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Conserved domains on  [gi|15223445|ref|NP_174039|]
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Leucine-rich repeat protein kinase family protein [Arabidopsis thaliana]

Protein Classification

serine/threonine-protein kinase family protein( domain architecture ID 10197261)

serine/threonine-protein kinase family protein may catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates

Gene Ontology:  GO:0004672|GO:0005524|GO:0006468
PubMed:  7768349
SCOP:  4003661

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
STKc_IRAK cd14066
Catalytic domain of the Serine/Threonine kinases, Interleukin-1 Receptor Associated Kinases ...
309-579 2.88e-85

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: 266.83  E-value: 2.88e-85
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 309 SSRTGVSYKADLPDGSALAVKRL--SACGFGEKQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLH 386
Cdd:cd14066   3 SGGFGTVYKGVLENGTVVAVKRLneMNCAASKKEFLTELEMLGRLRHPNLVRLLGYCLESDEKLLVYEYMPNGSLEDRLH 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 387 NGGLCDaVLDWPTRRAIGVGAAKGLAWLHHGCQPPYLHQFISSNVILLDDDFDARITDYGLAKLvgSRDSNDSSFNNGDL 466
Cdd:cd14066  83 CHKGSP-PLPWPQRLKIAKGIARGLEYLHEECPPPIIHGDIKSSNILLDEDFEPKLTDFGLARL--IPPSESVSKTSAVK 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 467 GELGYVAPEYSSTMVASLKGDVYGFGIVLLELVTGQKPLSvINGVEGFKGSLVDWVsQYLGTGRSKDAIDRSI--CDKGH 544
Cdd:cd14066 160 GTIGYLAPEYIRTGRVSTKSDVYSFGVVLLELLTGKPAVD-ENRENASRKDLVEWV-ESKGKEELEDILDKRLvdDDGVE 237
                       250       260       270
                ....*....|....*....|....*....|....*
gi 15223445 545 DEEILQFLKIACSCVVSRPKERPTMIQVYESLKNM 579
Cdd:cd14066 238 EEEVEALLRLALLCTRSDPSLRPSMKEVVQMLEKL 272
PLN00113 super family cl33413
leucine-rich repeat receptor-like protein kinase; Provisional
4-191 2.99e-20

leucine-rich repeat receptor-like protein kinase; Provisional


The actual alignment was detected with superfamily member PLN00113:

Pssm-ID: 215061 [Multi-domain]  Cd Length: 968  Bit Score: 95.30  E-value: 2.99e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445    4 IFITLLWLLFISSFLCssssAEDDVLCLQGLKNSLIDPSSRLSSWSfpnsSASSICKLTGVSCWNEkeNRIISLQL---- 79
Cdd:PLN00113  11 YLIFMLFFLFLNFSML----HAEELELLLSFKSSINDPLKYLSNWN----SSADVCLWQGITCNNS--SRVVSIDLsgkn 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445   80 --------------------QSMQLAGEIPESL-KLCRSLQSLDLSGNDLSGSIPSqicSWLPYLVTLDLSGNKLGGSIP 138
Cdd:PLN00113  81 isgkissaifrlpyiqtinlSNNQLSGPIPDDIfTTSSSLRYLNLSNNNFTGSIPR---GSIPNLETLDLSNNMLSGEIP 157
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 15223445  139 TQIVECKFLNALILSDNKLSGSIPSQLSRLDRLRRLSLAGNDLSGTIPSELAR 191
Cdd:PLN00113 158 NDIGSFSSLKVLDLGGNVLVGKIPNSLTNLTSLEFLTLASNQLVGQIPRELGQ 210
 
Name Accession Description Interval E-value
STKc_IRAK cd14066
Catalytic domain of the Serine/Threonine kinases, Interleukin-1 Receptor Associated Kinases ...
309-579 2.88e-85

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: 266.83  E-value: 2.88e-85
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 309 SSRTGVSYKADLPDGSALAVKRL--SACGFGEKQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLH 386
Cdd:cd14066   3 SGGFGTVYKGVLENGTVVAVKRLneMNCAASKKEFLTELEMLGRLRHPNLVRLLGYCLESDEKLLVYEYMPNGSLEDRLH 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 387 NGGLCDaVLDWPTRRAIGVGAAKGLAWLHHGCQPPYLHQFISSNVILLDDDFDARITDYGLAKLvgSRDSNDSSFNNGDL 466
Cdd:cd14066  83 CHKGSP-PLPWPQRLKIAKGIARGLEYLHEECPPPIIHGDIKSSNILLDEDFEPKLTDFGLARL--IPPSESVSKTSAVK 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 467 GELGYVAPEYSSTMVASLKGDVYGFGIVLLELVTGQKPLSvINGVEGFKGSLVDWVsQYLGTGRSKDAIDRSI--CDKGH 544
Cdd:cd14066 160 GTIGYLAPEYIRTGRVSTKSDVYSFGVVLLELLTGKPAVD-ENRENASRKDLVEWV-ESKGKEELEDILDKRLvdDDGVE 237
                       250       260       270
                ....*....|....*....|....*....|....*
gi 15223445 545 DEEILQFLKIACSCVVSRPKERPTMIQVYESLKNM 579
Cdd:cd14066 238 EEEVEALLRLALLCTRSDPSLRPSMKEVVQMLEKL 272
PLN00113 PLN00113
leucine-rich repeat receptor-like protein kinase; Provisional
73-578 7.67e-46

leucine-rich repeat receptor-like protein kinase; Provisional


Pssm-ID: 215061 [Multi-domain]  Cd Length: 968  Bit Score: 174.27  E-value: 7.67e-46
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445   73 RIISLQLQSMQLAGEIPESLKLCRSLQSLDLSGNDLSGSIPSQICSwLPYLVTLDLSGNKLGGSIPTQIVECKFLNALIL 152
Cdd:PLN00113 476 RLENLDLSRNQFSGAVPRKLGSLSELMQLKLSENKLSGEIPDELSS-CKKLVSLDLSHNQLSGQIPASFSEMPVLSQLDL 554
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445  153 SDNKLSGSIPSQLSRLDRLRRLSLAGNDLSGTIPSELA--RFGGDDFSGNNGLCG----KPLSRCGALNGRNLSIIIVAG 226
Cdd:PLN00113 555 SQNQLSGEIPKNLGNVESLVQVNISHNHLHGSLPSTGAflAINASAVAGNIDLCGgdttSGLPPCKRVRKTPSWWFYITC 634
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445  227 VLGAVgsLCVGLVIFWWFFIR--EGSRKKKgygagKSKDDSDWigllrshklvQVTLFQKPIVK-IKLGDLMAATNNfss 303
Cdd:PLN00113 635 TLGAF--LVLALVAFGFVFIRgrNNLELKR-----VENEDGTW----------ELQFFDSKVSKsITINDILSSLKE--- 694
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445  304 GNIDVSSRTGVSYKA-DLPDGSALAVKRLSACGFGEKQFRSEMnklGELRHPNLVPLLGYCVVEDERLLVYKHmVNGTLF 382
Cdd:PLN00113 695 ENVISRGKKGASYKGkSIKNGMQFVVKEINDVNSIPSSEIADM---GKLQHPNIVKLIGLCRSEKGAYLIHEY-IEGKNL 770
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445  383 SQLHNGglcdavLDWPTRRAIGVGAAKGLAWLHHGCQPPYLHQFISSNVILLDDDFDARITdYGLAKLVgsrdsndsSFN 462
Cdd:PLN00113 771 SEVLRN------LSWERRRKIAIGIAKALRFLHCRCSPAVVVGNLSPEKIIIDGKDEPHLR-LSLPGLL--------CTD 835
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445  463 NGDLGELGYVAPEYSSTMVASLKGDVYGFGIVLLELVTGQKPLSVINGVEgfkGSLVDWvSQYLGTGRSKDA-IDRSICD 541
Cdd:PLN00113 836 TKCFISSAYVAPETRETKDITEKSDIYGFGLILIELLTGKSPADAEFGVH---GSIVEW-ARYCYSDCHLDMwIDPSIRG 911
                        490       500       510
                 ....*....|....*....|....*....|....*....
gi 15223445  542 KG--HDEEILQFLKIACSCVVSRPKERPTMIQVYESLKN 578
Cdd:PLN00113 912 DVsvNQNEIVEVMNLALHCTATDPTARPCANDVLKTLES 950
STYKc smart00221
Protein kinase; unclassified specificity; Phosphotransferases. The specificity of this class ...
327-576 2.12e-26

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: 108.40  E-value: 2.12e-26
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445    327 AVKRL--SACGFGEKQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHNGGlcDAVLDWPTRRAIG 404
Cdd:smart00221  32 AVKTLkeDASEQQIEEFLREARIMRKLDHPNIVKLLGVCTEEEPLMIVMEYMPGGDLLDYLRKNR--PKELSLSDLLSFA 109
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445    405 VGAAKGLAWLHHGcqpPYLHQFISSNVILLDDDFDARITDYGLAKLVGSRDSNDSSfnngdLGELGY--VAPEYSSTMVA 482
Cdd:smart00221 110 LQIARGMEYLESK---NFIHRDLAARNCLVGENLVVKISDFGLSRDLYDDDYYKVK-----GGKLPIrwMAPESLKEGKF 181
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445    483 SLKGDVYGFGIVLLELVT-GQKPLSVINGVEgfkgslvdwVSQYLGTGRSKDAIDRsiCdkgHDEeilqFLKIACSCVVS 561
Cdd:smart00221 182 TSKSDVWSFGVLLWEIFTlGEEPYPGMSNAE---------VLEYLKKGYRLPKPPN--C---PPE----LYKLMLQCWAE 243
                          250
                   ....*....|....*
gi 15223445    562 RPKERPTMIQVYESL 576
Cdd:smart00221 244 DPEDRPTFSELVEIL 258
SPS1 COG0515
Serine/threonine protein kinase [Signal transduction mechanisms];
313-504 1.75e-22

Serine/threonine protein kinase [Signal transduction mechanisms];


Pssm-ID: 440281 [Multi-domain]  Cd Length: 482  Bit Score: 100.86  E-value: 1.75e-22
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 313 GVSYKA-DLPDGSALAVKRLSACGFGE----KQFRSEMNKLGELRHPNLVPLLGYcVVEDERL-LVYKHMVNGTLFSQLH 386
Cdd:COG0515  21 GVVYLArDLRLGRPVALKVLRPELAADpearERFRREARALARLNHPNIVRVYDV-GEEDGRPyLVMEYVEGESLADLLR 99
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 387 NGGlcdaVLDWPTRRAIGVGAAKGLAWLH-HGcqppYLHQFIS-SNvILLDDDFDARITDYGLAKLVGSRDSNDSSFnng 464
Cdd:COG0515 100 RRG----PLPPAEALRILAQLAEALAAAHaAG----IVHRDIKpAN-ILLTPDGRVKLIDFGIARALGGATLTQTGT--- 167
                       170       180       190       200
                ....*....|....*....|....*....|....*....|
gi 15223445 465 DLGELGYVAPEYSSTMVASLKGDVYGFGIVLLELVTGQKP 504
Cdd:COG0515 168 VVGTPGYMAPEQARGEPVDPRSDVYSLGVTLYELLTGRPP 207
PK_Tyr_Ser-Thr pfam07714
Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role ...
327-576 1.22e-21

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: 94.49  E-value: 1.22e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445   327 AVKRLsACGFGEKQ---FRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHNgglCDAVLDWPTRRAI 403
Cdd:pfam07714  32 AVKTL-KEGADEEEredFLEEASIMKKLDHPNIVKLLGVCTQGEPLYIVTEYMPGGDLLDFLRK---HKRKLTLKDLLSM 107
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445   404 GVGAAKGLAWLHHGcqpPYLHQFISSNVILLDDDFDARITDYGLAKLVGSRDSNDSSfnNGDLGELGYVAPEYSSTMVAS 483
Cdd:pfam07714 108 ALQIAKGMEYLESK---NFVHRDLAARNCLVSENLVVKISDFGLSRDIYDDDYYRKR--GGGKLPIKWMAPESLKDGKFT 182
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445   484 LKGDVYGFGIVLLELVT-GQKPLSVINGVEgfkgslvdwVSQYLGTGRskdaidRSICDKGHDEEILQFLKiacSCVVSR 562
Cdd:pfam07714 183 SKSDVWSFGVLLWEIFTlGEQPYPGMSNEE---------VLEFLEDGY------RLPQPENCPDELYDLMK---QCWAYD 244
                         250
                  ....*....|....
gi 15223445   563 PKERPTMIQVYESL 576
Cdd:pfam07714 245 PEDRPTFSELVEDL 258
PLN00113 PLN00113
leucine-rich repeat receptor-like protein kinase; Provisional
4-191 2.99e-20

leucine-rich repeat receptor-like protein kinase; Provisional


Pssm-ID: 215061 [Multi-domain]  Cd Length: 968  Bit Score: 95.30  E-value: 2.99e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445    4 IFITLLWLLFISSFLCssssAEDDVLCLQGLKNSLIDPSSRLSSWSfpnsSASSICKLTGVSCWNEkeNRIISLQL---- 79
Cdd:PLN00113  11 YLIFMLFFLFLNFSML----HAEELELLLSFKSSINDPLKYLSNWN----SSADVCLWQGITCNNS--SRVVSIDLsgkn 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445   80 --------------------QSMQLAGEIPESL-KLCRSLQSLDLSGNDLSGSIPSqicSWLPYLVTLDLSGNKLGGSIP 138
Cdd:PLN00113  81 isgkissaifrlpyiqtinlSNNQLSGPIPDDIfTTSSSLRYLNLSNNNFTGSIPR---GSIPNLETLDLSNNMLSGEIP 157
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 15223445  139 TQIVECKFLNALILSDNKLSGSIPSQLSRLDRLRRLSLAGNDLSGTIPSELAR 191
Cdd:PLN00113 158 NDIGSFSSLKVLDLGGNVLVGKIPNSLTNLTSLEFLTLASNQLVGQIPRELGQ 210
LRR COG4886
Leucine-rich repeat (LRR) protein [Transcription];
53-163 1.37e-10

Leucine-rich repeat (LRR) protein [Transcription];


Pssm-ID: 443914 [Multi-domain]  Cd Length: 414  Bit Score: 63.41  E-value: 1.37e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445  53 SSASSICKLTGVSCWNEKENRIISL--------QLQSMQLAG----EIPESLKLCRSLQSLDLSGNDLSgSIPSQICSwL 120
Cdd:COG4886 104 SGNEELSNLTNLESLDLSGNQLTDLpeelanltNLKELDLSNnqltDLPEPLGNLTNLKSLDLSNNQLT-DLPEELGN-L 181
                        90       100       110       120
                ....*....|....*....|....*....|....*....|...
gi 15223445 121 PYLVTLDLSGNKLgGSIPTQIVECKFLNALILSDNKLSgSIPS 163
Cdd:COG4886 182 TNLKELDLSNNQI-TDLPEPLGNLTNLEELDLSGNQLT-DLPE 222
LRRNT_2 pfam08263
Leucine rich repeat N-terminal domain; Leucine Rich Repeats pfam00560 are short sequence ...
24-67 3.00e-08

Leucine rich repeat N-terminal domain; Leucine Rich Repeats pfam00560 are short sequence motifs present in a number of proteins with diverse functions and cellular locations. Leucine Rich Repeats are often flanked by cysteine rich domains. This domain is often found at the N-terminus of tandem leucine rich repeats.


Pssm-ID: 462411 [Multi-domain]  Cd Length: 41  Bit Score: 49.99  E-value: 3.00e-08
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 15223445    24 AEDDVLCLQGLKNSLIDPSSRLSSWsfpNSSASSICKLTGVSCW 67
Cdd:pfam08263   1 LNDDGQALLAFKSSLNDPPGALSSW---NSSSSDPCSWTGVTCD 41
PknB_PASTA_kin NF033483
Stk1 family PASTA domain-containing Ser/Thr kinase;
341-504 3.17e-05

Stk1 family PASTA domain-containing Ser/Thr kinase;


Pssm-ID: 468045 [Multi-domain]  Cd Length: 563  Bit Score: 46.71  E-value: 3.17e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445  341 FRSEMNKLGELRHPNLVPLlgYCVVEDERLlVYKHM--VNG-TLFSQLHNGG--LCDAVLDWptrrAIGVGAAKGLAwlH 415
Cdd:NF033483  54 FRREAQSAASLSHPNIVSV--YDVGEDGGI-PYIVMeyVDGrTLKDYIREHGplSPEEAVEI----MIQILSALEHA--H 124
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445  416 HgcqppylHQFISSNV----ILLDDDFDARITDYGLAKLVGSrdsndSS--FNNGDLGELGYVAPEYSSTMVASLKGDVY 489
Cdd:NF033483 125 R-------NGIVHRDIkpqnILITKDGRVKVTDFGIARALSS-----TTmtQTNSVLGTVHYLSPEQARGGTVDARSDIY 192
                        170
                 ....*....|....*
gi 15223445  490 GFGIVLLELVTGQKP 504
Cdd:NF033483 193 SLGIVLYEMLTGRPP 207
 
Name Accession Description Interval E-value
STKc_IRAK cd14066
Catalytic domain of the Serine/Threonine kinases, Interleukin-1 Receptor Associated Kinases ...
309-579 2.88e-85

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: 266.83  E-value: 2.88e-85
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 309 SSRTGVSYKADLPDGSALAVKRL--SACGFGEKQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLH 386
Cdd:cd14066   3 SGGFGTVYKGVLENGTVVAVKRLneMNCAASKKEFLTELEMLGRLRHPNLVRLLGYCLESDEKLLVYEYMPNGSLEDRLH 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 387 NGGLCDaVLDWPTRRAIGVGAAKGLAWLHHGCQPPYLHQFISSNVILLDDDFDARITDYGLAKLvgSRDSNDSSFNNGDL 466
Cdd:cd14066  83 CHKGSP-PLPWPQRLKIAKGIARGLEYLHEECPPPIIHGDIKSSNILLDEDFEPKLTDFGLARL--IPPSESVSKTSAVK 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 467 GELGYVAPEYSSTMVASLKGDVYGFGIVLLELVTGQKPLSvINGVEGFKGSLVDWVsQYLGTGRSKDAIDRSI--CDKGH 544
Cdd:cd14066 160 GTIGYLAPEYIRTGRVSTKSDVYSFGVVLLELLTGKPAVD-ENRENASRKDLVEWV-ESKGKEELEDILDKRLvdDDGVE 237
                       250       260       270
                ....*....|....*....|....*....|....*
gi 15223445 545 DEEILQFLKIACSCVVSRPKERPTMIQVYESLKNM 579
Cdd:cd14066 238 EEEVEALLRLALLCTRSDPSLRPSMKEVVQMLEKL 272
STK_BAK1_like cd14664
Catalytic domain of the Serine/Threonine Kinase, BRI1 associated kinase 1 and related STKs; ...
313-578 1.01e-76

Catalytic domain of the Serine/Threonine Kinase, BRI1 associated kinase 1 and related STKs; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes three leucine-rich repeat receptor-like kinases (LRR-RLKs): Arabidopsis thaliana BAK1 and CLAVATA1 (CLV1), and Physcomitrella patens CLL1B clavata1-like receptor S/T protein kinase. BAK1 functions in various signaling pathways. It plays a role in BR (brassinosteroid)-regulated plant development as a co-receptor of BRASSINOSTEROID (BR) INSENSITIVE 1 (BRI1), the receptor for BRs, and is required for full activation of BR signaling. It also modulates pathways involved in plant resistance to pathogen infection (pattern-triggered immunity, PTI) and herbivore attack (wound- or herbivore feeding-induced accumulation of jasmonic acid (JA) and JA-isoleucine. 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 STK_BAK1-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: 271134 [Multi-domain]  Cd Length: 270  Bit Score: 244.71  E-value: 1.01e-76
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 313 GVSYKADLPDGSALAVKRLSACGF--GEKQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHNGGL 390
Cdd:cd14664   7 GTVYKGVMPNGTLVAVKRLKGEGTqgGDHGFQAEIQTLGMIRHRNIVRLRGYCSNPTTNLLVYEYMPNGSLGELLHSRPE 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 391 CDAVLDWPTRRAIGVGAAKGLAWLHHGCQPPYLHQFISSNVILLDDDFDARITDYGLAKLVGSRDSNDSSfnnGDLGELG 470
Cdd:cd14664  87 SQPPLDWETRQRIALGSARGLAYLHHDCSPLIIHRDVKSNNILLDEEFEAHVADFGLAKLMDDKDSHVMS---SVAGSYG 163
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 471 YVAPEYSSTMVASLKGDVYGFGIVLLELVTGQKPLSVINGVEGFkgSLVDWVSQYLGTGRSKDAIDRSICDKGHDEEILQ 550
Cdd:cd14664 164 YIAPEYAYTGKVSEKSDVYSYGVVLLELITGKRPFDEAFLDDGV--DIVDWVRGLLEEKKVEALVDPDLQGVYKLEEVEQ 241
                       250       260
                ....*....|....*....|....*...
gi 15223445 551 FLKIACSCVVSRPKERPTMIQVYESLKN 578
Cdd:cd14664 242 VFQVALLCTQSSPMERPTMREVVRMLEG 269
PLN00113 PLN00113
leucine-rich repeat receptor-like protein kinase; Provisional
73-578 7.67e-46

leucine-rich repeat receptor-like protein kinase; Provisional


Pssm-ID: 215061 [Multi-domain]  Cd Length: 968  Bit Score: 174.27  E-value: 7.67e-46
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445   73 RIISLQLQSMQLAGEIPESLKLCRSLQSLDLSGNDLSGSIPSQICSwLPYLVTLDLSGNKLGGSIPTQIVECKFLNALIL 152
Cdd:PLN00113 476 RLENLDLSRNQFSGAVPRKLGSLSELMQLKLSENKLSGEIPDELSS-CKKLVSLDLSHNQLSGQIPASFSEMPVLSQLDL 554
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445  153 SDNKLSGSIPSQLSRLDRLRRLSLAGNDLSGTIPSELA--RFGGDDFSGNNGLCG----KPLSRCGALNGRNLSIIIVAG 226
Cdd:PLN00113 555 SQNQLSGEIPKNLGNVESLVQVNISHNHLHGSLPSTGAflAINASAVAGNIDLCGgdttSGLPPCKRVRKTPSWWFYITC 634
                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445  227 VLGAVgsLCVGLVIFWWFFIR--EGSRKKKgygagKSKDDSDWigllrshklvQVTLFQKPIVK-IKLGDLMAATNNfss 303
Cdd:PLN00113 635 TLGAF--LVLALVAFGFVFIRgrNNLELKR-----VENEDGTW----------ELQFFDSKVSKsITINDILSSLKE--- 694
                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445  304 GNIDVSSRTGVSYKA-DLPDGSALAVKRLSACGFGEKQFRSEMnklGELRHPNLVPLLGYCVVEDERLLVYKHmVNGTLF 382
Cdd:PLN00113 695 ENVISRGKKGASYKGkSIKNGMQFVVKEINDVNSIPSSEIADM---GKLQHPNIVKLIGLCRSEKGAYLIHEY-IEGKNL 770
                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445  383 SQLHNGglcdavLDWPTRRAIGVGAAKGLAWLHHGCQPPYLHQFISSNVILLDDDFDARITdYGLAKLVgsrdsndsSFN 462
Cdd:PLN00113 771 SEVLRN------LSWERRRKIAIGIAKALRFLHCRCSPAVVVGNLSPEKIIIDGKDEPHLR-LSLPGLL--------CTD 835
                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445  463 NGDLGELGYVAPEYSSTMVASLKGDVYGFGIVLLELVTGQKPLSVINGVEgfkGSLVDWvSQYLGTGRSKDA-IDRSICD 541
Cdd:PLN00113 836 TKCFISSAYVAPETRETKDITEKSDIYGFGLILIELLTGKSPADAEFGVH---GSIVEW-ARYCYSDCHLDMwIDPSIRG 911
                        490       500       510
                 ....*....|....*....|....*....|....*....
gi 15223445  542 KG--HDEEILQFLKIACSCVVSRPKERPTMIQVYESLKN 578
Cdd:PLN00113 912 DVsvNQNEIVEVMNLALHCTATDPTARPCANDVLKTLES 950
STKc_IRAK1 cd14159
Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 1; ...
313-579 8.65e-42

Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 1; 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. IRAK1 plays a role in the activation of IRF3/7, STAT, and NFkB. It mediates IL-6 and IFN-gamma responses following IL-1 and IL-18 stimulation, respectively. It also plays an essential role in IFN-alpha induction downstream of TLR7 and TLR9. The IRAK1 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: 271061 [Multi-domain]  Cd Length: 296  Bit Score: 152.67  E-value: 8.65e-42
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 313 GVSYKADLPDgSALAVKRLSACGFGE-----KQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHN 387
Cdd:cd14159   7 GCVYQAVMRN-TEYAVKRLKEDSELDwsvvkNSFLTEVEKLSRFRHPNIVDLAGYSAQQGNYCLIYVYLPNGSLEDRLHC 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 388 GGLCDAvLDWPTRRAIGVGAAKGLAWLHHgCQPPYLHQFISSNVILLDDDFDARITDYGLAKLV--GSRDSNDSSFNNGD 465
Cdd:cd14159  86 QVSCPC-LSWSQRLHVLLGTARAIQYLHS-DSPSLIHGDVKSSNILLDAALNPKLGDFGLARFSrrPKQPGMSSTLARTQ 163
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 466 L--GELGYVAPEYSSTMVASLKGDVYGFGIVLLELVTGQKPLSViNGVEGFKgSLVDWVSQ-------YLGTGRSKDA-- 534
Cdd:cd14159 164 TvrGTLAYLPEEYVKTGTLSVEIDVYSFGVVLLELLTGRRAMEV-DSCSPTK-YLKDLVKEeeeaqhtPTTMTHSAEAqa 241
                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|....*
gi 15223445 535 --IDRSICDK-------GHDEEILQFL-KIACSCVVSRPKERPTMIQVYESLKNM 579
Cdd:cd14159 242 aqLATSICQKhldpqagPCPPELGIEIsQLACRCLHRRAKKRPPMTEVFQELERL 296
STKc_MAP3K-like cd13999
Catalytic domain of Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase-like Serine ...
323-576 1.33e-36

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: 136.90  E-value: 1.33e-36
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 323 GSALAVKRLSA---CGFGEKQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHNGGLcdaVLDWPT 399
Cdd:cd13999  16 GTDVAIKKLKVeddNDELLKEFRREVSILSKLRHPNIVQFIGACLSPPPLCIVTEYMPGGSLYDLLHKKKI---PLSWSL 92
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 400 RRAIGVGAAKGLAWLHhgcQPPYLHQFISSNVILLDDDFDARITDYGLAKLVgsrdSNDSSFNNGDLGELGYVAPEYSST 479
Cdd:cd13999  93 RLKIALDIARGMNYLH---SPPIIHRDLKSLNILLDENFTVKIADFGLSRIK----NSTTEKMTGVVGTPRWMAPEVLRG 165
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 480 MVASLKGDVYGFGIVLLELVTGQKPlsvingvegFKGSLVDWVSQYLGTGRskdaiDRSICDKGHDEEILQFLKIacsCV 559
Cdd:cd13999 166 EPYTEKADVYSFGIVLWELLTGEVP---------FKELSPIQIAAAVVQKG-----LRPPIPPDCPPELSKLIKR---CW 228
                       250
                ....*....|....*..
gi 15223445 560 VSRPKERPTMIQVYESL 576
Cdd:cd13999 229 NEDPEKRPSFSEIVKRL 245
STKc_IRAK4 cd14158
Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 4; ...
293-579 1.15e-32

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: 127.23  E-value: 1.15e-32
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 293 DLMAATNNF------SSGNIDVSSRTGVSYKADLPDgSALAVKRLSACGFGE-----KQFRSEMNKLGELRHPNLVPLLG 361
Cdd:cd14158   3 ELKNMTNNFderpisVGGNKLGEGGFGVVFKGYIND-KNVAVKKLAAMVDIStedltKQFEQEIQVMAKCQHENLVELLG 81
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 362 YCVVEDERLLVYKHMVNGTLFSQLH--NGGLcdaVLDWPTRRAIGVGAAKGLAWLHhgcQPPYLHQFISSNVILLDDDFD 439
Cdd:cd14158  82 YSCDGPQLCLVYTYMPNGSLLDRLAclNDTP---PLSWHMRCKIAQGTANGINYLH---ENNHIHRDIKSANILLDETFV 155
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 440 ARITDYGLAKlvGSRDSNDSSFNNGDLGELGYVAPEYSSTMVaSLKGDVYGFGIVLLELVTGQKP----------LSVIN 509
Cdd:cd14158 156 PKISDFGLAR--ASEKFSQTIMTERIVGTTAYMAPEALRGEI-TPKSDIFSFGVVLLEIITGLPPvdenrdpqllLDIKE 232
                       250       260       270       280       290       300       310
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 510 GVEGFKGSLVDWVSQYLGTGRSkdaidrsicdkghdEEILQFLKIACSCVVSRPKERPTMIQVYESLKNM 579
Cdd:cd14158 233 EIEDEEKTIEDYVDKKMGDWDS--------------TSIEAMYSVASQCLNDKKNRRPDIAKVQQLLQEL 288
STKc_RIP cd13978
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein; STKs catalyze ...
344-572 7.52e-28

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: 112.93  E-value: 7.52e-28
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 344 EMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHnggLCDAVLDWPTRRAIGVGAAKGLAWLHHgCQPPYL 423
Cdd:cd13978  42 EAEKMERARHSYVLPLLGVCVERRSLGLVMEYMENGSLKSLLE---REIQDVPWSLRFRIIHEIALGMNFLHN-MDPPLL 117
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 424 HQFISSNVILLDDDFDARITDYGLAKLVGSRDSNDSSFNNGDL-GELGYVAPEYSSTMVA--SLKGDVYGFGIVLLELVT 500
Cdd:cd13978 118 HHDLKPENILLDNHFHVKISDFGLSKLGMKSISANRRRGTENLgGTPIYMAPEAFDDFNKkpTSKSDVYSFAIVIWAVLT 197
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 15223445 501 GQKPLsvingvEGFKGSLVDWVSQYLGTGRSKDAIDRsICDKGHDEEILQFLKiacSCVVSRPKERPTMIQV 572
Cdd:cd13978 198 RKEPF------ENAINPLLIMQIVSKGDRPSLDDIGR-LKQIENVQELISLMI---RCWDGNPDARPTFLEC 259
PK_IRAK3 cd14160
Pseudokinase domain of Interleukin-1 Receptor Associated Kinase 3; The pseudokinase domain ...
339-576 4.78e-27

Pseudokinase domain of Interleukin-1 Receptor Associated Kinase 3; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. 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 (a pseudokinase in the case of IRAK3), 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. IRAK3 (or IRAK-M) is the only IRAK that does not show kinase activity. It is found only in monocytes and macrophages in humans, and functions as a negative regulator of TLR signaling including TLR-2 induced p38 activation. It also negatively regulates the alternative NFkB pathway in a TLR-2 specific manner. IRAK3 is downregulated in the monocytes of obese people, and is associated with high SOD2, a marker of mitochondrial oxidative stress. It is an important inhibitor of inflammation in association with obesity and metabolic syndrome. The IRAK3 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: 271062 [Multi-domain]  Cd Length: 276  Bit Score: 110.74  E-value: 4.78e-27
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 339 KQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHNGGLcDAVLDWPTRRAIGVGAAKGLAWLHHGC 418
Cdd:cd14160  37 KRFLSELEVLLLFQHPNILELAAYFTETEKFCLVYPYMQNGTLFDRLQCHGV-TKPLSWHERINILIGIAKAIHYLHNSQ 115
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 419 QPPYLHQFISSNVILLDDDFDARITDYGLAKLVGSRDSNDSSFN--NGDLGELGYVAPEYSSTMVASLKGDVYGFGIVLL 496
Cdd:cd14160 116 PCTVICGNISSANILLDDQMQPKLTDFALAHFRPHLEDQSCTINmtTALHKHLWYMPEEYIRQGKLSVKTDVYSFGIVIM 195
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 497 ELVTGQKPLsvingVEGFKGSLVDWVSQYLGTGRSKDA----IDRSI--CDKGHDeeiLQFLKIACSCVVSRPKERPTMI 570
Cdd:cd14160 196 EVLTGCKVV-----LDDPKHLQLRDLLHELMEKRGLDSclsfLDLKFppCPRNFS---AKLFRLAGRCTATKAKLRPDMD 267

                ....*.
gi 15223445 571 QVYESL 576
Cdd:cd14160 268 EVLQRL 273
STYKc smart00221
Protein kinase; unclassified specificity; Phosphotransferases. The specificity of this class ...
327-576 2.12e-26

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: 108.40  E-value: 2.12e-26
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445    327 AVKRL--SACGFGEKQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHNGGlcDAVLDWPTRRAIG 404
Cdd:smart00221  32 AVKTLkeDASEQQIEEFLREARIMRKLDHPNIVKLLGVCTEEEPLMIVMEYMPGGDLLDYLRKNR--PKELSLSDLLSFA 109
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445    405 VGAAKGLAWLHHGcqpPYLHQFISSNVILLDDDFDARITDYGLAKLVGSRDSNDSSfnngdLGELGY--VAPEYSSTMVA 482
Cdd:smart00221 110 LQIARGMEYLESK---NFIHRDLAARNCLVGENLVVKISDFGLSRDLYDDDYYKVK-----GGKLPIrwMAPESLKEGKF 181
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445    483 SLKGDVYGFGIVLLELVT-GQKPLSVINGVEgfkgslvdwVSQYLGTGRSKDAIDRsiCdkgHDEeilqFLKIACSCVVS 561
Cdd:smart00221 182 TSKSDVWSFGVLLWEIFTlGEEPYPGMSNAE---------VLEYLKKGYRLPKPPN--C---PPE----LYKLMLQCWAE 243
                          250
                   ....*....|....*
gi 15223445    562 RPKERPTMIQVYESL 576
Cdd:smart00221 244 DPEDRPTFSELVEIL 258
TyrKc smart00219
Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.
327-576 2.91e-26

Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.


