDTLLSESSHFTFVYDDnecSLVVLNTQADDSGVYTCTAKNLAGSVSCKAELTV 1634
Cdd:cd04969     27 KASPKPTISWSKGTELLTNSSRICILPDG---SLKIKNVTKSDEGKYTCFAVNFFGKANSTGSLSV 89

Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The VEGFR subfamily consists of VEGFR1 (Flt1), VEGFR2 (Flk1), VEGFR3 (Flt4), and similar proteins. VEGFR subfamily members are receptor PTKss (RTKs) containing an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and an intracellular catalytic domain. In VEGFR3, the fifth Ig-like domain is replaced by a disulfide bridge. The binding of VEGFRs to their ligands, the VEGFs, leads to receptor dimerization, activation, and intracellular signaling. There are five VEGF ligands in mammals, which bind, in an overlapping pattern to the three VEGFRs, which can form homo or heterodimers. VEGFRs regulate the cardiovascular system. They are critical for vascular development during embryogenesis and blood vessel formation in adults. They induce cellular functions common to other growth factor receptors such as cell migration, survival, and proliferation. The VEGFR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270647 [Multi-domain] Cd Length: 298 Bit Score: 57.50 E-value: 5.64e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1666 KEIGRGAFSYVKRV----IQKAGKLE-YAAKFIS--ARAKRKASALRELNILSHLDHE-RILYFHDAFEKKNA-VIIITE 1736
Cdd:cd05054     13 KPLGRGAFGKVIQAsafgIDKSATCRtVAVKMLKegATASEHKALMTELKILIHIGHHlNVVNLLGACTKPGGpLMVIVE 92

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1737 LCH----------------------------EELLDRLTKKSTILESEIRSSVrQLLEGINYLHQLDILHLDIKPDNILM 1788
Cdd:cd05054     93 FCKfgnlsnylrskreefvpyrdkgardveeEEDDDELYKEPLTLEDLICYSF-QVARGMEFLASRKCIHRDLAARNILL 171

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1207186029 1789 ADHssDQIRICDFGNAVKFMPDeAQYCKYGTP----EFVAPEIVNQTPVSKATDIWPIGVLTYLCLT-GVSPFAG 1858
Cdd:cd05054    172 SEN--NVVKICDFGLARDIYKD-PDYVRKGDArlplKWMAPESIFDKVYTTQSDVWSFGVLLWEIFSlGASPYPG 243

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 52.79 E-value: 6.00e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1207186029  789 DTVASTGTEVLLKCIIS-GTPLPEVIWKKDNTEVKNSPTHVVKIEGerHSLLIKWTKPSDAGTYTVTAVNEVGEVSSSA 866
Cdd:cd05724      6 DTQVAVGEMAVLECSPPrGHPEPTVSWRKDGQPLNLDNERVRIVDD--GNLLIAEARKSDEGTYKCVATNMVGERESRA 82

Fourth Ig-like domain from smooth muscle myosin light chain kinase and similar domains ; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain from smooth muscle myosin light chain kinase (MYLK) and similar domains. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of this group shows that the fourth Ig-like domain from myosin light chain kinase lacks this strand and thus belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409568 [Multi-domain] Cd Length: 90 Bit Score: 52.64 E-value: 6.09e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029   54 PPVFIRKMRNAAVGTGCDIRLKVAVAGDPQPTLYWYHNDDLVNMD------NQEYGGLWIRDCKPSDAGLYTCIATNHLG 127
Cdd:cd20976      1 APSFSSVPKDLEAVEGQDFVAQCSARGKPVPRITWIRNAQPLQYAadrstcEAGVGELHIQDVLPEDHGTYTCLAKNAAG 80

                           90
                   ....*....|
gi 1207186029  128 EARSSAVLAV 137
Cdd:cd20976     81 QVSCSAWVTV 90

C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myotilin. Mytolin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to the latter family contain multiple Ig-like domains and function as scaffolds, modulating the actin cytoskeleton. Myotilin is most abundant in skeletal and cardiac muscle and is involved in maintaining sarcomere integrity. It binds to alpha-actinin, filamin, and actin. Mutations in myotilin lead to muscle disorders. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409473 Cd Length: 92 Bit Score: 52.85 E-value: 6.27e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029   55 PVFIRKMRNAAVGTGCDIRLKVAVAGDPQPTLYW-------YHNDDLVNM--DNQEYGGLWIRDCKPSDAGLYTCIATNH 125
Cdd:cd05892      1 PMFIQKPQNKKVLEGDPVRLECQISAIPPPQIFWkknnemlQYNTDRISLyqDNCGRICLLIQNANKKDAGWYTVSAVNE 80

                           90
                   ....*....|..
gi 1207186029  126 LGEARSSAVLAV 137
Cdd:cd05892     81 AGVVSCNARLDV 92

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 52.85 E-value: 6.38e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 2867 LRDHVLLEGDPVTLSCLPAGSPHPHISWMKDKKPLEIDPRMNMIscPDGRqlLMIMKTTKKDAGLYECVAANPLATVTSS 2946
Cdd:cd04969      9 KKKILAAKGGDVIIECKPKASPKPTISWSKGTELLTNSSRICIL--PDGS--LKIKNVTKSDEGKYTCFAVNFFGKANST 84


                   ....*
gi 1207186029 2947 CVVSL 2951
Cdd:cd04969     85 GSLSV 89

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 51.95 E-value: 6.46e-08

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1207186029 1044 ALFECHVIGPQDTDVDWLSDGKLIQPALlNCKMHFDGKRCRLLLNSVHEDDSGTYTCKLSTAKEELTSS 1112
Cdd:cd00096      1 VTLTCSASGNPPPTITWYKNGKPLPPSS-RDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAGGSASA 68

C5 immunoglobulin (Ig) domain of cardiac myosin binding protein C (MyBP-C); The members here are composed of the C5 immunoglobulin (Ig) domain of cardiac myosin binding protein C (MyBP-C). MyBP-C consists of repeated domains, Ig and fibronectin type 3, and various linkers. Three isoforms of MYBP-C exist: slow-skeletal (ssMyBP-C), fast-skeletal (fsMyBP-C), and cardiac (cMyBP-C). cMYBP-C has insertions between and inside domains and an additional cardiac-specific Ig domain at the N-terminus. For cMYBP_C an interaction has been demonstrated between this C5 domain and the Ig C8 domain.

Pssm-ID: 409475 Cd Length: 86 Bit Score: 52.53 E-value: 7.21e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  939 VIEGQEVTMSVLVTGQPKPMLYWLRDRVTIKTGTRHIVQETEEGNFEMIIKSAQRSDTGVYTCKIINEYGTKQCEGKLEV 1018
Cdd:cd05894      7 VVAGNKLRLDVPISGEPAPTVTWSRGDKAFTATEGRVRVESYKDLSSFVIEGAEREDEGVYTITVTNPVGEDHASLFVKV 86

Catalytic domain of the Serine/Threonine kinase, Vacuolar protein sorting-associated protein 15; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Vps15 is a large protein consisting of an N-terminal kinase domain, a C-terminal WD-repeat containing domain, and an intermediate bridge domain that contain HEAT repeats. The kinase domain is necessary for the signaling functions of Vps15. Human Vps15 was previously called p150. It associates and regulates Vps34, also called Class III phosphoinositide 3-kinase (PI3K), which catalyzes the phosphorylation of D-myo-phosphatidylinositol (PtdIns). Vps34 is the only PI3K present in yeast. It plays an important role in the regulation of protein and vesicular trafficking and sorting, autophagy, trimeric G-protein signaling, and phagocytosis. The Vps15 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and PI3K.

Pssm-ID: 270882 [Multi-domain] Cd Length: 278 Bit Score: 56.88 E-value: 7.28e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3383 HSLIDRFR----YSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFGSaqtFNPLFL-----KQFS 3453
Cdd:cd13980     82 YNLYDRIStrpfLNLIEKKWIAFQLLHALNQCHKRGVCHGDIKTENVLVTSWNWVYLTDFAS---FKPTYLpednpADFS 158

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3454 -------------PP---IGTLDYMSPEMLKGDVVGPPADIWSIG-ILTYIMLSGRLPFT 3496
Cdd:cd13980    159 yffdtsrrrtcyiAPerfVDALTLDAESERRDGELTPAMDIFSLGcVIAELFTEGRPLFD 218

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.

Pssm-ID: 409406 [Multi-domain] Cd Length: 82 Bit Score: 52.21 E-value: 7.51e-08

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1207186029 1134 VIEGRNARFDCKVSGTPPPQVIWSHFDRPLEENEDIRILKEGGRHSLIISHVSNEDEGLYTVAARNSHGEDE 1205
Cdd:cd05748      4 VRAGESLRLDIPIKGRPTPTVTWSKDGQPLKETGRVQIETTASSTSLVIKNAKRSDSGKYTLTLKNSAGEKS 75

Catalytic domain of Serine/Threonine Kinase, Cell Division Cycle 2-like 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDC2L6 is also called CDK8-like and was previously referred to as CDK11. However, this is a confusing nomenclature as CDC2L6 is distinct from CDC2L1, which is represented by the two protein products from its gene, called CDK11(p110) and CDK11(p58), as well as the caspase-processed CDK11(p46). CDK11(p110), CDK11(p58), and CDK11(p46)do not belong to this subfamily. CDC2L6 is an associated protein of Mediator, a multiprotein complex that provides a platform to connect transcriptional and chromatin regulators and cofactors, in order to activate and mediate RNA polymerase II transcription. CDC2L6 is localized mainly in the nucleus amd exerts an opposing effect to CDK8 in VP16-dependent transcriptional activation by being a negative regulator. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDC2L6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270850 [Multi-domain] Cd Length: 318 Bit Score: 57.39 E-value: 7.85e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3343 QEYDILKSLHHEKIMALHEAYVT--PRYLVLISECCSgKELLHsLIDRFRYSEDD----------VVAYIVQILQGLDYL 3410
Cdd:cd07867     48 REIALLRELKHPNVIALQKVFLShsDRKVWLLFDYAE-HDLWH-IIKFHRASKANkkpmqlprsmVKSLLYQILDGIHYL 125

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3411 HSRRILHLDIKPENIIVT----YMNVVKIIDFGSAQTFN-PLF-LKQFSPPIGTLDYMSPEMLKGDVVGPPA-DIWSIGI 3483
Cdd:cd07867    126 HANWVLHRDLKPANILVMgegpERGRVKIADMGFARLFNsPLKpLADLDPVVVTFWYRAPELLLGARHYTKAiDIWAIGC 205


                   ....*..
gi 1207186029 3484 LTYIMLS 3490
Cdd:cd07867    206 IFAELLT 212

Catalytic domain of the Protein Tyrosine Kinases, Bruton's tyrosine kinase and Bone marrow kinase on the X chromosome; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Btk and Bmx (also named Etk) are members of the Tec-like subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, Btk contains the Tec homology (TH) domain with proline-rich and zinc-binding regions. Btk is expressed in B-cells, and a variety of myeloid cells including mast cells, platelets, neutrophils, and dendrictic cells. It interacts with a variety of partners, from cytosolic proteins to nuclear transcription factors, suggesting a diversity of functions. Stimulation of a diverse array of cell surface receptors, including antigen engagement of the B-cell receptor, leads to PH-mediated membrane translocation of Btk and subsequent phosphorylation by Src kinase and activation. Btk plays an important role in the life cycle of B-cells including their development, differentiation, proliferation, survival, and apoptosis. Mutations in Btk cause the primary immunodeficiency disease, X-linked agammaglobulinaemia (XLA) in humans. Bmx is primarily expressed in bone marrow and the arterial endothelium, and plays an important role in ischemia-induced angiogenesis. It facilitates arterial growth, capillary formation, vessel maturation, and bone marrow-derived endothelial progenitor cell mobilization. The Btk/Bmx subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173657 [Multi-domain] Cd Length: 256 Bit Score: 56.43 E-value: 7.88e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1666 KEIGRGAFSYVKRVIQKaGKLEYAAKFISARAKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITE-LCHEELLD 1744
Cdd:cd05113     10 KELGTGQFGVVKYGKWR-GQYDVAIKMIKEGSMSEDEFIEEAKVMMNLSHEKLVQLYGVCTKQRPIFIITEyMANGCLLN 88

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1745 RLTKKSTILE-SEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSdqIRICDFGNAvKFMPDEAQYCKYGTP--- 1820
Cdd:cd05113     89 YLREMRKRFQtQQLLEMCKDVCEAMEYLESKQFLHRDLAARNCLVNDQGV--VKVSDFGLS-RYVLDDEYTSSVGSKfpv 165

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*....
gi 1207186029 1821 EFVAPEIVNQTPVSKATDIWPIGVLTYLCLT-GVSPFAGENDRSSVLNI 1868
Cdd:cd05113    166 RWSPPEVLMYSKFSSKSDVWAFGVLMWEVYSlGKMPYERFTNSETVEHV 214

Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain, and a C-terminal domain; IRAK-4 lacks the C-terminal domain. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK4 plays a critical role in NFkB activation by its interaction with MyD88, which acts as a scaffold that enables IRAK4 to phosphorylate and activate IRAK1 and/or IRAK2. It also plays an important role in type I IFN production induced by TLR7/8/9. The IRAK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271060 [Multi-domain] Cd Length: 288 Bit Score: 56.74 E-value: 9.00e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1706 ELNILSHLDHE---RILYFHDAFEKknAVIIITELCHEELLDRLTKKSTI--LESEIRSSVRQ-LLEGINYLHQLDILHL 1779
Cdd:cd14158     64 EIQVMAKCQHEnlvELLGYSCDGPQ--LCLVYTYMPNGSLLDRLACLNDTppLSWHMRCKIAQgTANGINYLHENNHIHR 141

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1780 DIKPDNILMADHSSDqiRICDFGNA---VKFMPDEAQYCKYGTPEFVAPEIVnQTPVSKATDIWPIGVLTYLCLTGVSPF 1856
Cdd:cd14158    142 DIKSANILLDETFVP--KISDFGLArasEKFSQTIMTERIVGTTAYMAPEAL-RGEITPKSDIFSFGVVLLEIITGLPPV 218

                          170
                   ....*....|...
gi 1207186029 1857 AGENDRSSVLNIR 1869
Cdd:cd14158    219 DENRDPQLLLDIK 231

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNKs are mitogen-activated protein kinases (MAPKs) that are involved in many stress-activated responses including those during inflammation, neurodegeneration, apoptosis, and persistent pain sensitization, among others. They are also essential regulators of physiological and pathological processes and are involved in the pathogenesis of several diseases such as diabetes, atherosclerosis, stroke, Parkinson's and Alzheimer's. Vetebrates harbor three different JNK genes (Jnk1, Jnk2, and Jnk3) that are alternatively spliced to produce at least 10 isoforms. JNKs are specifically activated by the MAPK kinases MKK4 and MKK7, which are in turn activated by upstream MAPK kinase kinases as a result of different stimuli including stresses such as ultraviolet (UV) irradiation, hyperosmolarity, heat shock, or cytokines. JNKs activate a large number of different substrates based on specific stimulus, cell type, and cellular condition, and may be implicated in seemingly contradictory functions. The JNK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270840 [Multi-domain] Cd Length: 337 Bit Score: 57.04 E-value: 9.59e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1697 AKRkasALRELNILSHLDHERILYFHDAF------EKKNAVIIITELCHEELLDRLTKKstiLESEiRSS--VRQLLEGI 1768
Cdd:cd07850     43 AKR---AYRELVLMKLVNHKNIIGLLNVFtpqkslEEFQDVYLVMELMDANLCQVIQMD---LDHE-RMSylLYQMLCGI 115

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1769 NYLHQLDILHLDIKPDNILMADHSSdqIRICDFGNA----VKFMPdeaqyckygTPEFV-----APEIVNQTPVSKATDI 1839
Cdd:cd07850    116 KHLHSAGIIHRDLKPSNIVVKSDCT--LKILDFGLArtagTSFMM---------TPYVVtryyrAPEVILGMGYKENVDI 184

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1840 WPIGVLTYLCLTGVSPFAGE------NDRSSVL-------------NIRNY------------NVAFEESMF-------T 1881
Cdd:cd07850    185 WSVGCIMGEMIRGTVLFPGTdhidqwNKIIEQLgtpsdefmsrlqpTVRNYvenrpkyagysfEELFPDVLFppdseehN 264

                          250       260       270
                   ....*....|....*....|....*....|....*....
gi 1207186029 1882 DLC-HEAKGFVIKLLVADRL-RPDANECLRHP----WFK 1914
Cdd:cd07850    265 KLKaSQARDLLSKMLVIDPEkRISVDDALQHPyinvWYD 303

Catalytic domain of the Serine/Threonine Kinase, Homeodomain-Interacting Protein Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HIPK3 is a Fas-interacting protein that induces FADD (Fas-associated death domain) phosphorylation and mediates FasL-induced JNK activation. Overexpression of HIPK3 does not affect cell death, however its expression in prostate cancer cells contributes to increased resistance to Fas receptor-mediated apoptosis. HIPK3 also plays a role in regulating steroidogenic gene expression. In response to cAMP, HIPK3 activates the phosphorylation of JNK and c-Jun, leading to increased activity of the transcription factor SF-1 (Steroidogenic factor 1), a key regulator for steroid biosynthesis in the gonad and adrenal gland. HIPKs, originally identified by their ability to bind homeobox factors, are nuclear proteins containing catalytic kinase and homeobox-interacting domains as well as a PEST region overlapping with the speckle-retention signal (SRS). The HIPK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).

Pssm-ID: 271131 [Multi-domain] Cd Length: 330 Bit Score: 56.96 E-value: 9.70e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPESKQTVLQEYDILKSLHHE-----KIMALHEAYVTPRYLVLISE 3374
Cdd:cd14229      2 YEVLDFLGRGTFGQVVKCWKRGTNEIVAVKILKNHPSYARQGQIEVGILARLSNEnadefNFVRAYECFQHRNHTCLVFE 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3375 CCsgKELLHSLIDRFRYSE---DDVVAYIVQILQGLDYLHSRRILHLDIKPENII----VTYMNVVKIIDFGSAQTFNPL 3447
Cdd:cd14229     82 ML--EQNLYDFLKQNKFSPlplKVIRPILQQVATALKKLKSLGLIHADLKPENIMlvdpVRQPYRVKVIDFGSASHVSKT 159

                          170       180       190
                   ....*....|....*....|....*....|....*
gi 1207186029 3448 FLKQFsppIGTLDYMSPEMLKGDVVGPPADIWSIG 3482
Cdd:cd14229    160 VCSTY---LQSRYYRAPEIILGLPFCEAIDMWSLG 191

Catalytic domain of the Dual-specificity Protein Kinase, Dusty; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. Dusty protein kinase is also called Receptor-interacting protein kinase 5 (RIPK5 or RIP5) or RIP-homologous kinase. It is widely distributed in the central nervous system, and may be involved in inducing both caspase-dependent and caspase-independent cell death. The Dusty subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270877 [Multi-domain] Cd Length: 262 Bit Score: 56.34 E-value: 1.06e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1666 KEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASALR-ELNILSHL-DHERILYFHDAF-------EKKNAVIIITE 1736
Cdd:cd13975      6 RELGRGQYGVVYACDSWGGHFPCALKSVVPPDDKHWNDLAlEFHYTRSLpKHERIVSLHGSVidysyggGSSIAVLLIME 85

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1737 LCHEELLDRLtKKSTILESEIRSSVrQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDFGnavkFMPDEAQYCK 1816
Cdd:cd13975     86 RLHRDLYTGI-KAGLSLEERLQIAL-DVVEGIRFLHSQGLVHRDIKLKNVLL--DKKNRAKITDLG----FCKPEAMMSG 157

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*...
gi 1207186029 1817 --YGTPEFVAPEIVNQTpVSKATDIWPIGVLT-YLCLTGVS-PFAGEN 1860
Cdd:cd13975    158 siVGTPIHMAPELFSGK-YDNSVDVYAFGILFwYLCAGHVKlPEAFEQ 204

C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myotilin. Mytolin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to the latter family contain multiple Ig-like domains and function as scaffolds, modulating the actin cytoskeleton. Myotilin is most abundant in skeletal and cardiac muscle and is involved in maintaining sarcomere integrity. It binds to alpha-actinin, filamin, and actin. Mutations in myotilin lead to muscle disorders. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409473 Cd Length: 92 Bit Score: 52.08 E-value: 1.15e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  928 PAFLAVIGDQSVIEGQEVTMSVLVTGQPKPMLYWLRDRVTIKTGTRHI-VQETEEGNFEMIIKSAQRSDTGVYTCKIINE 1006
Cdd:cd05892      1 PMFIQKPQNKKVLEGDPVRLECQISAIPPPQIFWKKNNEMLQYNTDRIsLYQDNCGRICLLIQNANKKDAGWYTVSAVNE 80

                           90
                   ....*....|..
gi 1207186029 1007 YGTKQCEGKLEV 1018
Cdd:cd05892     81 AGVVSCNARLDV 92

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar domains; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three Ig-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans. This group also contains fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

Pssm-ID: 409393 [Multi-domain] Cd Length: 95 Bit Score: 52.22 E-value: 1.18e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1207186029  942 GQEVTMSVLVTGQPKPMLYWLRDRVTIKTGTRHIVQETEEGNFEMIIKSAQRSDTGVYTCKIINEYGTKQCEGKLEV 1018
Cdd:cd05729     19 ANKVRLECGAGGNPMPNITWLKDGKEFKKEHRIGGTKVEEKGWSLIIERAIPRDKGKYTCIVENEYGSINHTYDVDV 95

Catalytic (repeat 2) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak subfamily is composed of Jak1, Jak2, Jak3, TYK2, and similar proteins. They are PTKs, catalyzing the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jaks are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase catalytic domain. Most Jaks are expressed in a wide variety of tissues, except for Jak3, which is expressed only in hematopoietic cells. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). Jaks are also involved in regulating the surface expression of some cytokine receptors. The Jak-STAT pathway is involved in many biological processes including hematopoiesis, immunoregulation, host defense, fertility, lactation, growth, and embryogenesis. The Jak subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270634 [Multi-domain] Cd Length: 284 Bit Score: 56.24 E-value: 1.25e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1705 RELNILSHLDHERILYFH---DAFEKKNAVIIITELCHEELLDRLTK-KSTILESEIRSSVRQLLEGINYLHQLDILHLD 1780
Cdd:cd05038     55 REIEILRTLDHEYIVKYKgvcESPGRRSLRLIMEYLPSGSLRDYLQRhRDQIDLKRLLLFASQICKGMEYLGSQRYIHRD 134

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1207186029 1781 IKPDNILMAdhSSDQIRICDFGNAvKFMPDEAQYCKYGTPE-----FVAPEIVNQTPVSKATDIWPIGVLTYLCLT 1851
Cdd:cd05038    135 LAARNILVE--SEDLVKISDFGLA-KVLPEDKEYYYVKEPGespifWYAPECLRESRFSSASDVWSFGVTLYELFT 207

Catalytic domain of the Protein Tyrosine Kinase, Focal Adhesion Kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. FAK is a cytoplasmic (or nonreceptor) PTK that contains an autophosphorylation site and a FERM domain at the N-terminus, a central tyr kinase domain, proline-rich regions, and a C-terminal FAT (focal adhesion targeting) domain. FAK activity is dependent on integrin-mediated cell adhesion, which facilitates N-terminal autophosphorylation. Full activation is achieved by the phosphorylation of its two adjacent A-loop tyrosines. FAK is important in mediating signaling initiated at sites of cell adhesions and at growth factor receptors. Through diverse molecular interactions, FAK functions as a biosensor or integrator to control cell motility. It is a key regulator of cell survival, proliferation, migration and invasion, and thus plays an important role in the development and progression of cancer. Src binds to autophosphorylated FAK forming the FAK-Src dual kinase complex, which is activated in a wide variety of tumor cells and generates signals promoting growth and metastasis. FAK is being developed as a target for cancer therapy. The FAK subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 133187 [Multi-domain] Cd Length: 270 Bit Score: 55.89 E-value: 1.26e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3334 EPESKQTVLQEYDILKSLHHEKIMALHEAYV-TPRYLVLisECCSGKELLHSL-IDRFRYSEDDVVAYIVQILQGLDYLH 3411
Cdd:cd05056     47 SPSVREKFLQEAYIMRQFDHPHIVKLIGVITeNPVWIVM--ELAPLGELRSYLqVNKYSLDLASLILYAYQLSTALAYLE 124