Pssm-ID: 197581 [Multi-domain]  Cd Length: 257  Bit Score: 108.00  E-value: 2.91e-26
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445    327 AVKRLSACGFGE--KQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHNgglCDAVLDWPTRRAIG 404
Cdd:smart00219  32 AVKTLKEDASEQqiEEFLREARIMRKLDHPNVVKLLGVCTEEEPLYIVMEYMEGGDLLSYLRK---NRPKLSLSDLLSFA 108
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445    405 VGAAKGLAWLHHGcqpPYLHQFISSNVILLDDDFDARITDYGLAKLVGSRDSNDSsfnngDLGELGY--VAPEYSSTMVA 482
Cdd:smart00219 109 LQIARGMEYLESK---NFIHRDLAARNCLVGENLVVKISDFGLSRDLYDDDYYRK-----RGGKLPIrwMAPESLKEGKF 180
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445    483 SLKGDVYGFGIVLLELVT-GQKPLSVINGVEgfkgslvdwVSQYLGTGRSKDAIDRsiCdkgHDEeilqFLKIACSCVVS 561
Cdd:smart00219 181 TSKSDVWSFGVLLWEIFTlGEQPYPGMSNEE---------VLEYLKNGYRLPQPPN--C---PPE----LYDLMLQCWAE 242
                          250
                   ....*....|....*
gi 15223445    562 RPKERPTMIQVYESL 576
Cdd:smart00219 243 DPEDRPTFSELVEIL 257
PTKc cd00192
Catalytic domain of Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
327-577 5.47e-23

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: 98.77  E-value: 5.47e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 327 AVKRLSACGFGE--KQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTL--F---SQLHNGGLCDAVLDWPT 399
Cdd:cd00192  27 AVKTLKEDASESerKDFLKEARVMKKLGHPNVVRLLGVCTEEEPLYLVMEYMEGGDLldFlrkSRPVFPSPEPSTLSLKD 106
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 400 RRAIGVGAAKGLAWLHhgcQPPYLHQFISSNVILLDDDFDARITDYGLaklvgSRDSNDSsfNNGDLGELG-----YVAP 474
Cdd:cd00192 107 LLSFAIQIAKGMEYLA---SKKFVHRDLAARNCLVGEDLVVKISDFGL-----SRDIYDD--DYYRKKTGGklpirWMAP 176
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 475 EYSSTMVASLKGDVYGFGIVLLELVT-GQKPLSVINGVEgfkgslvdwVSQYLGTGRskdAIDR-SICdkghDEEILQFL 552
Cdd:cd00192 177 ESLKDGIFTSKSDVWSFGVLLWEIFTlGATPYPGLSNEE---------VLEYLRKGY---RLPKpENC----PDELYELM 240
                       250       260
                ....*....|....*....|....*
gi 15223445 553 KiacSCVVSRPKERPTMIQVYESLK 577
Cdd:cd00192 241 L---SCWQLDPEDRPTFSELVERLE 262
PKc cd00180
Catalytic domain of Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group ...
313-498 9.09e-23

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: 96.96  E-value: 9.09e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 313 GVSYKA-DLPDGSALAVKRLSACGFGE--KQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHNgg 389
Cdd:cd00180   7 GKVYKArDKETGKKVAVKVIPKEKLKKllEELLREIEILKKLNHPNIVKLYDVFETENFLYLVMEYCEGGSLKDLLKE-- 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 390 lCDAVLDWPTRRAIGVGAAKGLAWLHHgcqppylHQFI-----SSNvILLDDDFDARITDYGLAKLVGSRDSNDSSFNNG 464
Cdd:cd00180  85 -NKGPLSEEEALSILRQLLSALEYLHS-------NGIIhrdlkPEN-ILLDSDGTVKLADFGLAKDLDSDDSLLKTTGGT 155
                       170       180       190
                ....*....|....*....|....*....|....
gi 15223445 465 dlGELGYVAPEYSSTMVASLKGDVYGFGIVLLEL 498
Cdd:cd00180 156 --TPPYYAPPELLGGRYYGPKVDIWSLGVILYEL 187
SPS1 COG0515
Serine/threonine protein kinase [Signal transduction mechanisms];
313-504 1.75e-22

Serine/threonine protein kinase [Signal transduction mechanisms];


Pssm-ID: 440281 [Multi-domain]  Cd Length: 482  Bit Score: 100.86  E-value: 1.75e-22
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 313 GVSYKA-DLPDGSALAVKRLSACGFGE----KQFRSEMNKLGELRHPNLVPLLGYcVVEDERL-LVYKHMVNGTLFSQLH 386
Cdd:COG0515  21 GVVYLArDLRLGRPVALKVLRPELAADpearERFRREARALARLNHPNIVRVYDV-GEEDGRPyLVMEYVEGESLADLLR 99
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 387 NGGlcdaVLDWPTRRAIGVGAAKGLAWLH-HGcqppYLHQFIS-SNvILLDDDFDARITDYGLAKLVGSRDSNDSSFnng 464
Cdd:COG0515 100 RRG----PLPPAEALRILAQLAEALAAAHaAG----IVHRDIKpAN-ILLTPDGRVKLIDFGIARALGGATLTQTGT--- 167
                       170       180       190       200
                ....*....|....*....|....*....|....*....|
gi 15223445 465 DLGELGYVAPEYSSTMVASLKGDVYGFGIVLLELVTGQKP 504
Cdd:COG0515 168 VVGTPGYMAPEQARGEPVDPRSDVYSLGVTLYELLTGRPP 207
PK_Tyr_Ser-Thr pfam07714
Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role ...
327-576 1.22e-21

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: 94.49  E-value: 1.22e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445   327 AVKRLsACGFGEKQ---FRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHNgglCDAVLDWPTRRAI 403
Cdd:pfam07714  32 AVKTL-KEGADEEEredFLEEASIMKKLDHPNIVKLLGVCTQGEPLYIVTEYMPGGDLLDFLRK---HKRKLTLKDLLSM 107
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445   404 GVGAAKGLAWLHHGcqpPYLHQFISSNVILLDDDFDARITDYGLAKLVGSRDSNDSSfnNGDLGELGYVAPEYSSTMVAS 483
Cdd:pfam07714 108 ALQIAKGMEYLESK---NFVHRDLAARNCLVSENLVVKISDFGLSRDIYDDDYYRKR--GGGKLPIKWMAPESLKDGKFT 182
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445   484 LKGDVYGFGIVLLELVT-GQKPLSVINGVEgfkgslvdwVSQYLGTGRskdaidRSICDKGHDEEILQFLKiacSCVVSR 562
Cdd:pfam07714 183 SKSDVWSFGVLLWEIFTlGEQPYPGMSNEE---------VLEFLEDGY------RLPQPENCPDELYDLMK---QCWAYD 244
                         250
                  ....*....|....
gi 15223445   563 PKERPTMIQVYESL 576
Cdd:pfam07714 245 PEDRPTFSELVEDL 258
STKc_PknB_like cd14014
Catalytic domain of bacterial Serine/Threonine kinases, PknB and similar proteins; STKs ...
312-504 1.30e-21

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: 94.58  E-value: 1.30e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 312 TGVSYKA-DLPDGSALAVKRLSACGFGEKQFRS----EMNKLGELRHPNLVPLLGYcVVEDERL-LVYKHMVNGTLFSQL 385
Cdd:cd14014  13 MGEVYRArDTLLGRPVAIKVLRPELAEDEEFRErflrEARALARLSHPNIVRVYDV-GEDDGRPyIVMEYVEGGSLADLL 91
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 386 HNGGLcdavLDWPTRRAIGVGAAKGLAWLH-HGCqppyLHQFIS-SNvILLDDDFDARITDYGLAKLVGSRDSNDSSFNn 463
Cdd:cd14014  92 RERGP----LPPREALRILAQIADALAAAHrAGI----VHRDIKpAN-ILLTEDGRVKLTDFGIARALGDSGLTQTGSV- 161
                       170       180       190       200
                ....*....|....*....|....*....|....*....|.
gi 15223445 464 gdLGELGYVAPEYSSTMVASLKGDVYGFGIVLLELVTGQKP 504
Cdd:cd14014 162 --LGTPAYMAPEQARGGPVDPRSDIYSLGVVLYELLTGRPP 200
PKc_TNNI3K cd14064
Catalytic domain of the Dual-specificity protein kinase, TNNI3-interacting kinase; ...
323-506 5.61e-21

Catalytic domain of the Dual-specificity protein kinase, TNNI3-interacting 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. TNNI3K, also called cardiac ankyrin repeat kinase (CARK), is a cardiac-specific troponin I-interacting kinase that promotes cardiac myogenesis, improves cardiac performance, and protects the myocardium from ischemic injury. It contains N-terminal ankyrin repeats, a catalytic kinase domain, and a C-terminal serine-rich domain. TNNI3K exerts a disease-accelerating effect on cardiac dysfunction and reduced survival in mouse models of cardiomyopathy. The TNNI3K 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: 270966 [Multi-domain]  Cd Length: 254  Bit Score: 92.59  E-value: 5.61e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 323 GSALAVKRLSACGFGEKQ----FRSEMNKLGELRHPNLVPLLGYCVVEDERL-LVYKHMVNGTLFSQLHNGglcDAVLDW 397
Cdd:cd14064  16 NKIVAIKRYRANTYCSKSdvdmFCREVSILCRLNHPCVIQFVGACLDDPSQFaIVTQYVSGGSLFSLLHEQ---KRVIDL 92
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 398 PTRRAIGVGAAKGLAWLHHGCQPpYLHQFISSNVILLDDDFDARITDYGLAKLVGSRDSNDSSFNNGDlgeLGYVAPE-Y 476
Cdd:cd14064  93 QSKLIIAVDVAKGMEYLHNLTQP-IIHRDLNSHNILLYEDGHAVVADFGESRFLQSLDEDNMTKQPGN---LRWMAPEvF 168
                       170       180       190
                ....*....|....*....|....*....|
gi 15223445 477 SSTMVASLKGDVYGFGIVLLELVTGQKPLS 506
Cdd:cd14064 169 TQCTRYSIKADVFSYALCLWELLTGEIPFA 198
PLN00113 PLN00113
leucine-rich repeat receptor-like protein kinase; Provisional
4-191 2.99e-20

leucine-rich repeat receptor-like protein kinase; Provisional


Pssm-ID: 215061 [Multi-domain]  Cd Length: 968  Bit Score: 95.30  E-value: 2.99e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445    4 IFITLLWLLFISSFLCssssAEDDVLCLQGLKNSLIDPSSRLSSWSfpnsSASSICKLTGVSCWNEkeNRIISLQL---- 79
Cdd:PLN00113  11 YLIFMLFFLFLNFSML----HAEELELLLSFKSSINDPLKYLSNWN----SSADVCLWQGITCNNS--SRVVSIDLsgkn 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445   80 --------------------QSMQLAGEIPESL-KLCRSLQSLDLSGNDLSGSIPSqicSWLPYLVTLDLSGNKLGGSIP 138
Cdd:PLN00113  81 isgkissaifrlpyiqtinlSNNQLSGPIPDDIfTTSSSLRYLNLSNNNFTGSIPR---GSIPNLETLDLSNNMLSGEIP 157
                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|...
gi 15223445  139 TQIVECKFLNALILSDNKLSGSIPSQLSRLDRLRRLSLAGNDLSGTIPSELAR 191
Cdd:PLN00113 158 NDIGSFSSLKVLDLGGNVLVGKIPNSLTNLTSLEFLTLASNQLVGQIPRELGQ 210
S_TKc smart00220
Serine/Threonine protein kinases, catalytic domain; Phosphotransferases. Serine or ...
313-572 1.72e-18

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


Pssm-ID: 214567 [Multi-domain]  Cd Length: 254  Bit Score: 85.27  E-value: 1.72e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445    313 GVSYKA-DLPDGSALAVK--RLSACGFGEKQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLH-NG 388
Cdd:smart00220  13 GKVYLArDKKTGKLVAIKviKKKKIKKDRERILREIKILKKLKHPNIVRLYDVFEDEDKLYLVMEYCEGGDLFDLLKkRG 92
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445    389 GLCDAVLdwptrRAIGVGAAKGLAWLHHgcqppylHQFI-----SSNvILLDDDFDARITDYGLAKLVGSRDSNDSSFnn 463
Cdd:smart00220  93 RLSEDEA-----RFYLRQILSALEYLHS-------KGIVhrdlkPEN-ILLDEDGHVKLADFGLARQLDPGEKLTTFV-- 157
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445    464 gdlGELGYVAPE------YSStmvaslKGDVYGFGIVLLELVTGQKPlsvingvegFKGSL-VDWVSQYLGTGRSKDAID 536
Cdd:smart00220 158 ---GTPEYMAPEvllgkgYGK------AVDIWSLGVILYELLTGKPP---------FPGDDqLLELFKKIGKPKPPFPPP 219
                          250       260       270
                   ....*....|....*....|....*....|....*.
gi 15223445    537 RSICdkghDEEILQFLKiacSCVVSRPKERPTMIQV 572
Cdd:smart00220 220 EWDI----SPEAKDLIR---KLLVKDPEKRLTAEEA 248
PK_GC cd13992
Pseudokinase domain of membrane Guanylate Cyclase receptors; The pseudokinase domain shows ...
309-504 1.84e-18

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: 85.52  E-value: 1.84e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 309 SSRTGVS---YKADLPDGSALAVKRLSACGFGEKQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQL 385
Cdd:cd13992   8 SSHTGEPkyvKKVGVYGGRTVAIKHITFSRTEKRTILQELNQLKELVHDNLNKFIGICINPPNIAVVTEYCTRGSLQDVL 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 386 HNGglcDAVLDWPTRRAIGVGAAKGLAWLHHgcQPPYLHQFISSNVILLDDDFDARITDYGLAKLVGSRDSNDSSFNNGD 465
Cdd:cd13992  88 LNR---EIKMDWMFKSSFIKDIVKGMNYLHS--SSIGYHGRLKSSNCLVDSRWVVKLTDFGLRNLLEEQTNHQLDEDAQH 162
                       170       180       190       200
                ....*....|....*....|....*....|....*....|...
gi 15223445 466 LGELgYVAPE----YSSTMVASLKGDVYGFGIVLLELVTGQKP 504
Cdd:cd13992 163 KKLL-WTAPEllrgSLLEVRGTQKGDVYSFAIILYEILFRSDP 204
STKc_RIP4_like cd14025
Catalytic domain of the Serine/Threonine kinases, Receptor Interacting Protein 4 and similar ...
344-572 3.97e-18

Catalytic domain of the Serine/Threonine kinases, Receptor Interacting Protein 4 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of RIP4, ankyrin (ANK) repeat and kinase domain containing 1 (ANKK1), and similar proteins, all of which harbor C-terminal ANK repeats. RIP4, also called Protein Kinase C-associated kinase (PKK), regulates keratinocyte differentiation and cutaneous inflammation. It activates NF-kappaB and is important in the survival of diffuse large B-cell lymphoma cells. The ANKK1 protein, also called PKK2, has not been studied extensively. The ANKK1 gene, located less than 10kb downstream of the D2 dopamine receptor (DRD2) locus, is altered in the Taq1 A1 polymorphism, which is related to a reduced DRD2 binding affinity and consequently, to mental disorders. The RIP4-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: 270927 [Multi-domain]  Cd Length: 267  Bit Score: 84.47  E-value: 3.97e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 344 EMNKLGELRHPNLVPLLGYCvvEDERLLVYKHMVNGTLFSQLHNGGLCdavldWPTRRAIGVGAAKGLAWLHhGCQPPYL 423
Cdd:cd14025  45 EAKKMEMAKFRHILPVYGIC--SEPVGLVMEYMETGSLEKLLASEPLP-----WELRFRIIHETAVGMNFLH-CMKPPLL 116
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 424 HQFISSNVILLDDDFDARITDYGLAKLVGSRDSNDSSfNNGDLGELGYVAPE--YSSTMVASLKGDVYGFGIVLLELVTG 501
Cdd:cd14025 117 HLDLKPANILLDAHYHVKISDFGLAKWNGLSHSHDLS-RDGLRGTIAYLPPErfKEKNRCPDTKHDVYSFAIVIWGILTQ 195
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 15223445 502 QKPLSvingveGFKGSLVDWVSQYLGTGRSKDAIDRSicdkgHDEEILQFLKIACSCVVSRPKERPTMIQV 572
Cdd:cd14025 196 KKPFA------GENNILHIMVKVVKGHRPSLSPIPRQ-----RPSECQQMICLMKRCWDQDPRKRPTFQDI 255
STKc_MLK cd14061
Catalytic domain of the Serine/Threonine Kinases, Mixed Lineage Kinases; STKs catalyze the ...
338-579 1.30e-16

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: 80.13  E-value: 1.30e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 338 EKQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHNGGLCDAVL-DWptrrAIGVgaAKGLAWLHH 416
Cdd:cd14061  37 LENVRQEARLFWMLRHPNIIALRGVCLQPPNLCLVMEYARGGALNRVLAGRKIPPHVLvDW----AIQI--ARGMNYLHN 110
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 417 GCQPPYLHQFISSNVILL------DDDFDA--RITDYGLAKLVGSRDSNDSSfnngdlGELGYVAPEYSSTMVASLKGDV 488
Cdd:cd14061 111 EAPVPIIHRDLKSSNILIleaienEDLENKtlKITDFGLAREWHKTTRMSAA------GTYAWMAPEVIKSSTFSKASDV 184
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 489 YGFGIVLLELVTGQKPlsvingvegFKGslVDWVSQYLGTGRSKDAID-RSICdkghDEEILQFLKiacSCVVSRPKERP 567
Cdd:cd14061 185 WSYGVLLWELLTGEVP---------YKG--IDGLAVAYGVAVNKLTLPiPSTC----PEPFAQLMK---DCWQPDPHDRP 246
                       250
                ....*....|..
gi 15223445 568 TMIQVYESLKNM 579
Cdd:cd14061 247 SFADILKQLENI 258
STKc_RIP2 cd14026
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 2; STKs catalyze ...
344-509 1.74e-16

Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RIP2, also called RICK or CARDIAK, harbors a C-terminal Caspase Activation and Recruitment domain (CARD) belonging to the Death domain (DD) superfamily. It functions as an effector kinase downstream of the pattern recognition receptors from the Nod-like (NLR) family, Nod1 and Nod2, which recognizes bacterial peptidoglycans released upon infection. RIP2 may also be involved in regulating wound healing and keratinocyte proliferation. RIP kinases serve as essential sensors of cellular stress. The RIP2 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: 270928 [Multi-domain]  Cd Length: 284  Bit Score: 79.96  E-value: 1.74e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 344 EMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHNGGLCDAVLdWPTRRAIGVGAAKGLAWLHHgCQPPYL 423
Cdd:cd14026  47 EAEILHKARFSYILPILGICNEPEFLGIVTEYMTNGSLNELLHEKDIYPDVA-WPLRLRILYEIALGVNYLHN-MSPPLL 124
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 424 HQFISSNVILLDDDFDARITDYGLAK---LVGSRDSNDSSFNNGdlGELGYVAPEY---SSTMVASLKGDVYGFGIVLLE 497
Cdd:cd14026 125 HHDLKTQNILLDGEFHVKIADFGLSKwrqLSISQSRSSKSAPEG--GTIIYMPPEEyepSQKRRASVKHDIYSYAIIMWE 202
                       170
                ....*....|...
gi 15223445 498 LVTGQKPLS-VIN 509
Cdd:cd14026 203 VLSRKIPFEeVTN 215
PK_GC_unk cd14045
Pseudokinase domain of the unknown subfamily of membrane Guanylate Cyclase receptors; The ...
322-579 1.95e-16

Pseudokinase domain of the unknown subfamily 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: 270947 [Multi-domain]  Cd Length: 269  Bit Score: 79.52  E-value: 1.95e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 322 DGSALAVKRLSACGFG-EKQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHNGglcDAVLDWPTR 400
Cdd:cd14045  29 DGRTVAIKKIAKKSFTlSKRIRKEVKQVRELDHPNLCKFIGGCIEVPNVAIITEYCPKGSLNDVLLNE---DIPLNWGFR 105
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 401 RAIGVGAAKGLAWLHHGcqpPYLHQFISSNVILLDDDFDARITDYGLAKLVGSRDSNDSSFNNGDLGELgYVAPE-YSST 479
Cdd:cd14045 106 FSFATDIARGMAYLHQH---KIYHGRLKSSNCVIDDRWVCKIADYGLTTYRKEDGSENASGYQQRLMQV-YLPPEnHSNT 181
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 480 MV-ASLKGDVYGFGIVLLELVTGQKPL--SVINGVEGFKGSLVDWVsqylgtgrSKDAIDRSICDKGHDEEILQflkiac 556
Cdd:cd14045 182 DTePTQATDVYSYAIILLEIATRNDPVpeDDYSLDEAWCPPLPELI--------SGKTENSCPCPADYVELIRR------ 247
                       250       260
                ....*....|....*....|...
gi 15223445 557 sCVVSRPKERPTMIQVYESLKNM 579
Cdd:cd14045 248 -CRKNNPAQRPTFEQIKKTLHKI 269
PTKc_Frk_like cd05068
Catalytic domain of Fyn-related kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
327-577 3.41e-16

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: 78.99  E-value: 3.41e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 327 AVKRLSACGFGEKQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHNGGlcdAVLDWPTRRAIGVG 406
Cdd:cd05068  36 AVKTLKPGTMDPEDFLREAQIMKKLRHPKLIQLYAVCTLEEPIYIITELMKHGSLLEYLQGKG---RSLQLPQLIDMAAQ 112
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 407 AAKGLAWLHhgcQPPYLHQFISSNVILLDDDFDARITDYGLAKLVGSRDSNDSsfNNGDLGELGYVAPEYSSTMVASLKG 486
Cdd:cd05068 113 VASGMAYLE---SQNYIHRDLAARNVLVGENNICKVADFGLARVIKVEDEYEA--REGAKFPIKWTAPEAANYNRFSIKS 187
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 487 DVYGFGIVLLELVT-GQKPLSVINGVEgfkgslvdwVSQYLGTGRskdaidRSICDKGHDEeilQFLKIACSCVVSRPKE 565
Cdd:cd05068 188 DVWSFGILLTEIVTyGRIPYPGMTNAE---------VLQQVERGY------RMPCPPNCPP---QLYDIMLECWKADPME 249
                       250
                ....*....|..
gi 15223445 566 RPTmiqvYESLK 577
Cdd:cd05068 250 RPT----FETLQ 257
PTKc_Lck_Blk cd05067
Catalytic domain of the Protein Tyrosine Kinases, Lymphocyte-specific kinase and Blk; PTKs ...
326-579 1.15e-15

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: 77.23  E-value: 1.15e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 326 LAVKRLSACGFGEKQFRSEMNKLGELRHPNLVPLlgYCVVEDERL-LVYKHMVNGTLFSQLHNgglcDAVLDWPTRRAIG 404
Cdd:cd05067  34 VAIKSLKQGSMSPDAFLAEANLMKQLQHQRLVRL--YAVVTQEPIyIITEYMENGSLVDFLKT----PSGIKLTINKLLD 107
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 405 VGA--AKGLAWLHhgcQPPYLHQFISSNVILLDDDFDARITDYGLAKLVgsrDSNDSSFNNGDLGELGYVAPEYSSTMVA 482
Cdd:cd05067 108 MAAqiAEGMAFIE---ERNYIHRDLRAANILVSDTLSCKIADFGLARLI---EDNEYTAREGAKFPIKWTAPEAINYGTF 181
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 483 SLKGDVYGFGIVLLELVT-GQKPLSVINGVEgfkgslvdwVSQYLGTGRskdaidRSICDKGHDEEILQFLKiacSCVVS 561
Cdd:cd05067 182 TIKSDVWSFGILLTEIVThGRIPYPGMTNPE---------VIQNLERGY------RMPRPDNCPEELYQLMR---LCWKE 243
                       250
                ....*....|....*...
gi 15223445 562 RPKERPTmiqvYESLKNM 579
Cdd:cd05067 244 RPEDRPT----FEYLRSV 257
STKc_Raf cd14062
Catalytic domain of the Serine/Threonine Kinases, Raf (Rapidly Accelerated Fibrosarcoma) ...
327-576 2.05e-15

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: 76.28  E-value: 2.05e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 327 AVKRLSACGFGEKQ---FRSEMNKLGELRHPNLVPLLGyCVVEDERLLVYKHMVNGTLFSQLHnggLCDAVLDWPTRRAI 403
Cdd:cd14062  19 AVKKLNVTDPTPSQlqaFKNEVAVLRKTRHVNILLFMG-YMTKPQLAIVTQWCEGSSLYKHLH---VLETKFEMLQLIDI 94
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 404 GVGAAKGLAWLHhgcQPPYLHQFISSNVILLDDDFDARITDYGLAKlVGSRDSNDSSFNNgDLGELGYVAPEYSSTMVA- 482
Cdd:cd14062  95 ARQTAQGMDYLH---AKNIIHRDLKSNNIFLHEDLTVKIGDFGLAT-VKTRWSGSQQFEQ-PTGSILWMAPEVIRMQDEn 169
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 483 --SLKGDVYGFGIVLLELVTGQKPLSVINGvegfKGSLVDWVSQ-YLGTGRSKdaiDRSICDKghdeeilQFLKIACSCV 559
Cdd:cd14062 170 pySFQSDVYAFGIVLYELLTGQLPYSHINN----RDQILFMVGRgYLRPDLSK---VRSDTPK-------ALRRLMEDCI 235
                       250
                ....*....|....*..
gi 15223445 560 VSRPKERPTMIQVYESL 576
Cdd:cd14062 236 KFQRDERPLFPQILASL 252
PK_GC-2D cd14043
Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-2D; The pseudokinase domain ...
309-504 2.20e-15

Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-2D; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity and/or ATP binding. GC-2D is allso called Retinal Guanylyl Cyclase 1 (RETGC-1) or Rod Outer Segment membrane Guanylate Cyclase (ROS-GC). It is found in the photoreceptors of the retina where it anchors the reciprocal feedback loop between calcium and cGMP, which regulates the dark, light, and recovery phases in phototransduction. It is also found in other sensory neurons and may be a universal transduction component that plays a role in the perception of all senses. 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 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-2D 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: 270945 [Multi-domain]  Cd Length: 267  Bit Score: 76.68  E-value: 2.20e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 309 SSRTGVSYKAD------LPDGSALAVKRLSacgfgekqfRSEMNKLGELRHPNLVPLLGyCVVEDERL-LVYKHMVNGTL 381
Cdd:cd14043  14 SSNTGVAYEGDwvwlkkFPGGSHTELRPST---------KNVFSKLRELRHENVNLFLG-LFVDCGILaIVSEHCSRGSL 83
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 382 FSQLHNGglcDAVLDWPTRRAIGVGAAKGLAWLHHgcqPPYLHQFISSNVILLDDDFDARITDYGLAKLVGSRDSndsSF 461
Cdd:cd14043  84 EDLLRND---DMKLDWMFKSSLLLDLIKGMRYLHH---RGIVHGRLKSRNCVVDGRFVLKITDYGYNEILEAQNL---PL 154
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*..
gi 15223445 462 NNGDLGELGYVAPEYSSTMV----ASLKGDVYGFGIVLLELVTGQKP 504
Cdd:cd14043 155 PEPAPEELLWTAPELLRDPRlerrGTFPGDVFSFAIIMQEVIVRGAP 201
STKc_LRRK cd14000
Catalytic domain of the Serine/Threonine kinase, Leucine-Rich Repeat Kinase; STKs catalyze the ...
315-577 2.38e-15