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3412 SRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLKQFSP---PIgtlDYMSPEMLKGDVVGPPADIWSIGILTY-I 3487
Cdd:cd05056    125 SKRFVHRDIAARNVLVSSPDCVKLGDFGLSRYMEDESYYKASKgklPI---KWMAPESINFRRFTSASDVWMFGVCMWeI 201


                   ....*...
gi 1207186029 3488 MLSGRLPF 3495
Cdd:cd05056    202 LMLGVKPF 209

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 51.62 E-value: 1.33e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1207186029 2871 VLLEGDPVTLSCLPAGSPHPHISWMKDKKPLeiDPRMNMISCPDGRqlLMIMKTTKKDAGLYECVAANPLATVTSSCVV 2949
Cdd:cd20978     12 VVKGGQDVTLPCQVTGVPQPKITWLHNGKPL--QGPMERATVEDGT--LTIINVQPEDTGYYGCVATNEIGDIYTETLL 86

Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LIMK2 activation is induced by transforming growth factor-beta l (TGFb-l) and shares the same subcellular location as the cofilin family member twinfilin, which may be its biological substrate. LIMK2 plays a role in spermatogenesis, and may contribute to tumor progression and metastasis formation in some cancer cells. LIMKs phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They act downstream of Rho GTPases and are expressed ubiquitously. As regulators of actin dynamics, they contribute to diverse cellular functions such as cell motility, morphogenesis, differentiation, apoptosis, meiosis, mitosis, and neurite extension. LIMKs contain the LIM (two repeats), PDZ, and catalytic kinase domains. The LIMK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271124 [Multi-domain] Cd Length: 272 Bit Score: 56.11 E-value: 1.38e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYVKRVIQKA-GKLEYAAKFISARAKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITELCHEELLDRL 1746
Cdd:cd14222      1 LGKGFFGQAIKVTHKAtGKVMVMKELIRCDEETQKTFLTEVKVMRSLDHPNVLKFIGVLYKDKRLNLLTEFIEGGTLKDF 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1747 TKKSTILESEIRSS-VRQLLEGINYLHQLDILHLDIKPDNILMADHSSdqIRICDFG-------NAVKFMPDEA------ 1812
Cdd:cd14222     81 LRADDPFPWQQKVSfAKGIASGMAYLHSMSIIHRDLNSHNCLIKLDKT--VVVADFGlsrliveEKKKPPPDKPttkkrt 158

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*
gi 1207186029 1813 --------QYCKYGTPEFVAPEIVNQTPVSKATDIWPIGVLtyLC 1849
Cdd:cd14222    159 lrkndrkkRYTVVGNPYWMAPEMLNGKSYDEKVDIFSFGIV--LC 201

Catalytic domain of the Protein Tyrosine Kinases, Src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristylation sites (Srm) and Breast tumor kinase (Brk); PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Srm and Brk (also called protein tyrosine kinase 6) are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Brk has been found to be overexpressed in a majority of breast tumors. Src kinases in general contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr; they are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). Srm and Brk however, lack the N-terminal myristylation sites. Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. The Srm/Brk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 133248 [Multi-domain] Cd Length: 261 Bit Score: 55.90 E-value: 1.45e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1666 KEIGRGAFSYVKRVIQKaGKLEYAAKFISARAKRKASAL-RELNILSHLDHERILYFHDAFEKKNAVIIITELCHE---- 1740
Cdd:cd05148     12 RKLGSGYFGEVWEGLWK-NRVRVAIKILKSDDLLKQQDFqKEVQALKRLRHKHLISLFAVCSVGEPVYIITELMEKgsll 90

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1741 ELLDRLTKKSTILESEIRSSVrQLLEGINYLHQLDILHLDIKPDNILMADHSSdqIRICDFGNAVKFMPDEAQYCKYGTP 1820
Cdd:cd05148     91 AFLRSPEGQVLPVASLIDMAC-QVAEGMAYLEEQNSIHRDLAARNILVGEDLV--CKVADFGLARLIKEDVYLSSDKKIP 167

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1207186029 1821 -EFVAPEIVNQTPVSKATDIWPIGVLTYLCLT-GVSPFAGENDRSSVLNI-RNY 1871
Cdd:cd05148    168 yKWTAPEAASHGTFSTKSDVWSFGILLYEMFTyGQVPYPGMNNHEVYDQItAGY 221

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 51.73 E-value: 1.46e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1207186029 1260 VVEGREAVLRCKVAGLPYPTITWFHNGKRIdSTEDRKMTQFrDVHSLVVRCVCHAHGGVYKCVISNKVGKATCYSHLYV 1338
Cdd:cd20952     11 VAVGGTVVLNCQATGEPVPTISWLKDGVPL-LGKDERITTL-ENGSLQIKGAEKSDTGEYTCVALNLSGEATWSAVLDV 87

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin Superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.

Pssm-ID: 409420 [Multi-domain] Cd Length: 91 Bit Score: 51.85 E-value: 1.51e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  789 DTVASTGTEVLLKCIISGTPLPEVIWKKDN-TEVKNSPTHVVKIEGERHSLLIKWTKPSDAGTYTVTAVNEVGEVSSSAT 867
Cdd:cd05763      8 DITIRAGSTARLECAATGHPTPQIAWQKDGgTDFPAARERRMHVMPEDDVFFIVDVKIEDTGVYSCTAQNSAGSISANAT 87


                   ...
gi 1207186029  868 LFI 870
Cdd:cd05763     88 LTV 90

Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409582 Cd Length: 91 Bit Score: 51.64 E-value: 1.58e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1545 PTFETIMEDLDVNVGETPRFAVVVEGKPVPDILW-YKGDTLLSESSHFTFVYDDNECSLVVLNTQADDSGVYTCTAKNLA 1623
Cdd:cd20990      1 PHFLQAPGDLTVQEGKLCRMDCKVSGLPTPDLSWqLDGKPIRPDSAHKMLVRENGVHSLIIEPVTSRDAGIYTCIATNRA 80

                           90
                   ....*....|.
gi 1207186029 1624 GSVSCKAELTV 1634
Cdd:cd20990     81 GQNSFNLELVV 91

Pseudokinase domain of Tribbles Homolog 2; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. TRB2 binds and negatively regulates the mitogen activated protein kinase (MAPK) kinases, MKK7 and MEK1, which are activators of the MAPKs, ERK and JNK. It controls the activation of inflammatory monocytes, which is essential in innate immune responses and the pathogenesis of inflammatory diseases such as atherosclerosis. TRB2 expression is down-regulated in human acute myeloid leukaemia (AML), which may lead to enhanced cell survival and pathogenesis of the disease. TRB2 is one of three Tribbles Homolog (TRB) proteins present in vertebrates that are encoded by three separate genes. TRB proteins interact with many proteins involved in signalling pathways. They play scaffold-like regulatory functions and affect many cellular processes such as mitosis, apoptosis, and gene expression. The TRB2 subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270924 [Multi-domain] Cd Length: 242 Bit Score: 55.43 E-value: 1.61e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1745 RLTKKstILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSDQIRICDFGNA-VKFMPDEAQYCKYGTPEFV 1823
Cdd:cd14022     76 RTCKK--LREEEAARLFYQIASAVAHCHDGGLVLRDLKLRKFVFKDEERTRVKLESLEDAyILRGHDDSLSDKHGCPAYV 153

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1824 APEIVNQTPV--SKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNYNVAFEESmftdLCHEAKGFVIKLLvadRLR 1901
Cdd:cd14022    154 SPEILNTSGSysGKAADVWSLGVMLYTMLVGRYPFHDIEPSSLFSKIRRGQFNIPET----LSPKAKCLIRSIL---RRE 226

                          170
                   ....*....|....*.
gi 1207186029 1902 PD----ANECLRHPWF 1913
Cdd:cd14022    227 PSerltSQEILDHPWF 242

First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409566 [Multi-domain] Cd Length: 93 Bit Score: 51.58 E-value: 1.65e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1032 PVRDVMVKAGETALFECHVIGPQDTDVDWLSDGKLIQPALL-NCKMHFDGKRCRLLLNSVHEDDSGTYTCKLSTAKEELT 1110
Cdd:cd20974      6 PLQSVVVLEGSTATFEAHVSGKPVPEVSWFRDGQVISTSTLpGVQISFSDGRAKLSIPAVTKANSGRYSLTATNGSGQAT 85


                   ....*..
gi 1207186029 1111 SSAKLKV 1117
Cdd:cd20974     86 STAELLV 92

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNK2 is expressed in every cell and tissue type. It is specifically translocated to the mitochondria during dopaminergic cell death. Specific substrates include the microtubule-associated proteins DCX and Tau, as well as TIF-IA which is involved in ribosomal RNA synthesis regulation. Mice deficient in Jnk2 show protection against arthritis, type 1 diabetes, atherosclerosis, abdominal aortic aneurysm, cardiac cell death, TNF-induced liver damage, and tumor growth, indicating that JNK2 may play roles in the pathogenesis of these diseases. Initially it was thought that JNK1 and JNK2 were functionally redundant as mice deficient in either genes could survive but disruption of both genes resulted in lethality. However, recent studies have shown that JNK1 and JNK2 perform distinct functions through specific binding partners and substrates. JNKs are mitogen-activated protein kinases (MAPKs) that are involved in many stress-activated responses including those during inflammation, neurodegeneration, apoptosis, and persistent pain sensitization, among others. The JNK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143381 [Multi-domain] Cd Length: 359 Bit Score: 56.58 E-value: 1.83e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFIS------ARAKRkasALRELNILSHLDHERILYFHDAF------EKKN 1729
Cdd:cd07876     23 YQQLKPIGSGAQGIVCAAFDTVLGINVAVKKLSrpfqnqTHAKR---AYRELVLLKCVNHKNIISLLNVFtpqkslEEFQ 99

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1730 AVIIITELCHEELLDRLTKKstiLESEIRSSV-RQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDFGNA---- 1804
Cdd:cd07876    100 DVYLVMELMDANLCQVIHME---LDHERMSYLlYQMLCGIKHLHSAGIIHRDLKPSNIVV--KSDCTLKILDFGLArtac 174

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1805 VKFMPDEAQYCKYgtpeFVAPEIVNQTPVSKATDIWPIGVLTYLCLTGVSPFAG-------------------------- 1858
Cdd:cd07876    175 TNFMMTPYVVTRY----YRAPEVILGMGYKENVDIWSVGCIMGELVKGSVIFQGtdhidqwnkvieqlgtpsaefmnrlq 250

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1207186029 1859 ENDRSSVLNIRNY-NVAFEEsMFTDLC------------HEAKGFVIKLLVAD-RLRPDANECLRHPW 1912
Cdd:cd07876    251 PTVRNYVENRPQYpGISFEE-LFPDWIfpseserdklktSQARDLLSKMLVIDpDKRISVDEALRHPY 317

Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LIMKs phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They act downstream of Rho GTPases and are expressed ubiquitously. As regulators of actin dynamics, they contribute to diverse cellular functions such as cell motility, morphogenesis, differentiation, apoptosis, meiosis, mitosis, and neurite extension. LIMKs contain the LIM (two repeats), PDZ, and catalytic kinase domains. Vertebrate have two members, LIMK1 and LIMK2. The LIMK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271056 [Multi-domain] Cd Length: 272 Bit Score: 55.59 E-value: 1.90e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1668 IGRGAFSYVKRVIQKA-GKLEYAAKFISARAKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITELCHEELLDRL 1746
Cdd:cd14154      1 LGKGFFGQAIKVTHREtGEVMVMKELIRFDEEAQRNFLKEVKVMRSLDHPNVLKFIGVLYKDKKLNLITEYIPGGTLKDV 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1747 TK-KSTILESEIRSSV-RQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDFGNAvKFMPDE------------- 1811
Cdd:cd14154     81 LKdMARPLPWAQRVRFaKDIASGMAYLHSMNIIHRDLNSHNCLV--REDKTVVVADFGLA-RLIVEErlpsgnmspsetl 157

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*..
gi 1207186029 1812 ---------AQYCKYGTPEFVAPEIVNQTPVSKATDIWPIGVLtyLC 1849
Cdd:cd14154    158 rhlkspdrkKRYTVVGNPYWMAPEMLNGRSYDEKVDIFSFGIV--LC 202

Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409582 Cd Length: 91 Bit Score: 51.25 E-value: 2.03e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 2869 DHVLLEGDPVTLSCLPAGSPHPHISWMKDKKPLEIDPRMNMISCPDGRQLLMIMKTTKKDAGLYECVAAN 2938
Cdd:cd20990      9 DLTVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIRPDSAHKMLVRENGVHSLIIEPVTSRDAGIYTCIATN 78

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.

Pssm-ID: 409490 [Multi-domain] Cd Length: 99 Bit Score: 51.40 E-value: 2.15e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1249 PDFVKPLYDMDVVEGREAVLRCKVAGLPYPTITWFHNGKRIDSTEDRKMTQ--FRDVHSLVVRCVCH-----AHGGVYKC 1321
Cdd:cd07693      1 PRIVEHPSDLIVSKGDPATLNCKAEGRPTPTIQWLKNGQPLETDKDDPRSHriVLPSGSLFFLRVVHgrkgrSDEGVYVC 80

                           90
                   ....*....|
gi 1207186029 1322 VISNKVGKAT 1331
Cdd:cd07693     81 VAHNSLGEAV 90

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 51.35 E-value: 2.18e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1134 VIEGRNARFDCKVSGTPPPQVIWSHFDRPLEENEDIRILKEGGRhSLIISHVSNEDEGLYTVAARN-SHGEDECAAELYV 1212
Cdd:cd20970     14 AREGENATFMCRAEGSPEPEISWTRNGNLIIEFNTRYIVRENGT-TLTIRNIRRSDMGIYLCIASNgVPGSVEKRITLQV 92

Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409548 [Multi-domain] Cd Length: 96 Bit Score: 51.41 E-value: 2.32e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1207186029 1144 CKVSGTPPPQVIWSHFDRPLEENEDIRILKEGGRHSLIISHV--SN---EDEGLYTVAARNSHGEDECAAELYV 1212
Cdd:cd20956     23 CVASGNPLPQITWTLDGFPIPESPRFRVGDYVTSDGDVVSYVniSSvrvEDGGEYTCTATNDVGSVSHSARINV 96

Catalytic domain of the Protein Tyrosine Kinase, Hematopoietic cell kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Hck is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Hck is present in myeloid and lymphoid cells that play a role in the development of cancer. It may be important in the oncogenic signaling of the protein Tel-Abl, which induces a chronic myelogenous leukemia (CML)-like disease. Hck also acts as a negative regulator of G-CSF-induced proliferation of granulocytic precursors, suggesting a possible role in the development of acute myeloid leukemia (AML). In addition, Hck is essential in regulating the degranulation of polymorphonuclear leukocytes. Genetic polymorphisms affect the expression level of Hck, which affects PMN mediator release and influences the development of chronic obstructive pulmonary disease (COPD). Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Hck subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270658 [Multi-domain] Cd Length: 265 Bit Score: 55.03 E-value: 2.32e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1704 LRELNILSHLDHERILYFHdAFEKKNAVIIITELCHE-ELLDRLTKKS---TILESEIRSSVrQLLEGINYLHQLDILHL 1779
Cdd:cd05073     54 LAEANVMKTLQHDKLVKLH-AVVTKEPIYIITEFMAKgSLLDFLKSDEgskQPLPKLIDFSA-QIAEGMAFIEQRNYIHR 131

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1780 DIKPDNILMAdhSSDQIRICDFGNAvKFMPDEAQYCKYGTP---EFVAPEIVNQTPVSKATDIWPIGV-LTYLCLTGVSP 1855
Cdd:cd05073    132 DLRAANILVS--ASLVCKIADFGLA-RVIEDNEYTAREGAKfpiKWTAPEAINFGSFTIKSDVWSFGIlLMEIVTYGRIP 208


                   ...
gi 1207186029 1856 FAG 1858
Cdd:cd05073    209 YPG 211

Catalytic domain of the Protein Tyrosine Kinase, Fer; Protein Tyrosine Kinase (PTK) family; Fer kinase; catalytic (c) domain. The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Fer kinase is a member of the Fes subfamily of proteins which are cytoplasmic (or nonreceptor) tyr kinases containing an N-terminal region with FCH (Fes/Fer/CIP4 homology) and coiled-coil domains, followed by a SH2 domain, and a C-terminal catalytic domain. Fer kinase is expressed in a wide variety of tissues, and is found to reside in both the cytoplasm and the nucleus. It plays important roles in neuronal polarization and neurite development, cytoskeletal reorganization, cell migration, growth factor signaling, and the regulation of cell-cell interactions mediated by adherens junctions and focal adhesions. Fer kinase also regulates cell cycle progression in malignant cells.

Pssm-ID: 270668 [Multi-domain] Cd Length: 251 Bit Score: 55.01 E-value: 2.56e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1700 KASALRELNILSHLDHERILYFHDAFEKKNAVIIITELCHE-ELLDRLTKKSTILESE--IRSSVrQLLEGINYLHQLDI 1776
Cdd:cd05085     37 KIKFLSEARILKQYDHPNIVKLIGVCTQRQPIYIVMELVPGgDFLSFLRKKKDELKTKqlVKFSL-DAAAGMAYLESKNC 115

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1777 LHLDIKPDNILMADhsSDQIRICDFGNAVKfmPDEAQYCKYGTPE----FVAPEIVNQTPVSKATDIWPIGVLTYLCLT- 1851
Cdd:cd05085    116 IHRDLAARNCLVGE--NNALKISDFGMSRQ--EDDGVYSSSGLKQipikWTAPEALNYGRYSSESDVWSFGILLWETFSl 191

                          170
                   ....*....|...
gi 1207186029 1852 GVSPFAGENDRSS 1864
Cdd:cd05085    192 GVCPYPGMTNQQA 204

Pseudokinase domain of Tribbles Homolog 3; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. TRB3 binds and regulates ATF4, p65/RelA, and PKB (or Akt). It negatively regulates ATF4-mediated gene expression including that of CHOP (C/EBP homologous protein) and HO-1, which are both involved in modulating apoptosis. It also inhibits insulin-mediated phosphorylation of PKB and is a possible determinant of insulin resistance and related disorders. In osteoarthritic chondrocytes where it inhibits insulin-like growth factor 1-mediated cell survival, TRB3 is overexpressed, resulting in increased cell death. TRB3 is one of three Tribbles Homolog (TRB) proteins present in vertebrates that are encoded by three separate genes. TRB proteins interact with many proteins involved in signalling pathways. They play scaffold-like regulatory functions and affect many cellular processes such as mitosis, apoptosis, and gene expression. The TRB3 subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270926 [Multi-domain] Cd Length: 242 Bit Score: 54.50 E-value: 2.87e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1715 HERILYFHDAFEKKNAVIIITELCHEELLDRLTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSD 1794
Cdd:cd14024     44 HEGVCSVLEVVIGQDRAYAFFSRHYGDMHSHVRRRRRLSEDEARGLFTQMARAVAHCHQHGVILRDLKLRRFVFTDELRT 123

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1795 QIRICDFGNA-VKFMPDEAQYCKYGTPEFVAPEIVNQTPVS--KATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRNY 1871
Cdd:cd14024    124 KLVLVNLEDScPLNGDDDSLTDKHGCPAYVGPEILSSRRSYsgKAADVWSLGVCLYTMLLGRYPFQDTEPAALFAKIRRG 203

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....
gi 1207186029 1872 NVAFEESmftdLCHEAKGFVIKLL---VADRLRpdANECLRHPW 1912
Cdd:cd14024    204 AFSLPAW----LSPGARCLVSCMLrrsPAERLK--ASEILLHPW 241

serine/threonine kinase US3; Provisional

Pssm-ID: 165476 [Multi-domain] Cd Length: 501 Bit Score: 56.24 E-value: 2.97e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1690 AKFISArAKRKASALR-ELNILSHLDHERILYFHDAFEKKNAVIIITELCHEELL-----DRLTKKSTILESEIRSSVRQ 1763
Cdd:PHA03210   197 AKRVKA-GSRAAIQLEnEILALGRLNHENILKIEEILRSEANTYMITQKYDFDLYsfmydEAFDWKDRPLLKQTRAIMKQ 275

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1764 LLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDFGNAVKF-MPDEA-QYCKYGTPEFVAPEIVNQTPVSKATDIWP 1841
Cdd:PHA03210   276 LLCAVEYIHDKKLIHRDIKLENIFL--NCDGKIVLGDFGTAMPFeKEREAfDYGWVGTVATNSPEILAGDGYCEITDIWS 353


                   ....
gi 1207186029 1842 IGVL 1845
Cdd:PHA03210   354 CGLI 357

Immunoglobulin-like domain of human Aortic Preferentially Expressed Protein-1 (APEG-1) and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin I-set (IgI) domain of the Human Aortic Preferentially Expressed Protein-1 (APEG-1) and similar proteins. APEG-1 is a novel specific smooth muscle differentiation marker predicted to play a role in the growth and differentiation of arterial smooth muscle cells (SMCs). The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the human APEG-1 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409567 Cd Length: 91 Bit Score: 50.93 E-value: 3.05e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1545 PTFETIMEDLDVNVGETPRFAVVVEGKPVPDILWYKG-DTLLSESSHFTFVYDDNECSLVVLNTQADDSGVYTCTAKNLA 1623
Cdd:cd20975      1 PTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNrQPVRPDQRRFAEEAEGGLCRLRILAAERGDAGFYTCKAVNEY 80

                           90
                   ....*....|.
gi 1207186029 1624 GSVSCKAELTV 1634
Cdd:cd20975     81 GARQCEARLEV 91

Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409582 Cd Length: 91 Bit Score: 50.87 E-value: 3.35e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  928 PAFLAVIGDQSVIEGQEVTMSVLVTGQPKPMLYWLRDRVTIKTGTRHIVQETEEGNFEMIIKSAQRSDTGVYTCKIINEY 1007
Cdd:cd20990      1 PHFLQAPGDLTVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIRPDSAHKMLVRENGVHSLIIEPVTSRDAGIYTCIATNRA 80


                   .
gi 1207186029 1008 G 1008
Cdd:cd20990     81 G 81

C-terminal immunoglobulin (Ig)-like domain of M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of M-protein (also known as myomesin-2). M-protein is a structural protein localized to the M-band, a transverse structure in the center of the sarcomere, and is a candidate for M-band bridges. M-protein is modular consisting mainly of repetitive IG-like and fibronectin type III (FnIII) domains and has a muscle-type specific expression pattern. M-protein is present in fast fibers.

Pssm-ID: 143299 Cd Length: 92 Bit Score: 50.68 E-value: 3.39e-07

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1207186029  800 LKCIISGTPLPEVIWKKDNTEVKNSPTHVVKIE-GERHSLLIKWTKPSDAGTYTVTAVNEVG 860
Cdd:cd05891     21 LTCTVFGNPDPEVIWFKNDQDIELSEHYSVKLEqGKYASLTIKGVTSEDSGKYSINVKNKYG 82

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.