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: 76.50  E-value: 2.38e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 315 SYKADLPDGSALAVKRLSACGFGEKQFRSEMNKLGELRHPNLVPLLGYCVveDERLLVYKHMVNGTLFSQLHNGGLCDAV 394
Cdd:cd14000  31 SNFANVPADTMLRHLRATDAMKNFRLLRQELTVLSHLHHPSIVYLLGIGI--HPLMLVLELAPLGSLDHLLQQDSRSFAS 108
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 395 LDWPTRRAIGVGAAKGLAWLHHgcQPPYLHQFISSNVILLDDD----FDARITDYGLAKlvgsrdsndSSFNNGDL---G 467
Cdd:cd14000 109 LGRTLQQRIALQVADGLRYLHS--AMIIYRDLKSHNVLVWTLYpnsaIIIKIADYGISR---------QCCRMGAKgseG 177
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 468 ELGYVAPEYSS-TMVASLKGDVYGFGIVLLELVTGQKPLSvinGVEGFKgslvdwvSQYLGTGRSKDAIDRSICDKGHDE 546
Cdd:cd14000 178 TPGFRAPEIARgNVIYNEKVDVFSFGMLLYEILSGGAPMV---GHLKFP-------NEFDIHGGLRPPLKQYECAPWPEV 247
                       250       260       270
                ....*....|....*....|....*....|.
gi 15223445 547 EILQFLkiacsCVVSRPKERPTMIQVYESLK 577
Cdd:cd14000 248 EVLMKK-----CWKENPQQRPTAVTVVSILN 273
PTKc_Src_like cd05034
Catalytic domain of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of ...
327-581 2.42e-15

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: 76.17  E-value: 2.42e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 327 AVKRLSACGFGEKQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHNGGlcDAVLDWPTRRAIGVG 406
Cdd:cd05034  23 AVKTLKPGTMSPEAFLQEAQIMKKLRHDKLVQLYAVCSDEEPIYIVTELMSKGSLLDYLRTGE--GRALRLPQLIDMAAQ 100
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 407 AAKGLAWLHhgcQPPYLHQFISSNVILLDDDFDARITDYGLAKLVgsrDSNDSSFNNGDLGELGYVAPEYSSTMVASLKG 486
Cdd:cd05034 101 IASGMAYLE---SRNYIHRDLAARNILVGENNVCKVADFGLARLI---EDDEYTAREGAKFPIKWTAPEAALYGRFTIKS 174
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 487 DVYGFGIVLLELVT-GQKPLSVINGVEgfkgslvdwVSQYLGTGRskdaidRSICDKGHDEEILQflkIACSCVVSRPKE 565
Cdd:cd05034 175 DVWSFGILLYEIVTyGRVPYPGMTNRE---------VLEQVERGY------RMPKPPGCPDELYD---IMLQCWKKEPEE 236
                       250
                ....*....|....*.
gi 15223445 566 RPTmiqvYESLKNMAD 581
Cdd:cd05034 237 RPT----FEYLQSFLE 248
STKc_B-Raf cd14151
Catalytic domain of the Serine/Threonine Kinase, B-Raf (Rapidly Accelerated Fibrosarcoma) ...
304-580 2.52e-15

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: 76.64  E-value: 2.52e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 304 GNIDVSSRTGVSYKADLPDGS---ALAVKRLSACGFGEKQ---FRSEMNKLGELRHPNLVPLLGYcVVEDERLLVYKHMV 377
Cdd:cd14151   8 GQITVGQRIGSGSFGTVYKGKwhgDVAVKMLNVTAPTPQQlqaFKNEVGVLRKTRHVNILLFMGY-STKPQLAIVTQWCE 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 378 NGTLFSQLHnggLCDAVLDWPTRRAIGVGAAKGLAWLHhgcQPPYLHQFISSNVILLDDDFDARITDYGLAKlVGSRDSN 457
Cdd:cd14151  87 GSSLYHHLH---IIETKFEMIKLIDIARQTAQGMDYLH---AKSIIHRDLKSNNIFLHEDLTVKIGDFGLAT-VKSRWSG 159
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 458 DSSFNNGDlGELGYVAPE---YSSTMVASLKGDVYGFGIVLLELVTGQKPLSVINGvegfKGSLVDWVSQ-YLGTGRSKd 533
Cdd:cd14151 160 SHQFEQLS-GSILWMAPEvirMQDKNPYSFQSDVYAFGIVLYELMTGQLPYSNINN----RDQIIFMVGRgYLSPDLSK- 233
                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*..
gi 15223445 534 aiDRSICDKghdeeilQFLKIACSCVVSRPKERPTMIQVYESLKNMA 580
Cdd:cd14151 234 --VRSNCPK-------AMKRLMAECLKKKRDERPLFPQILASIELLA 271
STKc_IRAK2 cd14157
Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 2; ...
322-505 4.84e-15

Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 2; 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. IRAK2 plays a role in mediating NFkB activation by TLR3, TLR4, and TLR8. It is specifically targeted by the viral protein A52, which is important for virulence, to inhibit all IL-1/TLR pathways, indicating that IRAK2 has a predominant role in NFkB activation. It is redundant with IRAK1 in early signaling but is critical for late and sustained activation. The IRAK2 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: 271059 [Multi-domain]  Cd Length: 289  Bit Score: 76.03  E-value: 4.84e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 322 DGSALAVKRL-----SACGFGEKQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQL-HNGGlcDAVL 395
Cdd:cd14157  15 HGKQYVIKRLketecESPKSTERFFQTEVQICFRCCHPNILPLLGFCVESDCHCLIYPYMPNGSLQDRLqQQGG--SHPL 92
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 396 DWPTRRAIGVGAAKGLAWLHHGcqpPYLHQFISSNVILLDDDFDARITDYGLAKLVGSRDSNDSSFNNGDL-GELGYVAP 474
Cdd:cd14157  93 PWEQRLSISLGLLKAVQHLHNF---GILHGNIKSSNVLLDGNLLPKLGHSGLRLCPVDKKSVYTMMKTKVLqISLAYLPE 169
                       170       180       190
                ....*....|....*....|....*....|.
gi 15223445 475 EYSSTMVASLKGDVYGFGIVLLELVTGQKPL 505
Cdd:cd14157 170 DFVRHGQLTEKVDIFSCGVVLAEILTGIKAM 200
PK_eIF2AK_GCN2_rpt1 cd14012
Pseudokinase domain, repeat 1, of eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or ...
342-571 7.38e-15

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: 74.70  E-value: 7.38e-15
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 342 RSEMNKLGELRHPNLVPLLGYCVVEDERL------LVYKHMVNGTLFSQLHNGGlcdaVLDWPTRRAIGVGAAKGLAWLH 415
Cdd:cd14012  46 EKELESLKKLRHPNLVSYLAFSIERRGRSdgwkvyLLTEYAPGGSLSELLDSVG----SVPLDTARRWTLQLLEALEYLH 121
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 416 -----HGCqppyLHqfiSSNVILLDDDFD--ARITDYGLAKLVGSRDSNDSSFNngdLGELGYVAPEYS-STMVASLKGD 487
Cdd:cd14012 122 rngvvHKS----LH---AGNVLLDRDAGTgiVKLTDYSLGKTLLDMCSRGSLDE---FKQTYWLPPELAqGSKSPTRKTD 191
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 488 VYGFGIVLLELVTGQKPLSVINGVEGFKGSLVdwvsqylgtgrskdaidrsicdkgHDEEILQFLKiacSCVVSRPKERP 567
Cdd:cd14012 192 VWDLGLLFLQMLFGLDVLEKYTSPNPVLVSLD------------------------LSASLQDFLS---KCLSLDPKKRP 244

                ....
gi 15223445 568 TMIQ 571
Cdd:cd14012 245 TALE 248
STKc_MLK4 cd14146
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 4; STKs catalyze the ...
342-511 1.03e-14

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: 74.69  E-value: 1.03e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 342 RSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLfsqlhNGGLCDAVLDWPTRRA----------IGVGAAKGL 411
Cdd:cd14146  41 RQEAKLFSMLRHPNIIKLEGVCLEEPNLCLVMEFARGGTL-----NRALAAANAAPGPRRArripphilvnWAVQIARGM 115
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 412 AWLHHGCQPPYLHQFI-SSNVILLD----DDF---DARITDYGLAKlVGSRDSNDSSfnngdLGELGYVAPEYSSTMVAS 483
Cdd:cd14146 116 LYLHEEAVVPILHRDLkSSNILLLEkiehDDIcnkTLKITDFGLAR-EWHRTTKMSA-----AGTYAWMAPEVIKSSLFS 189
                       170       180
                ....*....|....*....|....*...
gi 15223445 484 LKGDVYGFGIVLLELVTGQKPLSVINGV 511
Cdd:cd14146 190 KGSDIWSYGVLLWELLTGEVPYRGIDGL 217
STKc_TAK1 cd14058
Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Activated ...
339-569 1.03e-14

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: 74.40  E-value: 1.03e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 339 KQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHNgglcdAVLDWPTRRAIGVG----AAKGLAWL 414
Cdd:cd14058  31 KAFEVEVRQLSRVDHPNIIKLYGACSNQKPVCLVMEYAEGGSLYNVLHG-----KEPKPIYTAAHAMSwalqCAKGVAYL 105
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 415 HHGCQPPYLHQFIS-SNVILLDDDFDARITDYGLAKlvgsrDSNDSSFNNGdlGELGYVAPEYSSTMVASLKGDVYGFGI 493
Cdd:cd14058 106 HSMKPKALIHRDLKpPNLLLTNGGTVLKICDFGTAC-----DISTHMTNNK--GSAAWMAPEVFEGSKYSEKCDVFSWGI 178
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 15223445 494 VLLELVTGQKPLSvinGVEGFKGSLVDWVSqylgTGRSKDAIdrsicdKGHDEEILQFLKiacSCVVSRPKERPTM 569
Cdd:cd14058 179 ILWEVITRRKPFD---HIGGPAFRIMWAVH----NGERPPLI------KNCPKPIESLMT---RCWSKDPEKRPSM 238
PLN03150 PLN03150
hypothetical protein; Provisional
26-243 1.04e-14

hypothetical protein; Provisional


Pssm-ID: 178695 [Multi-domain]  Cd Length: 623  Bit Score: 77.16  E-value: 1.04e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445   26 DDVLCLQGLKNSLIDPSsRLSsWSfPNSSASSICKLTGVSCWNEKENR---IISLQLQSMQLAGEIPESLKLCRSLQSLD 102
Cdd:PLN03150 372 EEVSALQTLKSSLGLPL-RFG-WN-GDPCVPQQHPWSGADCQFDSTKGkwfIDGLGLDNQGLRGFIPNDISKLRHLQSIN 448
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445  103 LSGNDLSGSIPSQIcswlpylvtldlsgnklgGSIPTqiveckfLNALILSDNKLSGSIPSQLSRLDRLRRLSLAGNDLS 182
Cdd:PLN03150 449 LSGNSIRGNIPPSL------------------GSITS-------LEVLDLSYNSFNGSIPESLGQLTSLRILNLNGNSLS 503
                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445  183 GTIPSEL-------ARFggdDFSGNNGLCGKP-LSRCGALNGRNLSIIIVAGVLgaVGSLC-VGLVIFWW 243
Cdd:PLN03150 504 GRVPAALggrllhrASF---NFTDNAGLCGIPgLRACGPHLSVGAKIGIAFGVS--VAFLFlVICAMCWW 568
STKc_MLK1 cd14145
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 1; STKs catalyze the ...
342-511 1.67e-14

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: 73.92  E-value: 1.67e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 342 RSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHNGGLC-DAVLDWptrraiGVGAAKGLAWLHHGCQP 420
Cdd:cd14145  53 RQEAKLFAMLKHPNIIALRGVCLKEPNLCLVMEFARGGPLNRVLSGKRIPpDILVNW------AVQIARGMNYLHCEAIV 126
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 421 PYLHQFI-SSNVILL----DDDFDAR---ITDYGLAKlVGSRDSNDSSfnngdLGELGYVAPEYSSTMVASLKGDVYGFG 492
Cdd:cd14145 127 PVIHRDLkSSNILILekveNGDLSNKilkITDFGLAR-EWHRTTKMSA-----AGTYAWMAPEVIRSSMFSKGSDVWSYG 200
                       170
                ....*....|....*....
gi 15223445 493 IVLLELVTGQKPLSVINGV 511
Cdd:cd14145 201 VLLWELLTGEVPFRGIDGL 219
PTKc_Src_Fyn_like cd14203
Catalytic domain of a subset of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
326-568 2.13e-14

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: 73.41  E-value: 2.13e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 326 LAVKRLSACGFGEKQFRSEMNKLGELRHPNLVPLlgYCVVEDERL-LVYKHMVNGTLFSQLHNGGlcDAVLDWPTRRAIG 404
Cdd:cd14203  22 VAIKTLKPGTMSPEAFLEEAQIMKKLRHDKLVQL--YAVVSEEPIyIVTEFMSKGSLLDFLKDGE--GKYLKLPQLVDMA 97
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 405 VGAAKGLAWLHhgcQPPYLHQFISSNVILLDDDFDARITDYGLAKLVgsrDSNDSSFNNGDLGELGYVAPEYSSTMVASL 484
Cdd:cd14203  98 AQIASGMAYIE---RMNYIHRDLRAANILVGDNLVCKIADFGLARLI---EDNEYTARQGAKFPIKWTAPEAALYGRFTI 171
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 485 KGDVYGFGIVLLELVT-GQKPLSVINGVEgfkgsLVDWVSQ-YlgtgrskdaidRSICDKGHDEEILQFLkiaCSCVVSR 562
Cdd:cd14203 172 KSDVWSFGILLTELVTkGRVPYPGMNNRE-----VLEQVERgY-----------RMPCPPGCPESLHELM---CQCWRKD 232

                ....*.
gi 15223445 563 PKERPT 568
Cdd:cd14203 233 PEERPT 238
PTKc_Yes cd05069
Catalytic domain of the Protein Tyrosine Kinase, Yes; PTKs catalyze the transfer of the ...
324-568 2.38e-14

Catalytic domain of the Protein Tyrosine Kinase, Yes; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Yes (or c-Yes) is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. c-Yes kinase is the cellular homolog of the oncogenic protein (v-Yes) encoded by the Yamaguchi 73 and Esh sarcoma viruses. It displays functional overlap with other Src subfamily members, particularly Src. It also shows some unique functions such as binding to occludins, transmembrane proteins that regulate extracellular interactions in tight junctions. Yes also associates with a number of proteins in different cell types that Src does not interact with, like JAK2 and gp130 in pre-adipocytes, and Pyk2 in treated pulmonary vein endothelial cells. Although the biological function of Yes remains unclear, it appears to have a role in regulating cell-cell interactions and vesicle trafficking in polarized cells. 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 Yes 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 (PI3K).


Pssm-ID: 270654 [Multi-domain]  Cd Length: 279  Bit Score: 73.57  E-value: 2.38e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 324 SALAVKRLSACGFGEKQFRSEMNKLGELRHPNLVPLlgYCVVEDERL-LVYKHMVNGTLFSQLHNGGlcDAVLDWPTRRA 402
Cdd:cd05069  37 TKVAIKTLKPGTMMPEAFLQEAQIMKKLRHDKLVPL--YAVVSEEPIyIVTEFMGKGSLLDFLKEGD--GKYLKLPQLVD 112
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 403 IGVGAAKGLAWLHhgcQPPYLHQFISSNVILLDDDFDARITDYGLAKLVgsrDSNDSSFNNGDLGELGYVAPEYSSTMVA 482
Cdd:cd05069 113 MAAQIADGMAYIE---RMNYIHRDLRAANILVGDNLVCKIADFGLARLI---EDNEYTARQGAKFPIKWTAPEAALYGRF 186
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 483 SLKGDVYGFGIVLLELVT-GQKPlsvingvegFKGSLVDWVSQYLGTGRskdaidRSICDKGHDEEILQFLKIacsCVVS 561
Cdd:cd05069 187 TIKSDVWSFGILLTELVTkGRVP---------YPGMVNREVLEQVERGY------RMPCPQGCPESLHELMKL---CWKK 248

                ....*..
gi 15223445 562 RPKERPT 568
Cdd:cd05069 249 DPDERPT 255
PKc_LIMK_like cd14065
Catalytic domain of the LIM domain kinase-like protein kinases; PKs catalyze the transfer of ...
344-499 2.70e-14

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: 72.91  E-value: 2.70e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 344 EMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHNGglcDAVLDWPTRRAIGVGAAKGLAWLHhgcQPPYL 423
Cdd:cd14065  38 EVKLMRRLSHPNILRFIGVCVKDNKLNFITEYVNGGTLEELLKSM---DEQLPWSQRVSLAKDIASGMAYLH---SKNII 111
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 424 HQFISSNVILL---DDDFDARITDYGLAKLVGsrdsnDSSFNNGD-------LGELGYVAPEYSSTMVASLKGDVYGFGI 493
Cdd:cd14065 112 HRDLNSKNCLVreaNRGRNAVVADFGLAREMP-----DEKTKKPDrkkrltvVGSPYWMAPEMLRGESYDEKVDVFSFGI 186

                ....*.
gi 15223445 494 VLLELV 499
Cdd:cd14065 187 VLCEII 192
STKc_MEKK1_plant cd06632
Catalytic domain of the Serine/Threonine Kinase, Plant Mitogen-Activated Protein (MAP) ...
322-574 2.82e-14

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: 73.21  E-value: 2.82e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 322 DGSALAVKRLSACGFGE------KQFRSEMNKLGELRHPNLVPLLGYCVVEDeRLLVYKHMVN-GTLFSQLHN-GGLCDA 393
Cdd:cd06632  24 TGDFFAVKEVSLVDDDKksresvKQLEQEIALLSKLRHPNIVQYYGTEREED-NLYIFLEYVPgGSIHKLLQRyGAFEEP 102
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 394 VLDWPTRRAIgvgaaKGLAWLHhgcQPPYLHQFISSNVILLDDDFDARITDYGLAKLVgSRDSNDSSFNngdlGELGYVA 473
Cdd:cd06632 103 VIRLYTRQIL-----SGLAYLH---SRNTVHRDIKGANILVDTNGVVKLADFGMAKHV-EAFSFAKSFK----GSPYWMA 169
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 474 PEysstmVASLKGDVYGF-------GIVLLELVTGQKPLSVINGVEG-FKgslvdwvsqylgTGRSKD--AIDRSICDKG 543
Cdd:cd06632 170 PE-----VIMQKNSGYGLavdiwslGCTVLEMATGKPPWSQYEGVAAiFK------------IGNSGElpPIPDHLSPDA 232
                       250       260       270
                ....*....|....*....|....*....|.
gi 15223445 544 HDeeilqFLKIacsCVVSRPKERPTMIQVYE 574
Cdd:cd06632 233 KD-----FIRL---CLQRDPEDRPTASQLLE 255
STKc_MLK2 cd14148
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 2; STKs catalyze the ...
339-511 5.64e-14

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: 72.33  E-value: 5.64e-14
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 339 KQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHNGGLCDAVL-DWptrraiGVGAAKGLAWLHHG 417
Cdd:cd14148  38 ENVRQEARLFWMLQHPNIIALRGVCLNPPHLCLVMEYARGGALNRALAGKKVPPHVLvNW------AVQIARGMNYLHNE 111
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 418 CQPPYLHQFI-SSNVILL-----DDDFDA--RITDYGLAKlVGSRDSNDSSfnngdLGELGYVAPEYSSTMVASLKGDVY 489
Cdd:cd14148 112 AIVPIIHRDLkSSNILILepienDDLSGKtlKITDFGLAR-EWHKTTKMSA-----AGTYAWMAPEVIRLSLFSKSSDVW 185
                       170       180
                ....*....|....*....|..
gi 15223445 490 GFGIVLLELVTGQKPLSVINGV 511
Cdd:cd14148 186 SFGVLLWELLTGEVPYREIDAL 207
STKc_MLTK cd14060
Catalytic domain of the Serine/Threonine Kinase, Mixed lineage kinase-Like mitogen-activated ...
313-579 1.12e-13

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: 71.14  E-value: 1.12e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 313 GVSYKAD-LPDGSALAVKRLSacgfgekQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHNGGL- 390
Cdd:cd14060   7 GSVYRAIwVSQDKEVAVKKLL-------KIEKEAEILSVLSHRNIIQFYGAILEAPNYGIVTEYASYGSLFDYLNSNESe 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 391 ---CDAVLDWPTRraigvgAAKGLAWLHHGCQPPYLHQFISSNVILLDDDFDARITDYGLAKLVGSrdsndsSFNNGDLG 467
Cdd:cd14060  80 emdMDQIMTWATD------IAKGMHYLHMEAPVKVIHRDLKSRNVVIAADGVLKICDFGASRFHSH------TTHMSLVG 147
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 468 ELGYVAPEYSSTMVASLKGDVYGFGIVLLELVTGQKPLsvingvEGFKGSLVDWVsqylgtgrskdaidrsICDKGHDEE 547
Cdd:cd14060 148 TFPWMAPEVIQSLPVSETCDTYSYGVVLWEMLTREVPF------KGLEGLQVAWL----------------VVEKNERPT 205
                       250       260       270
                ....*....|....*....|....*....|....*..
gi 15223445 548 I-----LQFLKIACSCVVSRPKERPTMIQVYESLKNM 579
Cdd:cd14060 206 IpsscpRSFAELMRRCWEADVKERPSFKQIIGILESM 242
PTKc_Csk_like cd05039
Catalytic domain of C-terminal Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
323-578 1.45e-13

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: 70.84  E-value: 1.45e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 323 GSALAVKRLSACGFGEKQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHNGGlcDAVLDWPTRRA 402
Cdd:cd05039  29 GQKVAVKCLKDDSTAAQAFLAEASVMTTLRHPNLVQLLGVVLEGNGLYIVTEYMAKGSLVDYLRSRG--RAVITRKDQLG 106
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 403 IGVGAAKGLAWLHhgcQPPYLHQFISSNVILLDDDFDARITDYGLAKlvgsrdsnDSSFNNgDLGEL--GYVAPEYSSTM 480
Cdd:cd05039 107 FALDVCEGMEYLE---SKKFVHRDLAARNVLVSEDNVAKVSDFGLAK--------EASSNQ-DGGKLpiKWTAPEALREK 174
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 481 VASLKGDVYGFGIVLLELVT-GQKPLSVIngvegfkgSLVDwVSQYLGTGRskdaidRSICDKGHDEEILQFLKiacSCV 559
Cdd:cd05039 175 KFSTKSDVWSFGILLWEIYSfGRVPYPRI--------PLKD-VVPHVEKGY------RMEAPEGCPPEVYKVMK---NCW 236
                       250
                ....*....|....*....
gi 15223445 560 VSRPKERPTMIQVYESLKN 578
Cdd:cd05039 237 ELDPAKRPTFKQLREKLEH 255
PTKc_Abl cd05052
Catalytic domain of the Protein Tyrosine Kinase, Abelson kinase; PTKs catalyze the transfer of ...
323-579 2.40e-13

Catalytic domain of the Protein Tyrosine Kinase, Abelson kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Abl (or c-Abl) is a ubiquitously-expressed cytoplasmic (or nonreceptor) PTK that contains SH3, SH2, and tyr kinase domains in its N-terminal region, as well as nuclear localization motifs, a putative DNA-binding domain, and F- and G-actin binding domains in its C-terminal tail. It also contains a short autoinhibitory cap region in its N-terminus. Abl function depends on its subcellular localization. In the cytoplasm, Abl plays a role in cell proliferation and survival. In response to DNA damage or oxidative stress, Abl is transported to the nucleus where it induces apoptosis. In chronic myelogenous leukemia (CML) patients, an aberrant translocation results in the replacement of the first exon of Abl with the BCR (breakpoint cluster region) gene. The resulting BCR-Abl fusion protein is constitutively active and associates into tetramers, resulting in a hyperactive kinase sending a continuous signal. This leads to uncontrolled proliferation, morphological transformation and anti-apoptotic effects. BCR-Abl is the target of selective inhibitors, such as imatinib (Gleevec), used in the treatment of CML. Abl2, also known as ARG (Abelson-related gene), is thought to play a cooperative role with Abl in the proper development of the nervous system. The Tel-ARG fusion protein, resulting from reciprocal translocation between chromosomes 1 and 12, is associated with acute myeloid leukemia (AML). The TEL gene is a frequent fusion partner of other tyr kinase oncogenes, including Tel/Abl, Tel/PDGFRbeta, and Tel/Jak2, found in patients with leukemia and myeloproliferative disorders. The Abl 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: 270645 [Multi-domain]  Cd Length: 263  Bit Score: 70.53  E-value: 2.40e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 323 GSALAVKRLSACGFGEKQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLH--NGGLCDAVldwpTR 400
Cdd:cd05052  31 NLTVAVKTLKEDTMEVEEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMPYGNLLDYLRecNREELNAV----VL 106
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 401 RAIGVGAAKGLAWLHHGCqppYLHQFISSNVILLDDDFDARITDYGLAKLVgsrDSNDSSFNNGDLGELGYVAPEYSSTM 480
Cdd:cd05052 107 LYMATQIASAMEYLEKKN---FIHRDLAARNCLVGENHLVKVADFGLSRLM---TGDTYTAHAGAKFPIKWTAPESLAYN 180
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 481 VASLKGDVYGFGIVLLELVT-GQKPLSvinGVEgfkgsLVDwVSQYLGTGRskdaidRSICDKGHDEEILQFLKiacSCV 559
Cdd:cd05052 181 KFSIKSDVWAFGVLLWEIATyGMSPYP---GID-----LSQ-VYELLEKGY------RMERPEGCPPKVYELMR---ACW 242
                       250       260
                ....*....|....*....|
gi 15223445 560 VSRPKERPTMIQVYESLKNM 579
Cdd:cd05052 243 QWNPSDRPSFAEIHQALETM 262
PTKc_Axl cd05075
Catalytic domain of the Protein Tyrosine Kinase, Axl; PTKs catalyze the transfer of the ...
322-579 2.45e-13

Catalytic domain of the Protein Tyrosine Kinase, Axl; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Axl is widely expressed in a variety of organs and cells including epithelial, mesenchymal, hematopoietic, as well as non-transformed cells. It is important in many cellular functions such as survival, anti-apoptosis, proliferation, migration, and adhesion. Axl was originally isolated from patients with chronic myelogenous leukemia and a chronic myeloproliferative disorder. It is overexpressed in many human cancers including colon, squamous cell, thyroid, breast, and lung carcinomas. Axl is a member of the TAM subfamily, composed of receptor PTKs (RTKs) containing an extracellular ligand-binding region with two immunoglobulin-like domains followed by two fibronectin type III repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to its ligands, Gas6 and protein S, leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. The Axl 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: 270660 [Multi-domain]  Cd Length: 277  Bit Score: 70.81  E-value: 2.45e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 322 DGSAL--AVK--RLSACGFGE-KQFRSEMNKLGELRHPNLVPLLGYCVVEDER------LLVYKHMVNGTLFSQLHNGGL 390
Cdd:cd05075  24 DDSVLkvAVKtmKIAICTRSEmEDFLSEAVCMKEFDHPNVMRLIGVCLQNTESegypspVVILPFMKHGDLHSFLLYSRL 103
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 391 CDAVLDWPTRRAIGVGA--AKGLAWLhhgCQPPYLHQFISSNVILLDDDFDARITDYGLAKLVgsrdSNDSSFNNGDLGE 468
Cdd:cd05075 104 GDCPVYLPTQMLVKFMTdiASGMEYL---SSKNFIHRDLAARNCMLNENMNVCVADFGLSKKI----YNGDYYRQGRISK 176
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 469 L--GYVAPEYSSTMVASLKGDVYGFGIVLLELVT-GQKPLSvinGVEgfKGSLVDWVSQylgTGRSKDAIDrsiCDKGhd 545
Cdd:cd05075 177 MpvKWIAIESLADRVYTTKSDVWSFGVTMWEIATrGQTPYP---GVE--NSEIYDYLRQ---GNRLKQPPD---CLDG-- 243
                       250       260       270
                ....*....|....*....|....*....|....
gi 15223445 546 eeilqFLKIACSCVVSRPKERPTMIQVYESLKNM 579
Cdd:cd05075 244 -----LYELMSSCWLLNPKDRPSFETLRCELEKI 272
STKc_ACVR2 cd14053
Catalytic domain of the Serine/Threonine Kinase, Activin Type II Receptor; STKs catalyze the ...
311-500 6.06e-13

Catalytic domain of the Serine/Threonine Kinase, Activin Type II Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ACVR2 belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, bone morphogenetic proteins (BMPs), activins, growth and differentiation factors (GDFs), 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 ACVR2, are high-affinity receptors which bind ligands, autophosphorylate, as well as trans-phosphorylate and activate low-affinity type I receptors. ACVR2 acts primarily as the receptors for activins, nodal, myostatin, GDF11, and a subset of BMPs. ACVR2 signaling impacts many cellular and physiological processes including reproductive and gonadal functions, myogenesis, bone remodeling and tooth development, kidney organogenesis, apoptosis, fibrosis, inflammation, and neurogenesis. Vertebrates contain two ACVR2 proteins, ACVR2a (or ActRIIA) and ACVR2b (or ActRIIB). The ACVR2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270955 [Multi-domain]  Cd Length: 290  Bit Score: 69.66  E-value: 6.06e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 311 RTGVSYKADLPDgSALAVKRlsacgFGEKQFRS-----EMNKLGELRHPNLVPLLG----YCVVEDERLLVYKHMVNGTL 381
Cdd:cd14053   7 RFGAVWKAQYLN-RLVAVKI-----FPLQEKQSwlterEIYSLPGMKHENILQFIGaekhGESLEAEYWLITEFHERGSL 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 382 FSQLHNGglcdaVLDWPTRRAIGVGAAKGLAWLH-------HGCQPPYLHQFISSNVILLDDDFDARITDYGLA-KLVGS 453
Cdd:cd14053  81 CDYLKGN-----VISWNELCKIAESMARGLAYLHedipatnGGHKPSIAHRDFKSKNVLLKSDLTACIADFGLAlKFEPG 155
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|..
gi 15223445 454 RDSNDSsfnNGDLGELGYVAPEY-----SSTMVASLKGDVYGFGIVLLELVT 500
Cdd:cd14053 156 KSCGDT---HGQVGTRRYMAPEVlegaiNFTRDAFLRIDMYAMGLVLWELLS 204
STKc_MLK3 cd14147
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 3; STKs catalyze the ...
342-511 7.22e-13

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: 68.90  E-value: 7.22e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 342 RSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHNGGLCDAVL-DWptrraiGVGAAKGLAWLHHGCQP 420
Cdd:cd14147  50 RQEARLFAMLAHPNIIALKAVCLEEPNLCLVMEYAAGGPLSRALAGRRVPPHVLvNW------AVQIARGMHYLHCEALV 123
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 421 PYLHQFISSNVILL------DD--DFDARITDYGLAklvgsRDSNDSSfNNGDLGELGYVAPEYSSTMVASLKGDVYGFG 492
Cdd:cd14147 124 PVIHRDLKSNNILLlqpienDDmeHKTLKITDFGLA-----REWHKTT-QMSAAGTYAWMAPEVIKASTFSKGSDVWSFG 197
                       170
                ....*....|....*....
gi 15223445 493 IVLLELVTGQKPLSVINGV 511
Cdd:cd14147 198 VLLWELLTGEVPYRGIDCL 216
PK_GC-A_B cd14042
Pseudokinase domain of the membrane Guanylate Cyclase receptors, GC-A and GC-B; The ...
338-579 7.61e-13

Pseudokinase domain of the membrane Guanylate Cyclase receptors, GC-A and GC-B; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity and/or ATP binding. GC-A binds and is activated by the atrial and B-type natriuretic peptides, ANP and BNP, which are important in blood pressure regulation and cardiac pathophysiology. GC-B binds the C-type natriuretic peptide, CNP, which is a potent vasorelaxant and functions in vascular remodeling and bone growth regulation. 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 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-A/B 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: 270944 [Multi-domain]  Cd Length: 279  Bit Score: 69.16  E-value: 7.61e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 338 EKQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHNgglcDAV-LDWPTRRAIGVGAAKGLAWLH- 415
Cdd:cd14042  46 TREVLKELKHMRDLQHDNLTRFIGACVDPPNICILTEYCPKGSLQDILEN----EDIkLDWMFRYSLIHDIVKGMHYLHd 121
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 416 -----HGcqppylhQFISSNViLLDDDFDARITDYGLAKLVGSRDSNDSSFNNgdLGELGYVAPEYSSTMVA----SLKG 486
Cdd:cd14042 122 seiksHG-------NLKSSNC-VVDSRFVLKITDFGLHSFRSGQEPPDDSHAY--YAKLLWTAPELLRDPNPpppgTQKG 191
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 487 DVYGFGIVLLELVTGQKPLsvinGVEGFKGSLVDWVSQYLGTGrSKDAIDRSICDKGHDEEILQFLkiaCSCVVSRPKER 566
Cdd:cd14042 192 DVYSFGIILQEIATRQGPF----YEEGPDLSPKEIIKKKVRNG-EKPPFRPSLDELECPDEVLSLM---QRCWAEDPEER 263
                       250
                ....*....|...
gi 15223445 567 PTMIQVYESLKNM 579
Cdd:cd14042 264 PDFSTLRNKLKKL 276
PTKc_Fyn cd05070
Catalytic domain of the Protein Tyrosine Kinase, Fyn; PTKs catalyze the transfer of the ...
324-512 8.92e-13

Catalytic domain of the Protein Tyrosine Kinase, Fyn; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Fyn and Yrk are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Fyn, together with Lck, plays a critical role in T-cell signal transduction by phosphorylating ITAM (immunoreceptor tyr activation motif) sequences on T-cell receptors, ultimately leading to the proliferation and differentiation of T-cells. In addition, Fyn is involved in the myelination of neurons, and is implicated in Alzheimer's and Parkinson's diseases. 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 Fyn/Yrk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase.


Pssm-ID: 270655 [Multi-domain]  Cd Length: 274  Bit Score: 68.94  E-value: 8.92e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 324 SALAVKRLSACGFGEKQFRSEMNKLGELRHPNLVPLlgYCVVEDERL-LVYKHMVNGTLFSQLHNGGlcDAVLDWPTRRA 402
Cdd:cd05070  34 TKVAIKTLKPGTMSPESFLEEAQIMKKLKHDKLVQL--YAVVSEEPIyIVTEYMSKGSLLDFLKDGE--GRALKLPNLVD 109
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 403 IGVGAAKGLAWLHhgcQPPYLHQFISSNVILLDDDFDARITDYGLAKLVgsrDSNDSSFNNGDLGELGYVAPEYSSTMVA 482
Cdd:cd05070 110 MAAQVAAGMAYIE---RMNYIHRDLRSANILVGNGLICKIADFGLARLI---EDNEYTARQGAKFPIKWTAPEAALYGRF 183
                       170       180       190
                ....*....|....*....|....*....|.
gi 15223445 483 SLKGDVYGFGIVLLELVT-GQKPLSVINGVE 512
Cdd:cd05070 184 TIKSDVWSFGILLTELVTkGRVPYPGMNNRE 214
STKc_TGFbR-like cd13998
Catalytic domain of Transforming Growth Factor beta Receptor-like Serine/Threonine Kinases; ...
311-499 1.42e-12

Catalytic domain of Transforming Growth Factor beta Receptor-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 receptors for the TGFbeta family of secreted signaling molecules including TGFbeta, bone morphogenetic proteins (BMPs), activins, growth and differentiation factors (GDFs), and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. There are two types of TGFbeta receptors included in this subfamily, I and II, that play different roles in signaling. For signaling to occur, the ligand first binds to the high-affinity type II receptor, which is followed by the recruitment of the low-affinity type I receptor to the complex and its activation through trans-phosphorylation by the type II receptor. The active type I receptor kinase starts intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. Different ligands interact with various combinations of types I and II receptors to elicit a specific signaling pathway. Activins primarily signal through combinations of ACVR1b/ALK7 and ACVR2a/b; myostatin and GDF11 through TGFbR1/ALK4 and ACVR2a/b; BMPs through ACVR1/ALK1 and BMPR2; and TGFbeta through TGFbR1 and TGFbR2. The TGFbR-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: 270900 [Multi-domain]  Cd Length: 289  Bit Score: 68.62  E-value: 1.42e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 311 RTGVSYKADLpDGSALAVKRLS----ACGFGEKQ-FRSEMnklgeLRHPNLVPLLgycvVEDER--------LLVYKHMV 377
Cdd:cd13998   7 RFGEVWKASL-KNEPVAVKIFSsrdkQSWFREKEiYRTPM-----LKHENILQFI----AADERdtalrtelWLVTAFHP 76
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 378 NGTL--FSQLHngglcdaVLDWPTRRAIGVGAAKGLAWLHH---GC---QPPYLHQFISSNVILLDDDFDARITDYGLAK 449
Cdd:cd13998  77 NGSL*dYLSLH-------TIDWVSLCRLALSVARGLAHLHSeipGCtqgKPAIAHRDLKSKNILVKNDGTCCIADFGLAV 149
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 15223445 450 LVGSRDSNDSSFNNGDLGELGYVAPEY------SSTMVASLKGDVYGFGIVLLELV 499
Cdd:cd13998 150 RLSPSTGEEDNANNGQVGTKRYMAPEVlegainLRDFESFKRVDIYAMGLVLWEMA 205
STKc_MAP3K12_13 cd14059
Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase ...
323-504 2.69e-12

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: 66.75  E-value: 2.69e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 323 GSALAVKRLsacgfgEKQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHNGG--LCDAVLDWPTr 400
Cdd:cd14059  16 GEEVAVKKV------RDEKETDIKHLRKLNHPNIIKFKGVCTQAPCYCILMEYCPYGQLYEVLRAGReiTPSLLVDWSK- 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 401 raigvGAAKGLAWLHhgcqppyLHQFI-----SSNVILLDDDFdARITDYGLAKLVGSRdSNDSSFNngdlGELGYVAPE 475
Cdd:cd14059  89 -----QIASGMNYLH-------LHKIIhrdlkSPNVLVTYNDV-LKISDFGTSKELSEK-STKMSFA----GTVAWMAPE 150
                       170       180
                ....*....|....*....|....*....
gi 15223445 476 YSSTMVASLKGDVYGFGIVLLELVTGQKP 504
Cdd:cd14059 151 VIRNEPCSEKVDIWSFGVVLWELLTGEIP 179
PTKc_EphR_A2 cd05063
Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A2; PTKs catalyze the ...
324-504 3.46e-12

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: 66.92  E-value: 3.46e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 324 SALAVKRLSAcGFGEKQ---FRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTL--FSQLHNGglcdavlDWP 398
Cdd:cd05063  34 VAVAIKTLKP-GYTEKQrqdFLSEASIMGQFSHHNIIRLEGVVTKFKPAMIITEYMENGALdkYLRDHDG-------EFS 105
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 399 TRRAIGV--GAAKGLAWLhhgCQPPYLHQFISSNVILLDDDFDARITDYGLAKLVgSRDSNDSSFNNGDLGELGYVAPEY 476
Cdd:cd05063 106 SYQLVGMlrGIAAGMKYL---SDMNYVHRDLAARNILVNSNLECKVSDFGLSRVL-EDDPEGTYTTSGGKIPIRWTAPEA 181
                       170       180
                ....*....|....*....|....*....
gi 15223445 477 SSTMVASLKGDVYGFGIVLLELVT-GQKP 504
Cdd:cd05063 182 IAYRKFTSASDVWSFGIVMWEVMSfGERP 210
PLN00113 PLN00113
leucine-rich repeat receptor-like protein kinase; Provisional
77-215 6.43e-12

leucine-rich repeat receptor-like protein kinase; Provisional


Pssm-ID: 215061 [Multi-domain]  Cd Length: 968  Bit Score: 68.72  E-value: 6.43e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445   77 LQLQSMQLAGEIPESLKLCRSLQSLDLSGNDLSGSIPSQICSwLPYLVTLDLSGNKLGGSIPTQIVECKFLNALILSDNK 156
Cdd:PLN00113 241 LDLVYNNLTGPIPSSLGNLKNLQYLFLYQNKLSGPIPPSIFS-LQKLISLDLSDNSLSGEIPELVIQLQNLEILHLFSNN 319
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 15223445  157 LSGSIPSQLSRLDRLRRLSLAGNDLSGTIPSELAR---FGGDDFSGNNgLCGK-PLSRCGALN 215
Cdd:PLN00113 320 FTGKIPVALTSLPRLQVLQLWSNKFSGEIPKNLGKhnnLTVLDLSTNN-LTGEiPEGLCSSGN 381
Pkinase pfam00069
Protein kinase domain;
313-572 7.99e-12

Protein kinase domain;


Pssm-ID: 459660 [Multi-domain]  Cd Length: 217  Bit Score: 64.96  E-value: 7.99e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445   313 GVSYKA-DLPDGSALAVKRLSACGFGE---KQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHng 388
Cdd:pfam00069  13 GTVYKAkHRDTGKIVAIKKIKKEKIKKkkdKNILREIKILKKLNHPNIVRLYDAFEDKDNLYLVLEYVEGGSLFDLLS-- 90
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445   389 glcdavldwptrraigvgaakglawlHHGCQPPYLHQFISSNVILldddfdaritdyGLAklvgsrdsNDSSFNNGDlGE 468
Cdd:pfam00069  91 --------------------------EKGAFSEREAKFIMKQILE------------GLE--------SGSSLTTFV-GT 123
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445   469 LGYVAPE------YSStmvaslKGDVYGFGIVLLELVTGQKPLSVINGVEGFKgslvdwvsQYLGTGRSKDAIDRSIcdk 542
Cdd:pfam00069 124 PWYMAPEvlggnpYGP------KVDVWSLGCILYELLTGKPPFPGINGNEIYE--------LIIDQPYAFPELPSNL--- 186
                         250       260       270
                  ....*....|....*....|....*....|
gi 15223445   543 ghDEEILQFLKiacSCVVSRPKERPTMIQV 572
Cdd:pfam00069 187 --SEEAKDLLK---KLLKKDPSKRLTATQA 211
PTKc_Src cd05071
Catalytic domain of the Protein Tyrosine Kinase, Src; PTKs catalyze the transfer of the ...
324-504 9.41e-12

Catalytic domain of the Protein Tyrosine Kinase, Src; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Src (or c-Src) is a cytoplasmic (or non-receptor) PTK, containing 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 with a conserved tyr. It is activated by autophosphorylation at the tyr kinase domain, and is negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). c-Src is the vertebrate homolog of the oncogenic protein (v-Src) from Rous sarcoma virus. Together with other Src subfamily proteins, it is involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. Src also play a role in regulating cell adhesion, invasion, and motility in cancer cells and tumor vasculature, contributing to cancer progression and metastasis. Elevated levels of Src kinase activity have been reported in a variety of human cancers. Several inhibitors of Src have been developed as anti-cancer drugs. Src is also implicated in acute inflammatory responses and osteoclast function. The Src 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: 270656 [Multi-domain]  Cd Length: 277  Bit Score: 65.86  E-value: 9.41e-12
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 324 SALAVKRLSACGFGEKQFRSEMNKLGELRHPNLVPLlgYCVVEDERL-LVYKHMVNGTLFSQLHngGLCDAVLDWPTRRA 402
Cdd:cd05071  34 TRVAIKTLKPGTMSPEAFLQEAQVMKKLRHEKLVQL--YAVVSEEPIyIVTEYMSKGSLLDFLK--GEMGKYLRLPQLVD 109
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 403 IGVGAAKGLAWLHhgcQPPYLHQFISSNVILLDDDFDARITDYGLAKLVgsrDSNDSSFNNGDLGELGYVAPEYSSTMVA 482
Cdd:cd05071 110 MAAQIASGMAYVE---RMNYVHRDLRAANILVGENLVCKVADFGLARLI---EDNEYTARQGAKFPIKWTAPEAALYGRF 183
                       170       180
                ....*....|....*....|...
gi 15223445 483 SLKGDVYGFGIVLLELVT-GQKP 504
Cdd:cd05071 184 TIKSDVWSFGILLTELTTkGRVP 206
STKc_A-Raf cd14150
Catalytic domain of the Serine/Threonine Kinase, A-Raf (Rapidly Accelerated Fibrosarcoma) ...
339-509 1.08e-11

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: 65.42  E-value: 1.08e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 339 KQFRSEMNKLGELRHPNLVPLLGYcVVEDERLLVYKHMVNGTLFSQLHnggLCDAVLDWPTRRAIGVGAAKGLAWLHhgc 418
Cdd:cd14150  41 QAFKNEMQVLRKTRHVNILLFMGF-MTRPNFAIITQWCEGSSLYRHLH---VTETRFDTMQLIDVARQTAQGMDYLH--- 113
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 419 QPPYLHQFISSNVILLDDDFDARITDYGLAKlVGSRDSNDSSFNNGDlGELGYVAPE---YSSTMVASLKGDVYGFGIVL 495
Cdd:cd14150 114 AKNIIHRDLKSNNIFLHEGLTVKIGDFGLAT-VKTRWSGSQQVEQPS-GSILWMAPEvirMQDTNPYSFQSDVYAYGVVL 191
                       170
                ....*....|....
gi 15223445 496 LELVTGQKPLSVIN 509
Cdd:cd14150 192 YELMSGTLPYSNIN 205
PKc_TESK cd14155
Catalytic domain of the Dual-specificity protein kinase, Testicular protein kinase; ...
344-582 1.45e-11

Catalytic domain of the Dual-specificity protein kinase, Testicular 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. TESK proteins phosphorylate cofilin and induce actin cytoskeletal reorganization. In the Drosphila eye, TESK is required for epithelial cell organization. Mammals contain two TESK proteins, TESK1 and TESK2, which are highly expressed in testis and play roles in spermatogenesis. TESK1 is found in testicular germ cells while TESK2 is expressed mainly in nongerminal Sertoli cells. TESK1 is stimulated by integrin-mediated signaling pathways. It regulates cell spreading and focal adhesion formation. The TESK 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: 271057 [Multi-domain]  Cd Length: 253  Bit Score: 64.80  E-value: 1.45e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 344 EMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHNgglcDAVLDWPTRRAIGVGAAKGLAWLHHgcQPPYL 423
Cdd:cd14155  38 EVQLMNRLSHPNILRFMGVCVHQGQLHALTEYINGGNLEQLLDS----NEPLSWTVRVKLALDIARGLSYLHS--KGIFH 111
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 424 HQFISSNVIL--LDDDFDARITDYGLAKLVGSRDSNDSSFNNgdLGELGYVAPEYSSTMVASLKGDVYGFGIVLLELVTG 501
Cdd:cd14155 112 RDLTSKNCLIkrDENGYTAVVGDFGLAEKIPDYSDGKEKLAV--VGSPYWMAPEVLRGEPYNEKADVFSYGIILCEIIAR 189
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 502 -QKPLSVINGVEGFKgslVDWvsqylgtgrskDAIDRSICDKGHDeeilqFLKIACSCVVSRPKERPTMIQVYESLKNMA 580
Cdd:cd14155 190 iQADPDYLPRTEDFG---LDY-----------DAFQHMVGDCPPD-----FLQLAFNCCNMDPKSRPSFHDIVKTLEEIL 250

                ..
gi 15223445 581 DK 582
Cdd:cd14155 251 EK 252
STKc_OSR1_SPAK cd06610
Catalytic domain of the Serine/Threonine Kinases, Oxidative stress response kinase and ...
312-506 1.99e-11

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: 64.69  E-value: 1.99e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 312 TGVSYKAD-LPDGSALAVKR--LSACGFGEKQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHNG 388
Cdd:cd06610  14 TAVVYAAYcLPKKEKVAIKRidLEKCQTSMDELRKEIQAMSQCNHPNVVSYYTSFVVGDELWLVMPLLSGGSLLDIMKSS 93
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 389 GLCDaVLDWPTRRAIGVGAAKGLAWLHHGCQppyLHQFISSNVILLDDDFDARITDYGLAKLVGSRDSNDSSFNNGDLGE 468
Cdd:cd06610  94 YPRG-GLDEAIIATVLKEVLKGLEYLHSNGQ---IHRDVKAGNILLGEDGSVKIADFGVSASLATGGDRTRKVRKTFVGT 169
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*
gi 15223445 469 LGYVAPE-------YSStmvaslKGDVYGFGIVLLELVTGQKPLS 506
Cdd:cd06610 170 PCWMAPEvmeqvrgYDF------KADIWSFGITAIELATGAAPYS 208
STKc_BMPR2_AMHR2 cd14054
Catalytic domain of the Serine/Threonine Kinases, Bone Morphogenetic Protein and ...
311-500 2.48e-11

Catalytic domain of the Serine/Threonine Kinases, Bone Morphogenetic Protein and Anti-Muellerian Hormone Type II Receptors; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BMPR2 and AMHR2 belong to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, BMPs, activins, growth and differentiation factors (GDFs), and AMH, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane region, and a cytoplasmic catalytic kinase domain. Type II receptors are high-affinity receptors which bind ligands, autophosphorylate, as well as trans-phosphorylate and activate low-affinity type I receptors. BMPR2 and AMHR2 act primarily as a receptor for BMPs and AMH, respectively. BMPs induce bone and cartilage formation, as well as regulate tooth, kidney, skin, hair, haematopoietic, and neuronal development. Mutations in BMPR2A is associated with familial pulmonary arterial hypertension. AMH is mainly responsible for the regression of Mullerian ducts during male sex differentiation. It is expressed exclusively by somatic cells of the gonads. Mutations in either AMH or AMHR2 cause persistent Mullerian duct syndrome (PMDS), a rare form of male pseudohermaphroditism characterized by the presence of Mullerian derivatives (ovary and tubes) in otherwise normally masculine males. The BMPR2/AMHR2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270956 [Multi-domain]  Cd Length: 300  Bit Score: 65.08  E-value: 2.48e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 311 RTGVSYKADLpDGSALAVKrlsACGFGEKQ-FRSEMN--KLGELRHPNLVPLLGYC--VVEDER---LLVYKHMVNGTLF 382
Cdd:cd14054   7 RYGTVWKGSL-DERPVAVK---VFPARHRQnFQNEKDiyELPLMEHSNILRFIGADerPTADGRmeyLLVLEYAPKGSLC 82
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 383 SQLHNGglcdaVLDWPTRRAIGVGAAKGLAWLH------HGCQPPYLHQFISSNVILLDDDFDARITDYGLA-KLVGSR- 454
Cdd:cd14054  83 SYLREN-----TLDWMSSCRMALSLTRGLAYLHtdlrrgDQYKPAIAHRDLNSRNVLVKADGSCVICDFGLAmVLRGSSl 157
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 15223445 455 ------DSNDSSFNngDLGELGYVAPEYSSTMV------ASLK-GDVYGFGIVLLELVT 500
Cdd:cd14054 158 vrgrpgAAENASIS--EVGTLRYMAPEVLEGAVnlrdceSALKqVDVYALGLVLWEIAM 214
PTKc_Tec_like cd05059
Catalytic domain of Tec-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
327-576 2.50e-11

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: 64.39  E-value: 2.50e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 327 AVKRLSACGFGEKQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLH-------NGGLCDAVLDwpt 399
Cdd:cd05059  32 AIKMIKEGSMSEDDFIEEAKVMMKLSHPKLVQLYGVCTKQRPIFIVTEYMANGCLLNYLRerrgkfqTEQLLEMCKD--- 108
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 400 rraigvgAAKGLAWLHHGCqppYLHQFISSNVILLDDDFDARITDYGLAKLVGSrDSNDSSFnnGDLGELGYVAPEYSST 479
Cdd:cd05059 109 -------VCEAMEYLESNG---FIHRDLAARNCLVGEQNVVKVSDFGLARYVLD-DEYTSSV--GTKFPVKWSPPEVFMY 175
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 480 MVASLKGDVYGFGIVLLELVTGQK-PLsvingvEGFKGS-LVDWVSQYLGTGRSKDAidrsicdkghDEEILQflkIACS 557
Cdd:cd05059 176 SKFSSKSDVWSFGVLMWEVFSEGKmPY------ERFSNSeVVEHISQGYRLYRPHLA----------PTEVYT---IMYS 236
                       250
                ....*....|....*....
gi 15223445 558 CVVSRPKERPTMIQVYESL 576
Cdd:cd05059 237 CWHEKPEERPTFKILLSQL 255
PKc_LIMK_like_unk cd14156
Catalytic domain of an unknown subfamily of LIM domain kinase-like protein kinases; PKs ...
344-499 2.97e-11

Catalytic domain of an unknown subfamily of 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. This group is composed of uncharacterized proteins with similarity to LIMK and Testicular or testis-specific protein kinase (TESK). 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: 271058 [Multi-domain]  Cd Length: 256  Bit Score: 64.08  E-value: 2.97e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 344 EMNKLGELRHPNLVPLLGYCvVEDERLLVYKHMVNGTLFSQLhnggLCDA--VLDWPTRRAIGVGAAKGLAWLHHgcQPP 421
Cdd:cd14156  38 EISLLQKLSHPNIVRYLGIC-VKDEKLHPILEYVSGGCLEEL----LAREelPLSWREKVELACDISRGMVYLHS--KNI 110
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 422 YLHQFISSNVIL--LDDDFDARITDYGLAKLVGSRDSNDSSFNNGDLGELGYVAPEYSSTMVASLKGDVYGFGIVLLELV 499
Cdd:cd14156 111 YHRDLNSKNCLIrvTPRGREAVVTDFGLAREVGEMPANDPERKLSLVGSAFWMAPEMLRGEPYDRKVDVFSFGIVLCEIL 190
PTKc_Lyn cd05072
Catalytic domain of the Protein Tyrosine Kinase, Lyn; PTKs catalyze the transfer of the ...
322-504 3.07e-11

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: 64.29  E-value: 3.07e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 322 DGSALAVKRLSACGFGEKQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHNGGLCDAVLdwPTRR 401
Cdd:cd05072  30 NSTKVAVKTLKPGTMSVQAFLEEANLMKTLQHDKLVRLYAVVTKEEPIYIITEYMAKGSLLDFLKSDEGGKVLL--PKLI 107
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 402 AIGVGAAKGLAWLHhgcQPPYLHQFISSNVILLDDDFDARITDYGLAKLVgsrDSNDSSFNNGDLGELGYVAPEYSSTMV 481
Cdd:cd05072 108 DFSAQIAEGMAYIE---RKNYIHRDLRAANVLVSESLMCKIADFGLARVI---EDNEYTAREGAKFPIKWTAPEAINFGS 181
                       170       180
                ....*....|....*....|....
gi 15223445 482 ASLKGDVYGFGIVLLELVT-GQKP 504
Cdd:cd05072 182 FTIKSDVWSFGILLYEIVTyGKIP 205
PTKc_Srm_Brk cd05148
Catalytic domain of the Protein Tyrosine Kinases, Src-related kinase lacking C-terminal ...
341-504 3.51e-11

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: 63.99  E-value: 3.51e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 341 FRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHNGGlcDAVLDWPTRRAIGVGAAKGLAWLHhgcQP 420
Cdd:cd05148  49 FQKEVQALKRLRHKHLISLFAVCSVGEPVYIITELMEKGSLLAFLRSPE--GQVLPVASLIDMACQVAEGMAYLE---EQ 123
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 421 PYLHQFISSNVILLDDDFDARITDYGLAKLVgsRDSNDSSFNNGDlgELGYVAPEYSSTMVASLKGDVYGFGIVLLELVT 500
Cdd:cd05148 124 NSIHRDLAARNILVGEDLVCKVADFGLARLI--KEDVYLSSDKKI--PYKWTAPEAASHGTFSTKSDVWSFGILLYEMFT 199

                ....*
gi 15223445 501 -GQKP 504
Cdd:cd05148 200 yGQVP 204
STKc_MEKK4 cd06626
Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP) ...
319-568 3.82e-11

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: 63.86  E-value: 3.82e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 319 DLPDGSALAVKRLSacgFGE------KQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHNGGLCD 392
Cdd:cd06626  21 NLDTGELMAMKEIR---FQDndpktiKEIADEMKVLEGLDHPNLVRYYGVEVHREEVYIFMEYCQEGTLEELLRHGRILD 97
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 393 AVLdwptrraIGVGAA---KGLAWLH-HGCqppyLHQFISSNVILLDDDFDARITDYGLAKLVGSRDSNDSSFN-NGDLG 467
Cdd:cd06626  98 EAV-------IRVYTLqllEGLAYLHeNGI----VHRDIKPANIFLDSNGLIKLGDFGSAVKLKNNTTTMAPGEvNSLVG 166
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 468 ELGYVAPEysSTMVASLKG-----DVYGFGIVLLELVTGQKPLSVINGVegfkgslvdWVSQY-LGTGRSKDAIDRS-IC 540
Cdd:cd06626 167 TPAYMAPE--VITGNKGEGhgraaDIWSLGCVVLEMATGKRPWSELDNE---------WAIMYhVGMGHKPPIPDSLqLS 235
                       250       260
                ....*....|....*....|....*...
gi 15223445 541 DKGHDeeilqFLKiacSCVVSRPKERPT 568
Cdd:cd06626 236 PEGKD-----FLS---RCLESDPKKRPT 255
STKc_LRRK2 cd14068
Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 2; STKs catalyze ...
341-576 4.61e-11

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: 63.43  E-value: 4.61e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 341 FRSEMNKLGELRHPNLVPLLGYCVveDERLLVYKHMVNGTL--FSQLHNGGLCDAVldwptRRAIGVGAAKGLAWLHHGC 418
Cdd:cd14068  34 LRQELVVLSHLHHPSLVALLAAGT--APRMLVMELAPKGSLdaLLQQDNASLTRTL-----QHRIALHVADGLRYLHSAM 106
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 419 qpPYLHQFISSNVILL----DDDFDARITDYGLAKLVGSRDSNDSSfnngdlGELGYVAPEYSSTMVA-SLKGDVYGFGI 493
Cdd:cd14068 107 --IIYRDLKPHNVLLFtlypNCAIIAKIADYGIAQYCCRMGIKTSE------GTPGFRAPEVARGNVIyNQQADVYSFGL 178
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 494 VLLELVTGQKPLsvingVEGFKgsLVDWVSQYLGTGRSKDAIDRSICDKGHDEEILqfLKiacSCVVSRPKERPTMIQVY 573
Cdd:cd14068 179 LLYDILTCGERI-----VEGLK--FPNEFDELAIQGKLPDPVKEYGCAPWPGVEAL--IK---DCLKENPQCRPTSAQVF 246

                ...
gi 15223445 574 ESL 576
Cdd:cd14068 247 DIL 249
PTKc_RET cd05045
Catalytic domain of the Protein Tyrosine Kinase, REarranged during Transfection protein; PTKs ...
318-504 4.76e-11

Catalytic domain of the Protein Tyrosine Kinase, REarranged during Transfection protein; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. RET is a receptor PTK (RTK) containing an extracellular region with four cadherin-like repeats, a calcium-binding site, and a cysteine-rich domain, a transmembrane segment, and an intracellular catalytic domain. It is part of a multisubunit complex that binds glial-derived neurotropic factor (GDNF) family ligands (GFLs) including GDNF, neurturin, artemin, and persephin. GFLs bind RET along with four GPI-anchored coreceptors, bringing two RET molecules together, leading to autophosphorylation, activation, and intracellular signaling. RET is essential for the development of the sympathetic, parasympathetic and enteric nervous systems, and the kidney. RET disruption by germline mutations causes diseases in humans including congenital aganglionosis of the gastrointestinal tract (Hirschsprung's disease) and three related inherited cancers: multiple endocrine neoplasia type 2A (MEN2A), MEN2B, and familial medullary thyroid carcinoma. The RET 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: 173631 [Multi-domain]  Cd Length: 290  Bit Score: 63.83  E-value: 4.76e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 318 ADLPDGSALAVKRLSAcGFGEKQFR---SEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLH-------- 386
Cdd:cd05045  25 KGRAGYTTVAVKMLKE-NASSSELRdllSEFNLLKQVNHPHVIKLYGACSQDGPLLLIVEYAKYGSLRSFLResrkvgps 103
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 387 ----NGGLCDAVLDWPTRRAIGVGAAKGLAW-LHHGCQppYL------HQFISSNVILLDDDFDARITDYGLAKLVGSRD 455
Cdd:cd05045 104 ylgsDGNRNSSYLDNPDERALTMGDLISFAWqISRGMQ--YLaemklvHRDLAARNVLVAEGRKMKISDFGLSRDVYEED 181
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|
gi 15223445 456 SNDSsfNNGDLGELGYVAPEYSSTMVASLKGDVYGFGIVLLELVT-GQKP 504
Cdd:cd05045 182 SYVK--RSKGRIPVKWMAIESLFDHIYTTQSDVWSFGVLLWEIVTlGGNP 229
PTKc_Btk_Bmx cd05113
Catalytic domain of the Protein Tyrosine Kinases, Bruton's tyrosine kinase and Bone marrow ...
326-576 4.77e-11

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: 63.36  E-value: 4.77e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 326 LAVKRLSACGFGEKQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHNGG----------LCDAVl 395
Cdd:cd05113  31 VAIKMIKEGSMSEDEFIEEAKVMMNLSHEKLVQLYGVCTKQRPIFIITEYMANGCLLNYLREMRkrfqtqqlleMCKDV- 109
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 396 dwptrraigvgaAKGLAWLHhgcQPPYLHQFISSNVILLDDDFDARITDYGLAKLVGSrDSNDSSFnnGDLGELGYVAPE 475
Cdd:cd05113 110 ------------CEAMEYLE---SKQFLHRDLAARNCLVNDQGVVKVSDFGLSRYVLD-DEYTSSV--GSKFPVRWSPPE 171
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 476 YSSTMVASLKGDVYGFGIVLLELVT-GQKPLSVINGVEgfkgsLVDWVSQYLGTGRSKDAIDRsicdkghdeeilqFLKI 554
Cdd:cd05113 172 VLMYSKFSSKSDVWAFGVLMWEVYSlGKMPYERFTNSE-----TVEHVSQGLRLYRPHLASEK-------------VYTI 233
                       250       260
                ....*....|....*....|..
gi 15223445 555 ACSCVVSRPKERPTMIQVYESL 576
Cdd:cd05113 234 MYSCWHEKADERPTFKILLSNI 255
PTKc_EphR_B cd05065
Catalytic domain of the Protein Tyrosine Kinases, Class EphB Ephrin Receptors; PTKs catalyze ...
326-512 5.66e-11