Pssm-ID: 409367 [Multi-domain] Cd Length: 89 Bit Score: 50.52 E-value: 3.41e-07

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1207186029 1136 EGRNARFDCKVSGTPPPQVIWSHFDRPLEE-NEDIRILKEGGrhSLIISHVSNEDEGLYTVAARNSHG 1202
Cdd:cd04978     13 PGETGELICEAEGNPQPTITWRLNGVPIEPaPEDMRRTVDGR--TLIFSNLQPNDTAVYQCNASNVHG 78

Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RIP1 harbors a C-terminal Death domain (DD), which binds death receptors (DRs) including TNF receptor 1, Fas, TNF-related apoptosis-inducing ligand receptor 1 (TRAILR1), and TRAILR2. It also interacts with other DD-containing adaptor proteins such as TRADD and FADD. RIP1 can also recruit other kinases including MEKK1, MEKK3, and RIP3 through an intermediate domain (ID) that bears a RIP homotypic interaction motif (RHIM). RIP1 plays a crucial role in determining a cell's fate, between survival or death, following exposure to stress signals. It is important in the signaling of NF-kappaB and MAPKs, and it links DR-associated signaling to reactive oxygen species (ROS) production. Abnormal RIP1 function may result in ROS accummulation affecting inflammatory responses, innate immunity, stress responses, and cell survival. RIP kinases serve as essential sensors of cellular stress. The RIP1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270929 [Multi-domain] Cd Length: 267 Bit Score: 54.81 E-value: 3.53e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1696 RAKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITELCHE-ELLDRLTKKSTILESEIRSsVRQLLEGINYLHQL 1774
Cdd:cd14027     31 CIEHNEALLEEGKMMNRLRHSRVVKLLGVILEEGKYSLVMEYMEKgNLMHVLKKVSVPLSVKGRI-ILEIIEGMAYLHGK 109

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1775 DILHLDIKPDNILMADHSsdQIRICDFGNAV-----KFMPDEAQY-------CKY--GTPEFVAPE---IVNQTPVSKaT 1837
Cdd:cd14027    110 GVIHKDLKPENILVDNDF--HIKIADLGLASfkmwsKLTKEEHNEqrevdgtAKKnaGTLYYMAPEhlnDVNAKPTEK-S 186

                          170       180
                   ....*....|....*....|....*.
gi 1207186029 1838 DIWPIGVLTYLCLTGVSPFagENDRS 1863
Cdd:cd14027    187 DVYSFAIVLWAIFANKEPY--ENAIN 210

First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409566 [Multi-domain] Cd Length: 93 Bit Score: 50.81 E-value: 3.59e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1249 PDFVKPLYDMDVVEGREAVLRCKVAGLPYPTITWFHNGKRID-STEDRKMTQFRDVHS-LVVRCVCHAHGGVYKCVISNK 1326
Cdd:cd20974      1 PVFTQPLQSVVVLEGSTATFEAHVSGKPVPEVSWFRDGQVIStSTLPGVQISFSDGRAkLSIPAVTKANSGRYSLTATNG 80

                           90
                   ....*....|...
gi 1207186029 1327 VGKATCYSHLYVT 1339
Cdd:cd20974     81 SGQATSTAELLVL 93

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 50.48 E-value: 3.62e-07

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1207186029   80 GDPQPTLYWYHNDDLVNMDNQEY-----GGLWIRDCKPSDAGLYTCIATNHLGEARSSA 133
Cdd:cd05724     24 GHPEPTVSWRKDGQPLNLDNERVrivddGNLLIAEARKSDEGTYKCVATNMVGERESRA 82

Catalytic domain of the Dual-specificity protein kinase, CDC-like kinase 3; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. CLK3 is predominantly expressed in mature spermatozoa, and might play a role in the fertilization process. CLKs are involved in the phosphorylation and regulation of serine/arginine-rich (SR) proteins, which play a crucial role in pre-mRNA splicing by directing splice site selection. SR proteins are phosphorylated first by SR protein kinases (SRPKs) at the N-terminus, which leads to its assembly into nuclear speckles where splicing factors are stored. CLKs phosphorylate the C-terminal part of SR proteins, causing the nuclear speckles to dissolve and splicing factors to be recruited at sites of active transcription. Based on a conserved "EHLAMMERILG" signature motif which may be crucial for substrate specificity, CLKs are also referred to as LAMMER kinases. CLKs autophosphorylate at tyrosine residues and phosphorylate their substrates exclusively on serine/threonine residues. The CLK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271116 [Multi-domain] Cd Length: 331 Bit Score: 55.40 E-value: 3.68e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3297 QKPYTFMDEKARGRFGVIRECRENATGNLYMA-KIVPYEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISEC 3375
Cdd:cd14214     12 QERYEIVGDLGEGTFGKVVECLDHARGKSQVAlKIIRNVGKYREAARLEINVLKKIKEKDKENKFLCVLMSDWFNFHGHM 91

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3376 CSGKELLHSLIDRFRySEDDVVAYIV--------QILQGLDYLHSRRILHLDIKPENIIV------TYMN---------- 3431
Cdd:cd14214     92 CIAFELLGKNTFEFL-KENNFQPYPLphirhmayQLCHALKFLHENQLTHTDLKPENILFvnsefdTLYNesksceeksv 170

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1207186029 3432 ---VVKIIDFGSAqTFNPlflKQFSPPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAE 3502
Cdd:cd14214    171 kntSIRVADFGSA-TFDH---EHHTTIVATRHYRPPEVILELGWAQPCDVWSLGCILFEYYRGFTLFQTHENRE 240

First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409566 [Multi-domain] Cd Length: 93 Bit Score: 50.81 E-value: 3.85e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1123 PLFTRKLDVLEVIEGRNARFDCKVSGTPPPQVIWSHFDR--PLEENEDIRILKEGGRHSLIISHVSNEDEGLYTVAARNS 1200
Cdd:cd20974      1 PVFTQPLQSVVVLEGSTATFEAHVSGKPVPEVSWFRDGQviSTSTLPGVQISFSDGRAKLSIPAVTKANSGRYSLTATNG 80

                           90
                   ....*....|..
gi 1207186029 1201 HGEDECAAELYV 1212
Cdd:cd20974     81 SGQATSTAELLV 92

Pseudokinase domain of STE20-related kinase adapter protein; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. STRAD forms a complex with the scaffolding protein MO25, and the serine/threonine kinase (STK), LKB1, resulting in the activation of the kinase. In the complex, LKB1 phosphorylates and activates adenosine monophosphate-activated protein kinases (AMPKs), which regulate cell energy metabolism and cell polarity. LKB1 is a tumor suppressor linked to the rare inherited disease, Peutz-Jeghers syndrome, which is characterized by a predisposition to benign polyps and hyperpigmentation of the buccal mucosa. There are two forms of STRAD, alpha and beta, that complex with LKB1 and MO25. The structure of STRAD-alpha is available and shows that this protein binds ATP, has an ordered activation loop, and adopts a closed conformation typical of fully active protein kinases. It does not possess activity due to nonconservative substitutions of essential catalytic residues. ATP binding enhances the affinity of STRAD for MO25. The conformation of STRAD-alpha stabilized through ATP and MO25 may be needed to activate LKB1. The STRAD subfamily is part of a larger superfamily that includes the catalytic domains of STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270856 [Multi-domain] Cd Length: 315 Bit Score: 54.99 E-value: 3.98e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1706 ELNILSHLDHERILYFHDAFEKKNAVIIITELCH----EELLDRlTKKSTILESEIRSSVRQLLEGINYLHQLDILHLDI 1781
Cdd:cd08216     49 EILTSRQLQHPNILPYVTSFVVDNDLYVVTPLMAygscRDLLKT-HFPEGLPELAIAFILRDVLNALEYIHSKGYIHRSV 127

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1782 KPDNILMAdhSSDQIRICDFGNAVKFMP-DEAQYCKYGTPEF-------VAPEIVNQ-----TPVSkatDIWPIGVLTYL 1848
Cdd:cd08216    128 KASHILIS--GDGKVVLSGLRYAYSMVKhGKRQRVVHDFPKSseknlpwLSPEVLQQnllgyNEKS---DIYSVGITACE 202

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1849 CLTGVSPFA-------------------------------GENDRSSVLNIRN--------YNVAFEESM--FTDLChea 1887
Cdd:cd08216    203 LANGVVPFSdmpatqmllekvrgttpqlldcstypleedsMSQSEDSSTEHPNnrdtrdipYQRTFSEAFhqFVELC--- 279

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|.
gi 1207186029 1888 kgfviklLVAD-RLRPDANECLRHPWFKTLnKGKSISTESL 1927
Cdd:cd08216    280 -------LQRDpELRPSASQLLAHSFFKQC-RRSNTSLLDL 312

C5 immunoglobulin (Ig) domain of cardiac myosin binding protein C (MyBP-C); The members here are composed of the C5 immunoglobulin (Ig) domain of cardiac myosin binding protein C (MyBP-C). MyBP-C consists of repeated domains, Ig and fibronectin type 3, and various linkers. Three isoforms of MYBP-C exist: slow-skeletal (ssMyBP-C), fast-skeletal (fsMyBP-C), and cardiac (cMyBP-C). cMYBP-C has insertions between and inside domains and an additional cardiac-specific Ig domain at the N-terminus. For cMYBP_C an interaction has been demonstrated between this C5 domain and the Ig C8 domain.

Pssm-ID: 409475 Cd Length: 86 Bit Score: 50.22 E-value: 4.11e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  791 VASTGTEVLLKCIISGTPLPEVIWKKDnTEVKNSPTHVVKIEG--ERHSLLIKWTKPSDAGTYTVTAVNEVGEvsSSATL 868
Cdd:cd05894      6 VVVAGNKLRLDVPISGEPAPTVTWSRG-DKAFTATEGRVRVESykDLSSFVIEGAEREDEGVYTITVTNPVGE--DHASL 82


                   ...
gi 1207186029  869 FIK 871
Cdd:cd05894     83 FVK 85

Catalytic domain of Epidermal Growth Factor Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EGFR (HER, ErbB) subfamily members include EGFR (HER1, ErbB1), HER2 (ErbB2), HER3 (ErbB3), HER4 (ErbB4), and similar proteins. They are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, resulting in the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. Collectively, they can recognize a variety of ligands including EGF, TGFalpha, and neuregulins, among others. All four subfamily members can form homo- or heterodimers. HER3 contains an impaired kinase domain and depends on its heterodimerization partner for activation. EGFR subfamily members are involved in signaling pathways leading to a broad range of cellular responses including cell proliferation, differentiation, migration, growth inhibition, and apoptosis. Gain of function alterations, through their overexpression, deletions, or point mutations in their kinase domains, have been implicated in various cancers. These receptors are targets of many small molecule inhibitors and monoclonal antibodies used in cancer therapy. The EGFR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270648 [Multi-domain] Cd Length: 279 Bit Score: 54.34 E-value: 4.29e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1666 KEIGRGAFSYVKRVIQK----AGKLEYAAKFISARAKRKASA--LRELNILSHLDHERILYFHdAFEKKNAVIIITELC- 1738
Cdd:cd05057     13 KVLGSGAFGTVYKGVWIpegeKVKIPVAIKVLREETGPKANEeiLDEAYVMASVDHPHLVRLL-GICLSSQVQLITQLMp 91

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1739 HEELLDRLTKKSTILESE-IRSSVRQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDFGNAVKFMPDEAQYCKY 1817
Cdd:cd05057     92 LGCLLDYVRNHRDNIGSQlLLNWCVQIAKGMSYLEEKRLVHRDLAARNVLV--KTPNHVKITDFGLAKLLDVDEKEYHAE 169

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*....
gi 1207186029 1818 G--TP-EFVAPEIVNQTPVSKATDIWPIGVLTYLCLT-GVSPFAGENDR 1862
Cdd:cd05057    170 GgkVPiKWMALESIQYRIYTHKSDVWSYGVTVWELMTfGAKPYEGIPAV 218

Catalytic domain of a subset of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily includes a subset of Src-like PTKs including Src, Fyn, Yrk, and Yes, which are all widely expressed. Yrk has been detected only in chickens. It is primarily found in neuronal and epithelial cells and in macrophages. It may play a role in inflammation and in response to injury. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells and tumor vasculature, contributing to cancer progression and metastasis. They are also implicated in acute inflammatory responses and osteoclast function. The Src/Fyn-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271105 [Multi-domain] Cd Length: 248 Bit Score: 54.15 E-value: 4.44e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1666 KEIGRGAFSYVKRVIQKaGKLEYAAKFISARAKRKASALRELNILSHLDHERILYFHdAFEKKNAVIIITE-LCHEELLD 1744
Cdd:cd14203      1 VKLGQGCFGEVWMGTWN-GTTKVAIKTLKPGTMSPEAFLEEAQIMKKLRHDKLVQLY-AVVSEEPIYIVTEfMSKGSLLD 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1745 RLTKKS--TILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSdqIRICDFGNAvKFMPDEAQYCKYGTP-- 1820
Cdd:cd14203     79 FLKDGEgkYLKLPQLVDMAAQIASGMAYIERMNYIHRDLRAANILVGDNLV--CKIADFGLA-RLIEDNEYTARQGAKfp 155

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....
gi 1207186029 1821 -EFVAPEIVNQTPVSKATDIWPIGVL-TYLCLTGVSPFAGENDR 1862
Cdd:cd14203    156 iKWTAPEAALYGRFTIKSDVWSFGILlTELVTKGRVPYPGMNNR 199

First C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409474 Cd Length: 92 Bit Score: 50.48 E-value: 4.80e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  928 PAFLAVIGDQSVIEGQEVTMSVLVTGQPKPMLYWLRDRVTIKTGTRH-IVQETEEGNFEMIIKSAQRSDTGVYTCKIINE 1006
Cdd:cd05893      1 PFFEMKLKHYKIFEGMPVTFTCRVAGNPKPKIYWFKDGKQISPKSDHyTIQRDLDGTCSLHTTASTLDDDGNYTIMAANP 80

                           90
                   ....*....|..
gi 1207186029 1007 YGTKQCEGKLEV 1018
Cdd:cd05893     81 QGRISCTGRLMV 92

Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jak1 is widely expressed in many tissues. Many cytokines are dependent on Jak1 for signaling, including those that use the shared receptor subunits common gamma chain (IL-2, IL-4, IL-7, IL-9, IL-15, IL-21) and gp130 (IL-6, IL-11, oncostatin M, G-CSF, and IFNs, among others). The many varied interactions of Jak1 and its ubiquitous expression suggest many biological roles. Jak1 is important in neurological development, as well as in lymphoid development and function. It also plays a role in the pathophysiology of cardiac hypertrophy and heart failure. A mutation in the ATP-binding site of Jak1 was identified in a human uterine leiomyosarcoma cell line, resulting in defective cytokine induction and antigen presentation, thus allowing the tumor to evade the immune system. Jak1 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The Jak1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 173644 [Multi-domain] Cd Length: 284 Bit Score: 54.55 E-value: 5.04e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1705 RELNILSHLDHERILYFHDAFEKK--NAVIIITELCH----EELLDRlTKKSTILESEIRSSVrQLLEGINYLHQLDILH 1778
Cdd:cd05079     55 KEIEILRNLYHENIVKYKGICTEDggNGIKLIMEFLPsgslKEYLPR-NKNKINLKQQLKYAV-QICKGMDYLGSRQYVH 132

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1207186029 1779 LDIKPDNILMadHSSDQIRICDFGNAVKFMPDEAQYC---KYGTPEF-VAPEIVNQTPVSKATDIWPIGVLTYLCLT 1851
Cdd:cd05079    133 RDLAARNVLV--ESEHQVKIGDFGLTKAIETDKEYYTvkdDLDSPVFwYAPECLIQSKFYIASDVWSFGVTLYELLT 207

Catalytic domain of the Serine/Threonine Kinase, Serine-aRginine Protein Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SRPK3 is highly expressed in the heart and skeletal muscles, and is controlled by a muscle-specific enhancer that is regulated by MEF2. It may play an important role in muscle development. SRPKs phosphorylate and regulate splicing factors from the SR protein family by specifically phosphorylating multiple serine residues residing in SR/RS dipeptide motifs (also known as RS domains). Phosphorylation of the RS domains enhances interaction with transportin SR and facilitates entry of the SR proteins into the nucleus. SRPKs contain a nonconserved insert domain, within the well-conserved catalytic kinase domain, that regulates their subcellular localization. The SRPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271120 [Multi-domain] Cd Length: 365 Bit Score: 55.03 E-value: 5.65e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKASALRELNIL--------SHLDHERILYFHDAFEKKNA--- 1730
Cdd:cd14218     12 YHVVRKLGWGHFSTVWLCWDIQRKRFVALKVVKSAVHYTETAVDEIKLLkcvrdsdpSDPKRETIVQLIDDFKISGVngv 91

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1731 -VIIITELCHEELLDRLTKKS--TILESEIRSSVRQLLEGINYLH-QLDILHLDIKPDNILMA----------------- 1789
Cdd:cd14218     92 hVCMVLEVLGHQLLKWIIKSNyqGLPLPCVKSILRQVLQGLDYLHtKCKIIHTDIKPENILMCvdegyvrrlaaeatiwq 171

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1790 -------------------------DHSSDQIR--ICDFGNAV---KFMPDEAQyckygTPEFVAPEIVNQTPVSKATDI 1839
Cdd:cd14218    172 qagapppsgssvsfgasdflvnplePQNADKIRvkIADLGNACwvhKHFTEDIQ-----TRQYRALEVLIGAEYGTPADI 246

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1840 WPIGVLTYLCLTG---VSPFAGE----------------------------------NDRSSVLNIRN------YNVAFE 1876
Cdd:cd14218    247 WSTACMAFELATGdylFEPHSGEdytrdedhiahivellgdipphfalsgrysreyfNRRGELRHIKNlkhwglYEVLVE 326

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*.
gi 1207186029 1877 E--------SMFTDlcheakgFVIKLL-VADRLRPDANECLRHPWF 1913
Cdd:cd14218    327 KyewpleqaAQFTD-------FLLPMMeFLPEKRATAAQCLQHPWL 365

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 50.20 E-value: 5.78e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1207186029 2866 KLRDHVLLEGDPVTLSCLPAGSPHPHISWMKDKK-PLEIDPRMNMIScpDGrQLLMIMKTTKKDAGLYECVAAN 2938
Cdd:cd20970      8 PSFTVTAREGENATFMCRAEGSPEPEISWTRNGNlIIEFNTRYIVRE--NG-TTLTIRNIRRSDMGIYLCIASN 78

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409564 [Multi-domain] Cd Length: 91 Bit Score: 49.89 E-value: 6.19e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1544 APTFETIMEDLDVNVGETPRFAVVVEGKPVPDILWYKGDTLLSESSHFTFVYDDNECSLVVLNTQADDSGVYTCTAKNLA 1623
Cdd:cd20972      1 PPQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKELQNSPDIQIHQEGDLHSLIIAEAFEEDTGRYSCLATNSV 80

                           90
                   ....*....|.
gi 1207186029 1624 GSVSCKAELTV 1634
Cdd:cd20972     81 GSDTTSAEIFV 91

First C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409474 Cd Length: 92 Bit Score: 50.10 E-value: 6.31e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1123 PLFTRKLDVLEVIEGRNARFDCKVSGTPPPQVIWSHFDRPLEENEDIRILKE--GGRHSLIISHVSNEDEGLYTVAARNS 1200
Cdd:cd05893      1 PFFEMKLKHYKIFEGMPVTFTCRVAGNPKPKIYWFKDGKQISPKSDHYTIQRdlDGTCSLHTTASTLDDDGNYTIMAANP 80

                           90
                   ....*....|..
gi 1207186029 1201 HGEDECAAELYV 1212
Cdd:cd05893     81 QGRISCTGRLMV 92

C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myotilin. Mytolin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to the latter family contain multiple Ig-like domains and function as scaffolds, modulating the actin cytoskeleton. Myotilin is most abundant in skeletal and cardiac muscle and is involved in maintaining sarcomere integrity. It binds to alpha-actinin, filamin, and actin. Mutations in myotilin lead to muscle disorders. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409473 Cd Length: 92 Bit Score: 49.77 E-value: 6.33e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1545 PTFETIMEDLDVNVGETPRFAVVVEGKPVPDILWYKGDTLLSESSHFTFVYDDN--ECSLVVLNTQADDSGVYTCTAKNL 1622
Cdd:cd05892      1 PMFIQKPQNKKVLEGDPVRLECQISAIPPPQIFWKKNNEMLQYNTDRISLYQDNcgRICLLIQNANKKDAGWYTVSAVNE 80

                           90
                   ....*....|..
gi 1207186029 1623 AGSVSCKAELTV 1634
Cdd:cd05892     81 AGVVSCNARLDV 92

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 49.70 E-value: 6.34e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1252 VKPLYDMDVVEGREAVLRCKVAGLPYPTITWfhngKRIDSTEDRKMTQFRDVHSLVVRCVCHAHGGVYKCVISNKVGKAT 1331
Cdd:cd05725      1 VKRPQNQVVLVDDSAEFQCEVGGDPVPTVRW----RKEDGELPKGRYEILDDHSLKIRKVTAGDMGSYTCVAENMVGKIE 76


                   ....*..
gi 1207186029 1332 CYSHLYV 1338
Cdd:cd05725     77 ASATLTV 83

Immunoglobulin domain I1 of the titin I-band and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin domain I1 of the titin I-band and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. The two sheets are linked together by a conserved disulfide bond between B strand and F strand. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig I1 domain of the titin I-band is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409543 [Multi-domain] Cd Length: 94 Bit Score: 50.11 E-value: 6.73e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1029 IIRPVRDVMVKAGETALFECHVIGPQDTDVDWLSDGKLIQPALL--NCKMHFDGKRCRLLLNSVHEDDSGTYTCKLSTAK 1106
Cdd:cd20951      3 FIIRLQSHTVWEKSDAKLRVEVQGKPDPEVKWYKNGVPIDPSSIpgKYKIESEYGVHVLHIRRVTVEDSAVYSAVAKNIH 82

                           90
                   ....*....|.
gi 1207186029 1107 EELTSSAKLKV 1117
Cdd:cd20951     83 GEASSSASVVV 93

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 49.81 E-value: 6.89e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  781 PVFEFPLQ--DTVASTGTEVLLKCIISGTPLPEVIWKKDNTEVKNSPT-HVVKIEGErhSLLIKWTKPSDAGTYTVTAVN 857
Cdd:cd20970      1 PVISTPQPsfTVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEFNTrYIVRENGT--TLTIRNIRRSDMGIYLCIASN 78

                           90
                   ....*....|..
gi 1207186029  858 EV-GEVSSSATL 868
Cdd:cd20970     79 GVpGSVEKRITL 90

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 49.77 E-value: 6.98e-07

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1207186029 1134 VIEGRNARFDCKVSGTPPPQVIWSHFDRPLEENEDIRILKEGgrhSLIISHVSNEDEGLYTVAARNSHGEDECAAELYV 1212
Cdd:cd04969     14 AAKGGDVIIECKPKASPKPTISWSKGTELLTNSSRICILPDG---SLKIKNVTKSDEGKYTCFAVNFFGKANSTGSLSV 89

Catalytic domain of the Protein Tyrosine Kinase, Interleukin-2-inducible T-cell Kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Itk, also known as Tsk or Emt, is a member of the Tec-like subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, Itk contains the Tec homology (TH) domain containing one proline-rich region and a zinc-binding region. Itk is expressed in T-cells and mast cells, and is important in their development and differentiation. Of the three Tec kinases expressed in T-cells, Itk plays the predominant role in T-cell receptor (TCR) signaling. It is activated by phosphorylation upon TCR crosslinking and is involved in the pathway resulting in phospholipase C-gamma1 activation and actin polymerization. It also plays a role in the downstream signaling of the T-cell costimulatory receptor CD28, the T-cell surface receptor CD2, and the chemokine receptor CXCR4. In addition, Itk is crucial for the development of T-helper(Th)2 effector responses. The Itk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 133243 [Multi-domain] Cd Length: 256 Bit Score: 53.42 E-value: 7.19e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1666 KEIGRGAFSYVKRVIQKAgKLEYAAKFISARAKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITELC-HEELLD 1744
Cdd:cd05112     10 QEIGSGQFGLVHLGYWLN-KDKVAIKTIREGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMeHGCLSD 88

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1745 RL-TKKSTILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSdqIRICDFGnAVKFMPDEAQYCKYGTP--- 1820
Cdd:cd05112     89 YLrTQRGLFSAETLLGMCLDVCEGMAYLEEASVIHRDLAARNCLVGENQV--VKVSDFG-MTRFVLDDQYTSSTGTKfpv 165

                          170       180
                   ....*....|....*....|....*..
gi 1207186029 1821 EFVAPEIVNQTPVSKATDIWPIGVLTY 1847
Cdd:cd05112    166 KWSSPEVFSFSRYSSKSDVWSFGVLMW 192

Immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain from the C-terminus of human titin x and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is gigantic; depending on isoform composition it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone and appears to function similar to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 143224 [Multi-domain] Cd Length: 92 Bit Score: 49.66 E-value: 7.63e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  938 SVIEGQEVTMSVLVTGQPKPMLYWLRDRVTIKTGTRHIVQETE-EGNFEmiIKSAQRSDTGVYTCKIINEYGTKQCEGKL 1016
Cdd:cd05747     14 TVSEGESARFSCDVDGEPAPTVTWMREGQIIVSSQRHQITSTEyKSTFE--ISKVQMSDEGNYTVVVENSEGKQEAQFTL 91

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 49.42 E-value: 7.84e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  936 DQSVIEGQEVTMSVLVTGQPKPMLYWLRDRVTIKTGTRHIVQEtEEGNFEmiIKSAQRSDTGVYTCKIINEYGTKQCEGK 1015
Cdd:cd20952      8 NQTVAVGGTVVLNCQATGEPVPTISWLKDGVPLLGKDERITTL-ENGSLQ--IKGAEKSDTGEYTCVALNLSGEATWSAV 84


                   ...
gi 1207186029 1016 LEV 1018
Cdd:cd20952     85 LDV 87

Catalytic domain of the Protein Kinase superfamily; The PK superfamily contains the large family of typical PKs that includes serine/threonine kinases (STKs), protein tyrosine kinases (PTKs), and dual-specificity PKs that phosphorylate both serine/threonine and tyrosine residues of target proteins, as well as pseudokinases that lack crucial residues for catalytic activity and/or ATP binding. It also includes phosphoinositide 3-kinases (PI3Ks), aminoglycoside 3'-phosphotransferases (APHs), choline kinase (ChoK), Actin-Fragmin Kinase (AFK), and the atypical RIO and Abc1p-like protein kinases. These proteins catalyze the transfer of the gamma-phosphoryl group from ATP to their target substrates; these include serine/threonine/tyrosine residues in proteins for typical or atypical PKs, the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives for PI3Ks, the 4-hydroxyl of PtdIns for PI4Ks, and other small molecule substrates for APH/ChoK and similar proteins such as aminoglycosides, macrolides, choline, ethanolamine, and homoserine.