Catalytic domain of the Protein Tyrosine Kinases, Class EphB Ephrin Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Class EphB receptors bind to transmembrane ephrin-B ligands. There are six vertebrate EphB receptors (EphB1-6), which display promiscuous interactions with three ephrin-B ligands. One exception is EphB2, which also interacts with ephrin A5. EphB receptors play important roles in synapse formation and plasticity, spine morphogenesis, axon guidance, and angiogenesis. In the intestinal epithelium, EphBs are Wnt signaling target genes that control cell compartmentalization. They function as suppressors of colon cancer progression. EphRs comprise the largest subfamily of receptor PTKs (RTKs). They 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. The EphB 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: 173638 [Multi-domain]  Cd Length: 269  Bit Score: 63.35  E-value: 5.66e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 326 LAVKRLSAcGFGEKQ---FRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTL--FSQLHNGglcdavlDWPTR 400
Cdd:cd05065  35 VAIKTLKS-GYTEKQrrdFLSEASIMGQFDHPNIIHLEGVVTKSRPVMIITEFMENGALdsFLRQNDG-------QFTVI 106
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 401 RAIGV--GAAKGLAWLhhgCQPPYLHQFISSNVILLDDDFDARITDYGLAKLVgSRDSNDSSFNNGDLGELG--YVAPEY 476
Cdd:cd05065 107 QLVGMlrGIAAGMKYL---SEMNYVHRDLAARNILVNSNLVCKVSDFGLSRFL-EDDTSDPTYTSSLGGKIPirWTAPEA 182
                       170       180       190       200
                ....*....|....*....|....*....|....*....|...
gi 15223445 477 SSTMVASLKGDVYGFGIVLLELVT-GQKPL------SVINGVE 512
Cdd:cd05065 183 IAYRKFTSASDVWSYGIVMWEVMSyGERPYwdmsnqDVINAIE 225
STKc_AGC cd05123
Catalytic domain of AGC family Serine/Threonine Kinases; STKs catalyze the transfer of the ...
338-504 7.58e-11

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: 62.53  E-value: 7.58e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 338 EKQFRSEMNKLGELRHPNLVPLLgYCVVEDERL-LVYKHMVNGTLFSQLHNGGlcdaVLDWPTRRAIGVGAAKGLAWLH- 415
Cdd:cd05123  37 VEHTLNERNILERVNHPFIVKLH-YAFQTEEKLyLVLDYVPGGELFSHLSKEG----RFPEERARFYAAEIVLALEYLHs 111
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 416 HGcqppYLHQFISSNVILLDDDFDARITDYGLAKLVGSRDSNDSSFnngdLGELGYVAPEYsstmvasLKGDVYG----- 490
Cdd:cd05123 112 LG----IIYRDLKPENILLDSDGHIKLTDFGLAKELSSDGDRTYTF----CGTPEYLAPEV-------LLGKGYGkavdw 176
                       170
                ....*....|....*.
gi 15223445 491 --FGIVLLELVTGQKP 504
Cdd:cd05123 177 wsLGVLLYEMLTGKPP 192
STKc_Rad53_Cds1 cd14098
Catalytic domain of the yeast Serine/Threonine Kinases, Rad53 and Cds1; STKs catalyze the ...
341-572 8.32e-11

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: 62.88  E-value: 8.32e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 341 FRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQL-HNGGLCDAVLdwptrRAIGVGAAKGLAWLH-HGC 418
Cdd:cd14098  48 FQREINILKSLEHPGIVRLIDWYEDDQHIYLVMEYVEGGDLMDFImAWGAIPEQHA-----RELTKQILEAMAYTHsMGI 122
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 419 QppylHQFISSNVILL--DDDFDARITDYGLAKLVGSrdsndSSFNNGDLGELGYVAPEYSSTMVASLKG------DVYG 490
Cdd:cd14098 123 T----HRDLKPENILItqDDPVIVKISDFGLAKVIHT-----GTFLVTFCGTMAYLAPEILMSKEQNLQGgysnlvDMWS 193
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 491 FGIVLLELVTGQKPlsvingvegFKGSLVDWVSQYLGTGR--SKDAIDRSICDKGHDeEILQFLKIacscvvsRPKERPT 568
Cdd:cd14098 194 VGCLVYVMLTGALP---------FDGSSQLPVEKRIRKGRytQPPLVDFNISEEAID-FILRLLDV-------DPEKRMT 256

                ....
gi 15223445 569 MIQV 572
Cdd:cd14098 257 AAQA 260
PTKc_Chk cd05083
Catalytic domain of the Protein Tyrosine Kinase, Csk homologous kinase; PTKs catalyze the ...
323-579 9.39e-11

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: 62.58  E-value: 9.39e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 323 GSALAVKRLSaCGFGEKQFRSEMNKLGELRHPNLVPLLGyCVVEDERLLVYKHMVNGTLFSQLHNGGlcDAVLDWPTRRA 402
Cdd:cd05083  29 GQKVAVKNIK-CDVTAQAFLEETAVMTKLQHKNLVRLLG-VILHNGLYIVMELMSKGNLVNFLRSRG--RALVPVIQLLQ 104
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 403 IGVGAAKGLAWLHhgcQPPYLHQFISSNVILLDDDFDARITDYGLAKlVGSRDSNDSSFnngdlgELGYVAPEYSSTMVA 482
Cdd:cd05083 105 FSLDVAEGMEYLE---SKKLVHRDLAARNILVSEDGVAKISDFGLAK-VGSMGVDNSRL------PVKWTAPEALKNKKF 174
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 483 SLKGDVYGFGIVLLELVT-GQKPLSVINgvegfkgslVDWVSQYLGTGRSKDAIDRSICDkghdeeilqFLKIACSCVVS 561
Cdd:cd05083 175 SSKSDVWSYGVLLWEVFSyGRAPYPKMS---------VKEVKEAVEKGYRMEPPEGCPPD---------VYSIMTSCWEA 236
                       250
                ....*....|....*...
gi 15223445 562 RPKERPTMIQVYESLKNM 579
Cdd:cd05083 237 EPGKRPSFKKLREKLEKE 254
PTKc_Mer cd14204
Catalytic Domain of the Protein Tyrosine Kinase, Mer; PTKs catalyze the transfer of the ...
293-582 9.70e-11

Catalytic Domain of the Protein Tyrosine Kinase, Mer; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Mer (or Mertk) is named after its original reported expression pattern (monocytes, epithelial, and reproductive tissues). It is required for the ingestion of apoptotic cells by phagocytes such as macrophages, retinal pigment epithelial cells, and dendritic cells. Mer is also important in maintaining immune homeostasis. Mer is a member of the TAM subfamily, composed of receptor PTKs (RTKs) containing an extracellular ligand-binding region with two immunoglobulin-like domains followed by two fibronectin type III repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands, Gas6 and protein S, leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. The Mer 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: 271106 [Multi-domain]  Cd Length: 284  Bit Score: 63.03  E-value: 9.70e-11
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 293 DLMAATNNFSSGNIDVSSRTGVSYKADL--PDGSAL--AVKRLSACGFGEKQ---FRSEMNKLGELRHPNLVPLLGYCVV 365
Cdd:cd14204   1 DVMIDRNLLSLGKVLGEGEFGSVMEGELqqPDGTNHkvAVKTMKLDNFSQREieeFLSEAACMKDFNHPNVIRLLGVCLE 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 366 EDER-----LLVYKHMVNGTLFSQLHNGGLCDAVLDWPTRRAIG--VGAAKGLAWLhhgCQPPYLHQFISSNVILLDDDF 438
Cdd:cd14204  81 VGSQripkpMVILPFMKYGDLHSFLLRSRLGSGPQHVPLQTLLKfmIDIALGMEYL---SSRNFLHRDLAARNCMLRDDM 157
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 439 DARITDYGLAKLVGSRDsndsSFNNGDLGEL--GYVAPEYSSTMVASLKGDVYGFGIVLLELVT-GQKPLSvinGVEGFK 515
Cdd:cd14204 158 TVCVADFGLSKKIYSGD----YYRQGRIAKMpvKWIAVESLADRVYTVKSDVWAFGVTMWEIATrGMTPYP---GVQNHE 230
                       250       260       270       280       290       300       310
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 15223445 516 gslvdwVSQYLGTG----RSKDAIDrsicdkghdeeilQFLKIACSCVVSRPKERPTMIQVYESLKNMADK 582
Cdd:cd14204 231 ------IYDYLLHGhrlkQPEDCLD-------------ELYDIMYSCWRSDPTDRPTFTQLRENLEKLLES 282
PTKc_Csk cd05082
Catalytic domain of the Protein Tyrosine Kinase, C-terminal Src kinase; PTKs catalyze the ...
339-579 1.05e-10

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: 62.31  E-value: 1.05e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 339 KQFRSEMNKLGELRHPNLVPLLGYCVVEDERL-LVYKHMVNGTLFSQLHNGGlcDAVLDWPTRRAIGVGAAKGLAWLHHG 417
Cdd:cd05082  44 QAFLAEASVMTQLRHSNLVQLLGVIVEEKGGLyIVTEYMAKGSLVDYLRSRG--RSVLGGDCLLKFSLDVCEAMEYLEGN 121
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 418 cqpPYLHQFISSNVILLDDDFDARITDYGLAKLVGSRDsndssfnngDLGEL--GYVAPEYSSTMVASLKGDVYGFGIVL 495
Cdd:cd05082 122 ---NFVHRDLAARNVLVSEDNVAKVSDFGLTKEASSTQ---------DTGKLpvKWTAPEALREKKFSTKSDVWSFGILL 189
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 496 LELVT-GQKPLSVIngvegfkgSLVDWVSQyLGTGRSKDAIDrsicdkGHDEEILQFLKiacSCVVSRPKERPTMIQVYE 574
Cdd:cd05082 190 WEIYSfGRVPYPRI--------PLKDVVPR-VEKGYKMDAPD------GCPPAVYDVMK---NCWHLDAAMRPSFLQLRE 251

                ....*
gi 15223445 575 SLKNM 579
Cdd:cd05082 252 QLEHI 256
PTKc_EphR cd05033
Catalytic domain of Ephrin Receptor Protein Tyrosine Kinases; PTKs catalyze the transfer of ...
327-515 1.25e-10

Catalytic domain of Ephrin Receptor Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EphRs comprise the largest subfamily of receptor PTKs (RTKs). They can be classified into two classes (EphA and EphB), according to their extracellular sequences, which largely correspond to binding preferences for either GPI-anchored ephrin-A ligands or transmembrane ephrin-B ligands. Vertebrates have ten EphA and six EphB receptors, which display promiscuous ligand interactions within each class. 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. This allows ephrin/EphR dimers to form, leading to the activation of the intracellular tyr kinase domain. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). The main effect of ephrin/EphR interaction is cell-cell repulsion or adhesion. Ephrin/EphR signaling is important in neural development and plasticity, cell morphogenesis and proliferation, cell-fate determination, embryonic development, tissue patterning, and angiogenesis.The EphR 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: 270629 [Multi-domain]  Cd Length: 266  Bit Score: 62.39  E-value: 1.25e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 327 AVKRLSAcGFGEKQ---FRSEMNKLGELRHPNLVPLLGycVVEDER--LLVYKHMVNGTLFSQLHNGglcDAVLDWPTRR 401
Cdd:cd05033  36 AIKTLKS-GYSDKQrldFLTEASIMGQFDHPNVIRLEG--VVTKSRpvMIVTEYMENGSLDKFLREN---DGKFTVTQLV 109
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 402 AIGVGAAKGLAWLHHGCqppYLHQFISSNVILLDDDFDARITDYGLAKLVgsRDSNDSSFNNGDLGELGYVAPEYSSTMV 481
Cdd:cd05033 110 GMLRGIASGMKYLSEMN---YVHRDLAARNILVNSDLVCKVSDFGLSRRL--EDSEATYTTKGGKIPIRWTAPEAIAYRK 184
                       170       180       190       200
                ....*....|....*....|....*....|....*....|..
gi 15223445 482 ASLKGDVYGFGIVLLELVT-GQKPL------SVINGVE-GFK 515
Cdd:cd05033 185 FTSASDVWSFGIVMWEVMSyGERPYwdmsnqDVIKAVEdGYR 226
LRR COG4886
Leucine-rich repeat (LRR) protein [Transcription];
53-163 1.37e-10

Leucine-rich repeat (LRR) protein [Transcription];


Pssm-ID: 443914 [Multi-domain]  Cd Length: 414  Bit Score: 63.41  E-value: 1.37e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445  53 SSASSICKLTGVSCWNEKENRIISL--------QLQSMQLAG----EIPESLKLCRSLQSLDLSGNDLSgSIPSQICSwL 120
Cdd:COG4886 104 SGNEELSNLTNLESLDLSGNQLTDLpeelanltNLKELDLSNnqltDLPEPLGNLTNLKSLDLSNNQLT-DLPEELGN-L 181
                        90       100       110       120
                ....*....|....*....|....*....|....*....|...
gi 15223445 121 PYLVTLDLSGNKLgGSIPTQIVECKFLNALILSDNKLSgSIPS 163
Cdd:COG4886 182 TNLKELDLSNNQI-TDLPEPLGNLTNLEELDLSGNQLT-DLPE 222
STKc_MEKK1 cd06630
Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP) ...
316-504 1.49e-10

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: 62.06  E-value: 1.49e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 316 YKA-DLPDGSALAVKRLSAC----GFGEK---QFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHN 387
Cdd:cd06630  17 YQArDVKTGTLMAVKQVSFCrnssSEQEEvveAIREEIRMMARLNHPNIVRMLGATQHKSHFNIFVEWMAGGSVASLLSK 96
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 388 -GGLCDAVLDWPTRRAIGvgaakGLAWLHHGCqppYLHQFISSNVILLDDD-FDARITDYGLAKLVGSRDSNDSSFNNGD 465
Cdd:cd06630  97 yGAFSENVIINYTLQILR-----GLAYLHDNQ---IIHRDLKGANLLVDSTgQRLRIADFGAAARLASKGTGAGEFQGQL 168
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*.
gi 15223445 466 LGELGYVAPEYsstmvasLKG-------DVYGFGIVLLELVTGQKP 504
Cdd:cd06630 169 LGTIAFMAPEV-------LRGeqygrscDVWSVGCVIIEMATAKPP 207
STKc_C-Raf cd14149
Catalytic domain of the Serine/Threonine Kinase, C-Raf (Rapidly Accelerated Fibrosarcoma) ...
339-509 2.09e-10

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: 61.97  E-value: 2.09e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 339 KQFRSEMNKLGELRHPNLVPLLGYcVVEDERLLVYKHMVNGTLFSQLHnggLCDAVLDWPTRRAIGVGAAKGLAWLHhgc 418
Cdd:cd14149  53 QAFRNEVAVLRKTRHVNILLFMGY-MTKDNLAIVTQWCEGSSLYKHLH---VQETKFQMFQLIDIARQTAQGMDYLH--- 125
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 419 QPPYLHQFISSNVILLDDDFDARITDYGLAKlVGSRDSNDSSFNNGDlGELGYVAPE---YSSTMVASLKGDVYGFGIVL 495
Cdd:cd14149 126 AKNIIHRDMKSNNIFLHEGLTVKIGDFGLAT-VKSRWSGSQQVEQPT-GSILWMAPEvirMQDNNPFSFQSDVYSYGIVL 203
                       170
                ....*....|....
gi 15223445 496 LELVTGQKPLSVIN 509
Cdd:cd14149 204 YELMTGELPYSHIN 217
PTKc_EphR_A cd05066
Catalytic domain of the Protein Tyrosine Kinases, Class EphA Ephrin Receptors; PTKs catalyze ...
309-504 2.36e-10

Catalytic domain of the Protein Tyrosine Kinases, Class EphA Ephrin Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of most class EphA receptors including EphA3, EphA4, EphA5, and EphA7, but excluding EphA1, EphA2 and EphA10. 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. One exception is EphA4, which also binds ephrins-B2/B3. EphA receptors and ephrin-A ligands are expressed in multiple areas of the developing brain, especially in the retina and tectum. They are part of a system controlling retinotectal mapping. EphRs comprise the largest subfamily of receptor PTKs (RTKs). 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 EphA 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: 270651 [Multi-domain]  Cd Length: 267  Bit Score: 61.42  E-value: 2.36e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 309 SSRTGVSYKADLPdgsaLAVKRLSAcGFGEKQ---FRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTL--FS 383
Cdd:cd05066  22 SGRLKLPGKREIP----VAIKTLKA-GYTEKQrrdFLSEASIMGQFDHPNIIHLEGVVTRSKPVMIVTEYMENGSLdaFL 96
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 384 QLHNGGLCDAVLDWPTRraigvGAAKGLAWLhhgCQPPYLHQFISSNVILLDDDFDARITDYGLAKLVgsRDSNDSSFNN 463
Cdd:cd05066  97 RKHDGQFTVIQLVGMLR-----GIASGMKYL---SDMGYVHRDLAARNILVNSNLVCKVSDFGLSRVL--EDDPEAAYTT 166
                       170       180       190       200
                ....*....|....*....|....*....|....*....|...
gi 15223445 464 -GDLGELGYVAPEYSSTMVASLKGDVYGFGIVLLELVT-GQKP 504
Cdd:cd05066 167 rGGKIPIRWTAPEAIAYRKFTSASDVWSYGIVMWEVMSyGERP 209
PTKc_Syk_like cd05060
Catalytic domain of Spleen Tyrosine Kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
320-578 3.57e-10

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: 60.83  E-value: 3.57e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 320 LPDGS--ALAVKRLSA--CGFGEKQFRSEMNKLGELRHPNLVPLLGYCvvEDERLLVYKHMVNGtlfsqlhnGGLCDAVL 395
Cdd:cd05060  18 MKSGKevEVAVKTLKQehEKAGKKEFLREASVMAQLDHPCIVRLIGVC--KGEPLMLVMELAPL--------GPLLKYLK 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 396 DWPTrraigVGAAKGLAWLHH-GCQPPYL------HQFISSNVILLDDDFDARITDYGLAKLVGSrDSNDSSFNNGDLGE 468
Cdd:cd05060  88 KRRE-----IPVSDLKELAHQvAMGMAYLeskhfvHRDLAARNVLLVNRHQAKISDFGMSRALGA-GSDYYRATTAGRWP 161
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 469 LGYVAPEYSSTMVASLKGDVYGFGIVLLELVT-GQKPLSVINGVEgfkgslvdwVSQYLGTGRskdaidRSICDKGHDEE 547
Cdd:cd05060 162 LKWYAPECINYGKFSSKSDVWSYGVTLWEAFSyGAKPYGEMKGPE---------VIAMLESGE------RLPRPEECPQE 226
                       250       260       270
                ....*....|....*....|....*....|.
gi 15223445 548 ILQflkIACSCVVSRPKERPTMIQVYESLKN 578
Cdd:cd05060 227 IYS---IMLSCWKYRPEDRPTFSELESTFRR 254
PK_ILK cd14057
Pseudokinase domain of Integrin Linked Kinase; The pseudokinase domain shows similarity to ...
339-518 3.91e-10

Pseudokinase domain of Integrin Linked Kinase; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. ILK contains N-terminal ankyrin repeats, a Pleckstrin Homology (PH) domain, and a C-terminal pseudokinase domain. It is a component of the IPP (ILK/PINCH/Parvin) complex that couples beta integrins to the actin cytoskeleton, and plays important roles in cell adhesion, spreading, invasion, and migration. ILK was initially thought to be an active kinase despite the lack of key conserved residues because of in vitro studies showing that it can phosphorylate certain protein substrates. However, in vivo experiments in Caenorhabditis elegans, Drosophila melanogaster, and mice (ILK-null and knock-in) proved that ILK is not an active kinase. In addition to actin cytoskeleton regulation, ILK also influences the microtubule network and mitotic spindle orientation. The pseudokinase domain of ILK binds several adaptor proteins including the parvins and paxillin. The ILK 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: 270959 [Multi-domain]  Cd Length: 251  Bit Score: 60.58  E-value: 3.91e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 339 KQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHNGglCDAVLDWPTRRAIGVGAAKGLAWLhHGC 418
Cdd:cd14057  37 RDFNEEYPRLRIFSHPNVLPVLGACNSPPNLVVISQYMPYGSLYNVLHEG--TGVVVDQSQAVKFALDIARGMAFL-HTL 113
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 419 QPPYLHQFISSNVILLDDDFDARITdYGLAKLvgsrdsndsSFNN-GDLGELGYVAPEYSSTMVASLK---GDVYGFGIV 494
Cdd:cd14057 114 EPLIPRHHLNSKHVMIDEDMTARIN-MADVKF---------SFQEpGKMYNPAWMAPEALQKKPEDINrrsADMWSFAIL 183
                       170       180
                ....*....|....*....|....*
gi 15223445 495 LLELVTGQKPLSVINGVE-GFKGSL 518
Cdd:cd14057 184 LWELVTREVPFADLSNMEiGMKIAL 208
PTKc_EGFR_like cd05057
Catalytic domain of Epidermal Growth Factor Receptor-like Protein Tyrosine Kinases; PTKs ...
339-512 5.28e-10

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: 60.51  E-value: 5.28e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 339 KQFRSEMNKLGELRHPNLVPLLGYCVVEdERLLVYKHMVNGTLFSQLHN-----GGLcdAVLDWptrraiGVGAAKGLAW 413
Cdd:cd05057  54 EEILDEAYVMASVDHPHLVRLLGICLSS-QVQLITQLMPLGCLLDYVRNhrdniGSQ--LLLNW------CVQIAKGMSY 124
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 414 L--HHgcqppYLHQFISSNVILLDDDFDARITDYGLAKLVgsrDSNDSSFN-NGDLGELGYVAPEYSSTMVASLKGDVYG 490
Cdd:cd05057 125 LeeKR-----LVHRDLAARNVLVKTPNHVKITDFGLAKLL---DVDEKEYHaEGGKVPIKWMALESIQYRIYTHKSDVWS 196
                       170       180
                ....*....|....*....|...
gi 15223445 491 FGIVLLELVT-GQKPLSVINGVE 512
Cdd:cd05057 197 YGVTVWELMTfGAKPYEGIPAVE 219
STKc_myosinIIIB_N cd06639
N-terminal Catalytic domain of the Serine/Threonine Kinase, Class IIIB myosin; STKs catalyze ...
313-512 9.18e-10

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: 60.01  E-value: 9.18e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 313 GVSYK-ADLPDGSALAVKRLSACGFGEKQFRSEMNKLGEL-RHPNLVPLLGYCVVEDE----RLLVYKHMVNGTLFSQLH 386
Cdd:cd06639  36 GKVYKvTNKKDGSLAAVKILDPISDVDEEIEAEYNILRSLpNHPNVVKFYGMFYKADQyvggQLWLVLELCNGGSVTELV 115
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 387 NGGL-CDAVLDWPTRRAIGVGAAKGLAWLHHGcqpPYLHQFISSNVILLDDDFDARITDYGL-AKLVGSRDSNDSSfnng 464
Cdd:cd06639 116 KGLLkCGQRLDEAMISYILYGALLGLQHLHNN---RIIHRDVKGNNILLTTEGGVKLVDFGVsAQLTSARLRRNTS---- 188
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*
gi 15223445 465 dLGELGYVAPE-------YSSTMVAslKGDVYGFGIVLLELVTGQKPLSVINGVE 512
Cdd:cd06639 189 -VGTPFWMAPEviaceqqYDYSYDA--RCDVWSLGITAIELADGDPPLFDMHPVK 240
PTKc_Itk cd05112
Catalytic domain of the Protein Tyrosine Kinase, Interleukin-2-inducible T-cell Kinase; PTKs ...
309-504 9.76e-10

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: 59.58  E-value: 9.76e-10
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 309 SSRTGVSYKADLPDGSALAVKRLSACGFGEKQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTL------- 381
Cdd:cd05112  14 SGQFGLVHLGYWLNKDKVAIKTIREGAMSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQAPICLVFEFMEHGCLsdylrtq 93
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 382 ---FSQLHNGGLCdavLDwptrraigvgAAKGLAWLHHGCqppYLHQFISSNVILLDDDFDARITDYGLAKLVGSrDSND 458
Cdd:cd05112  94 rglFSAETLLGMC---LD----------VCEGMAYLEEAS---VIHRDLAARNCLVGENQVVKVSDFGMTRFVLD-DQYT 156
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*..
gi 15223445 459 SSfnNGDLGELGYVAPEYSSTMVASLKGDVYGFGIVLLELVT-GQKP 504
Cdd:cd05112 157 SS--TGTKFPVKWSSPEVFSFSRYSSKSDVWSFGVLMWEVFSeGKIP 201
STKc_WNK cd13983
Catalytic domain of the Serine/Threonine kinase, With No Lysine (WNK) kinase; STKs catalyze ...
339-511 1.17e-09

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: 59.16  E-value: 1.17e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 339 KQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVY--KHMVNGTLFSQLHNGGlcdaVLDWPTRRAIGVGAAKGLAWLHh 416
Cdd:cd13983  45 QRFKQEIEILKSLKHPNIIKFYDSWESKSKKEVIFitELMTSGTLKQYLKRFK----RLKLKVIKSWCRQILEGLNYLH- 119
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 417 GCQPPYLHQ-------FISSNvillddDFDARITDYGLAKLVgsrdsnDSSFNNGDLGELGYVAPE-----YSStmvasl 484
Cdd:cd13983 120 TRDPPIIHRdlkcdniFINGN------TGEVKIGDLGLATLL------RQSFAKSVIGTPEFMAPEmyeehYDE------ 181
                       170       180       190
                ....*....|....*....|....*....|....*...
gi 15223445 485 KGDVYGFGIVLLELVTGQKPLS-----------VINGV 511
Cdd:cd13983 182 KVDIYAFGMCLLEMATGEYPYSectnaaqiykkVTSGI 219
STKc_16 cd13986
Catalytic domain of Serine/Threonine Kinase 16; STKs catalyze the transfer of the ...
319-581 1.24e-09

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: 59.62  E-value: 1.24e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 319 DLPDGSALAVKRLSaCGF--GEKQFRSEMNKLGELRHPNLVPLLGYCVVEDER--------LLVYKHmvnGTLFSQLHNg 388
Cdd:cd13986  21 DLSTGRLYALKKIL-CHSkeDVKEAMREIENYRLFNHPNILRLLDSQIVKEAGgkkevyllLPYYKR---GSLQDEIER- 95
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 389 gLCDAVLDWPTRR--AIGVGAAKGLAWLHHGCQPPYLHQFISSNVILLDDDFDARITDYGLA-----KLVGSRDSNDSSF 461
Cdd:cd13986  96 -RLVKGTFFPEDRilHIFLGICRGLKAMHEPELVPYAHRDIKPGNVLLSEDDEPILMDLGSMnpariEIEGRREALALQD 174
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 462 NNGDLGELGYVAPEY---SSTMVASLKGDVYGFGIVLLELVTGQKPLSVINGvegfKGslvDWVSQYLGTGRSKDAIDRS 538
Cdd:cd13986 175 WAAEHCTMPYRAPELfdvKSHCTIDEKTDIWSLGCTLYALMYGESPFERIFQ----KG---DSLALAVLSGNYSFPDNSR 247
                       250       260       270       280
                ....*....|....*....|....*....|....*....|...
gi 15223445 539 icdkgHDEEILQFLKiacSCVVSRPKERPTMIQVYESLKNMAD 581
Cdd:cd13986 248 -----YSEELHQLVK---SMLVVNPAERPSIDDLLSRVHDLIP 282
PTKc_Tyk2_rpt2 cd05080
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; PTKs catalyze ...
323-579 1.62e-09

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: 59.14  E-value: 1.62e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 323 GSALAVKRLSA-CGFG-EKQFRSEMNKLGELRHPNLVPLLGYCVVEDER--LLVYKHMVNGTLFSQL--HNGGLCDAVLd 396
Cdd:cd05080  33 GEMVAVKALKAdCGPQhRSGWKQEIDILKTLYHENIVKYKGCCSEQGGKslQLIMEYVPLGSLRDYLpkHSIGLAQLLL- 111
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 397 wptrraIGVGAAKGLAWLHhgcQPPYLHQFISSNVILLDDDFDARITDYGLAKLVGSRDSNDSSFNNGDlGELGYVAPEY 476
Cdd:cd05080 112 ------FAQQICEGMAYLH---SQHYIHRDLAARNVLLDNDRLVKIGDFGLAKAVPEGHEYYRVREDGD-SPVFWYAPEC 181
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 477 SSTMVASLKGDVYGFGIVLLELVT----GQKPLSVINGVEGFKGSLVDWVsqylgtgRSKDAIDRSI---CDKGHDEEIL 549
Cdd:cd05080 182 LKEYKFYYASDVWSFGVTLYELLThcdsSQSPPTKFLEMIGIAQGQMTVV-------RLIELLERGErlpCPDKCPQEVY 254
                       250       260       270
                ....*....|....*....|....*....|
gi 15223445 550 QFLKiacSCVVSRPKERPTMIQVYESLKNM 579
Cdd:cd05080 255 HLMK---NCWETEASFRPTFENLIPILKTV 281
PTKc_c-ros cd05044
Catalytic domain of the Protein Tyrosine Kinase, C-ros; PTKs catalyze the transfer of the ...
320-578 1.72e-09

Catalytic domain of the Protein Tyrosine Kinase, C-ros; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily contains c-ros, Sevenless, and similar proteins. The proto-oncogene c-ros encodes an orphan receptor PTK (RTK) with an unknown ligand. RTKs contain an extracellular ligand-binding domain, a transmembrane region, 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. C-ros is expressed in embryonic cells of the kidney, intestine and lung, but disappears soon after birth. It persists only in the adult epididymis. Male mice bearing inactive mutations of c-ros lack the initial segment of the epididymis and are infertile. The Drosophila protein, Sevenless, is required for the specification of the R7 photoreceptor cell during eye development. The c-ros 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: 270640 [Multi-domain]  Cd Length: 268  Bit Score: 58.97  E-value: 1.72e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 320 LPDGSA---LAVKRL--SACGFGEKQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHNG------ 388
Cdd:cd05044  20 LGDGSGetkVAVKTLrkGATDQEKAEFLKEAHLMSNFKHPNILKLLGVCLDNDPQYIILELMEGGDLLSYLRAArptaft 99
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 389 ----GLCDAVldwptrrAIGVGAAKGLAWLHhgcQPPYLHQFISS-NVILLDDDFDAR---ITDYGLAklvgsRD--SND 458
Cdd:cd05044 100 ppllTLKDLL-------SICVDVAKGCVYLE---DMHFVHRDLAArNCLVSSKDYRERvvkIGDFGLA-----RDiyKND 164
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 459 SSFNNGD-LGELGYVAPEYSSTMVASLKGDVYGFGIVLLELVT-GQKPLSVINGVEgfkgslvdwVSQYLGTGRSKDAID 536
Cdd:cd05044 165 YYRKEGEgLLPVRWMAPESLVDGVFTTQSDVWAFGVLMWEILTlGQQPYPARNNLE---------VLHFVRAGGRLDQPD 235
                       250       260       270       280
                ....*....|....*....|....*....|....*....|..
gi 15223445 537 RsiCdkghDEEILQFLKiacSCVVSRPKERPTMIQVYESLKN 578
Cdd:cd05044 236 N--C----PDDLYELML---RCWSTDPEERPSFARILEQLQN 268
PTKc_TAM cd05035
Catalytic Domain of TAM (Tyro3, Axl, Mer) Protein Tyrosine Kinases; PTKs catalyze the transfer ...
313-579 1.88e-09