Pssm-ID: 270870 [Multi-domain] Cd Length: 136 Bit Score: 50.90 E-value: 8.20e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3336 ESKQTVLQEYDILKSL--HHEKIMALHEAYVTPRYLVLISECCSGKELLHSLIDRFRySEDDVVAYIVQILQGLDYLHSR 3413
Cdd:cd13968     32 EEGEDLESEMDILRRLkgLELNIPKVLVTEDVDGPNILLMELVKGGTLIAYTQEEEL-DEKDVESIMYQLAECMRLLHSF 110

                           90       100
                   ....*....|....*....|....*.
gi 1207186029 3414 RILHLDIKPENIIVTYMNVVKIIDFG 3439
Cdd:cd13968    111 HLIHRDLNNDNILLSEDGNVKLIDFG 136

First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409566 [Multi-domain] Cd Length: 93 Bit Score: 49.66 E-value: 9.26e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1545 PTFETIMEDLDVNVGETPRFAVVVEGKPVPDILWYK-GD-TLLSESSHFTFVYDDNECSLVVLNTQADDSGVYTCTAKNL 1622
Cdd:cd20974      1 PVFTQPLQSVVVLEGSTATFEAHVSGKPVPEVSWFRdGQvISTSTLPGVQISFSDGRAKLSIPAVTKANSGRYSLTATNG 80

                           90
                   ....*....|..
gi 1207186029 1623 AGSVSCKAELTV 1634
Cdd:cd20974     81 SGQATSTAELLV 92

Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409550 [Multi-domain] Cd Length: 89 Bit Score: 49.10 E-value: 9.79e-07

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1123 PLFTRKLDVLEVIEGRNARFDCKVSGTPPPQVIWSHFDRPLEENEDIRILKEGgrhSLIISHV-SNEDEGLYTVAARNSH 1201
Cdd:cd20958      1 PPFIRPMGNLTAVAGQTLRLHCPVAGYPISSITWEKDGRRLPLNHRQRVFPNG---TLVIENVqRSSDEGEYTCTARNQQ 77


                   ..
gi 1207186029 1202 GE 1203
Cdd:cd20958     78 GQ 79

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.

Pssm-ID: 143205 [Multi-domain] Cd Length: 85 Bit Score: 49.14 E-value: 1.18e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1207186029 2875 GDPVTLSCLPAGSPHPHISWMKDKKPLeidPRMNMISCPDGRqlLMIMKTTKKDAGLYECVAANPLATVTSS 2946
Cdd:cd05728     14 GSSLRWECKASGNPRPAYRWLKNGQPL---ASENRIEVEAGD--LRITKLSLSDSGMYQCVAENKHGTIYAS 80

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.

Pssm-ID: 143205 [Multi-domain] Cd Length: 85 Bit Score: 48.75 E-value: 1.62e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029   57 FIRKMRNAAVGTGCDIRLKVAVAGDPQPTLYWYHNDDLVNMDNQ---EYGGLWIRDCKPSDAGLYTCIATNHLGEARSSA 133
Cdd:cd05728      2 WLKVISDTEADIGSSLRWECKASGNPRPAYRWLKNGQPLASENRievEAGDLRITKLSLSDSGMYQCVAENKHGTIYASA 81


                   ....
gi 1207186029  134 VLAV 137
Cdd:cd05728     82 ELAV 85

Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. VEGFR2 (or Flk1) binds the ligands VEGFA, VEGFC, VEGFD and VEGFE. VEGFR2 signaling is implicated in all aspects of normal and pathological vascular endothelial cell biology. It induces a variety of cellular effects including migration, survival, and proliferation. It is critical in regulating embryonic vascular development and angiogenesis. VEGFR2 is the major signal transducer in pathological angiogenesis including cancer and diabetic retinopathy, and is a target for inhibition in cancer therapy. The carboxyl terminus of VEGFR2 plays an important role in its autophosphorylation and activation. VEGFR2 is a member of the VEGFR subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of VEGFRs to their ligands, the VEGFs, leads to receptor dimerization, activation, and intracellular signaling. The VEGFR2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270681 [Multi-domain] Cd Length: 343 Bit Score: 53.06 E-value: 1.92e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1740 EELLDRLTKKSTILESEIRSSVrQLLEGINYLHQLDILHLDIKPDNILMADhsSDQIRICDFGNAVKFMPDeAQYCKYGT 1819
Cdd:cd05103    165 EAGQEDLYKDFLTLEDLICYSF-QVAKGMEFLASRKCIHRDLAARNILLSE--NNVVKICDFGLARDIYKD-PDYVRKGD 240

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 1207186029 1820 P----EFVAPEIVNQTPVSKATDIWPIGVLTYLCLT-GVSPFAG 1858
Cdd:cd05103    241 ArlplKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSlGASPYPG 284

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409564 [Multi-domain] Cd Length: 91 Bit Score: 48.73 E-value: 1.92e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  927 PPAFLAVIGDQSVIEGQEVTMSVLVTGQPKPMLYWLRDRVTIKTgTRHIVQETEEGNFEMIIKSAQRSDTGVYTCKIINE 1006
Cdd:cd20972      1 PPQFIQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKELQN-SPDIQIHQEGDLHSLIIAEAFEEDTGRYSCLATNS 79


                   ...
gi 1207186029 1007 YGT 1009
Cdd:cd20972     80 VGS 82

Third immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 143259 Cd Length: 88 Bit Score: 48.48 E-value: 2.03e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1207186029 1135 IEGRNARFDCKVSGTPPPQVIWSHFDRPLEENEDIRIlkEGGrhSLIISHVSNEDEGLYTVAARNSHGEDECAAELYVQ 1213
Cdd:cd05851     14 LKGQNVTLECFALGNPVPVIRWRKILEPMPATAEISM--SGA--VLKIFNIQPEDEGTYECEAENIKGKDKHQARVYVQ 88

Second Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409564 [Multi-domain] Cd Length: 91 Bit Score: 48.35 E-value: 2.20e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1030 IRPVRDVMVKAGETALFECHVIGPQDTDVDWLSDGKLIQPALlNCKMHFDGKRCRLLLNSVHEDDSGTYTCKLSTAKEEL 1109
Cdd:cd20972      5 IQKLRSQEVAEGSKVRLECRVTGNPTPVVRWFCEGKELQNSP-DIQIHQEGDLHSLIIAEAFEEDTGRYSCLATNSVGSD 83


                   ....*...
gi 1207186029 1110 TSSAKLKV 1117
Cdd:cd20972     84 TTSAEIFV 91

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.

Pssm-ID: 409541 [Multi-domain] Cd Length: 89 Bit Score: 48.48 E-value: 2.27e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1554 LDVNVGETPRFAVVVEGKPVPDILWYKGDTLLSESSHFTFVYDDNECSLVVLNTQADDSGVYTCTAKNLAGSVSCKAELT 1633
Cdd:cd20949      9 TTVKEGQSATILCEVKGEPQPNVTWHFNGQPISASVADMSKYRILADGLLINKVTQDDTGEYTCRAYQVNSIASDMQERT 88


                   .
gi 1207186029 1634 V 1634
Cdd:cd20949     89 V 89

Catalytic domain of Spleen Tyrosine Kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Syk-like subfamily is composed of Syk, ZAP-70, Shark, and similar proteins. They are cytoplasmic (or nonreceptor) PTKs containing two Src homology 2 (SH2) domains N-terminal to the catalytic tyr kinase domain. They are involved in the signaling downstream of activated receptors (including B-cell, T-cell, and Fc receptors) that contain ITAMs (immunoreceptor tyr activation motifs), leading to processes such as cell proliferation, differentiation, survival, adhesion, migration, and phagocytosis. Syk is important in B-cell receptor signaling, while Zap-70 is primarily expressed in T-cells and NK cells, and is a crucial component in T-cell receptor signaling. Syk also plays a central role in Fc receptor-mediated phagocytosis in the adaptive immune system. Shark is exclusively expressed in ectodermally derived epithelia, and is localized preferentially to the apical surface of the epithelial cells, it may play a role in a signaling pathway for epithelial cell polarity. The Syk-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270650 [Multi-domain] Cd Length: 257 Bit Score: 51.97 E-value: 2.40e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3334 EPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRyLVLISECCSGKELLHSLIDRFRYSEDDVVAYIVQILQGLDYLHSR 3413
Cdd:cd05060     36 EKAGKKEFLREASVMAQLDHPCIVRLIGVCKGEP-LMLVMELAPLGPLLKYLKKRREIPVSDLKELAHQVAMGMAYLESK 114

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3414 RILHLDIKPENIIVTYMNVVKIIDFG------------SAQTFNPLFLKQFSPP---IGTLDYMSpemlkgdvvgppaDI 3478
Cdd:cd05060    115 HFVHRDLAARNVLLVNRHQAKISDFGmsralgagsdyyRATTAGRWPLKWYAPEcinYGKFSSKS-------------DV 181

                          170       180
                   ....*....|....*....|
gi 1207186029 3479 WSIGILTYIMLS-GRLPFTE 3497
Cdd:cd05060    182 WSYGVTLWEAFSyGAKPYGE 201

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 48.17 E-value: 2.48e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1553 DLDVNVGETprfaVVVE-----GKPVPDILWYK-GDTLLSESSHFTFVYDDNecsLVVLNTQADDSGVYTCTAKNLAGS- 1625
Cdd:cd05724      6 DTQVAVGEM----AVLEcspprGHPEPTVSWRKdGQPLNLDNERVRIVDDGN---LLIAEARKSDEGTYKCVATNMVGEr 78


                   ....*....
gi 1207186029 1626 VSCKAELTV 1634
Cdd:cd05724     79 ESRAARLSV 87

Catalytic domain of the Dual-specificity protein kinases, CDC-like kinases 1 and 4; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. CLK1 plays a role in neuronal differentiation. CLKs are involved in the phosphorylation and regulation of serine/arginine-rich (SR) proteins, which play a crucial role in pre-mRNA splicing by directing splice site selection. SR proteins are phosphorylated first by SR protein kinases (SRPKs) at the N-terminus, which leads to its assembly into nuclear speckles where splicing factors are stored. CLKs phosphorylate the C-terminal part of SR proteins, causing the nuclear speckles to dissolve and splicing factors to be recruited at sites of active transcription. Based on a conserved "EHLAMMERILG" signature motif which may be crucial for substrate specificity, CLKs are also referred to as LAMMER kinases. CLKs autophosphorylate at tyrosine residues and phosphorylate their substrates exclusively on serine/threonine residues. The CLK1/4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271115 [Multi-domain] Cd Length: 330 Bit Score: 52.16 E-value: 3.29e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3389 FRYSEDDVVAYivQILQGLDYLHSRRILHLDIKPENIIV------------------TYMNV-VKIIDFGSAqTFNPlfl 3449
Cdd:cd14213    113 FPIDHIRNMAY--QICKSVNFLHHNKLTHTDLKPENILFvqsdyvvkynpkmkrderTLKNPdIKVVDFGSA-TYDD--- 186

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1207186029 3450 KQFSPPIGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLPFTENDPAE 3502
Cdd:cd14213    187 EHHSTLVSTRHYRAPEVILALGWSQPCDVWSIGCILIEYYLGFTVFQTHDSKE 239

Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409548 [Multi-domain] Cd Length: 96 Bit Score: 47.94 E-value: 3.29e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1207186029 1567 VVEGKPVPDILWYKGDTLLSESSHFT---FVYDDNEcslVV--LN---TQADDSGVYTCTAKNLAGSVSCKAELTV 1634
Cdd:cd20956     24 VASGNPLPQITWTLDGFPIPESPRFRvgdYVTSDGD---VVsyVNissVRVEDGGEYTCTATNDVGSVSHSARINV 96

Catalytic domain of the Serine/Threonine Kinase, Homeodomain-Interacting Protein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HIPK1 has been implicated in regulating eye size, lens formation, and retinal morphogenesis during late embryogenesis. It also contributes to the regulation of haematopoiesis and leukaemogenesis by phosphorylating and repressing the transcription factor c-Myb, which is crucial in T- and B-cell development. In glucose-deprived conditions, HIPK1 phosphorylates Daxx, leading to its relocalization from the nucleus to the cytoplasm, where it binds and stabilizes ASK1 (apoptosis signal-regulating kinase 1), a mitogen-activated protein kinase (MAPK) kinase kinase that activates the JNK and p38 MAPK pathways. HIPKs, originally identified by their ability to bind homeobox factors, are nuclear proteins containing catalytic kinase and homeobox-interacting domains as well as a PEST region overlapping with the speckle-retention signal (SRS). The HIPK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271130 [Multi-domain] Cd Length: 355 Bit Score: 52.40 E-value: 3.71e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPESKQTVLQEYDILKSLHHEK-----IMALHEAYVTPRYLVLISE 3374
Cdd:cd14228     17 YEVLEFLGRGTFGQVAKCWKRSTKEIVAIKILKNHPSYARQGQIEVSILSRLSSENadeynFVRSYECFQHKNHTCLVFE 96

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3375 CCsgKELLHSLIDRFRYSEDDVvAYIVQILQ----GLDYLHSRRILHLDIKPENII----VTYMNVVKIIDFGSAQTFNP 3446
Cdd:cd14228     97 ML--EQNLYDFLKQNKFSPLPL-KYIRPILQqvatALMKLKSLGLIHADLKPENIMlvdpVRQPYRVKVIDFGSASHVSK 173

                          170       180       190
                   ....*....|....*....|....*....|....*.
gi 1207186029 3447 LFLKQFsppIGTLDYMSPEMLKGDVVGPPADIWSIG 3482
Cdd:cd14228    174 AVCSTY---LQSRYYRAPEIILGLPFCEAIDMWSLG 206

Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LRRK1 is one of two vertebrate LRRKs which show complementary expression in the brain. It can form heterodimers with LRRK2, and may influence the age of onset of LRRK2-associated Parkinson's disease. LRRKs are also classified as ROCO proteins because they contain a ROC (Ras of complex proteins)/GTPase domain followed by a COR (C-terminal of ROC) domain of unknown function. In addition, LRRKs contain a catalytic kinase domain and protein-protein interaction motifs including a WD40 domain, LRRs and ankyrin (ANK) repeats. LRRKs possess both GTPase and kinase activities, with the ROC domain acting as a molecular switch for the kinase domain, cycling between a GTP-bound state which drives kinase activity and a GDP-bound state which decreases the activity. The LRRK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270969 [Multi-domain] Cd Length: 276 Bit Score: 51.50 E-value: 3.97e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1694 SARAKRKASALR-ELNILSHLDHERILYFhdafekknAVIIITELCHEELLDRLTKKSTILESEIRSS------------ 1760
Cdd:cd14067     47 AADAMKNFSEFRqEASMLHSLQHPCIVYL--------IGISIHPLCFALELAPLGSLNTVLEENHKGSsfmplghmltfk 118

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1761 -VRQLLEGINYLHQLDILHLDIKPDNIL---MADHSSDQIRICDFGNAVKFMPDEAQYCKyGTPEFVAPEIVNQTPVSKA 1836
Cdd:cd14067    119 iAYQIAAGLAYLHKKNIIFCDLKSDNILvwsLDVQEHINIKLSDYGISRQSFHEGALGVE-GTPGYQAPEIRPRIVYDEK 197

                          170       180
                   ....*....|....*....|....
gi 1207186029 1837 TDIWPIGVLTYLCLTGVSPFAGEN 1860
Cdd:cd14067    198 VDMFSYGMVLYELLSGQRPSLGHH 221

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 47.40 E-value: 4.04e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1133 EVIEGRNARFDCKVS-GTPPPQVIWSHFDRPL-EENEDIRILKEGgrhSLIISHVSNEDEGLYTVAARNSHGEDEC-AAE 1209
Cdd:cd05724      8 QVAVGEMAVLECSPPrGHPEPTVSWRKDGQPLnLDNERVRIVDDG---NLLIAEARKSDEGTYKCVATNMVGERESrAAR 84


                   ...
gi 1207186029 1210 LYV 1212
Cdd:cd05724     85 LSV 87

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 47.00 E-value: 4.66e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029   58 IRKMRNAAVGTGCDIRLKVAVAGDPQPTLYWYHNDDlvNMDNQEY-----GGLWIRDCKPSDAGLYTCIATNHLGEARSS 132
Cdd:cd05725      1 VKRPQNQVVLVDDSAEFQCEVGGDPVPTVRWRKEDG--ELPKGRYeilddHSLKIRKVTAGDMGSYTCVAENMVGKIEAS 78


                   ....*
gi 1207186029  133 AVLAV 137
Cdd:cd05725     79 ATLTV 83

Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409582 Cd Length: 91 Bit Score: 47.40 E-value: 4.72e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  789 DTVASTGTEVLLKCIISGTPLPEVIWKKDNTEVKNSPTHVVKI-EGERHSLLIKWTKPSDAGTYTVTAVNEVGEVSSSAT 867
Cdd:cd20990      9 DLTVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIRPDSAHKMLVrENGVHSLIIEPVTSRDAGIYTCIATNRAGQNSFNLE 88


                   ...
gi 1207186029  868 LFI 870
Cdd:cd20990     89 LVV 91

Pseudokinase domain of membrane Guanylate Cyclase receptors; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs lack a critical aspartate involved in ATP binding and does not exhibit kinase activity. It functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270894 [Multi-domain] Cd Length: 268 Bit Score: 51.24 E-value: 5.18e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1689 AAKFISARAKRKASALRELNILSHLDHERILYFHDAFEKKNAVIIITELCHE-ELLDRLTKKSTILESEIRSS-VRQLLE 1766
Cdd:cd13992     29 AIKHITFSRTEKRTILQELNQLKELVHDNLNKFIGICINPPNIAVVTEYCTRgSLQDVLLNREIKMDWMFKSSfIKDIVK 108

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1767 GINYLHQLDI-LHLDIKPDNILMADHSsdQIRICDFGNA-------VKFMPDEAQYCK--YGTPEFV--APEIVNQTPvs 1834
Cdd:cd13992    109 GMNYLHSSSIgYHGRLKSSNCLVDSRW--VVKLTDFGLRnlleeqtNHQLDEDAQHKKllWTAPELLrgSLLEVRGTQ-- 184

                          170       180       190
                   ....*....|....*....|....*....|....*.
gi 1207186029 1835 kATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNIRN 1870
Cdd:cd13992    185 -KGDVYSFAIILYEILFRSDPFALEREVAIVEKVIS 219

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 47.50 E-value: 5.19e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029   47 SVYPTPTPPVfirkmrNAAVGTGCDIRLKVAVAGDPQPTLYWYHNDDLVNMDNQEY------GGLWIRDCKPSDAGLYTC 120
Cdd:cd20970      1 PVISTPQPSF------TVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEFNTRYivrengTTLTIRNIRRSDMGIYLC 74

                           90
                   ....*....|....*...
gi 1207186029  121 IATNHL-GEARSSAVLAV 137
Cdd:cd20970     75 IASNGVpGSVEKRITLQV 92

Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. VEGFR1 (or Flt1) binds VEGFA, VEGFB, and placenta growth factor (PLGF). It regulates monocyte and macrophage migration, vascular permeability, haematopoiesis, and the recruitment of haematopietic progenitor cells from the bone marrow. VEGFR1 is a member of the VEGFR subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of VEGFRs to their ligands, the VEGFs, leads to receptor dimerization, activation, and intracellular signaling. The VEGFR1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271109 [Multi-domain] Cd Length: 340 Bit Score: 51.54 E-value: 6.50e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1740 EELLDRLTKKSTILESEIRSSVrQLLEGINYLHQLDILHLDIKPDNILMADhsSDQIRICDFGNAVKFM--PDEAQYCKY 1817
Cdd:cd14207    166 EEDSGDFYKRPLTMEDLISYSF-QVARGMEFLSSRKCIHRDLAARNILLSE--NNVVKICDFGLARDIYknPDYVRKGDA 242

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 1207186029 1818 GTP-EFVAPEIVNQTPVSKATDIWPIGVLTYLCLT-GVSPFAG 1858
Cdd:cd14207    243 RLPlKWMAPESIFDKIYSTKSDVWSYGVLLWEIFSlGASPYPG 285

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin Superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.

Pssm-ID: 409420 [Multi-domain] Cd Length: 91 Bit Score: 46.84 E-value: 7.56e-06

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029   57 FIRKMRNAAVGTGCDIRLKVAVAGDPQPTLYWyhnddlvnmdnQEYGG-------------------LWIRDCKPSDAGL 117
Cdd:cd05763      2 FTKTPHDITIRAGSTARLECAATGHPTPQIAW-----------QKDGGtdfpaarerrmhvmpeddvFFIVDVKIEDTGV 70

                           90       100
                   ....*....|....*....|.
gi 1207186029  118 YTCIATNHLGEARSSAVLAVL 138
Cdd:cd05763     71 YSCTAQNSAGSISANATLTVL 91

Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409548 [Multi-domain] Cd Length: 96 Bit Score: 46.78 E-value: 8.98e-06

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1207186029 1268 LRCKVAGLPYPTITWFHNGKRIDSTEDRKMTQFR----DVHSLV----VRCvchAHGGVYKCVISNKVGKAT 1331
Cdd:cd20956     21 LKCVASGNPLPQITWTLDGFPIPESPRFRVGDYVtsdgDVVSYVnissVRV---EDGGEYTCTATNDVGSVS 89

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 46.30 E-value: 9.84e-06

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1207186029 1479 ASVTWKRGGVTLSNRPGLFelSMPDDdqhTLKLCKVKSSDVGQLTCIANNKYGSDSCVLTLEM 1541
Cdd:cd04969     32 PTISWSKGTELLTNSSRIC--ILPDG---SLKIKNVTKSDEGKYTCFAVNFFGKANSTGSLSV 89

Catalytic domain of the Serine/Threonine Kinase, Homeodomain-Interacting Protein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HIPK2, the most studied HIPK, is a coregulator of many transcription factors and cofactors including homeodomain proteins (Nkx and HOX families), Smad1-4, Pax6, c-Myb, AML1, the histone acetyltransferase p300, and the tumor repressor p53, among others. It regulates gene transcription during development and in DNA damage response (DDR), and mediates cell processes such as apoptosis, survival, differentiation, and proliferation. HIPK2 mediates apoptosis by phosphorylating and activating p53 during DDR, resulting in the activation of apoptotic genes. In the absence of p53, HIPK2 targets the anti-apoptotic corepressor C-terminal binding protein (CtBP), leading to CtBP's degradation and the promotion of apoptosis. HIPKs, originally identified by their ability to bind homeobox factors, are nuclear proteins containing catalytic kinase and homeobox-interacting domains as well as a PEST region overlapping with the speckle-retention signal (SRS). The HIPK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271129 [Multi-domain] Cd Length: 355 Bit Score: 50.86 E-value: 1.13e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPESKQTVLQEYDILKSLHHE-----KIMALHEAYVTPRYLVLISE 3374
Cdd:cd14227     17 YEVLEFLGRGTFGQVVKCWKRGTNEIVAIKILKNHPSYARQGQIEVSILARLSTEsaddyNFVRAYECFQHKNHTCLVFE 96

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3375 CCsgKELLHSLIDRFRYSEDDVvAYIVQILQ----GLDYLHSRRILHLDIKPENIIVTYMN----VVKIIDFGSAQTFNP 3446
Cdd:cd14227     97 ML--EQNLYDFLKQNKFSPLPL-KYIRPILQqvatALMKLKSLGLIHADLKPENIMLVDPSrqpyRVKVIDFGSASHVSK 173

                          170       180       190
                   ....*....|....*....|....*....|....*.
gi 1207186029 3447 LFLKQFsppIGTLDYMSPEMLKGDVVGPPADIWSIG 3482
Cdd:cd14227    174 AVCSTY---LQSRYYRAPEIILGLPFCEAIDMWSLG 206

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 46.23 E-value: 1.20e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1032 PVRDVMVKAGETALFECHVIGPQDTDVDWLSDGKLIQPALLNCKMHfdgkRCRLLLNSVHEDDSGTYTCKLSTAKEELTS 1111
Cdd:cd20978      7 PEKNVVVKGGQDVTLPCQVTGVPQPKITWLHNGKPLQGPMERATVE----DGTLTIINVQPEDTGYYGCVATNEIGDIYT 82


                   ....*.
gi 1207186029 1112 SAKLKV 1117
Cdd:cd20978     83 ETLLHV 88

Immunoglobulin I-set domain;

Pssm-ID: 400151 [Multi-domain] Cd Length: 90 Bit Score: 46.10 E-value: 1.43e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1207186029 1480 SVTWKRGGVTLSNRPglfELSM-PDDDQHTLKLCKVKSSDVGQLTCIANNKYGSDSCVLTLE 1540
Cdd:pfam07679   31 EVSWFKDGQPLRSSD---RFKVtYEGGTYTLTISNVQPDDSGKYTCVATNSAGEAEASAELT 89

Catalytic domain of the Serine/Threonine Kinase, Plant B-type Cyclin-Dependent protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The plant-specific B-type CDKs are expressed from the late S to the M phase of the cell cycle. They are characterized by the cyclin binding motif PPT[A/T]LRE. They play a role in controlling mitosis and integrating developmental pathways, such as stomata and leaf development. CdkB has been shown to associate with both cyclin B, which controls G2/M transition, and cyclin D, which acts as a mediator in linking extracellular signals to the cell cycle. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CdkB subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270830 [Multi-domain] Cd Length: 294 Bit Score: 49.83 E-value: 1.43e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1660 DYYDVHKEIGRGAFSYVKRVIQKA-GKLeYAAKFISARAKRK---ASALRELNILSHLDHE----RILYFHDAFEK-KNA 1730
Cdd:cd07837      1 DAYEKLEKIGEGTYGKVYKARDKNtGKL-VALKKTRLEMEEEgvpSTALREVSLLQMLSQSiyivRLLDVEHVEENgKPL 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1731 VIIITELCHEEL---LDRLTKKST--ILESEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMaDHSSDQIRICDFGNAV 1805
Cdd:cd07837     80 LYLVFEYLDTDLkkfIDSYGRGPHnpLPAKTIQSFMYQLCKGVAHCHSHGVMHRDLKPQNLLV-DKQKGLLKIADLGLGR 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1806 KF-MPDEAQYCKYGTPEFVAPEI-VNQTPVSKATDIWPIGVLTYLCLTGVSPFAGENDRSSVLNI--------------- 1868
Cdd:cd07837    159 AFtIPIKSYTHEIVTLWYRAPEVlLGSTHYSTPVDMWSVGCIFAEMSRKQPLFPGDSELQQLLHIfrllgtpneevwpgv 238

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1207186029 1869 ---RNYNVAFE------ESMFTDLCHEAKGFVIKLLVADRL-RPDANECLRHPWF 1913
Cdd:cd07837    239 sklRDWHEYPQwkpqdlSRAVPDLEPEGVDLLTKMLAYDPAkRISAKAALQHPYF 293

Catalytic domain of the Protein Tyrosine Kinase, Fes; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Fes (or Fps) is a cytoplasmic (or nonreceptor) PTK containing an N-terminal region with FCH (Fes/Fer/CIP4 homology) and coiled-coil domains, followed by a SH2 domain, and a C-terminal catalytic domain. The genes for Fes (feline sarcoma) and Fps (Fujinami poultry sarcoma) were first isolated from tumor-causing retroviruses. The viral oncogenes encode chimeric Fes proteins consisting of Gag sequences at the N-termini, resulting in unregulated PTK activity. Fes kinase is expressed in myeloid, vascular endothelial, epithelial, and neuronal cells. It plays important roles in cell growth and differentiation, angiogenesis, inflammation and immunity, and cytoskeletal regulation. A recent study implicates Fes kinase as a tumor suppressor in colorectal cancer. The Fes subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270667 [Multi-domain] Cd Length: 252 Bit Score: 49.54 E-value: 1.48e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1666 KEIGRGAFSYVKrviqkAGKLEYAAKFISARAKR-------KASALRELNILSHLDHERILYFHDAFEKKNAVIIITELC 1738
Cdd:cd05084      2 ERIGRGNFGEVF-----SGRLRADNTPVAVKSCRetlppdlKAKFLQEARILKQYSHPNIVRLIGVCTQKQPIYIVMELV 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1739 HE-ELLDRLTKKSTILE-SEIRSSVRQLLEGINYLHQLDILHLDIKPDNILMADHSSdqIRICDFGnavkfMPDEAQYCK 1816
Cdd:cd05084     77 QGgDFLTFLRTEGPRLKvKELIRMVENAAAGMEYLESKHCIHRDLAARNCLVTEKNV--LKISDFG-----MSREEEDGV 149

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1817 YGTP--------EFVAPEIVNQTPVSKATDIWPIGVLTYLCLT-GVSPFA 1857
Cdd:cd05084    150 YAATggmkqipvKWTAPEALNYGRYSSESDVWSFGILLWETFSlGAVPYA 199

First C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409474 Cd Length: 92 Bit Score: 45.86 E-value: 1.69e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1249 PDFVKPLYDMDVVEGREAVLRCKVAGLPYPTITWFHNGKRIDSTEDRKMTQfRDVHSlvvRCVCHAHG------GVYKCV 1322
Cdd:cd05893      1 PFFEMKLKHYKIFEGMPVTFTCRVAGNPKPKIYWFKDGKQISPKSDHYTIQ-RDLDG---TCSLHTTAstldddGNYTIM 76

                           90
                   ....*....|....*.
gi 1207186029 1323 ISNKVGKATCYSHLYV 1338
Cdd:cd05893     77 AANPQGRISCTGRLMV 92

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin Superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.

Pssm-ID: 409420 [Multi-domain] Cd Length: 91 Bit Score: 45.69 E-value: 1.73e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1034 RDVMVKAGETALFECHVIGPQDTDVDWLSDGKLIQPALLNCKMHFDGKRCRLLLNSVHEDDSGTYTCKLSTAKEELTSSA 1113
Cdd:cd05763      7 HDITIRAGSTARLECAATGHPTPQIAWQKDGGTDFPAARERRMHVMPEDDVFFIVDVKIEDTGVYSCTAQNSAGSISANA 86


                   ....*
gi 1207186029 1114 KLKVI 1118
Cdd:cd05763     87 TLTVL 91

Catalytic domain of the Serine/Threonine Kinase, Homeodomain-Interacting Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HIPKs, originally identified by their ability to bind homeobox factors, are nuclear proteins containing catalytic kinase and homeobox-interacting domains as well as a PEST region overlapping with the speckle-retention signal (SRS). They show speckled localization in the nucleus, apart from the nucleoles. They play roles in the regulation of many nuclear pathways including gene transcription, cell survival, proliferation, differentiation, development, and DNA damage response. Vertebrates contain three HIPKs (HIPK1-3) and mammals harbor an additional family member HIPK4, which does not contain a homeobox-interacting domain and is localized in the cytoplasm. HIPK2, the most studied HIPK, is a coregulator of many transcription factors and cofactors and it regulates gene transcription during development and in DNA damage response. The HIPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 271113 [Multi-domain] Cd Length: 329 Bit Score: 49.75 E-value: 1.95e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3300 YTFMDEKARGRFGVIRECRENATGNLYMAKIVPYEPESKQTVLQEYDILKSLHHEKIMALHeayvtpryLVLISECCSGK 3379
Cdd:cd14211      1 YEVLEFLGRGTFGQVVKCWKRGTNEIVAIKILKNHPSYARQGQIEVSILSRLSQENADEFN--------FVRAYECFQHK 72

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3380 -------ELL-HSLIDRFRYSEDD--VVAYI----VQILQGLDYLHSRRILHLDIKPENII----VTYMNVVKIIDFGSA 3441
Cdd:cd14211     73 nhtclvfEMLeQNLYDFLKQNKFSplPLKYIrpilQQVLTALLKLKSLGLIHADLKPENIMlvdpVRQPYRVKVIDFGSA 152

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|.
gi 1207186029 3442 QTFNPLFLkqfSPPIGTLDYMSPEMLKGDVVGPPADIWSIG 3482
Cdd:cd14211    153 SHVSKAVC---STYLQSRYYRAPEIILGLPFCEAIDMWSLG 190

Immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain from the C-terminus of human titin x and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is gigantic; depending on isoform composition it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone and appears to function similar to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 143224 [Multi-domain] Cd Length: 92 Bit Score: 45.42 E-value: 2.21e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1207186029 1258 MDVVEGREAVLRCKVAGLPYPTITWFHNGKRIDSTEDRKMTQFRDVHSLVVRCVCHAHGGVYKCVISNKVGK 1329
Cdd:cd05747     13 LTVSEGESARFSCDVDGEPAPTVTWMREGQIIVSSQRHQITSTEYKSTFEISKVQMSDEGNYTVVVENSEGK 84

Immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain from the C-terminus of human titin x and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is gigantic; depending on isoform composition it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone and appears to function similar to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 143224 [Multi-domain] Cd Length: 92 Bit Score: 45.42 E-value: 2.26e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1543 VAPTFETIMEDLDVNVGETPRFAVVVEGKPVPDILWYKGDTLLSESSHFTFVYDDNECSLVVLNTQADDSGVYTCTAKNL 1622
Cdd:cd05747      2 LPATILTKPRSLTVSEGESARFSCDVDGEPAPTVTWMREGQIIVSSQRHQITSTEYKSTFEISKVQMSDEGNYTVVVENS 81

                           90
                   ....*....|.
gi 1207186029 1623 AGSVSCKAELT 1633
Cdd:cd05747     82 EGKQEAQFTLT 92

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNK3 is expressed primarily in the brain, and to a lesser extent in the heart and testis. Mice deficient in JNK3 are protected against kainic acid-induced seizures, stroke, sciatic axotomy neural death, and neuronal death due to NGF deprivation, oxidative stress, or exposure to beta-amyloid peptide. This suggests that JNK3 may play roles in the pathogenesis of these diseases. JNKs are mitogen-activated protein kinases (MAPKs) that are involved in many stress-activated responses including those during inflammation, neurodegeneration, apoptosis, and persistent pain sensitization, among others. The JNK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143379 [Multi-domain] Cd Length: 355 Bit Score: 49.70 E-value: 2.39e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1697 AKRkasALRELNILSHLDHERILYFHDAF------EKKNAVIIITELCHEELLDRLTKKstiLESEIRSSV-RQLLEGIN 1769
Cdd:cd07874     60 AKR---AYRELVLMKCVNHKNIISLLNVFtpqkslEEFQDVYLVMELMDANLCQVIQME---LDHERMSYLlYQMLCGIK 133

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1770 YLHQLDILHLDIKPDNILMadHSSDQIRICDFGNA----VKFMPDEAQYCKYgtpeFVAPEIVNQTPVSKATDIWPIGVL 1845
Cdd:cd07874    134 HLHSAGIIHRDLKPSNIVV--KSDCTLKILDFGLArtagTSFMMTPYVVTRY----YRAPEVILGMGYKENVDIWSVGCI 207

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 45.53 E-value: 2.44e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1249 PDFVK-PLYDMD-VVEGREAVLRCKVAGLPYPTITW------FHNGKRIDSTEDRkmtqfrdvhSLVVRCVCHAHGGVYK 1320
Cdd:cd04969      1 PDFELnPVKKKIlAAKGGDVIIECKPKASPKPTISWskgtelLTNSSRICILPDG---------SLKIKNVTKSDEGKYT 71

                           90
                   ....*....|....*...
gi 1207186029 1321 CVISNKVGKATCYSHLYV 1338
Cdd:cd04969     72 CFAVNFFGKANSTGSLSV 89

C-terminal immunoglobulin (Ig)-like domain of M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of M-protein (also known as myomesin-2). M-protein is a structural protein localized to the M-band, a transverse structure in the center of the sarcomere, and is a candidate for M-band bridges. M-protein is modular consisting mainly of repetitive IG-like and fibronectin type III (FnIII) domains and has a muscle-type specific expression pattern. M-protein is present in fast fibers.

Pssm-ID: 143299 Cd Length: 92 Bit Score: 45.29 E-value: 2.46e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1545 PTFETIMEdldvnvGETPRFAVVVEGKPVPDILWYKGDTLLSESSHFTFVYDDNE-CSLVVLNTQADDSGVYTCTAKNLA 1623
Cdd:cd05891      8 PDVVTIME------GKTLNLTCTVFGNPDPEVIWFKNDQDIELSEHYSVKLEQGKyASLTIKGVTSEDSGKYSINVKNKY 81


                   .
gi 1207186029 1624 G 1624
Cdd:cd05891     82 G 82

Stk1 family PASTA domain-containing Ser/Thr kinase;

Pssm-ID: 468045 [Multi-domain] Cd Length: 563 Bit Score: 50.18 E-value: 2.72e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1762 RQLLEGINYLHQLDILHLDIKPDNILMADhsSDQIRICDFG-------------NAVkfMpdeaqyckyGTPEFVAPEIV 1828
Cdd:NF033483   114 IQILSALEHAHRNGIVHRDIKPQNILITK--DGRVKVTDFGiaralssttmtqtNSV--L---------GTVHYLSPEQA 180

                           90       100       110
                   ....*....|....*....|....*....|..
gi 1207186029 1829 NQTPVSKATDIWPIGVLTYLCLTGVSPFAGEN 1860
Cdd:NF033483   181 RGGTVDARSDIYSLGIVLYEMLTGRPPFDGDS 212

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.

Pssm-ID: 143205 [Multi-domain] Cd Length: 85 Bit Score: 44.90 E-value: 2.79e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1547 FETIMEDLDVNVGETPRFAVVVEGKPVPDILWYK-GDTLLSESShftfVYDDN-ECSLVVLNTQadDSGVYTCTAKNLAG 1624
Cdd:cd05728      2 WLKVISDTEADIGSSLRWECKASGNPRPAYRWLKnGQPLASENR----IEVEAgDLRITKLSLS--DSGMYQCVAENKHG 75

                           90
                   ....*....|
gi 1207186029 1625 SVSCKAELTV 1634
Cdd:cd05728     76 TIYASAELAV 85

Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jak3 is expressed only in hematopoietic cells. It binds the shared receptor subunit common gamma chain and thus, is essential in the signaling of cytokines that use it such as IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. Jak3 is important in lymphoid development and myeloid cell differentiation. Inactivating mutations in Jak3 have been reported in humans with severe combined immunodeficiency (SCID). Jak3 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal catalytic tyr kinase domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270665 [Multi-domain] Cd Length: 283 Bit Score: 49.12 E-value: 2.86e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1705 RELNILSHLDHERILYFHD---AFEKKNAVIIITELCHEELLDRLTKKSTILE-SEIRSSVRQLLEGINYLHQLDILHLD 1780
Cdd:cd05081     54 REIQILKALHSDFIVKYRGvsyGPGRRSLRLVMEYLPSGCLRDFLQRHRARLDaSRLLLYSSQICKGMEYLGSRRCVHRD 133

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1207186029 1781 IKPDNILMadHSSDQIRICDFGNAvKFMPDEAQYC----KYGTPEF-VAPEIVNQTPVSKATDIWPIGVLTYLCLT 1851
Cdd:cd05081    134 LAARNILV--ESEAHVKIADFGLA-KLLPLDKDYYvvrePGQSPIFwYAPESLSDNIFSRQSDVWSFGVVLYELFT 206

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNK1 is expressed in every cell and tissue type. It specifically binds with JAMP (JNK1-associated membrane protein), which regulates the duration of JNK1 activity in response to stimuli. Specific JNK1 substrates include Itch and SG10, which are implicated in Th2 responses and airway inflammation, and microtubule dynamics and axodendritic length, respectively. Mice deficient in JNK1 are protected against arthritis, obesity, type 2 diabetes, cardiac cell death, and non-alcoholic liver disease, suggesting that JNK1 may play roles in the pathogenesis of these diseases. Initially, it was thought that JNK1 and JNK2 were functionally redundant as mice deficient in either genes could survive but disruption of both genes resulted in lethality. However, recent studies have shown that JNK1 and JNK2 perform distinct functions through specific binding partners and substrates. JNKs are mitogen-activated protein kinases that are involved in many stress-activated responses including those during inflammation, neurodegeneration, apoptosis, and persistent pain sensitization, among others. The JNK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 143380 [Multi-domain] Cd Length: 364 Bit Score: 49.27 E-value: 3.00e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFIS------ARAKRkasALRELNILSHLDHERILYFHDAF------EKKN 1729
Cdd:cd07875     26 YQNLKPIGSGAQGIVCAAYDAILERNVAIKKLSrpfqnqTHAKR---AYRELVLMKCVNHKNIIGLLNVFtpqkslEEFQ 102

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1730 AVIIITELCHEELLDRLTKKstiLESEIRSSV-RQLLEGINYLHQLDILHLDIKPDNILMadHSSDQIRICDFGNA---- 1804
Cdd:cd07875    103 DVYIVMELMDANLCQVIQME---LDHERMSYLlYQMLCGIKHLHSAGIIHRDLKPSNIVV--KSDCTLKILDFGLArtag 177

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|.
gi 1207186029 1805 VKFMPDEAQYCKYgtpeFVAPEIVNQTPVSKATDIWPIGVL 1845
Cdd:cd07875    178 TSFMMTPYVVTRY----YRAPEVILGMGYKENVDIWSVGCI 214

C5 immunoglobulin (Ig) domain of cardiac myosin binding protein C (MyBP-C); The members here are composed of the C5 immunoglobulin (Ig) domain of cardiac myosin binding protein C (MyBP-C). MyBP-C consists of repeated domains, Ig and fibronectin type 3, and various linkers. Three isoforms of MYBP-C exist: slow-skeletal (ssMyBP-C), fast-skeletal (fsMyBP-C), and cardiac (cMyBP-C). cMYBP-C has insertions between and inside domains and an additional cardiac-specific Ig domain at the N-terminus. For cMYBP_C an interaction has been demonstrated between this C5 domain and the Ig C8 domain.