Catalytic Domain of TAM (Tyro3, Axl, Mer) Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The TAM subfamily consists of Tyro3 (or Sky), Axl, Mer (or Mertk), and similar proteins. TAM subfamily members are receptor tyr kinases (RTKs) containing an extracellular ligand-binding region with two immunoglobulin-like domains followed by two fibronectin type III repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands, Gas6 and protein S, leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. TAM proteins are implicated in a variety of cellular effects including survival, proliferation, migration, and phagocytosis. They are also associated with several types of cancer as well as inflammatory, autoimmune, vascular, and kidney diseases. The TAM 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: 270631 [Multi-domain]  Cd Length: 273  Bit Score: 59.09  E-value: 1.88e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 313 GVSYKADLP--DGSAL--AVKRLSACGFGEKQ---FRSEMNKLGELRHPNLVPLLGYCVVEDER------LLVYKHMVNG 379
Cdd:cd05035  13 GSVMEAQLKqdDGSQLkvAVKTMKVDIHTYSEieeFLSEAACMKDFDHPNVMRLIGVCFTASDLnkppspMVILPFMKHG 92
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 380 TLFSQLHNGGLCDAVLDWPTRRAI--GVGAAKGLAWLhhgCQPPYLHQFISSNVILLDDDFDARITDYGLAKLVGSRDsn 457
Cdd:cd05035  93 DLHSYLLYSRLGGLPEKLPLQTLLkfMVDIAKGMEYL---SNRNFIHRDLAARNCMLDENMTVCVADFGLSRKIYSGD-- 167
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 458 dsSFNNGDLGEL--GYVAPEYSSTMVASLKGDVYGFGIVLLELVT-GQKPLSvinGVEGFKgslvdwVSQYLGTG-RSKD 533
Cdd:cd05035 168 --YYRQGRISKMpvKWIALESLADNVYTSKSDVWSFGVTMWEIATrGQTPYP---GVENHE------IYDYLRNGnRLKQ 236
                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*..
gi 15223445 534 AIDrsiC-DKGHDeeilqflkIACSCVVSRPKERPTMIQVYESLKNM 579
Cdd:cd05035 237 PED---ClDEVYF--------LMYFCWTVDPKDRPTFTKLREVLENI 272
STKc_Bck1_like cd06629
Catalytic domain of the Serine/Threonine Kinases, fungal Bck1-like Mitogen-Activated Protein ...
342-568 2.60e-09

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: 58.55  E-value: 2.60e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 342 RSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHN-GGLCDAVLDWPTRRAIgvgaaKGLAWLHhgcQP 420
Cdd:cd06629  56 KSEIDTLKDLDHPNIVQYLGFEETEDYFSIFLEYVPGGSIGSCLRKyGKFEEDLVRFFTRQIL-----DGLAYLH---SK 127
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 421 PYLHQFISSNVILLDDDFDARITDYGLaklvgSRDSNDSSFNNGDL---GELGYVAPE--YSSTMVASLKGDVYGFGIVL 495
Cdd:cd06629 128 GILHRDLKADNILVDLEGICKISDFGI-----SKKSDDIYGNNGATsmqGSVFWMAPEviHSQGQGYSAKVDIWSLGCVV 202
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 15223445 496 LELVTGQKPLSVINGVEG-FKgslvdwvsqyLGTGRSKDAI--DRSICDKGHDeeilqFLKiacSCVVSRPKERPT 568
Cdd:cd06629 203 LEMLAGRRPWSDDEAIAAmFK----------LGNKRSAPPVpeDVNLSPEALD-----FLN---ACFAIDPRDRPT 260
STKc_HAL4_like cd13994
Catalytic domain of Fungal Halotolerance protein 4-like Serine/Threonine kinases; STKs ...
314-575 3.77e-09

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: 57.70  E-value: 3.77e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 314 VSYKADLPDGSALAVKRL------SACGFGEKQFRSEMNKLGELRHPNLVPLLGYCVVE-DERLLVYKHMVNGTLFSQLH 386
Cdd:cd13994  11 IVTKKNPRSGVLYAVKEYrrrddeSKRKDYVKRLTSEYIISSKLHHPNIVKVLDLCQDLhGKWCLVMEYCPGGDLFTLIE 90
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 387 NGGLCDAVldwpTRRAIGVGAAKGLAWLH-HGCqppyLHQFISSNVILLDDDFDARITDYGLAKLVGSRDSNDSSFNNGD 465
Cdd:cd13994  91 KADSLSLE----EKDCFFKQILRGVAYLHsHGI----AHRDLKPENILLDEDGVLKLTDFGTAEVFGMPAEKESPMSAGL 162
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 466 LGELGYVAPE-YSSTMVASLKGDVYGFGIVLLELVTGQKP--LSVINGVEG--FKGSLVDWVSQYLGTGRSKDAIDRSIc 540
Cdd:cd13994 163 CGSEPYMAPEvFTSGSYDGRAVDVWSCGIVLFALFTGRFPwrSAKKSDSAYkaYEKSGDFTNGPYEPIENLLPSECRRL- 241
                       250       260       270
                ....*....|....*....|....*....|....*
gi 15223445 541 dkghdeeILQFLKIacscvvsRPKERPTMIQVYES 575
Cdd:cd13994 242 -------IYRMLHP-------DPEKRITIDEALND 262
STKc_PAK3 cd06656
Catalytic domain of the Protein Serine/Threonine Kinase, p21-activated kinase 3; Serine ...
312-578 3.85e-09

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: 58.19  E-value: 3.85e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 312 TGVSYKA-DLPDGSALAVKRLSACGFGEKQFR-SEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLfsqlhNGG 389
Cdd:cd06656  32 SGTVYTAiDIATGQEVAIKQMNLQQQPKKELIiNEILVMRENKNPNIVNYLDSYLVGDELWVVMEYLAGGSL-----TDV 106
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 390 LCDAVLDWPTRRAIGVGAAKGLAWLHHGcqpPYLHQFISSNVILLDDDFDARITDYGLAKLVGSRDSNDSSFnngdLGEL 469
Cdd:cd06656 107 VTETCMDEGQIAAVCRECLQALDFLHSN---QVIHRDIKSDNILLGMDGSVKLTDFGFCAQITPEQSKRSTM----VGTP 179
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 470 GYVAPEYSSTMVASLKGDVYGFGIVLLELVTGQKP-----------LSVINGV------EGFKGSLVDWVSQYLgtgrsK 532
Cdd:cd06656 180 YWMAPEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPylnenplralyLIATNGTpelqnpERLSAVFRDFLNRCL-----E 254
                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|
gi 15223445 533 DAIDRsicdKGHDEEILQ--FLKIAcscvvsRPKER--PTMIQVYESLKN 578
Cdd:cd06656 255 MDVDR----RGSAKELLQhpFLKLA------KPLSSltPLIIAAKEAIKN 294
STKc_EIF2AK4_GCN2_rpt2 cd14046
Catalytic domain, repeat 2, of the Serine/Threonine kinase, eukaryotic translation Initiation ...
322-498 3.93e-09

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: 58.15  E-value: 3.93e-09
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 322 DGSALAVKRLSACGfGEKQFR---SEMNKLGELRHPNLVPLLGyCVVEDERLlvYKHM---VNGTLFSQLHNGGLCDAVL 395
Cdd:cd14046  30 DGRYYAIKKIKLRS-ESKNNSrilREVMLLSRLNHQHVVRYYQ-AWIERANL--YIQMeycEKSTLRDLIDSGLFQDTDR 105
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 396 DWPTRRAIgvgaAKGLAWLH-HGCqppyLHQFISSNVILLDDDFDARITDYGLAK-----------LVGSRDSNDSSFN- 462
Cdd:cd14046 106 LWRLFRQI----LEGLAYIHsQGI----IHRDLKPVNIFLDSNGNVKIGDFGLATsnklnvelatqDINKSTSAALGSSg 177
                       170       180       190       200
                ....*....|....*....|....*....|....*....|
gi 15223445 463 --NGDLGELGYVAPEYSSTMVASL--KGDVYGFGIVLLEL 498
Cdd:cd14046 178 dlTGNVGTALYVAPEVQSGTKSTYneKVDMYSLGIIFFEM 217
STKc_PAK1 cd06654
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 1; STKs catalyze the ...
312-555 1.06e-08

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: 57.04  E-value: 1.06e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 312 TGVSYKA-DLPDGSALAVKRLSACGFGEKQFR-SEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLfsqlhNGG 389
Cdd:cd06654  33 SGTVYTAmDVATGQEVAIRQMNLQQQPKKELIiNEILVMRENKNPNIVNYLDSYLVGDELWVVMEYLAGGSL-----TDV 107
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 390 LCDAVLDWPTRRAIGVGAAKGLAWLHHGcqpPYLHQFISSNVILLDDDFDARITDYGLAKLVGSRDSNDSSFnngdLGEL 469
Cdd:cd06654 108 VTETCMDEGQIAAVCRECLQALEFLHSN---QVIHRDIKSDNILLGMDGSVKLTDFGFCAQITPEQSKRSTM----VGTP 180
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 470 GYVAPEYSSTMVASLKGDVYGFGIVLLELVTGQKP-----------LSVINGV------EGFKGSLVDWVSQYLgtgrsk 532
Cdd:cd06654 181 YWMAPEVVTRKAYGPKVDIWSLGIMAIEMIEGEPPylnenplralyLIATNGTpelqnpEKLSAIFRDFLNRCL------ 254
                       250       260
                ....*....|....*....|....*
gi 15223445 533 daiDRSICDKGHDEEIL--QFLKIA 555
Cdd:cd06654 255 ---EMDVEKRGSAKELLqhQFLKIA 276
STKc_LIMK cd14154
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase; STKs catalyze the transfer ...
338-499 1.14e-08

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: 56.36  E-value: 1.14e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 338 EKQFRSEMNKLGELRHPNLVPLLGyCVVEDERL-LVYKHMVNGTLFSQLHNgglCDAVLDWPTRRAIGVGAAKGLAWLHH 416
Cdd:cd14154  34 QRNFLKEVKVMRSLDHPNVLKFIG-VLYKDKKLnLITEYIPGGTLKDVLKD---MARPLPWAQRVRFAKDIASGMAYLHS 109
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 417 GCqppYLHQFISSNVILLDDDFDARITDYGLAKL-VGSRDSNDSSFNNGDLGELGYVAPEYSSTMVAS--------LKG- 486
Cdd:cd14154 110 MN---IIHRDLNSHNCLVREDKTVVVADFGLARLiVEERLPSGNMSPSETLRHLKSPDRKKRYTVVGNpywmapemLNGr 186
                       170
                ....*....|....*....
gi 15223445 487 ------DVYGFGIVLLELV 499
Cdd:cd14154 187 sydekvDIFSFGIVLCEII 205
PTKc_Jak_rpt2 cd05038
Catalytic (repeat 2) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak subfamily ...
323-500 1.17e-08

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: 56.62  E-value: 1.17e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 323 GSALAVKRLSACGFGEKQ--FRSEMNKLGELRHPNLVPLLGYCVVEDER--LLVYKHMVNGTLFSQLHNGglcDAVLDWP 398
Cdd:cd05038  33 GEQVAVKSLQPSGEEQHMsdFKREIEILRTLDHEYIVKYKGVCESPGRRslRLIMEYLPSGSLRDYLQRH---RDQIDLK 109
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 399 TRRAIGVGAAKGLAWLHhgcQPPYLHQFISSNVILLDDDFDARITDYGLAKLVGSRDSNDSSFNNGDLGELGYvAPEYSS 478
Cdd:cd05038 110 RLLLFASQICKGMEYLG---SQRYIHRDLAARNILVESEDLVKISDFGLAKVLPEDKEYYYVKEPGESPIFWY-APECLR 185
                       170       180
                ....*....|....*....|..
gi 15223445 479 TMVASLKGDVYGFGIVLLELVT 500
Cdd:cd05038 186 ESRFSSASDVWSFGVTLYELFT 207
LRR COG4886
Leucine-rich repeat (LRR) protein [Transcription];
2-163 1.25e-08

Leucine-rich repeat (LRR) protein [Transcription];


Pssm-ID: 443914 [Multi-domain]  Cd Length: 414  Bit Score: 57.25  E-value: 1.25e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445   2 KKIFITLLWLLFISSFLCSSSSAEDDVLCLQGLKNSLIDPSSRLSSWSFPNSSASSICKLTGVSCWNEKENRIISLQLQS 81
Cdd:COG4886  19 ELLTTLILLLLLLLLLLALLLLSLLSLLLLLTLLLSLLLRDLLLSSLLLLLSLLLLLLLSLLLLSLLLLGLTDLGDLTNL 98
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445  82 MQLAGEIPESLKLCRSLQSLDLSGNDLSgSIPSQICSwLPYLVTLDLSGNKLgGSIPTQIVECKFLNALILSDNKLSgSI 161
Cdd:COG4886  99 TELDLSGNEELSNLTNLESLDLSGNQLT-DLPEELAN-LTNLKELDLSNNQL-TDLPEPLGNLTNLKSLDLSNNQLT-DL 174

                ..
gi 15223445 162 PS 163
Cdd:COG4886 175 PE 176
PTKc_InsR_like cd05032
Catalytic domain of Insulin Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer ...
327-578 1.36e-08

Catalytic domain of Insulin Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The InsR subfamily is composed of InsR, Insulin-like Growth Factor-1 Receptor (IGF-1R), and similar proteins. InsR and IGF-1R are receptor PTKs (RTKs) composed of two alphabeta heterodimers. Binding of the ligand (insulin, IGF-1, or IGF-2) to the extracellular alpha subunit activates the intracellular tyr kinase domain of the transmembrane beta subunit. Receptor activation leads to autophosphorylation, stimulating downstream kinase activities, which initiate signaling cascades and biological function. InsR and IGF-1R, which share 84% sequence identity in their kinase domains, display physiologically distinct yet overlapping functions in cell growth, differentiation, and metabolism. InsR activation leads primarily to metabolic effects while IGF-1R activation stimulates mitogenic pathways. In cells expressing both receptors, InsR/IGF-1R hybrids are found together with classical receptors. Both receptors can interact with common adaptor molecules such as IRS-1 and IRS-2. The InsR-like subfamily 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: 173625 [Multi-domain]  Cd Length: 277  Bit Score: 56.20  E-value: 1.36e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 327 AVKRLSACG-FGEK-QFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQL--------HNGGLcdavlD 396
Cdd:cd05032  40 AIKTVNENAsMRERiEFLNEASVMKEFNCHHVVRLLGVVSTGQPTLVVMELMAKGDLKSYLrsrrpeaeNNPGL-----G 114
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 397 WPTR-RAIGVGA--AKGLAWLHhgcQPPYLHQFISSNVILLDDDFDARITDYGLAKLVGSRDSndssFNNGDLGELG--Y 471
Cdd:cd05032 115 PPTLqKFIQMAAeiADGMAYLA---AKKFVHRDLAARNCMVAEDLTVKIGDFGMTRDIYETDY----YRKGGKGLLPvrW 187
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 472 VAPEYSSTMVASLKGDVYGFGIVLLELVT-GQKPlsvingvegfkgslvdwvsqYLgtGRSKDAIDRSICDKGH------ 544
Cdd:cd05032 188 MAPESLKDGVFTTKSDVWSFGVVLWEMATlAEQP--------------------YQ--GLSNEEVLKFVIDGGHldlpen 245
                       250       260       270
                ....*....|....*....|....*....|....*
gi 15223445 545 -DEEILQFLKIacsCVVSRPKERPTMIQVYESLKN 578
Cdd:cd05032 246 cPDKLLELMRM---CWQYNPKMRPTFLEIVSSLKD 277
STKc_Nek10 cd08528
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
343-572 1.59e-08

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: 55.97  E-value: 1.59e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 343 SEMNKLGE-LRHPNLVPLLGyCVVEDERLLVYKHMVNGTLFSQLHNGgLCDAVLDWPTRR--AIGVGAAKGLAWLHHgcQ 419
Cdd:cd08528  57 SEVNIIKEqLRHPNIVRYYK-TFLENDRLYIVMELIEGAPLGEHFSS-LKEKNEHFTEDRiwNIFVQMVLALRYLHK--E 132
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 420 PPYLHQFISSNVILLDDDFDARITDYGLAKlvgsRDSNDSSFNNGDLGELGYVAPEYSSTMVASLKGDVYGFGIVLLELV 499
Cdd:cd08528 133 KQIVHRDLKPNNIMLGEDDKVTITDFGLAK----QKGPESSKMTSVVGTILYSCPEIVQNEPYGEKADIWALGCILYQMC 208
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 15223445 500 TGQKPLSVINgVEGFKGSLVDWVSQYLGTGRSKDAIDRSIcdkghdeeilqflkiaCSCVVSRPKERPTMIQV 572
Cdd:cd08528 209 TLQPPFYSTN-MLTLATKIVEAEYEPLPEGMYSDDITFVI----------------RSCLTPDPEARPDIVEV 264
STKc_TGFbR2_like cd14055
Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Type II ...
338-500 1.71e-08

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: 56.23  E-value: 1.71e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 338 EKQFRSEMNklgeLRHPNLVPLLGycvVEDERLLVYKHMvngTLFSQLH-NGGLCD----AVLDWPTRRAIGVGAAKGLA 412
Cdd:cd14055  43 EKDIFTDAS----LKHENILQFLT---AEERGVGLDRQY---WLITAYHeNGSLQDyltrHILSWEDLCKMAGSLARGLA 112
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 413 WLHHGCQP------PYLHQFISSNVILLDDDFDARITDYGLAKLVGSRDSNDSSFNNGDLGELGYVAPEYSSTMV----- 481
Cdd:cd14055 113 HLHSDRTPcgrpkiPIAHRDLKSSNILVKNDGTCVLADFGLALRLDPSLSVDELANSGQVGTARYMAPEALESRVnledl 192
                       170       180
                ....*....|....*....|
gi 15223445 482 ASLKG-DVYGFGIVLLELVT 500
Cdd:cd14055 193 ESFKQiDVYSMALVLWEMAS 212
PTKc_Tie cd05047
Catalytic domain of Tie Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
327-581 2.09e-08

Catalytic domain of Tie Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tie proteins, consisting of Tie1 and Tie2, are receptor PTKs (RTKs) containing an extracellular region, a transmembrane segment, and an intracellular catalytic domain. The extracellular region contains an immunoglobulin (Ig)-like domain, three epidermal growth factor (EGF)-like domains, a second Ig-like domain, and three fibronectin type III repeats. Tie receptors are specifically expressed in endothelial cells and hematopoietic stem cells. The angiopoietins (Ang-1 to Ang-4) serve as ligands for Tie2, while no specific ligand has been identified for Tie1. The binding of Ang-1 to Tie2 leads to receptor autophosphorylation and activation, promoting cell migration and survival. In contrast, Ang-2 binding to Tie2 does not result in the same response, suggesting that Ang-2 may function as an antagonist. In vivo studies of Tie1 show that it is critical in vascular development. The Tie 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: 270641 [Multi-domain]  Cd Length: 270  Bit Score: 55.82  E-value: 2.09e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 327 AVKRLS--ACGFGEKQFRSEMNKLGEL-RHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHNgglcDAVLDWPTRRAI 403
Cdd:cd05047  26 AIKRMKeyASKDDHRDFAGELEVLCKLgHHPNIINLLGACEHRGYLYLAIEYAPHGNLLDFLRK----SRVLETDPAFAI 101
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 404 GVGAAKGLA-------------WLHHGCQPPYLHQFISSNVILLDDDFDARITDYGLAKlvgsrdsNDSSFNNGDLGELG 470
Cdd:cd05047 102 ANSTASTLSsqqllhfaadvarGMDYLSQKQFIHRDLAARNILVGENYVAKIADFGLSR-------GQEVYVKKTMGRLP 174
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 471 --YVAPEYSSTMVASLKGDVYGFGIVLLELVT-GQKPLSVINGVEgfkgsLVDWVSQYLGTGRSKDAidrsicdkghDEE 547
Cdd:cd05047 175 vrWMAIESLNYSVYTTNSDVWSYGVLLWEIVSlGGTPYCGMTCAE-----LYEKLPQGYRLEKPLNC----------DDE 239
                       250       260       270
                ....*....|....*....|....*....|....
gi 15223445 548 ILQFLKiacSCVVSRPKERPTMIQVYESLKNMAD 581
Cdd:cd05047 240 VYDLMR---QCWREKPYERPSFAQILVSLNRMLE 270
STKc_ACVR2a cd14141
Catalytic domain of the Serine/Threonine Kinase, Activin Type IIA Receptor; STKs catalyze the ...
306-500 2.32e-08

Catalytic domain of the Serine/Threonine Kinase, Activin Type IIA Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ACVR2a (or ActRIIA) belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, bone morphogenetic proteins (BMPs), activins, growth and differentiation factors (GDFs), 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. ACVR2b is one of two ACVR2 receptors found in vertebrates. Type II receptors are high-affinity receptors which bind ligands, autophosphorylate, as well as trans-phosphorylate and activate low-affinity type I receptors. ACVR2 acts primarily as the receptors for activins, nodal, myostatin, GDF11, and a subset of BMPs. ACVR2 signaling impacts many cellular and physiological processes including reproductive and gonadal functions, myogenesis, bone remodeling and tooth development, kidney organogenesis, apoptosis, fibrosis, inflammation, and neurogenesis. The ACVR2a subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271043 [Multi-domain]  Cd Length: 290  Bit Score: 55.82  E-value: 2.32e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 306 IDVSSRTGVSYKADLPDgSALAVKRLSACGFGEKQFRSEMNKLGELRHPNLVPLLGY----CVVEDERLLVYKHMVNGTL 381
Cdd:cd14141   2 IKARGRFGCVWKAQLLN-EYVAVKIFPIQDKLSWQNEYEIYSLPGMKHENILQFIGAekrgTNLDVDLWLITAFHEKGSL 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 382 FSQLHNGglcdaVLDWPTRRAIGVGAAKGLAWLHH-------GCQPPYLHQFISSNVILLDDDFDARITDYGLA-KLVGS 453
Cdd:cd14141  81 TDYLKAN-----VVSWNELCHIAQTMARGLAYLHEdipglkdGHKPAIAHRDIKSKNVLLKNNLTACIADFGLAlKFEAG 155
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|..
gi 15223445 454 RDSNDSsfnNGDLGELGYVAPEYSSTMV-----ASLKGDVYGFGIVLLELVT 500
Cdd:cd14141 156 KSAGDT---HGQVGTRRYMAPEVLEGAInfqrdAFLRIDMYAMGLVLWELAS 204
PTKc_Ror cd05048
Catalytic Domain of the Protein Tyrosine Kinases, Receptor tyrosine kinase-like Orphan ...
313-504 2.48e-08

Catalytic Domain of the Protein Tyrosine Kinases, Receptor tyrosine kinase-like Orphan Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Ror subfamily consists of Ror1, Ror2, and similar proteins. Ror proteins are orphan receptor PTKs (RTKs) containing an extracellular region with immunoglobulin-like, cysteine-rich, and kringle domains, a transmembrane segment, and an intracellular catalytic domain. Ror RTKs are unrelated to the nuclear receptor subfamily called retinoid-related orphan receptors (RORs). RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain. Ror kinases are expressed in many tissues during development. They play important roles in bone and heart formation. Mutations in human Ror2 result in two different bone development genetic disorders, recessive Robinow syndrome and brachydactyly type B. Drosophila Ror is expressed only in the developing nervous system during neurite outgrowth and neuronal differentiation, suggesting a role for Drosophila Ror in neural development. More recently, mouse Ror1 and Ror2 have also been found to play an important role in regulating neurite growth in central neurons. Ror1 and Ror2 are believed to have some overlapping and redundant functions. The Ror 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: 270642 [Multi-domain]  Cd Length: 283  Bit Score: 55.46  E-value: 2.48e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 313 GVSYKADL----PDGSA--LAVKRL--SACGFGEKQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTL--F 382
Cdd:cd05048  19 GKVYKGELlgpsSEESAisVAIKTLkeNASPKTQQDFRREAELMSDLQHPNIVCLLGVCTKEQPQCMLFEYMAHGDLheF 98
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 383 SQLHN------GGLCDA----VLDWPTRRAIGVGAAKGLAWL--HHgcqppYLHQFISSNVILLDDDFDARITDYGLAKL 450
Cdd:cd05048  99 LVRHSphsdvgVSSDDDgtasSLDQSDFLHIAIQIAAGMEYLssHH-----YVHRDLAARNCLVGDGLTVKISDFGLSRD 173
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 15223445 451 VGSRD-----SNdssfnngDLGELGYVAPE---YSSTMVASlkgDVYGFGIVLLELVT-GQKP 504
Cdd:cd05048 174 IYSSDyyrvqSK-------SLLPVRWMPPEailYGKFTTES---DVWSFGVVLWEIFSyGLQP 226
STKc_RIP1 cd14027
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 1; STKs catalyze ...
351-574 2.59e-08

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: 55.20  E-value: 2.59e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 351 LRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHNGGLCDAVldwptRRAIGVGAAKGLAWLHhgcQPPYLHQFISSN 430
Cdd:cd14027  48 LRHSRVVKLLGVILEEGKYSLVMEYMEKGNLMHVLKKVSVPLSV-----KGRIILEIIEGMAYLH---GKGVIHKDLKPE 119
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 431 VILLDDDFDARITDYGLAKL-VGSRDSND----------SSFNNGdlGELGYVAPEYSSTMVA--SLKGDVYGFGIVLLE 497
Cdd:cd14027 120 NILVDNDFHIKIADLGLASFkMWSKLTKEehneqrevdgTAKKNA--GTLYYMAPEHLNDVNAkpTEKSDVYSFAIVLWA 197
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 498 LVTGQKPLSvingvegfkgslvdwvsqylgTGRSKDAIDRSICDKGHDE----------EILQFLKiacSCVVSRPKERP 567
Cdd:cd14027 198 IFANKEPYE---------------------NAINEDQIIMCIKSGNRPDvdditeycprEIIDLMK---LCWEANPEARP 253

                ....*..
gi 15223445 568 TMIQVYE 574
Cdd:cd14027 254 TFPGIEE 260
STKc_WNK4 cd14033
Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 4; STKs catalyze ...
326-506 2.64e-08

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: 55.39  E-value: 2.64e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 326 LAVKRLSAcgfGEKQ-FRSEMNKLGELRHPNLV--------PLLGY-CVVederlLVYKHMVNGTLFSQLHN-GGLCDAV 394
Cdd:cd14033  34 LQTRKLSK---GERQrFSEEVEMLKGLQHPNIVrfydswksTVRGHkCII-----LVTELMTSGTLKTYLKRfREMKLKL 105
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 395 LDWPTRRAIgvgaaKGLAWLHHGCqPPYLHQFIS-SNVILLDDDFDARITDYGLAKLvgsrdsNDSSFNNGDLGELGYVA 473
Cdd:cd14033 106 LQRWSRQIL-----KGLHFLHSRC-PPILHRDLKcDNIFITGPTGSVKIGDLGLATL------KRASFAKSVIGTPEFMA 173
                       170       180       190
                ....*....|....*....|....*....|....
gi 15223445 474 PE-YSSTMVASLkgDVYGFGIVLLELVTGQKPLS 506
Cdd:cd14033 174 PEmYEEKYDEAV--DVYAFGMCILEMATSEYPYS 205
STKc_PDK1 cd05581
Catalytic domain of the Serine/Threonine Kinase, Phosphoinositide-dependent kinase 1; STKs ...
316-526 2.67e-08

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: 55.30  E-value: 2.67e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 316 YKA-DLPDGSALAVKRLSacgfgeKQFRSEMNK----------LGELRHPNLVPLlgYCVVEDERLL--VYKHMVNGTLF 382
Cdd:cd05581  18 VLAkEKETGKEYAIKVLD------KRHIIKEKKvkyvtiekevLSRLAHPGIVKL--YYTFQDESKLyfVLEYAPNGDLL 89
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 383 SQLHNGGlcdaVLDWPTRRAIgvgaakgLAWLHHGCQppYLHQ--FISSNV----ILLDDDFDARITDYGLAKLVGSRDS 456
Cdd:cd05581  90 EYIRKYG----SLDEKCTRFY-------TAEIVLALE--YLHSkgIIHRDLkpenILLDEDMHIKITDFGTAKVLGPDSS 156
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 457 NDSSFNNGDLGELG-------------YVAPEYSSTMVASLKGDVYGFGIVLLELVTGQKPlsvingvegFKGSlvdwvS 523
Cdd:cd05581 157 PESTKGDADSQIAYnqaraasfvgtaeYVSPELLNEKPAGKSSDLWALGCIIYQMLTGKPP---------FRGS-----N 222

                ...
gi 15223445 524 QYL 526
Cdd:cd05581 223 EYL 225
LRRNT_2 pfam08263
Leucine rich repeat N-terminal domain; Leucine Rich Repeats pfam00560 are short sequence ...
24-67 3.00e-08

Leucine rich repeat N-terminal domain; Leucine Rich Repeats pfam00560 are short sequence motifs present in a number of proteins with diverse functions and cellular locations. Leucine Rich Repeats are often flanked by cysteine rich domains. This domain is often found at the N-terminus of tandem leucine rich repeats.


Pssm-ID: 462411 [Multi-domain]  Cd Length: 41  Bit Score: 49.99  E-value: 3.00e-08
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....
gi 15223445    24 AEDDVLCLQGLKNSLIDPSSRLSSWsfpNSSASSICKLTGVSCW 67
Cdd:pfam08263   1 LNDDGQALLAFKSSLNDPPGALSSW---NSSSSDPCSWTGVTCD 41
PTKc_Met_Ron cd05058
Catalytic domain of the Protein Tyrosine Kinases, Met and Ron; PTKs catalyze the transfer of ...
340-530 3.26e-08

Catalytic domain of the Protein Tyrosine Kinases, Met and Ron; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Met and Ron are receptor PTKs (RTKs) composed of an alpha-beta heterodimer. The extracellular alpha chain is disulfide linked to the beta chain, which contains an extracellular ligand-binding region with a sema domain, a PSI domain and four IPT repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. Met binds to the ligand, hepatocyte growth factor/scatter factor (HGF/SF), and is also called the HGF receptor. HGF/Met signaling plays a role in growth, transformation, cell motility, invasion, metastasis, angiogenesis, wound healing, and tissue regeneration. Aberrant expression of Met through mutations or gene amplification is associated with many human cancers including hereditary papillary renal and gastric carcinomas. The ligand for Ron is macrophage stimulating protein (MSP). Ron signaling is important in regulating cell motility, adhesion, proliferation, and apoptosis. Aberrant Ron expression is implicated in tumorigenesis and metastasis. The Met/Ron 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: 270649 [Multi-domain]  Cd Length: 262  Bit Score: 55.17  E-value: 3.26e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 340 QFRSEMNKLGELRHPNLVPLLGYCV-VEDERLLVYKHMVNGTLF----SQLHNGGLCDAVldwptrrAIGVGAAKGLAWL 414
Cdd:cd05058  42 QFLKEGIIMKDFSHPNVLSLLGICLpSEGSPLVVLPYMKHGDLRnfirSETHNPTVKDLI-------GFGLQVAKGMEYL 114
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 415 hhgCQPPYLHQFISSNVILLDDDFDARITDYGLAKLVGSRDSNDSSFNNGDLGELGYVAPEYSSTMVASLKGDVYGFGIV 494
Cdd:cd05058 115 ---ASKKFVHRDLAARNCMLDESFTVKVADFGLARDIYDKEYYSVHNHTGAKLPVKWMALESLQTQKFTTKSDVWSFGVL 191
                       170       180       190
                ....*....|....*....|....*....|....*..
gi 15223445 495 LLELVT-GQKPLSVINGVEgfkgslvdwVSQYLGTGR 530
Cdd:cd05058 192 LWELMTrGAPPYPDVDSFD---------ITVYLLQGR 219
PTKc_Zap-70 cd05115
Catalytic domain of the Protein Tyrosine Kinase, Zeta-chain-associated protein of 70kDa; PTKs ...
338-577 3.27e-08

Catalytic domain of the Protein Tyrosine Kinase, Zeta-chain-associated protein of 70kDa; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Zap-70 is a cytoplasmic (or nonreceptor) PTK containing two Src homology 2 (SH2) domains N-terminal to the catalytic tyr kinase domain. Zap-70 is primarily expressed in T-cells and NK cells, and is a crucial component in T-cell receptor (TCR) signaling. Zap-70 binds the phosphorylated ITAM (immunoreceptor tyr activation motif) sequences of the activated TCR zeta-chain through its SH2 domains, leading to its phosphorylation and activation. It then phosphorylates target proteins, which propagate the signals to downstream pathways. Zap-70 is hardly detected in normal peripheral B-cells, but is present in some B-cell malignancies. It is used as a diagnostic marker for chronic lymphocytic leukemia (CLL) as it is associated with the more aggressive subtype of the disease. The Zap-70 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: 270686 [Multi-domain]  Cd Length: 269  Bit Score: 54.95  E-value: 3.27e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 338 EKQFRSEMNKLGELRH----PNLVPLLGYCvvEDERLLVYKHMVNGTLFSQLHNGglcdavldwpTRRAIGVG------- 406
Cdd:cd05115  44 EKAVRDEMMREAQIMHqldnPYIVRMIGVC--EAEALMLVMEMASGGPLNKFLSG----------KKDEITVSnvvelmh 111
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 407 -AAKGLAWLHhgcQPPYLHQFISSNVILLDDDFDARITDYGLAKLVGSRDSNDSSFNNGDLgELGYVAPEYSSTMVASLK 485
Cdd:cd05115 112 qVSMGMKYLE---EKNFVHRDLAARNVLLVNQHYAKISDFGLSKALGADDSYYKARSAGKW-PLKWYAPECINFRKFSSR 187
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 486 GDVYGFGIVLLELVT-GQKPLSVINGVEgfkgslvdwVSQYLGTGRSKDaidrsiCDKGHDEEILQFLKiacSCVVSRPK 564
Cdd:cd05115 188 SDVWSYGVTMWEAFSyGQKPYKKMKGPE---------VMSFIEQGKRMD------CPAECPPEMYALMS---DCWIYKWE 249
                       250
                ....*....|...
gi 15223445 565 ERPTMIQVYESLK 577
Cdd:cd05115 250 DRPNFLTVEQRMR 262
STKc_PAK_II cd06648
Catalytic domain of the Serine/Threonine Kinase, Group II p21-activated kinase; STKs catalyze ...
323-505 4.30e-08

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: 54.76  E-value: 4.30e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 323 GSALAVKRLSAcgfgEKQFRSEM--NKLGELR---HPNLVPLLGYCVVEDERLLVYKHMVNGTLfsqlhngglCDAV--- 394
Cdd:cd06648  32 GRQVAVKKMDL----RKQQRRELlfNEVVIMRdyqHPNIVEMYSSYLVGDELWVVMEFLEGGAL---------TDIVtht 98
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 395 -LDWPTRRAIGVGAAKGLAWLH-HGCqppyLHQFISSNVILLDDDFDARITDYGLAKLVgsrdSNDSSFNNGDLGELGYV 472
Cdd:cd06648  99 rMNEEQIATVCRAVLKALSFLHsQGV----IHRDIKSDSILLTSDGRVKLSDFGFCAQV----SKEVPRRKSLVGTPYWM 170
                       170       180       190
                ....*....|....*....|....*....|...
gi 15223445 473 APEYSSTMVASLKGDVYGFGIVLLELVTGQKPL 505
Cdd:cd06648 171 APEVISRLPYGTEVDIWSLGIMVIEMVDGEPPY 203
PTKc_Hck cd05073
Catalytic domain of the Protein Tyrosine Kinase, Hematopoietic cell kinase; PTKs catalyze the ...
324-504 4.55e-08

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: 54.65  E-value: 4.55e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 324 SALAVKRLSACGFGEKQFRSEMNKLGELRHPNLVPLlgYCVVEDERL-LVYKHMVNGTLFSQLHNgglcDAVLDWPTRRA 402
Cdd:cd05073  36 TKVAVKTMKPGSMSVEAFLAEANVMKTLQHDKLVKL--HAVVTKEPIyIITEFMAKGSLLDFLKS----DEGSKQPLPKL 109
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 403 IGVGA--AKGLAWLHhgcQPPYLHQFISSNVILLDDDFDARITDYGLAKLVgsrDSNDSSFNNGDLGELGYVAPEYSSTM 480
Cdd:cd05073 110 IDFSAqiAEGMAFIE---QRNYIHRDLRAANILVSASLVCKIADFGLARVI---EDNEYTAREGAKFPIKWTAPEAINFG 183
                       170       180
                ....*....|....*....|....*
gi 15223445 481 VASLKGDVYGFGIVLLELVT-GQKP 504
Cdd:cd05073 184 SFTIKSDVWSFGILLMEIVTyGRIP 208
LRR COG4886
Leucine-rich repeat (LRR) protein [Transcription];
87-163 5.47e-08

Leucine-rich repeat (LRR) protein [Transcription];


Pssm-ID: 443914 [Multi-domain]  Cd Length: 414  Bit Score: 55.32  E-value: 5.47e-08
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 15223445  87 EIPESLKLCRSLQSLDLSGNDLSgSIPSQIcSWLPYLVTLDLSGNKLgGSIPtQIVECKFLNALILSDNKLSgSIPS 163
Cdd:COG4886 196 DLPEPLGNLTNLEELDLSGNQLT-DLPEPL-ANLTNLETLDLSNNQL-TDLP-ELGNLTNLEELDLSNNQLT-DLPP 267
STKc_LIMK2 cd14222
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 2; STKs catalyze the ...
314-502 5.75e-08

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: 54.56  E-value: 5.75e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 314 VSYKADlpdGSALAVKRLSACGF-GEKQFRSEMNKLGELRHPNLVPLLGyCVVEDERL-LVYKHMVNGTLFSQLHNGGLC 391
Cdd:cd14222  12 VTHKAT---GKVMVMKELIRCDEeTQKTFLTEVKVMRSLDHPNVLKFIG-VLYKDKRLnLLTEFIEGGTLKDFLRADDPF 87
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 392 davlDWPTRRAIGVGAAKGLAWLHHGCqppYLHQFISSNVILLDDDFDARITDYGLAKLVGSRD---------------- 455
Cdd:cd14222  88 ----PWQQKVSFAKGIASGMAYLHSMS---IIHRDLNSHNCLIKLDKTVVVADFGLSRLIVEEKkkpppdkpttkkrtlr 160
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*..
gi 15223445 456 SNDSSFNNGDLGELGYVAPEYSSTMVASLKGDVYGFGIVLLELVtGQ 502
Cdd:cd14222 161 KNDRKKRYTVVGNPYWMAPEMLNGKSYDEKVDIFSFGIVLCEII-GQ 206
STKc_LRRK1 cd14067
Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 1; STKs catalyze ...
340-578 6.36e-08

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: 54.20  E-value: 6.36e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 340 QFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVN-GTLFSQLHNGGLCDAVLDWPTRRaIGVGAAKGLAWLHHgc 418
Cdd:cd14067  56 EFRQEASMLHSLQHPCIVYLIGISIHPLCFALELAPLGSlNTVLEENHKGSSFMPLGHMLTFK-IAYQIAAGLAYLHK-- 132
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 419 QPPYLHQFISSNVIL--LD--DDFDARITDYGLAKlvgsrdsndSSFNNGDLG---ELGYVAPEYSSTMVASLKGDVYGF 491
Cdd:cd14067 133 KNIIFCDLKSDNILVwsLDvqEHINIKLSDYGISR---------QSFHEGALGvegTPGYQAPEIRPRIVYDEKVDMFSY 203
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 492 GIVLLELVTGQKPLSVINGVEgfkgslvdwVSQYLGTGRskdaidRSICdkGHDEEIlQFLKIAC---SCVVSRPKERPT 568
Cdd:cd14067 204 GMVLYELLSGQRPSLGHHQLQ---------IAKKLSKGI------RPVL--GQPEEV-QFFRLQAlmmECWDTKPEKRPL 265
                       250
                ....*....|
gi 15223445 569 MIQVYESLKN 578
Cdd:cd14067 266 ACSVVEQMKD 275
PTKc_Musk cd05050
Catalytic domain of the Protein Tyrosine Kinase, Muscle-specific kinase; PTKs catalyze the ...
326-504 6.42e-08

Catalytic domain of the Protein Tyrosine Kinase, Muscle-specific kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Musk is a receptor PTK (RTK) containing an extracellular region with four immunoglobulin-like domains and a cysteine-rich cluster, a transmembrane segment, and an intracellular catalytic domain. Musk is expressed and concentrated in the postsynaptic membrane in skeletal muscle. It is essential for the establishment of the neuromuscular junction (NMJ), a peripheral synapse that conveys signals from motor neurons to muscle cells. Agrin, a large proteoglycan released from motor neurons, stimulates Musk autophosphorylation and activation, leading to the clustering of acetylcholine receptors (AChRs). To date, there is no evidence to suggest that agrin binds directly to Musk. Mutations in AChR, Musk and other partners are responsible for diseases of the NMJ, such as the autoimmune syndrome myasthenia gravis. The Musk 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: 133181 [Multi-domain]  Cd Length: 288  Bit Score: 54.45  E-value: 6.42e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 326 LAVKRLS--ACGFGEKQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTL-----------FSQLHNGGLCD 392
Cdd:cd05050  38 VAVKMLKeeASADMQADFQREAALMAEFDHPNIVKLLGVCAVGKPMCLLFEYMAYGDLneflrhrspraQCSLSHSTSSA 117
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 393 AV-------LDWPTRRAIGVGAAKGLAWLhhgCQPPYLHQFISSNVILLDDDFDARITDYGLAKLVGSRDSNDSSFNngD 465
Cdd:cd05050 118 RKcglnplpLSCTEQLCIAKQVAAGMAYL---SERKFVHRDLATRNCLVGENMVVKIADFGLSRNIYSADYYKASEN--D 192
                       170       180       190       200
                ....*....|....*....|....*....|....*....|
gi 15223445 466 LGELGYVAPEYSSTMVASLKGDVYGFGIVLLELVT-GQKP 504
Cdd:cd05050 193 AIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSyGMQP 232
STKc_PAK_I cd06647
Catalytic domain of the Serine/Threonine Kinase, Group I p21-activated kinase; STKs catalyze ...
312-504 6.47e-08

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: 54.16  E-value: 6.47e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 312 TGVSYKA-DLPDGSALAVKRLSACGFGEKQFR-SEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHNGG 389
Cdd:cd06647  20 SGTVYTAiDVATGQEVAIKQMNLQQQPKKELIiNEILVMRENKNPNIVNYLDSYLVGDELWVVMEYLAGGSLTDVVTETC 99
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 390 LCDAVLDWPTRRAIgvgaaKGLAWLHHGcqpPYLHQFISSNVILLDDDFDARITDYGLAKLVGSRDSNDSSFnngdLGEL 469
Cdd:cd06647 100 MDEGQIAAVCRECL-----QALEFLHSN---QVIHRDIKSDNILLGMDGSVKLTDFGFCAQITPEQSKRSTM----VGTP 167
                       170       180       190
                ....*....|....*....|....*....|....*
gi 15223445 470 GYVAPEYSSTMVASLKGDVYGFGIVLLELVTGQKP 504
Cdd:cd06647 168 YWMAPEVVTRKAYGPKVDIWSLGIMAIEMVEGEPP 202
STKc_EIF2AK cd13996
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
313-576 8.21e-08

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: 53.84  E-value: 8.21e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 313 GVSYKA-DLPDGSALAVKRL---SACGFGEKQFRsEMNKLGELRHPNLVpllGY--CVVEDERLlvYKHM---VNGTLFS 383
Cdd:cd13996  20 GSVYKVrNKVDGVTYAIKKIrltEKSSASEKVLR-EVKALAKLNHPNIV---RYytAWVEEPPL--YIQMelcEGGTLRD 93
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 384 QLHNGGLC---DAVLDWPTRRAIGvgaaKGLAWLHHGCqppYLHQFIS-SNVILLDDDFDARITDYGLAKLVG----SRD 455
Cdd:cd13996  94 WIDRRNSSsknDRKLALELFKQIL----KGVSYIHSKG---IVHRDLKpSNIFLDNDDLQVKIGDFGLATSIGnqkrELN 166
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 456 SNDSSFNNGD------LGELGYVAPEYSSTMVASLKGDVYGFGIVLLELV----TGQKPLSVINGVEgfKGSLVDWvsqy 525
Cdd:cd13996 167 NLNNNNNGNTsnnsvgIGTPLYASPEQLDGENYNEKADIYSLGIILFEMLhpfkTAMERSTILTDLR--NGILPES---- 240
                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|.
gi 15223445 526 lgtgrskdaidrsiCDKGHDEEIlQFLKiacSCVVSRPKERPTMIQVYESL 576
Cdd:cd13996 241 --------------FKAKHPKEA-DLIQ---SLLSKNPEERPSAEQLLRSL 273
STKc_Mos cd13979
Catalytic domain of the Serine/Threonine kinase, Oocyte maturation factor Mos; STKs catalyze ...
313-509 9.92e-08

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: 53.54  E-value: 9.92e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 313 GVSYKAdLPDGSALAVKRLSAC---GFGEKQFRSEMNKLgELRHPNLVPLLGYCVVEDER---LLVYKHMVNGTLfSQLH 386
Cdd:cd13979  17 GSVYKA-TYKGETVAVKIVRRRrknRASRQSFWAELNAA-RLRHENIVRVLAAETGTDFAslgLIIMEYCGNGTL-QQLI 93
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 387 NGGlcDAVLDWPTRRAIGVGAAKGLAWLH-HGCqppyLHQFISSNVILLDDDFDARITDYGLAKLVGSRDSNDSSFNNGD 465
Cdd:cd13979  94 YEG--SEPLPLAHRILISLDIARALRFCHsHGI----VHLDVKPANILISEQGVCKLCDFGCSVKLGEGNEVGTPRSHIG 167
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....
gi 15223445 466 lGELGYVAPEYSSTMVASLKGDVYGFGIVLLELVTGQKPLSVIN 509
Cdd:cd13979 168 -GTYTYRAPELLKGERVTPKADIYSFGITLWQMLTRELPYAGLR 210
PTKc_Fes_like cd05041
Catalytic domain of Fes-like Protein Tyrosine Kinases; Protein Tyrosine Kinase (PTK) family; ...
316-577 1.18e-07

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: 53.22  E-value: 1.18e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 316 YKADL-PDGSALAVK--RLSACGFGEKQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHNGGlcd 392
Cdd:cd05041  12 YRGVLkPDNTEVAVKtcRETLPPDLKRKFLQEARILKQYDHPNIVKLIGVCVQKQPIMIVMELVPGGSLLTFLRKKG--- 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 393 AVLDWPTRRAIGVGAAKGLAWLHHGCqppYLHQFISSNVILLDDDFDARITDYGLaklvgSRDSNDSSFNNGD-LGEL-- 469
Cdd:cd05041  89 ARLTVKQLLQMCLDAAAGMEYLESKN---CIHRDLAARNCLVGENNVLKISDFGM-----SREEEDGEYTVSDgLKQIpi 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 470 GYVAPEYSSTMVASLKGDVYGFGIVLLELVTGqkplsvinGVEGFKGslvdWVSQylgtgRSKDAID---RSICDKGHDE 546
Cdd:cd05041 161 KWTAPEALNYGRYTSESDVWSFGILLWEIFSL--------GATPYPG----MSNQ-----QTREQIEsgyRMPAPELCPE 223
                       250       260       270
                ....*....|....*....|....*....|.
gi 15223445 547 EILQFLKiacSCVVSRPKERPTMIQVYESLK 577
Cdd:cd05041 224 AVYRLML---QCWAYDPENRPSFSEIYNELQ 251
STKc_AMPK-like cd14003
Catalytic domain of AMP-activated protein kinase-like Serine/Threonine Kinases; STKs catalyze ...
319-504 1.31e-07

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: 52.91  E-value: 1.31e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 319 DLPDGSALAVK---RLSACGFGEKQFRSEMNKLGELRHPNLVPLlgYCVVEDER--LLVYKHMVNGTLFSQLHNGGlcda 393
Cdd:cd14003  21 HKLTGEKVAIKiidKSKLKEEIEEKIKREIEIMKLLNHPNIIKL--YEVIETENkiYLVMEYASGGELFDYIVNNG---- 94
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 394 VLDWPTRRAIGVGAAKGLAWLH-HGCqppyLHQFISSNVILLDDDFDARITDYGLaklvgSRDSNDSSFNNGDLGELGYV 472
Cdd:cd14003  95 RLSEDEARRFFQQLISAVDYCHsNGI----VHRDLKLENILLDKNGNLKIIDFGL-----SNEFRGGSLLKTFCGTPAYA 165
                       170       180       190
                ....*....|....*....|....*....|....*...
gi 15223445 473 APE------YSSTMVaslkgDVYGFGIVLLELVTGQKP 504
Cdd:cd14003 166 APEvllgrkYDGPKA-----DVWSLGVILYAMLTGYLP 198
PTKc_Jak3_rpt2 cd05081
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 3; PTKs catalyze the ...
323-500 1.45e-07

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: 53.36  E-value: 1.45e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 323 GSALAVKRLSACGFGEKQ-FRSEMNKLGELRHPNLVPLLGYCVVEDER--LLVYKHMVNGTL--FSQLHNgglcdAVLDW 397
Cdd:cd05081  33 GALVAVKQLQHSGPDQQRdFQREIQILKALHSDFIVKYRGVSYGPGRRslRLVMEYLPSGCLrdFLQRHR-----ARLDA 107
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 398 PTRRAIGVGAAKGLAWLhhGCQPpYLHQFISSNVILLDDDFDARITDYGLAKLVgSRDSNDSSFNNGDLGELGYVAPEYS 477
Cdd:cd05081 108 SRLLLYSSQICKGMEYL--GSRR-CVHRDLAARNILVESEAHVKIADFGLAKLL-PLDKDYYVVREPGQSPIFWYAPESL 183
                       170       180
                ....*....|....*....|...
gi 15223445 478 STMVASLKGDVYGFGIVLLELVT 500
Cdd:cd05081 184 SDNIFSRQSDVWSFGVVLYELFT 206
PTK_Ryk cd05043
Pseudokinase domain of Ryk (Receptor related to tyrosine kinase); Ryk is a receptor tyr kinase ...
341-576 1.48e-07

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: 53.22  E-value: 1.48e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 341 FRSEMNKLGELRHPNLVPLLGYCVVEDERLLV-YKHMVNGTLFSQLHNGGLCDAVLD--WPTRRAI--GVGAAKGLAWLH 415
Cdd:cd05043  54 LLQESSLLYGLSHQNLLPILHVCIEDGEKPMVlYPYMNWGNLKLFLQQCRLSEANNPqaLSTQQLVhmALQIACGMSYLH 133
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 416 -HGCqppyLHQFISSNVILLDDDFDARITDYGLaklvgSRDSNDSSFNN-GDlGE---LGYVAPEYSSTMVASLKGDVYG 490
Cdd:cd05043 134 rRGV----IHKDIAARNCVIDDELQVKITDNAL-----SRDLFPMDYHClGD-NEnrpIKWMSLESLVNKEYSSASDVWS 203
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 491 FGIVLLELVT-GQKPLSVINGVEgfkgslvdwVSQYLGTG-RSKDAIDrsiCDkghDEeilQFLKIACsCVVSRPKERPT 568
Cdd:cd05043 204 FGVLLWELMTlGQTPYVEIDPFE---------MAAYLKDGyRLAQPIN---CP---DE---LFAVMAC-CWALDPEERPS 264

                ....*...
gi 15223445 569 MIQVYESL 576
Cdd:cd05043 265 FQQLVQCL 272
STKc_WNK3 cd14031
Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 3; STKs catalyze ...
338-506 1.90e-07

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: 52.80  E-value: 1.90e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 338 EKQFRSEMNKLGELRHPNLVPLLGY---------CVVederlLVYKHMVNGTLFSQLHNGglcdAVLDWPTRRAIGVGAA 408
Cdd:cd14031  53 QQRFKEEAEMLKGLQHPNIVRFYDSwesvlkgkkCIV-----LVTELMTSGTLKTYLKRF----KVMKPKVLRSWCRQIL 123
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 409 KGLAWLHHGcQPPYLHQFIS-SNVILLDDDFDARITDYGLAKLVgsrdsnDSSFNNGDLGELGYVAPE-YSSTMVASLkg 486
Cdd:cd14031 124 KGLQFLHTR-TPPIIHRDLKcDNIFITGPTGSVKIGDLGLATLM------RTSFAKSVIGTPEFMAPEmYEEHYDESV-- 194
                       170       180
                ....*....|....*....|
gi 15223445 487 DVYGFGIVLLELVTGQKPLS 506
Cdd:cd14031 195 DVYAFGMCMLEMATSEYPYS 214
PHA02988 PHA02988
hypothetical protein; Provisional
340-504 2.14e-07

hypothetical protein; Provisional


Pssm-ID: 165291 [Multi-domain]  Cd Length: 283  Bit Score: 52.82  E-value: 2.14e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445  340 QFRSEMNKLGELRHPNLVPLLGYCV-VEDE--RL-LVYKHMVNGTLFSQLHNgglcDAVLDWPTRRAIGVGAAKGLAWLH 415
Cdd:PHA02988  64 ITENEIKNLRRIDSNNILKIYGFIIdIVDDlpRLsLILEYCTRGYLREVLDK----EKDLSFKTKLDMAIDCCKGLYNLY 139
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445  416 HGCQPPYLHqfISSNVILLDDDFDARITDYGLAKLVGSRDSNDSSFnngdlgeLGYVAPEYSSTMVA--SLKGDVYGFGI 493
Cdd:PHA02988 140 KYTNKPYKN--LTSVSFLVTENYKLKIICHGLEKILSSPPFKNVNF-------MVYFSYKMLNDIFSeyTIKDDIYSLGV 210
                        170
                 ....*....|.
gi 15223445  494 VLLELVTGQKP 504
Cdd:PHA02988 211 VLWEIFTGKIP 221
PTKc_Tyro3 cd05074
Catalytic domain of the Protein Tyrosine Kinase, Tyro3; PTKs catalyze the transfer of the ...
317-579 2.26e-07

Catalytic domain of the Protein Tyrosine Kinase, Tyro3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tyro3 (or Sky) is predominantly expressed in the central nervous system and the brain, and functions as a neurotrophic factor. It is also expressed in osteoclasts and has a role in bone resorption. Tyro3 is a member of the TAM subfamily, composed of receptor PTKs (RTKs) containing an extracellular ligand-binding region with two immunoglobulin-like domains followed by two fibronectin type III repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands, Gas6 and protein S, leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. The Tyro3 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: 270659 [Multi-domain]  Cd Length: 284  Bit Score: 52.61  E-value: 2.26e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 317 KADLPDGSALAVKRLSA---CGFGEKQFRSEMNKLGELRHPNLVPLLGYCVVEDER------LLVYKHMVNGTLFSQLHN 387
Cdd:cd05074  31 KSEDGSFQKVAVKMLKAdifSSSDIEEFLREAACMKEFDHPNVIKLIGVSLRSRAKgrlpipMVILPFMKHGDLHTFLLM 110
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 388 GGLCDAVLDWPTRRAIG--VGAAKGLAWLHhgcQPPYLHQFISSNVILLDDDFDARITDYGLAKLVGSRDsndsSFNNGD 465
Cdd:cd05074 111 SRIGEEPFTLPLQTLVRfmIDIASGMEYLS---SKNFIHRDLAARNCMLNENMTVCVADFGLSKKIYSGD----YYRQGC 183
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 466 LGEL--GYVAPEYSSTMVASLKGDVYGFGIVLLELVT-GQKPLSVINGVEgfkgslvdwVSQYLGTG-RSKDAIDrsiCd 541
Cdd:cd05074 184 ASKLpvKWLALESLADNVYTTHSDVWAFGVTMWEIMTrGQTPYAGVENSE---------IYNYLIKGnRLKQPPD---C- 250
                       250       260       270
                ....*....|....*....|....*....|....*...
gi 15223445 542 kghDEEILQFLkiaCSCVVSRPKERPTMIQVYESLKNM 579
Cdd:cd05074 251 ---LEDVYELM---CQCWSPEPKCRPSFQHLRDQLELI 282
STKc_WNK2_like cd14032
Catalytic domain of With No Lysine (WNK) 2-like Serine/Threonine kinases; STKs catalyze the ...
339-506 2.69e-07

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: 52.39  E-value: 2.69e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 339 KQFRSEMNKLGELRHPNLVPLLGY---------CVVederlLVYKHMVNGTLFSQLHNGglcdAVLDWPTRRAIGVGAAK 409
Cdd:cd14032  45 QRFKEEAEMLKGLQHPNIVRFYDFwescakgkrCIV-----LVTELMTSGTLKTYLKRF----KVMKPKVLRSWCRQILK 115
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 410 GLAWLHHGcQPPYLHQFIS-SNVILLDDDFDARITDYGLAKLvgsrdsNDSSFNNGDLGELGYVAPE-YSSTMVASLkgD 487
Cdd:cd14032 116 GLLFLHTR-TPPIIHRDLKcDNIFITGPTGSVKIGDLGLATL------KRASFAKSVIGTPEFMAPEmYEEHYDESV--D 186
                       170
                ....*....|....*....
gi 15223445 488 VYGFGIVLLELVTGQKPLS 506
Cdd:cd14032 187 VYAFGMCMLEMATSEYPYS 205
STKc_Nek3 cd08219
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
342-505 2.81e-07

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: 52.28  E-value: 2.81e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 342 RSEMNKLGELRHPNLVP-------------LLGYCvvEDERLLVYKHMVNGTLFSQlhngglcDAVLDWPTRRAIGVgaa 408
Cdd:cd08219  46 RKEAVLLAKMKHPNIVAfkesfeadghlyiVMEYC--DGGDLMQKIKLQRGKLFPE-------DTILQWFVQMCLGV--- 113
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 409 kglawlHHGCQPPYLHQFISSNVILLDDDFDARITDYGLAKLVgsrdSNDSSFNNGDLGELGYVAPEYSSTMVASLKGDV 488
Cdd:cd08219 114 ------QHIHEKRVLHRDIKSKNIFLTQNGKVKLGDFGSARLL----TSPGAYACTYVGTPYYVPPEIWENMPYNNKSDI 183
                       170
                ....*....|....*..
gi 15223445 489 YGFGIVLLELVTGQKPL 505
Cdd:cd08219 184 WSLGCILYELCTLKHPF 200
PTKc_Fer cd05085
Catalytic domain of the Protein Tyrosine Kinase, Fer; Protein Tyrosine Kinase (PTK) family; ...
313-497 5.27e-07

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: 51.16  E-value: 5.27e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 313 GVSYKADLPDGSALAVKrlsACGFGEKQ-----FRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHN 387
Cdd:cd05085  10 GEVYKGTLKDKTPVAVK---TCKEDLPQelkikFLSEARILKQYDHPNIVKLIGVCTQRQPIYIVMELVPGGDFLSFLRK 86
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 388 GglcDAVLDWPTRRAIGVGAAKGLAWLH-HGCqppyLHQFISSNVILLDDDFDARITDYGLaklvgSRDSNDSSFNNGDL 466
Cdd:cd05085  87 K---KDELKTKQLVKFSLDAAAGMAYLEsKNC----IHRDLAARNCLVGENNALKISDFGM-----SRQEDDGVYSSSGL 154
                       170       180       190
                ....*....|....*....|....*....|...
gi 15223445 467 GE--LGYVAPEYSSTMVASLKGDVYGFGIVLLE 497
Cdd:cd05085 155 KQipIKWTAPEALNYGRYSSESDVWSFGILLWE 187
PTKc_EphR_A10 cd05064
Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A10; PTKs catalyze the ...
317-515 5.36e-07

Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A10; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EphA10, which contains an inactive tyr kinase domain, may function to attenuate signals of co-clustered active receptors. EphA10 is mainly expressed in the testis. Ephrin/EphR interaction 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. EphRs comprise the largest subfamily of receptor tyr kinases (RTKs). In general, 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). The EphA10 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: 133195 [Multi-domain]  Cd Length: 266  Bit Score: 51.46  E-value: 5.36e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 317 KADLPdgsaLAVKRLSAcGFGEKQ---FRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTL--FSQLHNGGLC 391
Cdd:cd05064  31 KRELP----VAIHTLRA-GCSDKQrrgFLAEALTLGQFDHSNIVRLEGVITRGNTMMIVTEYMSNGALdsFLRKHEGQLV 105
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 392 DAVLdwptrRAIGVGAAKGLAWLhhgCQPPYLHQFISSNVILLDDDFDARITDYGLaklvGSRDSNDSSFNN-GDLGELG 470
Cdd:cd05064 106 AGQL-----MGMLPGLASGMKYL---SEMGYVHKGLAAHKVLVNSDLVCKISGFRR----LQEDKSEAIYTTmSGKSPVL 173
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|...
gi 15223445 471 YVAPEYSSTMVASLKGDVYGFGIVLLELVT-GQKPL------SVINGVE-GFK 515
Cdd:cd05064 174 WAAPEAIQYHHFSSASDVWSFGIVMWEVMSyGERPYwdmsgqDVIKAVEdGFR 226
PK_KSR cd14063
Pseudokinase domain of Kinase Suppressor of Ras; The pseudokinase domain shows similarity to ...
339-582 5.49e-07