Pssm-ID: 409475 Cd Length: 86 Bit Score: 44.83 E-value: 3.12e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1556 VNVGETPRFAVVVEGKPVPDILWYKGDTLLSESSHFTFVYDDNECS-LVVLNTQADDSGVYTCTAKNLAG 1624
Cdd:cd05894      7 VVAGNKLRLDVPISGEPAPTVTWSRGDKAFTATEGRVRVESYKDLSsFVIEGAEREDEGVYTITVTNPVG 76

Fifth Ig-like domain of Roundabout (Robo) homolog 1/2, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth Ig-like domain of Roundabout (Robo) homolog 1/2 and similar domains. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, -2, and -3), and three mammalian Slit homologs (Slit-1,-2, -3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, -2, and -3 are expressed by commissural neurons in the vertebrate spinal cord and Slits 1, -2, -3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of slit responsiveness, antagonizes slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. The fifth Ig-like domain of Robo 1 and 2 is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors

Pssm-ID: 409544 [Multi-domain] Cd Length: 87 Bit Score: 44.79 E-value: 3.72e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1134 VIEGRNARFDCKVSGTPPPQVIWSHFDRPLE-ENEDIRILKEGgrhSLIISHVSNEDEGLYTVAARNSHGEDECAAELYV 1212
Cdd:cd20952     11 VAVGGTVVLNCQATGEPVPTISWLKDGVPLLgKDERITTLENG---SLQIKGAEKSDTGEYTCVALNLSGEATWSAVLDV 87

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 44.70 E-value: 3.75e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1207186029 1257 DMDVVEGREAVLRCKVA-GLPYPTITWFHNGKRIDSTEDRKMTqfRDVHSLVVRCVCHAHGGVYKCVISNKVG 1328
Cdd:cd05724      6 DTQVAVGEMAVLECSPPrGHPEPTVSWRKDGQPLNLDNERVRI--VDDGNLLIAEARKSDEGTYKCVATNMVG 76

Immunoglobulin-like domain of human Aortic Preferentially Expressed Protein-1 (APEG-1) and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin I-set (IgI) domain of the Human Aortic Preferentially Expressed Protein-1 (APEG-1) and similar proteins. APEG-1 is a novel specific smooth muscle differentiation marker predicted to play a role in the growth and differentiation of arterial smooth muscle cells (SMCs). The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the human APEG-1 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409567 Cd Length: 91 Bit Score: 44.77 E-value: 3.87e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029   55 PVFIRKMRNAAVGTGCDIRLKVAVAGDPQPTLYWYHNDDLVNMDNQEYGG--------LWIRDCKPSDAGLYTCIATNHL 126
Cdd:cd20975      1 PTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEeaegglcrLRILAAERGDAGFYTCKAVNEY 80

                           90
                   ....*....|.
gi 1207186029  127 GEARSSAVLAV 137
Cdd:cd20975     81 GARQCEARLEV 91

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 44.70 E-value: 4.30e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1030 IRPvRDVMVKAGETALFEChviGP----QDTDVDWLSDGKLIqpALLNCKMHF--DGKrcrLLLNSVHEDDSGTYTCKLS 1103
Cdd:cd05724      2 VEP-SDTQVAVGEMAVLEC---SPprghPEPTVSWRKDGQPL--NLDNERVRIvdDGN---LLIAEARKSDEGTYKCVAT 72

                           90
                   ....*....|....*
gi 1207186029 1104 -TAKEELTSSAKLKV 1117
Cdd:cd05724     73 nMVGERESRAARLSV 87

Pseudokinase domain of Ryk (Receptor related to tyrosine kinase); Ryk is a receptor tyr kinase (RTK) containing an extracellular region with two leucine-rich motifs, a transmembrane segment, and an intracellular inactive pseudokinase domain, which shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. The extracellular region of Ryk shows homology to the N-terminal domain of Wnt inhibitory factor-1 (WIF) and serves as the ligand (Wnt) binding domain of Ryk. Ryk is expressed in many different tissues both during development and in adults, suggesting a widespread function. It acts as a chemorepulsive axon guidance receptor of Wnt glycoproteins and is responsible for the establishment of axon tracts during the development of the central nervous system. In addition, studies in mice reveal that Ryk is essential in skeletal, craniofacial, and cardiac development. Thus, it appears Ryk is involved in signal transduction despite its lack of kinase activity. Ryk may function as an accessory protein that modulates the signals coming from catalytically active partner RTKs such as the Eph receptors. The Ryk subfamily is part of a larger superfamily that includes other pseudokinases and the catalytic domains of active kinases including PTKs, protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270639 [Multi-domain] Cd Length: 279 Bit Score: 48.22 E-value: 4.58e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1763 QLLEGINYLHQLDILHLDIKPDNILMADHSsdQIRICDFGNAVKFMPDEaqYCKYGTPE-----FVAPEIVNQTPVSKAT 1837
Cdd:cd05043    124 QIACGMSYLHRRGVIHKDIAARNCVIDDEL--QVKITDNALSRDLFPMD--YHCLGDNEnrpikWMSLESLVNKEYSSAS 199

                           90       100
                   ....*....|....*....|.
gi 1207186029 1838 DIWPIGVLTY-LCLTGVSPFA 1857
Cdd:cd05043    200 DVWSFGVLLWeLMTLGQTPYV 220

Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Type II Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TGFbR2 belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, bone morphogenetic proteins, activins, growth and differentiation factors, and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane region, and a cytoplasmic catalytic kinase domain. Type II receptors, such as TGFbR2, are high-affinity receptors which bind ligands, autophosphorylate, as well as trans-phosphorylate and activate low-affinity type I receptors. TGFbR2 acts as the receptor for TGFbeta, which is crucial in growth control and homeostasis in many different tissues. It plays roles in regulating apoptosis and in maintaining the balance between self renewal and cell loss. It also plays a key role in maintaining vascular integrity and in regulating responses to genotoxic stress. Mutations in TGFbR2 can cause aortic aneurysm disorders such as Loeys-Dietz and Marfan syndromes. The TGFbR2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270957 [Multi-domain] Cd Length: 295 Bit Score: 48.53 E-value: 4.69e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3307 ARGRFGVI--RECRENATGNLYM--AKIVPYEpeSKQTVLQEYDILK--SLHHEKIMALHEAYV----TPRYLVLISECC 3376
Cdd:cd14055      4 GKGRFAEVwkAKLKQNASGQYETvaVKIFPYE--EYASWKNEKDIFTdaSLKHENILQFLTAEErgvgLDRQYWLITAYH 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3377 SGKELLHSLIDRFrYSEDDVVAYIVQILQGLDYLHSRR---------ILHLDIKPENIIVTYMNVVKIIDFGSAQTFNP- 3446
Cdd:cd14055     82 ENGSLQDYLTRHI-LSWEDLCKMAGSLARGLAHLHSDRtpcgrpkipIAHRDLKSSNILVKNDGTCVLADFGLALRLDPs 160

                          170       180
                   ....*....|....*....|...
gi 1207186029 3447 LFLKQF--SPPIGTLDYMSPEML 3467
Cdd:cd14055    161 LSVDELanSGQVGTARYMAPEAL 183

Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The EphA2 receptor is overexpressed in tumor cells and tumor blood vessels in a variety of cancers including breast, prostate, lung, and colon. As a result, it is an attractive target for drug design since its inhibition could affect several aspects of tumor progression. EphRs comprise the largest subfamily of receptor PTKs (RTKs). Class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. EphRs contain an ephrin binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). Ephrin/EphR interaction mainly results in cell-cell repulsion or adhesion, making it important in neural development and plasticity, cell morphogenesis, cell-fate determination, embryonic development, tissue patterning, and angiogenesis. The EphA2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K).

Pssm-ID: 133194 [Multi-domain] Cd Length: 268 Bit Score: 48.05 E-value: 4.70e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3333 YEPESKQTVLQEYDILKSLHHEKIMALHEAYVTPRYLVLISECCSGKELLHSLIDR-FRYSEDDVVAYIVQILQGLDYLH 3411
Cdd:cd05063     45 YTEKQRQDFLSEASIMGQFSHHNIIRLEGVVTKFKPAMIITEYMENGALDKYLRDHdGEFSSYQLVGMLRGIAAGMKYLS 124

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3412 SRRILHLDIKPENIIVTYMNVVKIIDFGSAQTFNPLFLKQFSPPIGTLD--YMSPEMLKGDVVGPPADIWSIGILTY-IM 3488
Cdd:cd05063    125 DMNYVHRDLAARNILVNSNLECKVSDFGLSRVLEDDPEGTYTTSGGKIPirWTAPEAIAYRKFTSASDVWSFGIVMWeVM 204


                   ....*....
gi 1207186029 3489 LSGRLPFTE 3497
Cdd:cd05063    205 SFGERPYWD 213

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.

Pssm-ID: 409406 [Multi-domain] Cd Length: 82 Bit Score: 44.12 E-value: 4.87e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1207186029   69 GCDIRLKVAVAGDPQPTLYWYHNDDLVNMDNQ-------EYGGLWIRDCKPSDAGLYTCIATNHLGEArsSAVLAV 137
Cdd:cd05748      7 GESLRLDIPIKGRPTPTVTWSKDGQPLKETGRvqiettaSSTSLVIKNAKRSDSGKYTLTLKNSAGEK--SATINV 80

First C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409474 Cd Length: 92 Bit Score: 44.70 E-value: 5.15e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  781 PVFEFPLQDTVASTGTEVLLKCIISGTPLPEVIWKKDNTEVKNSPTHVV---KIEGErHSLLIKWTKPSDAGTYTVTAVN 857
Cdd:cd05893      1 PFFEMKLKHYKIFEGMPVTFTCRVAGNPKPKIYWFKDGKQISPKSDHYTiqrDLDGT-CSLHTTASTLDDDGNYTIMAAN 79

                           90
                   ....*....|...
gi 1207186029  858 EVGEVSSSATLFI 870
Cdd:cd05893     80 PQGRISCTGRLMV 92

Second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the second immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of the Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit-2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409389 [Multi-domain] Cd Length: 87 Bit Score: 44.31 E-value: 5.23e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  926 EPPAFLAVIGDQSVIEGQEVTmsvlvtGQPKPMLYWLRDRVTIKTGTRHiVQETEEGNfeMIIKSAQRSDTGVYTCKIIN 1005
Cdd:cd05724      3 EPSDTQVAVGEMAVLECSPPR------GHPEPTVSWRKDGQPLNLDNER-VRIVDDGN--LLIAEARKSDEGTYKCVATN 73


                   ....*
gi 1207186029 1006 EYGTK 1010
Cdd:cd05724     74 MVGER 78

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar domains; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three Ig-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans. This group also contains fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

Pssm-ID: 409393 [Multi-domain] Cd Length: 95 Bit Score: 44.52 E-value: 5.56e-05

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1207186029 1268 LRCKVAGLPYPTITWFHNGKRIDSTEDRKMTQFRDVH-SLVVRCVCHAHGGVYKCVISNKVGKAtcySHLYVTDI 1341
Cdd:cd05729     24 LECGAGGNPMPNITWLKDGKEFKKEHRIGGTKVEEKGwSLIIERAIPRDKGKYTCIVENEYGSI---NHTYDVDV 95

Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. VEGFR3 (or Flt4) preferentially binds the ligands VEGFC and VEGFD. VEGFR3 is essential for lymphatic endothelial cell (EC) development and function. It has been shown to regulate adaptive immunity during corneal transplantation. VEGFR3 is upregulated on blood vascular ECs in pathological conditions such as vascular tumors and the periphery of solid tumors. It plays a role in cancer progression and lymph node metastasis. Missense mutations in the VEGFR3 gene are associated with primary human lymphedema. VEGFR3 is a member of the VEGFR subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and an intracellular catalytic domain. In VEGFR3, the fifth Ig-like domain is replaced by a disulfide bridge. The binding of VEGFRs to their ligands, the VEGFs, leads to receptor dimerization, activation, and intracellular signaling. The VEGFR3 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270680 [Multi-domain] Cd Length: 336 Bit Score: 48.44 E-value: 6.24e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1763 QLLEGINYLHQLDILHLDIKPDNILMADhsSDQIRICDFGNAVKFMPDeAQYCKYGTP----EFVAPEIVNQTPVSKATD 1838
Cdd:cd05102    180 QVARGMEFLASRKCIHRDLAARNILLSE--NNVVKICDFGLARDIYKD-PDYVRKGSArlplKWMAPESIFDKVYTTQSD 256

                           90       100
                   ....*....|....*....|.
gi 1207186029 1839 IWPIGVLTYLCLT-GVSPFAG 1858
Cdd:cd05102    257 VWSFGVLLWEIFSlGASPYPG 277

Fifth immunoglobulin (Ig) domain of contactin; The members here are composed of the fifth immunoglobulin (Ig) domain of contactins. Contactins are neural cell adhesion molecules and are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. The first four Ig domains form the intermolecular binding fragment, which arranges as a compact U-shaped module via contacts between Ig domains 1 and 4, and between Ig domains 2 and 3. Contactin-2 (TAG-1, axonin-1) may play a part in the neuronal processes of neurite outgrowth, axon guidance and fasciculation, and neuronal migration. This group also includes contactin-1 and contactin-5. The different contactins show different expression patterns in the central nervous system. During development and in adulthood, contactin-2 is transiently expressed in subsets of central and peripheral neurons. Contactin-5 is expressed specifically in the rat postnatal nervous system, peaking at about 3 weeks postnatal, and a lack of contactin-5 (NB-2) results in an impairment of neuronal activity in the rat auditory system. Contactin-5 is highly expressed in the adult human brain in the occipital lobe and in the amygdala. Contactin-1 is differentially expressed in tumor tissues and may, through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma.

Pssm-ID: 409358 [Multi-domain] Cd Length: 89 Bit Score: 43.99 E-value: 7.08e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  940 IEGQEVTMSVLV----TGQPKPMLYWLRDRVTIKTGTRhiVQETEEGNfeMIIKSAQRSDTGVYTCKIINEYGTKQCEGK 1015
Cdd:cd04969     11 KILAAKGGDVIIeckpKASPKPTISWSKGTELLTNSSR--ICILPDGS--LKIKNVTKSDEGKYTCFAVNFFGKANSTGS 86


                   ...
gi 1207186029 1016 LEV 1018
Cdd:cd04969     87 LSV 89

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin Superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.

Pssm-ID: 409420 [Multi-domain] Cd Length: 91 Bit Score: 44.15 E-value: 7.80e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1125 FTRKLDVLEVIEGRNARFDCKVSGTPPPQVIWSH---FDRPLEENEDIRILKEGGrhSLIISHVSNEDEGLYTVAARNSH 1201
Cdd:cd05763      2 FTKTPHDITIRAGSTARLECAATGHPTPQIAWQKdggTDFPAARERRMHVMPEDD--VFFIVDVKIEDTGVYSCTAQNSA 79

                           90
                   ....*....|.
gi 1207186029 1202 GEDECAAELYV 1212
Cdd:cd05763     80 GSISANATLTV 90

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.

Pssm-ID: 409541 [Multi-domain] Cd Length: 89 Bit Score: 43.86 E-value: 8.43e-05

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1207186029 1038 VKAGETALFECHVIGPQDTDVDWLSDGKLIQPALLNCKmHFDGKRCRLLLNSVHEDDSGTYTCK 1101
Cdd:cd20949     11 VKEGQSATILCEVKGEPQPNVTWHFNGQPISASVADMS-KYRILADGLLINKVTQDDTGEYTCR 73

Catalytic domain of the Serine/Threonine kinases, Spindle assembly checkpoint proteins Bub1 and BubR1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Bub1 (Budding uninhibited by benzimidazoles 1), BubR1, and similar proteins. They contain an N-terminal Bub1/Mad3 homology domain essential for Cdc20 binding and a C-terminal kinase domain. Bub1 and BubR1 are involved in SAC, a surveillance system that delays metaphase to anaphase transition by blocking the activity of APC/C (the anaphase promoting complex) until all chromosomes achieve proper attachments to the mitotic spindle, to avoid chromosome missegregation. Impaired SAC leads to genomic instabilities and tumor development. Bub1 and BubR1 facilitate the localization of SAC proteins to kinetochores and regulate kinetochore-microtubule (K-MT) attachments. Repression studies of Bub1 and BubR1 show that they exert an additive effect in misalignment phenotypes and may function cooperatively or in parallel pathways in regulating K-MT attachments. The Bub1/BubR1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270883 [Multi-domain] Cd Length: 298 Bit Score: 47.35 E-value: 8.92e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3308 RGRFGVIREC---RENATGNLYMAKIVpyepesKQTVLQEYDILKSLHH--------EKIMALHEAYVTPRYLVLISECC 3376
Cdd:cd13981     10 EGGYASVYLAkddDEQSDGSLVALKVE------KPPSIWEFYICDQLHSrlknsrlrESISGAHSAHLFQDESILVMDYS 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3377 SGKELLhSLIDRFRYS------EDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVT--------------YMNVV-KI 3435
Cdd:cd13981     84 SQGTLL-DVVNKMKNKtgggmdEPLAMFFTIELLKVVEALHEVGIIHGDIKPDNFLLRleicadwpgegengWLSKGlKL 162

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1207186029 3436 IDFGSAQTFNpLFLKQFSPP--IGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGR 3492
Cdd:cd13981    163 IDFGRSIDMS-LFPKNQSFKadWHTDSFDCIEMREGRPWTYQIDYFGIAATIHVMLFGK 220

C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein (also known as myomesin-2). Myomesin and M-protein are both structural proteins localized to the M-band, a transverse structure in the center of the sarcomere, and are candidates for M-band bridges. Both proteins are modular, consisting mainly of repetitive Ig-like and fibronectin type III (FnIII) domains. Myomesin is expressed in all types of vertebrate striated muscle; M-protein has a muscle-type specific expression pattern. Myomesin is present in both slow and fast fibers; M-protein is present only in fast fibers. It has been suggested that myomesin acts as a molecular spring with alternative splicing as a means of modifying its elasticity.

Pssm-ID: 319300 Cd Length: 92 Bit Score: 43.73 E-value: 9.45e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 2872 LLEGDPVTLSCLPAGSPHPHISWMKDKKPLEIDPRMNMiSCPDGRQLLM-IMKTTKKDAGLYECVAANPLATVTSSCVVS 2950
Cdd:cd05737     13 IMEGKTLNLTCNVWGDPPPEVSWLKNDQALAFLDHCNL-KVEAGRTVYFtINGVSSEDSGKYGLVVKNKYGSETSDVTVS 91


                   .
gi 1207186029 2951 L 2951
Cdd:cd05737     92 V 92

C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein (also known as myomesin-2). Myomesin and M-protein are both structural proteins localized to the M-band, a transverse structure in the center of the sarcomere, and are candidates for M-band bridges. Both proteins are modular, consisting mainly of repetitive Ig-like and fibronectin type III (FnIII) domains. Myomesin is expressed in all types of vertebrate striated muscle; M-protein has a muscle-type specific expression pattern. Myomesin is present in both slow and fast fibers; M-protein is present only in fast fibers. It has been suggested that myomesin acts as a molecular spring with alternative splicing as a means of modifying its elasticity.

Pssm-ID: 319300 Cd Length: 92 Bit Score: 43.73 E-value: 1.03e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  800 LKCIISGTPLPEVIWKKDNTEVKNSPTHVVKIEGERH-SLLIKWTKPSDAGTYTVTAVNEVGEVSSSATL 868
Cdd:cd05737     21 LTCNVWGDPPPEVSWLKNDQALAFLDHCNLKVEAGRTvYFTINGVSSEDSGKYGLVVKNKYGSETSDVTV 90

Catalytic domain of the Serine/Threonine protein kinase, Pten INduced Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PINK1 contains an N-terminal mitochondrial targeting sequence, a catalytic domain, and a C-terminal regulatory region. It plays an important role in maintaining mitochondrial homeostasis. It protects cells against oxidative stress-induced apoptosis by phosphorylating the chaperone TNFR-associated protein 1 (TRAP1), also called Hsp75. Phosphorylated TRAP1 prevents cytochrome c release and peroxide-induced apoptosis. PINK1 interacts with Omi/HtrA2, a serine protease, and Parkin, an E3 ubiquitin ligase, in different pathways to promote mitochondrial health. The parkin gene is the most commonly mutated gene in autosomal recessive familial parkinsonism. Mutations within the catalytic domain of PINK1 are also associated with Parkinson's disease. The PINK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270920 [Multi-domain] Cd Length: 313 Bit Score: 47.10 E-value: 1.19e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3400 IVQILQGLDYLHSRRILHLDIKPENIIVTYMN----VVKIIDFGSAQTFNPLFLKqfsppigtLDYMSPEMLKGD----- 3470
Cdd:cd14018    144 ILQLLEGVDHLVRHGIAHRDLKSDNILLELDFdgcpWLVIADFGCCLADDSIGLQ--------LPFSSWYVDRGGnaclm 215

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3471 -------VVGP-------PADIWSIGILTYIMLSGRLPFTENDPAETEARIQAAKfDLSKLYQNVSQSASLFIKKILCSY 3536
Cdd:cd14018    216 apevstaVPGPgvvinysKADAWAVGAIAYEIFGLSNPFYGLGDTMLESRSYQES-QLPALPSAVPPDVRQVVKDLLQRD 294


                   ....*.
gi 1207186029 3537 PWARPT 3542
Cdd:cd14018    295 PNKRVS 300

C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein (also known as myomesin-2). Myomesin and M-protein are both structural proteins localized to the M-band, a transverse structure in the center of the sarcomere, and are candidates for M-band bridges. Both proteins are modular, consisting mainly of repetitive Ig-like and fibronectin type III (FnIII) domains. Myomesin is expressed in all types of vertebrate striated muscle; M-protein has a muscle-type specific expression pattern. Myomesin is present in both slow and fast fibers; M-protein is present only in fast fibers. It has been suggested that myomesin acts as a molecular spring with alternative splicing as a means of modifying its elasticity.

Pssm-ID: 319300 Cd Length: 92 Bit Score: 43.35 E-value: 1.23e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1545 PTFETIMEDLDVNVgetprfAVVVEGKPVPDILWYKGDTLLSESSHFTF-VYDDNECSLVVLNTQADDSGVYTCTAKNLA 1623
Cdd:cd05737      8 PDVVTIMEGKTLNL------TCNVWGDPPPEVSWLKNDQALAFLDHCNLkVEAGRTVYFTINGVSSEDSGKYGLVVKNKY 81


                   ..
gi 1207186029 1624 GS 1625
Cdd:cd05737     82 GS 83

Immunoglobulin like; IG domains that cannot be classified into one of IGv1, IGc1, IGc2, IG.

Pssm-ID: 214653 [Multi-domain] Cd Length: 85 Bit Score: 42.88 E-value: 1.47e-04

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  1460 VYMVEKQPLSITVTLNHV-NASVTWKRGGVTLSNRPGLFELSmPDDDQHTLKLCKVKSSDVGQLTCIANNKYGSDSCVLT 1538
Cdd:smart00410    4 VTVKEGESVTLSCEASGSpPPEVTWYKQGGKLLAESGRFSVS-RSGSTSTLTISNVTPEDSGTYTCAATNSSGSASSGTT 82


                    ..
gi 1207186029  1539 LE 1540
Cdd:smart00410   83 LT 84

Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409548 [Multi-domain] Cd Length: 96 Bit Score: 43.32 E-value: 1.53e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029   54 PPVFIRKMRNAAVGTGCDIRLKVAVAGDPQPTLYWYHND------------DLVNMDNQEYGGLWIRDCKPSDAGLYTCI 121
Cdd:cd20956      1 APVLLETFSEQTLQPGPSVSLKCVASGNPLPQITWTLDGfpipesprfrvgDYVTSDGDVVSYVNISSVRVEDGGEYTCT 80

                           90
                   ....*....|....*.
gi 1207186029  122 ATNHLGEARSSAVLAV 137
Cdd:cd20956     81 ATNDVGSVSHSARINV 96

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.

Pssm-ID: 409541 [Multi-domain] Cd Length: 89 Bit Score: 43.09 E-value: 1.55e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1207186029  790 TVASTGTEV------LLKCIISGTPLPEVIWKKDNTEVKNSPTHVVKIEGERHSLLIKWTKPSDAGTYTVTAVN 857
Cdd:cd20949      3 TENAYVTTVkegqsaTILCEVKGEPQPNVTWHFNGQPISASVADMSKYRILADGLLINKVTQDDTGEYTCRAYQ 76

Immunoglobulin (Ig)-like ectodomain of the LRIG1 (Leucine-rich Repeats And Immunoglobulin-like Domains Protein 1) and similar proteins; member of the I-set of IgSF domains; The members here are composed of subgroup of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. The ectodomain of LRIG1 has two distinct regions: the proposed 15 LRRs and three Ig-like domains closer to the membrane. LRIG1 has been reported to interact with many receptor tyrosine kinases, GDNF/c-Ret, E-cadherin, JAK/STAT, c-Met, and the EGFR family signaling systems. Immunoglobulin Superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The structure of the LRIG1 extracellular Ig domain lacks a C" strand and thus is better described as a member of the I-set of IgSF domains.

Pssm-ID: 409420 [Multi-domain] Cd Length: 91 Bit Score: 42.99 E-value: 1.62e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 2863 FHIKLRDHVLLEGDPVTLSCLPAGSPHPHISWMKDKK---PLEIDPRMNMISCPDgrqLLMIMKTTKKDAGLYECVAANP 2939
Cdd:cd05763      2 FTKTPHDITIRAGSTARLECAATGHPTPQIAWQKDGGtdfPAARERRMHVMPEDD---VFFIVDVKIEDTGVYSCTAQNS 78

                           90
                   ....*....|..
gi 1207186029 2940 LATVTSSCVVSL 2951
Cdd:cd05763     79 AGSISANATLTV 90

Third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein), and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein) and similar proteins. WFIKKN is a secreted protein that consists of multiple types of protease inhibitory modules, including two tandem Kunitz-type protease inhibitor-domains. The Ig superfamily is a heterogenous group of proteins built on a common fold comprised of a sandwich of two beta sheets. Members of the Ig superfamily are components of immunoglobulin, neuroglia, cell surface glycoproteins, such as T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409422 [Multi-domain] Cd Length: 95 Bit Score: 42.92 E-value: 1.81e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  786 PLQDTVASTGTEVLLkCIISGTPLPEVIWKK---DNTEVKNSPTHVVK--IEGERHSLLIKWTKPSDAGTYTVTAVNEVG 860
Cdd:cd05765      7 PTHQTVKVGETASFH-CDVTGRPQPEITWEKqvpGKENLIMRPNHVRGnvVVTNIGQLVIYNAQPQDAGLYTCTARNSGG 85


                   ..
gi 1207186029  861 EV 862
Cdd:cd05765     86 LL 87

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar domains; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three Ig-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans. This group also contains fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

Pssm-ID: 409393 [Multi-domain] Cd Length: 95 Bit Score: 42.98 E-value: 2.27e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1207186029   59 RKMRNAAVGTGCDIRLKVAVAGDPQPTLYWYHNDDLVNMDNQEYGG--------LWIRDCKPSDAGLYTCIATNHLGE 128
Cdd:cd05729      9 MEEREHALPAANKVRLECGAGGNPMPNITWLKDGKEFKKEHRIGGTkveekgwsLIIERAIPRDKGKYTCIVENEYGS 86

Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409550 [Multi-domain] Cd Length: 89 Bit Score: 42.55 E-value: 2.40e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1551 MEDLDVNVGETPRFAVVVEGKPVPDILWYKGDTLLSESsHFTFVYDDNecSLVVLNTQ-ADDSGVYTCTAKNLAG-SVSC 1628
Cdd:cd20958      7 MGNLTAVAGQTLRLHCPVAGYPISSITWEKDGRRLPLN-HRQRVFPNG--TLVIENVQrSSDEGEYTCTARNQQGqSASR 83


                   ....*.
gi 1207186029 1629 KAELTV 1634
Cdd:cd20958     84 SVFVKV 89

Fourth Ig domain of the neural cell adhesion molecule contactin-2, and similar domains; The members here are composed of the fourth Ig domain of the neural cell adhesion molecule contactin-2. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-2 (also called TAG-1, axonin-1) facilitates cell adhesion by homophilic binding between molecules in apposed membranes. The first four Ig domains form the intermolecular binding fragment which arranges as a compact U-shaped module by contacts between Ig domains 1 and 4, and domains 2 and 3. It has been proposed that a linear zipper-like array forms, from contactin-2 molecules alternatively provided by the two apposed membranes.

Pssm-ID: 143205 [Multi-domain] Cd Length: 85 Bit Score: 42.20 E-value: 2.83e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  787 LQDTVASTGTEVLLKCIISGTPLPEVIWKKdNTEVKNSPThvvKIEGERHSLLIKWTKPSDAGTYTVTAVNEVGEVSSSA 866
Cdd:cd05728      6 ISDTEADIGSSLRWECKASGNPRPAYRWLK-NGQPLASEN---RIEVEAGDLRITKLSLSDSGMYQCVAENKHGTIYASA 81


                   ..
gi 1207186029  867 TL 868
Cdd:cd05728     82 EL 83

Fourth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409548 [Multi-domain] Cd Length: 96 Bit Score: 42.55 E-value: 2.86e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  927 PPAFLAVIGDQSVIEGQEVTMSVLVTGQPKPMLYWLRDRVTIKTGTRHIV--QETEEG------NfemiIKSAQRSDTGV 998
Cdd:cd20956      1 APVLLETFSEQTLQPGPSVSLKCVASGNPLPQITWTLDGFPIPESPRFRVgdYVTSDGdvvsyvN----ISSVRVEDGGE 76

                           90       100
                   ....*....|....*....|
gi 1207186029  999 YTCKIINEYGTKQCEGKLEV 1018
Cdd:cd20956     77 YTCTATNDVGSVSHSARINV 96

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.

Pssm-ID: 409367 [Multi-domain] Cd Length: 89 Bit Score: 42.44 E-value: 2.95e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1553 DLDVNVGETPRFAVVVEGKPVPDILWYKGDTLLSESShFTFVYDDNECSLVVLNTQADDSGVYTCTAKNLAGSVSCKAEL 1632
Cdd:cd04978      8 SLVLSPGETGELICEAEGNPQPTITWRLNGVPIEPAP-EDMRRTVDGRTLIFSNLQPNDTAVYQCNASNVHGYLLANAFL 86


                   ..
gi 1207186029 1633 TV 1634
Cdd:cd04978     87 HV 88

104 kDa microneme/rhoptry antigen; Provisional

Pssm-ID: 185628 [Multi-domain] Cd Length: 943 Bit Score: 46.99 E-value: 3.05e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  492 QVLQKLQDRERAQLAQLEQEmrerDQAKERSPPKSP-------------------------SRRRKDHlaQQPPERAETK 546
Cdd:PTZ00449   483 QEIKKLIKKSKKKLAPIEEE----DSDKHDEPPEGPeasglppkapgdkegeegehedskeSDEPKEG--GKPGETKEGE 556

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  547 VvsttGLEPSPPEAMSLSDLPgQRSPRFRGP----SPSRDSTRRSPtveisamaeERPRgraeSPSRNVlemtlrkvepR 622
Cdd:PTZ00449   557 V----GKKPGPAKEHKPSKIP-TLSKKPEFPkdpkHPKDPEEPKKP---------KRPR----SAQRPT----------R 608

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  623 PASPLVKRVVRVQEVPQANDQPMHRKTPIEVSLRKLERRPESPlvqgetvaiQDFPVQAPPKPPRVSSSSSSEEKMELEV 702
Cdd:PTZ00449   609 PKSPKLPELLDIPKSPKRPESPKSPKRPPPPQRPSSPERPEGP---------KIIKSPKPPKSPKPPFDPKFKEKFYDDY 679

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  703 TPPPPPLKLTIPKIIVEEEPMETDTPVEKTEKAVKVGTGKDEKHQRSRGRGRRQRPM-SPELESSDDSyvSAGEDPLEAP 781
Cdd:PTZ00449   680 LDAAAKSKETKTTVVLDESFESILKETLPETPGTPFTTPRPLPPKLPRDEEFPFEPIgDPDAEQPDDI--EFFTPPEEER 757

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1207186029  782 VF------EFPLQDTVAStgtEVLLKCIISGTPLPEVIWKKDNTEVKNSPT 826
Cdd:PTZ00449   758 TFfhetpaDTPLPDILAE---EFKEEDIHAETGEPDEAMKRPDSPSEHEDK 805

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar domains; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three Ig-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans. This group also contains fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

Pssm-ID: 409393 [Multi-domain] Cd Length: 95 Bit Score: 42.59 E-value: 3.16e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1207186029 2868 RDHVLLEGDPVTLSCLPAGSPHPHISWMKDKKPLEIDPRMNMISCPDGRQLLMIMKTTKKDAGLYECVAANPLATV 2943
Cdd:cd05729     12 REHALPAANKVRLECGAGGNPMPNITWLKDGKEFKKEHRIGGTKVEEKGWSLIIERAIPRDKGKYTCIVENEYGSI 87

Immunoglobulin (Ig)-like domain of titin and similar proteins; The members here are composed of the immunoglobulin (Ig)-like domain found in titin-like proteins and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is a giant protein; depending on isoform composition, it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone. It appears to function similarly to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. Within the sarcomere, titin is also attached to or is associated with myosin binding protein C (MyBP-C). MyBP-C appears to contribute to the generation of passive tension by titin and like titin has repeated Ig-like and FN-III domains. Also included in this group are worm twitchin and insect projectin, thick filament proteins of invertebrate muscle which also have repeated Ig-like and FN-III domains.

Pssm-ID: 409406 [Multi-domain] Cd Length: 82 Bit Score: 41.81 E-value: 3.19e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1207186029 2874 EGDPVTLsCLP-AGSPHPHISWMKDKKPLEIDPRMNMISCPDgRQLLMIMKTTKKDAGLYECVAANPLATVTSSCVV 2949
Cdd:cd05748      6 AGESLRL-DIPiKGRPTPTVTWSKDGQPLKETGRVQIETTAS-STSLVIKNAKRSDSGKYTLTLKNSAGEKSATINV 80

First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409566 [Multi-domain] Cd Length: 93 Bit Score: 42.34 E-value: 3.50e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  939 VIEGQEVTMSVLVTGQPKPMLYWLRDRVTIKTGTRHIVQ-ETEEGNFEMIIKSAQRSDTGVYTCKIINEYGTKQCEGKLE 1017
Cdd:cd20974     12 VLEGSTATFEAHVSGKPVPEVSWFRDGQVISTSTLPGVQiSFSDGRAKLSIPAVTKANSGRYSLTATNGSGQATSTAELL 91


                   ..
gi 1207186029 1018 VK 1019
Cdd:cd20974     92 VL 93

C-terminal immunoglobulin (Ig)-like domain of M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of M-protein (also known as myomesin-2). M-protein is a structural protein localized to the M-band, a transverse structure in the center of the sarcomere, and is a candidate for M-band bridges. M-protein is modular consisting mainly of repetitive IG-like and fibronectin type III (FnIII) domains and has a muscle-type specific expression pattern. M-protein is present in fast fibers.

Pssm-ID: 143299 Cd Length: 92 Bit Score: 42.20 E-value: 3.54e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1207186029  938 SVIEGQEVTMSVLVTGQPKPMLYWLRDRVTIKTgTRHIVQETEEGNF-EMIIKSAQRSDTGVYTCKIINEYG 1008
Cdd:cd05891     12 TIMEGKTLNLTCTVFGNPDPEVIWFKNDQDIEL-SEHYSVKLEQGKYaSLTIKGVTSEDSGKYSINVKNKYG 82

Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409550 [Multi-domain] Cd Length: 89 Bit Score: 42.17 E-value: 3.61e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029   54 PPvFIRKMRNAAVGTGCDIRLKVAVAGDPQPTLYWYHNDD-LVNMDNQEY---GGLWIRDC-KPSDAGLYTCIATNHLGE 128
Cdd:cd20958      1 PP-FIRPMGNLTAVAGQTLRLHCPVAGYPISSITWEKDGRrLPLNHRQRVfpnGTLVIENVqRSSDEGEYTCTARNQQGQ 79


                   ....*.
gi 1207186029  129 ARSSAV 134
Cdd:cd20958     80 SASRSV 85

Catalytic domain of the Serine/Threonine protein kinase, Tau-Tubulin Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TTBK is a neuron-specific kinase that phosphorylates the microtubule-associated protein tau and promotes its aggregation. Higher vertebrates contain two TTBK proteins, TTBK1 and TTBK2, both of which have been implicated in neurodegeneration. TTBK1 has been linked to Alzheimer's disease (AD) while TTBK2 is associated with spinocerebellar ataxia type 11 (SCA11). Both AD and SCA11 patients show the presence of neurofibrillary tangles in the brain. The Drosophila TTBK homolog, Asator, is an essential protein that localizes to the mitotic spindle during mitosis and may be involved in regulating microtubule dynamics and function. The TTBK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270919 [Multi-domain] Cd Length: 263 Bit Score: 45.33 E-value: 4.00e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3309 GRFGVIRECRENATGNLYMAKIvpyepESKQT---VLQ-EYDILKSL----HHEKIMalhEAYVTPRYLVLISECCsGK- 3379
Cdd:cd14017     11 GGFGEIYKVRDVVDGEEVAMKV-----ESKSQpkqVLKmEVAVLKKLqgkpHFCRLI---GCGRTERYNYIVMTLL-GPn 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3380 --ELLHSLIDRfRYSEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTY----MNVVKIIDFGSAQTFNPLFLKQFS 3453
Cdd:cd14017     82 laELRRSQPRG-KFSVSTTLRLGIQILKAIEDIHEVGFLHRDVKPSNFAIGRgpsdERTVYILDFGLARQYTNKDGEVER 160

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*..
gi 1207186029 3454 PP------IGTLDYMSPEMLKGDVVGPPADIWSIGILTYIMLSGRLP 3494
Cdd:cd14017    161 PPrnaagfRGTVRYASVNAHRNKEQGRRDDLWSWFYMLIEFVTGQLP 207

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.

Pssm-ID: 409541 [Multi-domain] Cd Length: 89 Bit Score: 41.93 E-value: 4.40e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1207186029  938 SVIEGQEVTMSVLVTGQPKPMLYWLRDRVTIKTGTRHIvQETEEGNFEMIIKSAQRSDTGVYTCKIINEYGTKQ 1011
Cdd:cd20949     10 TVKEGQSATILCEVKGEPQPNVTWHFNGQPISASVADM-SKYRILADGLLINKVTQDDTGEYTCRAYQVNSIAS 82

agrin-responsive first immunoglobulin-like domains (Ig1) of the MuSK ectodomain; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin-like domains (Ig1) of the Muscle-specific kinase (MuSK). MuSK is a receptor tyrosine kinase specifically expressed in skeletal muscle, where it plays a central role in the formation and maintenance of the neuromuscular junction (NMJ). MuSK is activated by agrin, a neuron-derived heparan sulfate proteoglycan. The activation of MUSK in myotubes regulates the formation of NMJs through the regulation of different processes including the specific expression of genes in subsynaptic nuclei, the reorganization of the actin cytoskeleton and the clustering of the acetylcholine receptors (AChR) in the postsynaptic membrane. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the MuSK lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409562 [Multi-domain] Cd Length: 92 Bit Score: 41.72 E-value: 5.26e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1035 DVMVKAGETALFECHVIGPQDTDVDWLSDGKLIQPALLNCKMHFDGKrcRLLLNSVHEDDSGTYTCKLST-AKEELTSSA 1113
Cdd:cd20970     11 TVTAREGENATFMCRAEGSPEPEISWTRNGNLIIEFNTRYIVRENGT--TLTIRNIRRSDMGIYLCIASNgVPGSVEKRI 88


                   ....
gi 1207186029 1114 KLKV 1117
Cdd:cd20970     89 TLQV 92

Catalytic domain of the Serine/Threonine kinase, PDLIM1 interacting kinase 1 like; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PDIK1L is also called STK35 or CLIK-1. It is predominantly a nuclear protein which is capable of autophosphorylation. Through its interaction with the PDZ-LIM protein CLP-36, it is localized to actin stress fibers. The PDIK1L subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).

Pssm-ID: 270879 [Multi-domain] Cd Length: 322 Bit Score: 45.24 E-value: 5.54e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1662 YDVHKEIGRGAFSYVKRVIQKAGKLEYAAKFISARAKRKAS-ALRELNILSHLD--HERILYFHDAFEKKNAVI------ 1732
Cdd:cd13977      2 YSLIREVGRGSYGVVYEAVVRRTGARVAVKKIRCNAPENVElALREFWALSSIQrqHPNVIQLEECVLQRDGLAqrmshg 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1733 ------------------------------IITELC-----HEELLDRLTKKSTIleseiRSSVRQLLEGINYLHQLDIL 1777
Cdd:cd13977     82 ssksdlylllvetslkgercfdprsacylwFVMEFCdggdmNEYLLSRRPDRQTN-----TSFMLQLSSALAFLHRNQIV 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1778 HLDIKPDNILMADHSSDQI-RICDFG-----NAVKFMPDE-AQYCKY------GTPEFVAPEIVNQTPVSKAtDIWPIGV 1844
Cdd:cd13977    157 HRDLKPDNILISHKRGEPIlKVADFGlskvcSGSGLNPEEpANVNKHflssacGSDFYMAPEVWEGHYTAKA-DIFALGI 235


                   ...
gi 1207186029 1845 LTY 1847
Cdd:cd13977    236 IIW 238

Immunoglobulin domain; This family contains immunoglobulin-like domains.

Pssm-ID: 464046 [Multi-domain] Cd Length: 78 Bit Score: 41.01 E-value: 5.69e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1207186029 1451 PVIIDKPDIVYMVEKQPLSITVTLNHVN-ASVTWKRGGVTLSNRPGLFelSMPDDDQHTLKLCKVKSSDVGQLTCIANN 1528
Cdd:pfam13927    2 PVITVSPSSVTVREGETVTLTCEATGSPpPTITWYKNGEPISSGSTRS--RSLSGSNSTLTISNVTRSDAGTYTCVASN 78

Fourth immunoglobulin (Ig)-like domain of hemolin, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fourth immunoglobulin (Ig)-like domain of hemolin and similar proteins. Hemolin, an insect immunoglobulin superfamily (IgSF) member containing four Ig-like domains, is a lipopolysaccharide-binding immune protein induced during bacterial infection. Hemolin shares significant sequence similarity with the first four Ig-like domains of the transmembrane cell adhesion molecules (CAMs) of the L1 family. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The fourth Ig-like domain of hemolin is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409570 [Multi-domain] Cd Length: 88 Bit Score: 41.22 E-value: 5.98e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1451 PVIIDKPDI-VYMVEKQPLSITVTLNHV-NASVTWKRGGVTLSNRPGLFELsmpddDQHTLKLCKVKSSDVGQLTCIANN 1528
Cdd:cd20978      1 PKFIQKPEKnVVVKGGQDVTLPCQVTGVpQPKITWLHNGKPLQGPMERATV-----EDGTLTIINVQPEDTGYYGCVATN 75


                   ...
gi 1207186029 1529 KYG 1531
Cdd:cd20978     76 EIG 78

Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409550 [Multi-domain] Cd Length: 89 Bit Score: 41.40 E-value: 6.19e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  786 PLQDTVASTGTEVLLKCIISGTPLPEVIWKKDNTEVKNSPTHVVKIEGerhSLLIK-WTKPSDAGTYTVTAVNEVGEvSS 864
Cdd:cd20958      6 PMGNLTAVAGQTLRLHCPVAGYPISSITWEKDGRRLPLNHRQRVFPNG---TLVIEnVQRSSDEGEYTCTARNQQGQ-SA 81


                   ....*..
gi 1207186029  865 SATLFIK 871
Cdd:cd20958     82 SRSVFVK 88

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.

Pssm-ID: 409367 [Multi-domain] Cd Length: 89 Bit Score: 41.28 E-value: 6.44e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029   58 IRKMRNAAVGTGCDIRLKVAVAGDPQPTLYWYHN--------DDLVNMDNQeyGGLWIRDCKPSDAGLYTCIATNHLGEA 129
Cdd:cd04978      3 IIEPPSLVLSPGETGELICEAEGNPQPTITWRLNgvpiepapEDMRRTVDG--RTLIFSNLQPNDTAVYQCNASNVHGYL 80


                   ....*....
gi 1207186029  130 RSSAVLAVL 138
Cdd:cd04978     81 LANAFLHVL 89

Catalytic domain of the Serine/Threonine kinase, SINK-homologous inhibitory kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SHIK, also referred to as STK40 or LYK4, is a cytoplasmic and nuclear protein that is involved in the negative regulation of NF-kappaB- and p53-mediated transcription. It was identified as a protein related to SINK, a p65-interacting protein that inhibits p65 phosphorylation by the catalytic subunit of PKA, thereby inhibiting transcriptional competence of NF-kappaB. The SHIK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 270876 [Multi-domain] Cd Length: 290 Bit Score: 44.70 E-value: 7.31e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1771 LHQLDILHLDIKPDNILMaDHSSDQIRICDFGNAVKFM-PDEAQYCKYGTPEFVAPEIVNQTPVS-KATDIWPIGVLTYL 1848
Cdd:cd13974    148 LHKKNIVHRDLKLGNMVL-NKRTRKITITNFCLGKHLVsEDDLLKDQRGSPAYISPDVLSGKPYLgKPSDMWALGVVLFT 226


                   ....*...
gi 1207186029 1849 CLTGVSPF 1856
Cdd:cd13974    227 MLYGQFPF 234

Second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor, and similar domains; member of the I-set of IgSF domains; The members here are composed of the second immunoglobulin (Ig)-like domain of fibroblast growth factor (FGF) receptor. FGF receptors bind FGF signaling polypeptides. FGFs participate in multiple processes such as morphogenesis, development, and angiogenesis. FGFs bind to four FGF receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, FGFR4). Receptor diversity is controlled by alternative splicing producing splice variants with different ligand binding characteristics and different expression patterns. FGFRs have an extracellular region comprised of three Ig-like domains, a single transmembrane helix, and an intracellular tyrosine kinase domain. Ligand binding and specificity reside in the Ig-like domains 2 and 3, and the linker region that connects these two. FGFR activation and signaling depend on FGF-induced dimerization, a process involving cell surface heparin or heparin sulfate proteoglycans. This group also contains fibroblast growth factor (FGF) receptor like-1(FGFRL1). FGFRL1 does not have a protein tyrosine kinase domain at its C-terminus; neither does its cytoplasmic domain appear to interact with a signaling partner. It has been suggested that FGFRL1 may not have any direct signaling function, but instead acts as a decoy receptor trapping FGFs and preventing them from binding other receptors.

Pssm-ID: 409393 [Multi-domain] Cd Length: 95 Bit Score: 41.44 E-value: 7.38e-04

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1207186029 1137 GRNARFDCKVSGTPPPQVIWSHFDRPLEENEDIRILKEGGRH-SLIISHVSNEDEGLYTVAARNSHGE 1203
Cdd:cd05729     19 ANKVRLECGAGGNPMPNITWLKDGKEFKKEHRIGGTKVEEKGwSLIIERAIPRDKGKYTCIVENEYGS 86

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.

Pssm-ID: 409541 [Multi-domain] Cd Length: 89 Bit Score: 41.16 E-value: 7.46e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1207186029 1251 FVKPLYDMDVVEGREAVLRCKVAGLPYPTITWFHNGKRIdSTEDRKMTQFR-DVHSLVVRCVCHAHGGVYKC 1321
Cdd:cd20949      2 FTENAYVTTVKEGQSATILCEVKGEPQPNVTWHFNGQPI-SASVADMSKYRiLADGLLINKVTQDDTGEYTC 72

First Ig-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the first immunoglobulin (Ig)-like domain of the giant muscle protein titin Z1z2 in the sarcomeric Z-disk and similar proteins. Titin is a key component in the assembly and functioning of vertebrate striated muscles. By providing connections at the level of individual microfilaments, it contributes to the fine balance of forces between the two halves of the sarcomere. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the titin Z1z2 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409566 [Multi-domain] Cd Length: 93 Bit Score: 41.18 E-value: 8.67e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029   55 PVFIRKMRNAAVGTGCDIRLKVAVAGDPQPTLYWYHNDDLVNMD---------NQEYGGLWIRDCKPSDAGLYTCIATNH 125
Cdd:cd20974      1 PVFTQPLQSVVVLEGSTATFEAHVSGKPVPEVSWFRDGQVISTStlpgvqisfSDGRAKLSIPAVTKANSGRYSLTATNG 80

                           90
                   ....*....|...
gi 1207186029  126 LGEARSSAVLAVL 138
Cdd:cd20974     81 SGQATSTAELLVL 93

Third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein), and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein) and similar proteins. WFIKKN is a secreted protein that consists of multiple types of protease inhibitory modules, including two tandem Kunitz-type protease inhibitor-domains. The Ig superfamily is a heterogenous group of proteins built on a common fold comprised of a sandwich of two beta sheets. Members of the Ig superfamily are components of immunoglobulin, neuroglia, cell surface glycoproteins, such as T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409422 [Multi-domain] Cd Length: 95 Bit Score: 41.00 E-value: 9.41e-04

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1207186029 2875 GDPVTLSCLPAGSPHPHISWMK---DKKPLEIDP---RMNMISCPDGRqlLMIMKTTKKDAGLYECVAANP 2939
Cdd:cd05765     15 GETASFHCDVTGRPQPEITWEKqvpGKENLIMRPnhvRGNVVVTNIGQ--LVIYNAQPQDAGLYTCTARNS 83

Third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig)-like domain in Robo (roundabout) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, Robo3), and three mammalian Slit homologs (Slit-1,Slit-2, Slit-3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit-1, Slit-2, and Slit-3 are expressed at the ventral midline. Robo-3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409390 [Multi-domain] Cd Length: 83 Bit Score: 40.46 E-value: 9.95e-04

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 2869 DHVLLEGDPVTLSCLPAGSPHPHISWMKDKKPLeidprmnmiscPDGR------QLLMIMKTTKKDAGLYECVAANPLAT 2942
Cdd:cd05725      6 NQVVLVDDSAEFQCEVGGDPVPTVRWRKEDGEL-----------PKGRyeilddHSLKIRKVTAGDMGSYTCVAENMVGK 74


                   ....
gi 1207186029 2943 VTSS 2946
Cdd:cd05725     75 IEAS 78

Third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein), and similar domains; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin-like domain of the human WFIKKN (WAP, follistatin, immunoglobulin, Kunitz and NTR domain-containing protein) and similar proteins. WFIKKN is a secreted protein that consists of multiple types of protease inhibitory modules, including two tandem Kunitz-type protease inhibitor-domains. The Ig superfamily is a heterogenous group of proteins built on a common fold comprised of a sandwich of two beta sheets. Members of the Ig superfamily are components of immunoglobulin, neuroglia, cell surface glycoproteins, such as T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409422 [Multi-domain] Cd Length: 95 Bit Score: 41.00 E-value: 1.04e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1207186029 1137 GRNARFDCKVSGTPPPQVIWshfDRPLEENEDIRILKEGGRHSLIISHVSN--------EDEGLYTVAARNSHG 1202
Cdd:cd05765     15 GETASFHCDVTGRPQPEITW---EKQVPGKENLIMRPNHVRGNVVVTNIGQlviynaqpQDAGLYTCTARNSGG 85

Third immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 143259 Cd Length: 88 Bit Score: 40.78 E-value: 1.07e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  781 PVFEFPLQDTVASTGTEVLLKCIISGTPLPEVIWKKDNTEVKNSpthvVKIEGERHSLLIKWTKPSDAGTYTVTAVNEVG 860
Cdd:cd05851      2 ADINVKFKDTYALKGQNVTLECFALGNPVPVIRWRKILEPMPAT----AEISMSGAVLKIFNIQPEDEGTYECEAENIKG 77

                           90
                   ....*....|.
gi 1207186029  861 EVSSSATLFIK 871
Cdd:cd05851     78 KDKHQARVYVQ 88

Catalytic domain of the Protein Tyrosine Kinase, C-terminal Src kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Csk catalyzes the tyr phosphorylation of the regulatory C-terminal tail of Src kinases, resulting in their inactivation. Csk is expressed in a wide variety of tissues. As a negative regulator of Src, Csk plays a role in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. Csk is a cytoplasmic (or nonreceptor) PTK containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. To inhibit Src kinases, Csk is translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. In addition, Csk also shows Src-independent functions. It is a critical component in G-protein signaling, and plays a role in cytoskeletal reorganization and cell migration. The Csk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 133213 [Multi-domain] Cd Length: 256 Bit Score: 43.82 E-value: 1.15e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1654 KMRRLTdyydVHKEIGRGAFSYVKRVIQKAGKLeyAAKFISARAKRKAsALRELNILSHLDHERILYFHDAF-EKKNAVI 1732
Cdd:cd05082      4 NMKELK----LLQTIGKGEFGDVMLGDYRGNKV--AVKCIKNDATAQA-FLAEASVMTQLRHSNLVQLLGVIvEEKGGLY 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1733 IITE-LCHEELLDRL-TKKSTILESE--IRSSVrQLLEGINYLHQLDILHLDIKPDNILMadhSSDQI-RICDFG--NAV 1805
Cdd:cd05082     77 IVTEyMAKGSLVDYLrSRGRSVLGGDclLKFSL-DVCEAMEYLEGNNFVHRDLAARNVLV---SEDNVaKVSDFGltKEA 152

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|..
gi 1207186029 1806 KFMPDEAQYckygTPEFVAPEIVNQTPVSKATDIWPIGVLTY 1847
Cdd:cd05082    153 SSTQDTGKL----PVKWTAPEALREKKFSTKSDVWSFGILLW 190

Fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related); The members here are composed of the fourth immunoglobulin (Ig)-like domain of L1, Ng-CAM (Neuron-glia CAM cell adhesion molecule), and NrCAM (Ng-CAM-related). These proteins belong to the L1 subfamily of cell adhesion molecules (CAMs) and are comprised of an extracellular region having six Ig-like domains and five fibronectin type III domains, a transmembrane region and an intracellular domain. These molecules are primarily expressed in the nervous system. L1 is associated with an X-linked recessive disorder, X-linked hydrocephalus, MASA syndrome, or spastic paraplegia type 1, that involves abnormalities of axonal growth.

Pssm-ID: 409367 [Multi-domain] Cd Length: 89 Bit Score: 40.51 E-value: 1.44e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1029 IIRPVRDVmVKAGETALFECHVIG-PQDTdVDWLSDGKLIQPALLNCKMHFDGKrcRLLLNSVHEDDSGTYTCKLSTAKE 1107
Cdd:cd04978      3 IIEPPSLV-LSPGETGELICEAEGnPQPT-ITWRLNGVPIEPAPEDMRRTVDGR--TLIFSNLQPNDTAVYQCNASNVHG 78

                           90
                   ....*....|.
gi 1207186029 1108 ELTSSAKLKVI 1118
Cdd:cd04978     79 YLLANAFLHVL 89

Third immunoglobulin (Ig) domain of contactin-1; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the third immunoglobulin (Ig) domain of the neural cell adhesion molecule contactin-1. Contactins are comprised of six Ig domains followed by four fibronectin type III (FnIII) domains anchored to the membrane by glycosylphosphatidylinositol. Contactin-1 is differentially expressed in tumor tissues and may through a RhoA mechanism, facilitate invasion and metastasis of human lung adenocarcinoma. This group belongs to the I-set of IgSF domains.

Pssm-ID: 143259 Cd Length: 88 Bit Score: 40.39 E-value: 1.47e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1207186029 1570 GKPVPDILWYKGDTLLSESSHFTFvyddNECSLVVLNTQADDSGVYTCTAKNLAGSVSCKAELTVH 1635
Cdd:cd05851     27 GNPVPVIRWRKILEPMPATAEISM----SGAVLKIFNIQPEDEGTYECEAENIKGKDKHQARVYVQ 88

C-terminal immunoglobulin (Ig)-like domain of myotilin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myotilin. Mytolin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to the latter family contain multiple Ig-like domains and function as scaffolds, modulating the actin cytoskeleton. Myotilin is most abundant in skeletal and cardiac muscle and is involved in maintaining sarcomere integrity. It binds to alpha-actinin, filamin, and actin. Mutations in myotilin lead to muscle disorders. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409473 Cd Length: 92 Bit Score: 40.14 E-value: 1.74e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1249 PDFVKPLYDMDVVEGREAVLRCKVAGLPYPTITWFHNGKRIDSTEDRkMTQFRD---VHSLVVRCVCHAHGGVYKCVISN 1325
Cdd:cd05892      1 PMFIQKPQNKKVLEGDPVRLECQISAIPPPQIFWKKNNEMLQYNTDR-ISLYQDncgRICLLIQNANKKDAGWYTVSAVN 79

                           90
                   ....*....|...
gi 1207186029 1326 KVGKATCYSHLYV 1338
Cdd:cd05892     80 EAGVVSCNARLDV 92

Immunoglobulin (Ig)-like domain of human titin C terminus and similar proteins; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the fifth immunoglobulin (Ig)-like domain from the C-terminus of human titin x and similar proteins. Titin (also called connectin) is a fibrous sarcomeric protein specifically found in vertebrate striated muscle. Titin is gigantic; depending on isoform composition it ranges from 2970 to 3700 kDa, and is of a length that spans half a sarcomere. Titin largely consists of multiple repeats of Ig-like and fibronectin type 3 (FN-III)-like domains. Titin connects the ends of myosin thick filaments to Z disks and extends along the thick filament to the H zone and appears to function similar to an elastic band, keeping the myosin filaments centered in the sarcomere during muscle contraction or stretching. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 143224 [Multi-domain] Cd Length: 92 Bit Score: 40.03 E-value: 1.83e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029  778 LEAPVFEFPLQDTVaSTGTEVLLKCIISGTPLPEVIWKKDNTEVKNSPTHVVKIEGERHSLLIKWTKPSDAGTYTVTAVN 857
Cdd:cd05747      2 LPATILTKPRSLTV-SEGESARFSCDVDGEPAPTVTWMREGQIIVSSQRHQITSTEYKSTFEISKVQMSDEGNYTVVVEN 80

                           90
                   ....*....|.
gi 1207186029  858 EVGEVSSSATL 868
Cdd:cd05747     81 SEGKQEAQFTL 91

Immunoglobulin-like domain of human Aortic Preferentially Expressed Protein-1 (APEG-1) and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin I-set (IgI) domain of the Human Aortic Preferentially Expressed Protein-1 (APEG-1) and similar proteins. APEG-1 is a novel specific smooth muscle differentiation marker predicted to play a role in the growth and differentiation of arterial smooth muscle cells (SMCs). The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the human APEG-1 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409567 Cd Length: 91 Bit Score: 40.15 E-value: 1.84e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1249 PDFVKPLYDMDVVEGREAVLRCKVAGLPYPTITWFHNGKRIDSTEDRKMTQFRD-VHSLVVRCVCHAHGGVYKCVISNKV 1327
Cdd:cd20975      1 PTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQRRFAEEAEGgLCRLRILAAERGDAGFYTCKAVNEY 80

                           90
                   ....*....|.
gi 1207186029 1328 GKATCYSHLYV 1338
Cdd:cd20975     81 GARQCEARLEV 91

C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin, and similar domains; member of the I-set IgSF domains; The members here are composed of the C-terminal immunoglobulin-like domain of the myosin-associated giant protein kinase Twitchin and similar proteins, including Caenorhabditis elegans and Aplysia californica Twitchin, Drosophila melanogaster Projectin, and similar proteins. These are very large muscle proteins containing multiple immunoglobulin (Ig)-like and fibronectin type III (FN3) domains and a single kinase domain near the C-terminus. In humans these proteins are called Titin. The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. The Ig-like domain of the Twitchin is a member of the I-set IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins (titin, telokin, and twitchin), the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D.

Pssm-ID: 409541 [Multi-domain] Cd Length: 89 Bit Score: 40.01 E-value: 2.04e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1207186029 2874 EGDPVTLSCLPAGSPHPHISWMKDKKPLEID----PRMNMIScpDGrqlLMIMKTTKKDAGLYECVAAN 2938
Cdd:cd20949     13 EGQSATILCEVKGEPQPNVTWHFNGQPISASvadmSKYRILA--DG---LLINKVTQDDTGEYTCRAYQ 76

Second C-terminal immunoglobulin (Ig)-like domain of palladin; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of palladin. Palladin belongs to the palladin-myotilin-myopalladin family. Proteins belonging to this family contain multiple Ig-like domains and function as scaffolds, modulating actin cytoskeleton. Palladin binds to alpha-actinin ezrin, vasodilator-stimulated phosphoprotein VASP, SPIN90 (also known as DIP or mDia interacting protein), and Src. Palladin also binds F-actin directly, via its Ig3 domain. Palladin is expressed as several alternatively spliced isoforms, having various combinations of Ig-like domains, in a cell-type-specific manner. It has been suggested that palladin's different Ig-like domains may be specialized for distinct functions. This group belongs to the I-set of IgSF domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409582 Cd Length: 91 Bit Score: 39.70 E-value: 2.35e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029   55 PVFIRKMRNAAVGTGCDIRLKVAVAGDPQPTLYWYHNDDLVNMDN------QEYG--GLWIRDCKPSDAGLYTCIATNHL 126
Cdd:cd20990      1 PHFLQAPGDLTVQEGKLCRMDCKVSGLPTPDLSWQLDGKPIRPDSahkmlvRENGvhSLIIEPVTSRDAGIYTCIATNRA 80

                           90
                   ....*....|.
gi 1207186029  127 GEARSSAVLAV 137
Cdd:cd20990     81 GQNSFNLELVV 91

Immunoglobulin domain; The members here are composed of the immunoglobulin (Ig) domain found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, including T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, including butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond. Ig superfamily (IgSF) domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Typically, the V-set domains have A, B, E, and D strands in one sheet and A', G, F, C, C' and C" in the other. The structures in C1-set are smaller than those in the V-set; they have one beta sheet that is formed by strands A, B, E, and D and the other by strands G, F, C, and C'. Moreover, a C1-set Ig domain contains a short C' strand (three residues) and lacks A' and C" strand. Unlike other Ig domain sets, C2-set structures do not have a D strand. Like the V-set Ig domains, members of the I-set have a discontinuous A strand, but lack a C" strand.

Pssm-ID: 409353 [Multi-domain] Cd Length: 70 Bit Score: 38.85 E-value: 2.69e-03

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1207186029 1478 NASVTWKRGGVTLSNRPglFELSMPDDDQHTLKLCKVKSSDVGQLTCIANNKYG 1531
Cdd:cd00096     12 PPTITWYKNGKPLPPSS--RDSRRSELGNGTLTISNVTLEDSGTYTCVASNSAG 63

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.

Pssm-ID: 409490 [Multi-domain] Cd Length: 99 Bit Score: 39.84 E-value: 2.90e-03

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1207186029   80 GDPQPTLYWYHNDDLVNMDNQEY---------GGLWIRDCKP-----SDAGLYTCIATNHLGEARS 131
Cdd:cd07693     26 GRPTPTIQWLKNGQPLETDKDDPrshrivlpsGSLFFLRVVHgrkgrSDEGVYVCVAHNSLGEAVS 91

C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein; member of the I-set of Ig superfamily (IgSF) domains; The members here are composed of the C-terminal immunoglobulin (Ig)-like domain of myomesin and M-protein (also known as myomesin-2). Myomesin and M-protein are both structural proteins localized to the M-band, a transverse structure in the center of the sarcomere, and are candidates for M-band bridges. Both proteins are modular, consisting mainly of repetitive Ig-like and fibronectin type III (FnIII) domains. Myomesin is expressed in all types of vertebrate striated muscle; M-protein has a muscle-type specific expression pattern. Myomesin is present in both slow and fast fibers; M-protein is present only in fast fibers. It has been suggested that myomesin acts as a molecular spring with alternative splicing as a means of modifying its elasticity.

Pssm-ID: 319300 Cd Length: 92 Bit Score: 39.50 E-value: 3.06e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1248 MPDFVKplydmdVVEGREAVLRCKVAGLPYPTITWFHNGKRIDSTE--DRKMTQFRDVhSLVVRCVCHAHGGVYKCVISN 1325
Cdd:cd05737      7 LPDVVT------IMEGKTLNLTCNVWGDPPPEVSWLKNDQALAFLDhcNLKVEAGRTV-YFTINGVSSEDSGKYGLVVKN 79


                   ....*.
gi 1207186029 1326 KVGKAT 1331
Cdd:cd05737     80 KYGSET 85

Catalytic domain of the Protein Tyrosine Kinase, Spleen tyrosine kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Syk is a cytoplasmic (or nonreceptor) PTK containing two Src homology 2 (SH2) domains N-terminal to the catalytic tyr kinase domain. Syk was first cloned from the spleen, and its function in hematopoietic cells is well-established. It is involved in the signaling downstream of activated receptors (including B-cell and Fc receptors) that contain ITAMs (immunoreceptor tyr activation motifs), leading to processes such as cell proliferation, differentiation, survival, adhesion, migration, and phagocytosis. More recently, Syk expression has been detected in other cell types (including epithelial cells, vascular endothelial cells, neurons, hepatocytes, and melanocytes), suggesting a variety of biological functions in non-immune cells. Syk plays a critical role in maintaining vascular integrity and in wound healing during embryogenesis. It also regulates Vav3, which is important in osteoclast function including bone development. In breast epithelial cells, where Syk acts as a negative regulator for EGFR signaling, loss of Syk expression is associated with abnormal proliferation during cancer development suggesting a potential role as a tumor suppressor. In mice, Syk has been shown to inhibit malignant transformation of mammary epithelial cells induced with murine mammary tumor virus (MMTV). The Syk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

Pssm-ID: 133247 [Multi-domain] Cd Length: 257 Bit Score: 41.87 E-value: 4.16e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 3382 LHSLIDRFRY-SEDDVVAYIVQILQGLDYLHSRRILHLDIKPENIIVTYMNVVKIIDFG--SAQTFNPLFLKQFSPPIGT 3458
Cdd:cd05116     82 LNKFLQKNRHvTEKNITELVHQVSMGMKYLEESNFVHRDLAARNVLLVTQHYAKISDFGlsKALRADENYYKAQTHGKWP 161

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1207186029 3459 LDYMSPEMLKGDVVGPPADIWSIGILTYIMLS-GRLPFTENDPAETEARIQAAK 3511
Cdd:cd05116    162 VKWYAPECMNYYKFSSKSDVWSFGVLMWEAFSyGQKPYKGMKGNEVTQMIEKGE 215

Immunoglobulin-like domain of human Aortic Preferentially Expressed Protein-1 (APEG-1) and similar proteins; a member of the I-set of IgSF domains; The members here are composed of the immunoglobulin I-set (IgI) domain of the Human Aortic Preferentially Expressed Protein-1 (APEG-1) and similar proteins. APEG-1 is a novel specific smooth muscle differentiation marker predicted to play a role in the growth and differentiation of arterial smooth muscle cells (SMCs). The Ig superfamily (IgSF) is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. IgSF domains can be divided into 4 main classes based on their structures and sequences: the Variable (V), Constant 1 (C1), Constant 2 (C2), and Intermediate (I) sets. Unlike the V-set, one of the distinctive features of I-set domains is the lack of a C" strand. The structure of the human APEG-1 lacks this strand and thus it belongs to the I-set of the IgSF. I-set domains are found in several cell adhesion molecules (such as VCAM, ICAM, and MADCAM), and are also present in numerous other diverse protein families, including several tyrosine-protein kinase receptors, the hemolymph protein hemolin, the muscle proteins titin, telokin, and twitchin, the neuronal adhesion molecule axonin-1, and the signaling molecule semaphorin 4D that is involved in axonal guidance, immune function and angiogenesis.

Pssm-ID: 409567 Cd Length: 91 Bit Score: 38.61 E-value: 5.59e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1123 PLFTRKLDVLEVIEGRNARFDCKVSGTPPPQVIWSHFDRPLEENEDiRILKEG--GRHSLIISHVSNEDEGLYTVAARNS 1200
Cdd:cd20975      1 PTFKVSLMDQSVREGQDVIMSIRVQGEPKPVVSWLRNRQPVRPDQR-RFAEEAegGLCRLRILAAERGDAGFYTCKAVNE 79

                           90
                   ....*....|..
gi 1207186029 1201 HGEDECAAELYV 1212
Cdd:cd20975     80 YGARQCEARLEV 91

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.

Pssm-ID: 409490 [Multi-domain] Cd Length: 99 Bit Score: 38.69 E-value: 7.32e-03

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1207186029 1134 VIEGRNARFDCKVSGTPPPQVIWSHFDRPLEENEDIR-----ILKEGGRHSLIISH--VSNEDEGLYTVAARNSHGE 1203
Cdd:cd07693     12 VSKGDPATLNCKAEGRPTPTIQWLKNGQPLETDKDDPrshriVLPSGSLFFLRVVHgrKGRSDEGVYVCVAHNSLGE 88

First immunoglobulin (Ig)-like constant domain in Robo (roundabout) receptors, and similar domains; The members here are composed of the first immunoglobulin (Ig)-like domain in Roundabout (Robo) receptors. Robo receptors play a role in the development of the central nervous system (CNS), and are receptors of Slit protein. Slit is a repellant secreted by the neural cells in the midline. Slit acts through Robo to prevent most neurons from crossing the midline from either side. Three mammalian Robo homologs (Robo1, Robo2, and Robo3), and three mammalian Slit homologs (Slit1, Slit2, Slit3), have been identified. Commissural axons, which cross the midline, express low levels of Robo; longitudinal axons, which avoid the midline, express high levels of Robo. Robo1, Robo2, and Robo3 are expressed by commissural neurons in the vertebrate spinal cord and Slit1, Slit2,and Slit3 are expressed at the ventral midline. Robo3 is a divergent member of the Robo family which instead of being a positive regulator of Slit responsiveness, antagonizes Slit responsiveness in precrossing axons. The Slit-Robo interaction is mediated by the second leucine-rich repeat (LRR) domain of Slit and the two N-terminal Ig domains of Robo, Ig1 and Ig2. The primary Robo binding site for Slit2 has been shown by surface plasmon resonance experiments and mutational analysis to be is the Ig1 domain, while the Ig2 domain has been proposed to harbor a weak secondary binding site.

Pssm-ID: 409490 [Multi-domain] Cd Length: 99 Bit Score: 38.69 E-value: 7.68e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1553 DLDVNVGETPRFAVVVEGKPVPDILWYKG------DTLLSESSHftFVYDDNecSL----VVLNTQAD-DSGVYTCTAKN 1621
Cdd:cd07693      9 DLIVSKGDPATLNCKAEGRPTPTIQWLKNgqpletDKDDPRSHR--IVLPSG--SLfflrVVHGRKGRsDEGVYVCVAHN 84

                           90
                   ....*....|....
gi 1207186029 1622 LAG-SVSCKAELTV 1634
Cdd:cd07693     85 SLGeAVSRNASLEV 98

Fifth immunoglobulin domain of the Drosophila melanogaster Dscam protein, and similar domains; a member of the I-set of IgSF domains; The members here are composed of the fifth immunoglobulin domain of the Drosophila melanogaster Down syndrome cell adhesion molecule (DSCAM) protein and similar proteins. Down syndrome cell adhesion molecule (DSCAM) is a cell adhesion molecule that plays critical roles in neural development, including axon guidance and branching, axon target recognition, self-avoidance and synaptic formation. DSCAM belongs to the immunoglobulin superfamily and contributes to defects in the central nervous system in Down syndrome patients. Vertebrate DSCAMs differ from Drosophila Dscam1 in that they lack the extensive alternative splicing that occurs in the insect gene. Drosophila melanogaster Dscam has 38,016 isoforms generated by the alternative splicing of four variable exon clusters, which allows every neuron in the fly to display a distinctive set of Dscam proteins on its cell surface. Drosophila Dscam1 is a cell-surface protein that plays important roles in neural development and axon tiling of neurons. It is shown that thousands of isoforms bind themselves through specific homophilic (self-binding) interactions, a process which mediates cellular self-recognition. Drosophila Dscam2 is also alternatively spliced and plays a key role in the development of two visual system neurons, monopolar cells L1 and L2. This group is a member of the I-set Ig domains, having A-B-E-D strands in one beta-sheet and A'-G-F-C-C' in the other. Like the V-set Ig domains, members of the I-set have a discontinuous A strand but lack a C" strand.

Pssm-ID: 409550 [Multi-domain] Cd Length: 89 Bit Score: 37.93 E-value: 9.01e-03

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207186029 1030 IRPVRDVMVKAGETALFECHVIG-PQDTdVDWLSDGKLIqPALLNCKMHFDGKrcrLLLNSVH-EDDSGTYTCkLSTAKE 1107
Cdd:cd20958      4 IRPMGNLTAVAGQTLRLHCPVAGyPISS-ITWEKDGRRL-PLNHRQRVFPNGT---LVIENVQrSSDEGEYTC-TARNQQ 77

                           90
                   ....*....|
gi 1207186029 1108 ELTSSAKLKV 1117
Cdd:cd20958     78 GQSASRSVFV 87