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: 51.20  E-value: 5.49e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 339 KQFRSEMNKLGELRHPNLVPLLGYCVvEDERLLVYKHMVNG-TLFSQLHNGglcDAVLDWPTRRAIGVGAAKGLAWLHhg 417
Cdd:cd14063  41 EAFKEEVAAYKNTRHDNLVLFMGACM-DPPHLAIVTSLCKGrTLYSLIHER---KEKFDFNKTVQIAQQICQGMGYLH-- 114
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 418 cQPPYLHQFISSNVILLDDDfDARITDYGLAKLVGSrdsNDSSFNNGDL----GELGYVAPEYSSTMVASL--------- 484
Cdd:cd14063 115 -AKGIIHKDLKSKNIFLENG-RVVITDFGLFSLSGL---LQPGRREDTLvipnGWLCYLAPEIIRALSPDLdfeeslpft 189
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 485 -KGDVYGFGIVLLELVTGQKPlsvingvegFKGSLVDWVSQYLGTGRSKDAIDRSICDKGHDeeILQFlkiacsCVVSRP 563
Cdd:cd14063 190 kASDVYAFGTVWYELLAGRWP---------FKEQPAESIIWQVGCGKKQSLSQLDIGREVKD--ILMQ------CWAYDP 252
                       250
                ....*....|....*....
gi 15223445 564 KERPTMIQVYESLKNMADK 582
Cdd:cd14063 253 EKRPTFSDLLRMLERLPKK 271
PTKc_FGFR4 cd05099
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 4; PTKs ...
343-598 5.92e-07

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: 51.50  E-value: 5.92e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 343 SEMNKLGEL-RHPNLVPLLGYCVVEDERLLVYKHMVNGTL-----------------FSQLHNGGLCdavldWPTRRAIG 404
Cdd:cd05099  66 SEMELMKLIgKHKNIINLLGVCTQEGPLYVIVEYAAKGNLreflrarrppgpdytfdITKVPEEQLS-----FKDLVSCA 140
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 405 VGAAKGLAWLH-HGCqppyLHQFISSNVILLDDDFDARITDYGLAKLVGSRDSNDSSfNNGDLgELGYVAPEYSSTMVAS 483
Cdd:cd05099 141 YQVARGMEYLEsRRC----IHRDLAARNVLVTEDNVMKIADFGLARGVHDIDYYKKT-SNGRL-PVKWMAPEALFDRVYT 214
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 484 LKGDVYGFGIVLLELVT-GQKPLSVINGVEGFKgslvdwvsqYLGTGRSKDaidrsiCDKGHDEEILQFLKiacSCVVSR 562
Cdd:cd05099 215 HQSDVWSFGILMWEIFTlGGSPYPGIPVEELFK---------LLREGHRMD------KPSNCTHELYMLMR---ECWHAV 276
                       250       260       270
                ....*....|....*....|....*....|....*.
gi 15223445 563 PKERPTMIQVYESLKNMAdkHGVSEHYDEFPLVFNK 598
Cdd:cd05099 277 PTQRPTFKQLVEALDKVL--AAVSEEYLDLSMPFEQ 310
STKc_GRK5 cd05632
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 5; STKs ...
407-505 6.65e-07

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: 51.51  E-value: 6.65e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 407 AAKGLAWLHHGCQPPYLHQFISSNVILLDDDFDARITDYGLAKLVGSRDSNdssfnNGDLGELGYVAPEYSSTMVASLKG 486
Cdd:cd05632 110 AAEILCGLEDLHRENTVYRDLKPENILLDDYGHIRISDLGLAVKIPEGESI-----RGRVGTVGYMAPEVLNNQRYTLSP 184
                        90
                ....*....|....*....
gi 15223445 487 DVYGFGIVLLELVTGQKPL 505
Cdd:cd05632 185 DYWGLGCLIYEMIEGQSPF 203
PTK_CCK4 cd05046
Pseudokinase domain of the Protein Tyrosine Kinase, Colon Carcinoma Kinase 4; CCK4, also ...
341-578 8.13e-07

Pseudokinase domain of the Protein Tyrosine Kinase, Colon Carcinoma Kinase 4; CCK4, also called protein tyrosine kinase 7 (PTK7), is an orphan receptor PTK (RTK) containing an extracellular region with seven immunoglobulin domains, 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. Studies in mice reveal that CCK4 is essential for neural development. Mouse embryos containing a truncated CCK4 die perinatally and display craniorachischisis, a severe form of neural tube defect. The mechanism of action of the CCK4 pseudokinase is still unknown. Other pseudokinases such as HER3 rely on the activity of partner RTKs. The CCK4 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: 133178 [Multi-domain]  Cd Length: 275  Bit Score: 50.93  E-value: 8.13e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 341 FRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTL-----FSQLHNGGLCDAVLDWPTRRAIGVGAAKGLAWLH 415
Cdd:cd05046  55 FRRELDMFRKLSHKNVVRLLGLCREAEPHYMILEYTDLGDLkqflrATKSKDEKLKPPPLSTKQKVALCTQIALGMDHLS 134
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 416 HGcqpPYLHQFISSNVILLDDDFDARITDYGLAKLVGSRDSNdsSFNNGdLGELGYVAPEYSSTMVASLKGDVYGFGIVL 495
Cdd:cd05046 135 NA---RFVHRDLAARNCLVSSQREVKVSLLSLSKDVYNSEYY--KLRNA-LIPLRWLAPEAVQEDDFSTKSDVWSFGVLM 208
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 496 LELVTgqkplsviNGVEGFKGSLVDWVSQYLGTGRSKDAIDRSICDKGHdeeilqflKIACSCVVSRPKERPTMIQVYES 575
Cdd:cd05046 209 WEVFT--------QGELPFYGLSDEEVLNRLQAGKLELPVPEGCPSRLY--------KLMTRCWAVNPKDRPSFSELVSA 272

                ...
gi 15223445 576 LKN 578
Cdd:cd05046 273 LGE 275
STKc_WNK1 cd14030
Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 1; STKs catalyze ...
339-506 8.18e-07

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: 51.20  E-value: 8.18e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 339 KQFRSEMNKLGELRHPNLV--------PLLGY-CVVederlLVYKHMVNGTLFSQLHNGglcdAVLDWPTRRAIGVGAAK 409
Cdd:cd14030  69 QRFKEEAGMLKGLQHPNIVrfydswesTVKGKkCIV-----LVTELMTSGTLKTYLKRF----KVMKIKVLRSWCRQILK 139
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 410 GLAWLHHGCqPPYLHQFIS-SNVILLDDDFDARITDYGLAKLvgsrdsNDSSFNNGDLGELGYVAPE-YSSTMVASLkgD 487
Cdd:cd14030 140 GLQFLHTRT-PPIIHRDLKcDNIFITGPTGSVKIGDLGLATL------KRASFAKSVIGTPEFMAPEmYEEKYDESV--D 210
                       170
                ....*....|....*....
gi 15223445 488 VYGFGIVLLELVTGQKPLS 506
Cdd:cd14030 211 VYAFGMCMLEMATSEYPYS 229
PTKc_Jak2_rpt2 cd14205
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 2; PTKs catalyze the ...
323-500 8.27e-07

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: 51.17  E-value: 8.27e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 323 GSALAVKRLS-ACGFGEKQFRSEMNKLGELRHPNLVPLLGYCVVEDER--LLVYKHMVNGTLFSQLHNGglcDAVLDWPT 399
Cdd:cd14205  33 GEVVAVKKLQhSTEEHLRDFEREIEILKSLQHDNIVKYKGVCYSAGRRnlRLIMEYLPYGSLRDYLQKH---KERIDHIK 109
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 400 RRAIGVGAAKGLAWLhhgCQPPYLHQFISSNVILLDDDFDARITDYGLAKLVgSRDSNDSSFNNGDLGELGYVAPEYSST 479
Cdd:cd14205 110 LLQYTSQICKGMEYL---GTKRYIHRDLATRNILVENENRVKIGDFGLTKVL-PQDKEYYKVKEPGESPIFWYAPESLTE 185
                       170       180
                ....*....|....*....|.
gi 15223445 480 MVASLKGDVYGFGIVLLELVT 500
Cdd:cd14205 186 SKFSVASDVWSFGVVLYELFT 206
STKc_ACVR2b cd14140
Catalytic domain of the Serine/Threonine Kinase, Activin Type IIB Receptor; STKs catalyze the ...
381-500 9.61e-07

Catalytic domain of the Serine/Threonine Kinase, Activin Type IIB Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ACVR2b (or ActRIIB) belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, bone morphogenetic proteins (BMPs), activins, growth and differentiation factors (GDFs), 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. ACVR2b is one of two ACVR2 receptors found in vertebrates. Type II receptors are high-affinity receptors which bind ligands, autophosphorylate, as well as trans-phosphorylate and activate low-affinity type I receptors. ACVR2 acts primarily as the receptors for activins, nodal, myostatin, GDF11, and a subset of BMPs. ACVR2 signaling impacts many cellular and physiological processes including reproductive and gonadal functions, myogenesis, bone remodeling and tooth development, kidney organogenesis, apoptosis, fibrosis, inflammation, and neurogenesis. The ACVR2b subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271042 [Multi-domain]  Cd Length: 291  Bit Score: 50.80  E-value: 9.61e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 381 LFSQLHN-GGLCD----AVLDWPTRRAIGVGAAKGLAWLHH--------GCQPPYLHQFISSNVILLDDDFDARITDYGL 447
Cdd:cd14140  70 LITAFHDkGSLTDylkgNIVSWNELCHIAETMARGLSYLHEdvprckgeGHKPAIAHRDFKSKNVLLKNDLTAVLADFGL 149
                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 15223445 448 A-KLVGSRDSNDSsfnNGDLGELGYVAPEYSSTMV-----ASLKGDVYGFGIVLLELVT 500
Cdd:cd14140 150 AvRFEPGKPPGDT---HGQVGTRRYMAPEVLEGAInfqrdSFLRIDMYAMGLVLWELVS 205
PTKc_HER4 cd05110
Catalytic domain of the Protein Tyrosine Kinase, HER4; PTKs catalyze the transfer of the ...
340-504 1.07e-06

Catalytic domain of the Protein Tyrosine Kinase, HER4; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. HER4 (ErbB4) is a member of the EGFR (HER, ErbB) subfamily of proteins, which 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, leading to the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. Ligands that bind HER4 fall into two groups, the neuregulins (or heregulins) and some EGFR (HER1) ligands including betacellulin, HBEGF, and epiregulin. All four neuregulins (NRG1-4) interact with HER4. Upon ligand binding, HER4 forms homo- or heterodimers with other HER proteins. HER4 is essential in embryonic development. It is implicated in mammary gland, cardiac, and neural development. As a postsynaptic receptor of NRG1, HER4 plays an important role in synaptic plasticity and maturation. The impairment of NRG1/HER4 signaling may contribute to schizophrenia. The HER4 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: 173655 [Multi-domain]  Cd Length: 303  Bit Score: 50.84  E-value: 1.07e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 340 QFRSEMNKLGELRHPNLVPLLGYCVVEDERlLVYKHMVNGTLFSQLH----NGGlCDAVLDWptrraiGVGAAKGLAWLH 415
Cdd:cd05110  55 EFMDEALIMASMDHPHLVRLLGVCLSPTIQ-LVTQLMPHGCLLDYVHehkdNIG-SQLLLNW------CVQIAKGMMYLE 126
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 416 hgcQPPYLHQFISSNVILLDDDFDARITDYGLAKLVgsrdSNDSSFNNGDLGEL--GYVAPEYSSTMVASLKGDVYGFGI 493
Cdd:cd05110 127 ---ERRLVHRDLAARNVLVKSPNHVKITDFGLARLL----EGDEKEYNADGGKMpiKWMALECIHYRKFTHQSDVWSYGV 199
                       170
                ....*....|..
gi 15223445 494 VLLELVT-GQKP 504
Cdd:cd05110 200 TIWELMTfGGKP 211
STKc_Aurora-A cd14116
Catalytic domain of the Serine/Threonine kinase, Aurora-A kinase; STKs catalyze the transfer ...
338-537 1.10e-06

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: 50.34  E-value: 1.10e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 338 EKQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHNGGLCDAvldwpTRRAIGVGA-AKGLAWLHh 416
Cdd:cd14116  49 EHQLRREVEIQSHLRHPNILRLYGYFHDATRVYLILEYAPLGTVYRELQKLSKFDE-----QRTATYITElANALSYCH- 122
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 417 gcQPPYLHQFISSNVILLDDDFDARITDYGLAklVGSRDSNDSSFnngdLGELGYVAPEYSSTMVASLKGDVYGFGIVLL 496
Cdd:cd14116 123 --SKRVIHRDIKPENLLLGSAGELKIADFGWS--VHAPSSRRTTL----CGTLDYLPPEMIEGRMHDEKVDLWSLGVLCY 194
                       170       180       190       200
                ....*....|....*....|....*....|....*....|..
gi 15223445 497 ELVTGQKPLSVINGVEGFKG-SLVDWVSQYLGTGRSKDAIDR 537
Cdd:cd14116 195 EFLVGKPPFEANTYQETYKRiSRVEFTFPDFVTEGARDLISR 236
PTKc_Ror1 cd05090
Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor ...
340-504 1.18e-06

Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Ror kinases are expressed in many tissues during development. Avian Ror1 was found to be involved in late limb development. Studies in mice reveal that Ror1 is important in the regulation of neurite growth in central neurons, as well as in respiratory development. Loss of Ror1 also enhances the heart and skeletal abnormalities found in Ror2-deficient mice. Ror proteins are orphan receptor PTKs (RTKs) containing an extracellular region with immunoglobulin-like, cysteine-rich, and kringle domains, a transmembrane segment, and an intracellular catalytic domain. Ror RTKs are unrelated to the nuclear receptor subfamily called retinoid-related orphan receptors (RORs). RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain. The Ror1 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: 270672 [Multi-domain]  Cd Length: 283  Bit Score: 50.40  E-value: 1.18e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 340 QFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQL-------------HNGGLCDAVLDWPTRRAIGVG 406
Cdd:cd05090  53 EFQQEASLMTELHHPNIVCLLGVVTQEQPVCMLFEFMNQGDLHEFLimrsphsdvgcssDEDGTVKSSLDHGDFLHIAIQ 132
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 407 AAKGLAWLhhgCQPPYLHQFISSNVILLDDDFDARITDYGLAKLVGSRDSndSSFNNGDLGELGYVAPEYSSTMVASLKG 486
Cdd:cd05090 133 IAAGMEYL---SSHFFVHKDLAARNILVGEQLHVKISDLGLSREIYSSDY--YRVQNKSLLPIRWMPPEAIMYGKFSSDS 207
                       170
                ....*....|....*....
gi 15223445 487 DVYGFGIVLLELVT-GQKP 504
Cdd:cd05090 208 DIWSFGVVLWEIFSfGLQP 226
STKc_TAO3 cd06633
Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 3; STKs catalyze ...
326-514 1.29e-06

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: 50.42  E-value: 1.29e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 326 LAVKRLSACG--FGEK--QFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMV-NGTLFSQLHNGGLCDAVLdwptr 400
Cdd:cd06633  49 VAIKKMSYSGkqTNEKwqDIIKEVKFLQQLKHPNTIEYKGCYLKDHTAWLVMEYCLgSASDLLEVHKKPLQEVEI----- 123
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 401 RAIGVGAAKGLAWLHHGCQppyLHQFISSNVILLDDDFDARITDYGLAklvgSRDSNDSSFnngdLGELGYVAPEYSSTM 480
Cdd:cd06633 124 AAITHGALQGLAYLHSHNM---IHRDIKAGNILLTEPGQVKLADFGSA----SIASPANSF----VGTPYWMAPEVILAM 192
                       170       180       190
                ....*....|....*....|....*....|....*..
gi 15223445 481 VASL---KGDVYGFGIVLLELVTGQKPLSVINGVEGF 514
Cdd:cd06633 193 DEGQydgKVDIWSLGITCIELAERKPPLFNMNAMSAL 229
PKc_TOPK cd14001
Catalytic domain of the Dual-specificity protein kinase, Lymphokine-activated killer ...
324-578 1.72e-06

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: 50.09  E-value: 1.72e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 324 SALAVKRL-SACGFG-----EKQFRSEMNKLGELRHPNLVpllGYcvvederllvykhmvngTLFSQLHNGGLCDAVLDW 397
Cdd:cd14001  29 SPWAVKKInSKCDKGqrslyQERLKEEAKILKSLNHPNIV---GF-----------------RAFTKSEDGSLCLAMEYG 88
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 398 PT--------RRAIGVGA-------------AKGLAWLHHgcQPPYLHQFISSNVILLDDDFDA-RITDYGLA-KLvgsr 454
Cdd:cd14001  89 GKslndlieeRYEAGLGPfpaatilkvalsiARALEYLHN--EKKILHGDIKSGNVLIKGDFESvKLCDFGVSlPL---- 162
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 455 DSNDSSFNNGDLGELG---YVAPE-YSSTMVASLKGDVYGFGIVLLELVTGQKP-LSVING-----VEGFKGSLVDwVSQ 524
Cdd:cd14001 163 TENLEVDSDPKAQYVGtepWKAKEaLEEGGVITDKADIFAYGLVLWEMMTLSVPhLNLLDIedddeDESFDEDEED-EEA 241
                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|....
gi 15223445 525 YLGTGRSKDAIDRSICDKGHDEEILQFlkiaCSCVVSRPKERPTMIQVYESLKN 578
Cdd:cd14001 242 YYGTLGTRPALNLGELDDSYQKVIELF----YACTQEDPKDRPSAAHIVEALEA 291
PTKc_PDGFR cd05055
Catalytic domain of the Protein Tyrosine Kinases, Platelet Derived Growth Factor Receptors; ...
326-500 2.04e-06

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: 49.79  E-value: 2.04e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 326 LAVKRLSACG-FGEKQ-FRSE---MNKLGElrHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHNGGlcDAVLDWPTR 400
Cdd:cd05055  68 VAVKMLKPTAhSSEREaLMSElkiMSHLGN--HENIVNLLGACTIGGPILVITEYCCYGDLLNFLRRKR--ESFLTLEDL 143
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 401 RAIGVGAAKGLAWL-HHGCqppyLHQFISSNVILLDDDFDARITDYGLAKLVGSrDSNDSSFNNGDLgELGYVAPEYSST 479
Cdd:cd05055 144 LSFSYQVAKGMAFLaSKNC----IHRDLAARNVLLTHGKIVKICDFGLARDIMN-DSNYVVKGNARL-PVKWMAPESIFN 217
                       170       180
                ....*....|....*....|.
gi 15223445 480 MVASLKGDVYGFGIVLLELVT 500
Cdd:cd05055 218 CVYTFESDVWSYGILLWEIFS 238
STKc_LIMK1 cd14221
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 1; STKs catalyze the ...
338-499 2.12e-06

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: 49.57  E-value: 2.12e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 338 EKQFRSEMNKLGELRHPNLVPLLGyCVVEDERL-LVYKHMVNGTLFSQLHNgglCDAVLDWPTRRAIGVGAAKGLAWLHh 416
Cdd:cd14221  34 QRTFLKEVKVMRCLEHPNVLKFIG-VLYKDKRLnFITEYIKGGTLRGIIKS---MDSHYPWSQRVSFAKDIASGMAYLH- 108
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 417 gcQPPYLHQFISSNVILLDDDFDARITDYGLAKLVGSRDSNDSSFNNGD----------LGELGYVAPEYSSTMVASLKG 486
Cdd:cd14221 109 --SMNIIHRDLNSHNCLVRENKSVVVADFGLARLMVDEKTQPEGLRSLKkpdrkkrytvVGNPYWMAPEMINGRSYDEKV 186
                       170
                ....*....|...
gi 15223445 487 DVYGFGIVLLELV 499
Cdd:cd14221 187 DVFSFGIVLCEII 199
PTKc_TrkB cd05093
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase B; PTKs catalyze ...
326-504 2.59e-06

Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase B; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. TrkB is a receptor PTK (RTK) containing an extracellular region with arrays of leucine-rich motifs flanked by two cysteine-rich clusters followed by two immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. Binding of TrkB to its ligands, brain-derived neurotrophic factor (BDNF) or neurotrophin 4 (NT4), results in receptor oligomerization and activation of the catalytic domain. TrkB is broadly expressed in the nervous system and in some non-neural tissues. It plays important roles in cell proliferation, differentiation, and survival. BDNF/Trk signaling plays a key role in regulating activity-dependent synaptic plasticity. TrkB also contributes to protection against gp120-induced neuronal cell death. TrkB overexpression is associated with poor prognosis in neuroblastoma (NB) and other human cancers. It acts as a suppressor of anoikis (detachment-induced apoptosis) and contributes to tumor metastasis. The TrkB 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: 270675 [Multi-domain]  Cd Length: 288  Bit Score: 49.65  E-value: 2.59e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 326 LAVKRLS-ACGFGEKQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHNGGlCDAV---------- 394
Cdd:cd05093  38 VAVKTLKdASDNARKDFHREAELLTNLQHEHIVKFYGVCVEGDPLIMVFEYMKHGDLNKFLRAHG-PDAVlmaegnrpae 116
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 395 LDWPTRRAIGVGAAKGLAWLhhgCQPPYLHQFISSNVILLDDDFDARITDYGLAKLVGSRDSndSSFNNGDLGELGYVAP 474
Cdd:cd05093 117 LTQSQMLHIAQQIAAGMVYL---ASQHFVHRDLATRNCLVGENLLVKIGDFGMSRDVYSTDY--YRVGGHTMLPIRWMPP 191
                       170       180       190
                ....*....|....*....|....*....|.
gi 15223445 475 EYSSTMVASLKGDVYGFGIVLLELVT-GQKP 504
Cdd:cd05093 192 ESIMYRKFTTESDVWSLGVVLWEIFTyGKQP 222
STKc_TSSK6-like cd14164
Catalytic domain of testis-specific serine/threonine kinase 6 and similar proteins; STKs ...
329-504 2.59e-06

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: 49.09  E-value: 2.59e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 329 KRLSACGFGEKQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHNGGLCDAVLDwptrRAIGVGAA 408
Cdd:cd14164  35 RRRASPDFVQKFLPRELSILRRVNHPNIVQMFECIEVANGRLYIVMEAAATDLLQKIQEVHHIPKDLA----RDMFAQMV 110
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 409 KGLAWLHhgcQPPYLHQFIS-SNVILLDDDFDARITDYGLAKLVGSRDSNDSSFnngdLGELGYVAPE-YSSTMVASLKG 486
Cdd:cd14164 111 GAVNYLH---DMNIVHRDLKcENILLSADDRKIKIADFGFARFVEDYPELSTTF----CGSRAYTPPEvILGTPYDPKKY 183
                       170
                ....*....|....*...
gi 15223445 487 DVYGFGIVLLELVTGQKP 504
Cdd:cd14164 184 DVWSLGVVLYVMVTGTMP 201
STKc_PAK cd06614
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase; STKs catalyze the ...
312-504 3.23e-06

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: 48.75  E-value: 3.23e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 312 TGVSYKA-DLPDGSALAVKRLSACGFGEKQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTL--------- 381
Cdd:cd06614  13 SGEVYKAtDRATGKEVAIKKMRLRKQNKELIINEILIMKECKHPNIVDYYDSYLVGDELWVVMEYMDGGSLtdiitqnpv 92
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 382 -FSQLHNGGLCDAVLdwptrraigvgaaKGLAWLH-HGCqppyLHQFISSNVILLDDDFDARITDYGLAKLVGSRDSNDS 459
Cdd:cd06614  93 rMNESQIAYVCREVL-------------QGLEYLHsQNV----IHRDIKSDNILLSKDGSVKLADFGFAAQLTKEKSKRN 155
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*
gi 15223445 460 SFnngdLGELGYVAPEYSSTMVASLKGDVYGFGIVLLELVTGQKP 504
Cdd:cd06614 156 SV----VGTPYWMAPEVIKRKDYGPKVDIWSLGIMCIEMAEGEPP 196
PTKc_Aatyk3 cd14206
Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 3; PTKs ...
330-504 3.32e-06

Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Aatyk3, also called lemur tyrosine kinase 3 (Lmtk3) is a receptor kinase containing a transmembrane segment and a long C-terminal cytoplasmic tail with a catalytic domain. The function of Aatyk3 is still unknown. The Aatyk3 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: 271108 [Multi-domain]  Cd Length: 276  Bit Score: 49.18  E-value: 3.32e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 330 RLSACGFGEKQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHNGGLCDAVL-DWPTR-----RAI 403
Cdd:cd14206  33 RVSAGPLEQRKFISEAQPYRSLQHPNILQCLGLCTETIPFLLIMEFCQLGDLKRYLRAQRKADGMTpDLPTRdlrtlQRM 112
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 404 GVGAAKGLAWLHhgcQPPYLHQFISSNVILLDDDFDARITDYGLAKlvgSRDSNDSSFNNGDLG-ELGYVAPE-----YS 477
Cdd:cd14206 113 AYEITLGLLHLH---KNNYIHSDLALRNCLLTSDLTVRIGDYGLSH---NNYKEDYYLTPDRLWiPLRWVAPElldelHG 186
                       170       180       190
                ....*....|....*....|....*....|
gi 15223445 478 STMVA--SLKGDVYGFGIVLLELVT-GQKP 504
Cdd:cd14206 187 NLIVVdqSKESNVWSLGVTIWELFEfGAQP 216
PTKc_Tie1 cd05089
Catalytic domain of the Protein Tyrosine Kinase, Tie1; Protein Tyrosine Kinase (PTK) family; ...
339-581 3.38e-06

Catalytic domain of the Protein Tyrosine Kinase, Tie1; Protein Tyrosine Kinase (PTK) family; Tie1; 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. Tie1 is a receptor tyr kinase (RTK) containing an extracellular region, a transmembrane segment, and an intracellular catalytic domain. The extracellular region contains an immunoglobulin (Ig)-like domain, three epidermal growth factor (EGF)-like domains, a second Ig-like domain, and three fibronectin type III repeats. Tie receptors are specifically expressed in endothelial cells and hematopoietic stem cells. No specific ligand has been identified for Tie1, although the angiopoietin, Ang-1, binds to Tie1 through integrins at high concentrations. In vivo studies of Tie1 show that it is critical in vascular development.


Pssm-ID: 270671 [Multi-domain]  Cd Length: 297  Bit Score: 49.23  E-value: 3.38e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 339 KQFRSEMNKLGEL-RHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHNGGLCD------------AVLDWPTRRAIGV 405
Cdd:cd05089  47 RDFAGELEVLCKLgHHPNIINLLGACENRGYLYIAIEYAPYGNLLDFLRKSRVLEtdpafakehgtaSTLTSQQLLQFAS 126
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 406 GAAKGLAWLhhgCQPPYLHQFISSNVILLDDDFDARITDYGLAKlvgsrdsNDSSFNNGDLGELG--YVAPEYSSTMVAS 483
Cdd:cd05089 127 DVAKGMQYL---SEKQFIHRDLAARNVLVGENLVSKIADFGLSR-------GEEVYVKKTMGRLPvrWMAIESLNYSVYT 196
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 484 LKGDVYGFGIVLLELVT-GQKPLSVINGVEgfkgsLVDWVSQYLGTGRSKDAidrsicdkghDEEILQFLKiacSCVVSR 562
Cdd:cd05089 197 TKSDVWSFGVLLWEIVSlGGTPYCGMTCAE-----LYEKLPQGYRMEKPRNC----------DDEVYELMR---QCWRDR 258
                       250
                ....*....|....*....
gi 15223445 563 PKERPTMIQVYESLKNMAD 581
Cdd:cd05089 259 PYERPPFSQISVQLSRMLE 277
PTKc_FGFR cd05053
Catalytic domain of the Protein Tyrosine Kinases, Fibroblast Growth Factor Receptors; PTKs ...
324-579 3.68e-06

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: 48.95  E-value: 3.68e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 324 SALAVKRL--SACGFGEKQFRSEMNKLGEL-RHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHN----GGLCDAVLD 396
Cdd:cd05053  44 VTVAVKMLkdDATEKDLSDLVSEMEMMKMIgKHKNIINLLGACTQDGPLYVVVEYASKGNLREFLRArrppGEEASPDDP 123
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 397 WPTRRAI--------GVGAAKGLAWLhhgCQPPYLHQFISSNVILLDDDFDARITDYGLAklvgsRDSNDSSF----NNG 464
Cdd:cd05053 124 RVPEEQLtqkdlvsfAYQVARGMEYL---ASKKCIHRDLAARNVLVTEDNVMKIADFGLA-----RDIHHIDYyrktTNG 195
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 465 DLgELGYVAPEYSSTMVASLKGDVYGFGIVLLELVT-GQKPLSVINGVEGFKgslvdwvsqYLGTGRSkdaidrsiCDKG 543
Cdd:cd05053 196 RL-PVKWMAPEALFDRVYTHQSDVWSFGVLLWEIFTlGGSPYPGIPVEELFK---------LLKEGHR--------MEKP 257
                       250       260       270
                ....*....|....*....|....*....|....*.
gi 15223445 544 HDEEiLQFLKIACSCVVSRPKERPTMIQVYESLKNM 579
Cdd:cd05053 258 QNCT-QELYMLMRDCWHEVPSQRPTFKQLVEDLDRI 292
PTKc_Tec_Rlk cd05114
Catalytic domain of the Protein Tyrosine Kinases, Tyrosine kinase expressed in hepatocellular ...
326-581 4.24e-06

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: 48.70  E-value: 4.24e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 326 LAVKRLSACGFGEKQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHN--GGLCDAVLdwptrRAI 403
Cdd:cd05114  31 VAIKAIREGAMSEEDFIEEAKVMMKLTHPKLVQLYGVCTQQKPIYIVTEFMENGCLLNYLRQrrGKLSRDML-----LSM 105
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 404 GVGAAKGLAWLHhgcQPPYLHQFISSNVILLDDDFDARITDYGLAKLVGSrDSNDSSFnnGDLGELGYVAPEYSSTMVAS 483
Cdd:cd05114 106 CQDVCEGMEYLE---RNNFIHRDLAARNCLVNDTGVVKVSDFGMTRYVLD-DQYTSSS--GAKFPVKWSPPEVFNYSKFS 179
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 484 LKGDVYGFGIVLLELVT-GQKPLSVINGVEgfkgsLVDWVSQYLGTGRSKDAIDrsicdkghdeeilQFLKIACSCVVSR 562
Cdd:cd05114 180 SKSDVWSFGVLMWEVFTeGKMPFESKSNYE-----VVEMVSRGHRLYRPKLASK-------------SVYEVMYSCWHEK 241
                       250
                ....*....|....*....
gi 15223445 563 PKERPTMIQVYESLKNMAD 581
Cdd:cd05114 242 PEGRPTFADLLRTITEIAE 260
PTK_HER3 cd05111
Pseudokinase domain of the Protein Tyrosine Kinase, HER3; HER3 (ErbB3) is a member of the EGFR ...
345-508 4.63e-06

Pseudokinase domain of the Protein Tyrosine Kinase, HER3; HER3 (ErbB3) is a member of the EGFR (HER, ErbB) subfamily of proteins, which 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, leading to the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. HER3 contains an impaired tyr kinase domain, which lacks crucial residues for catalytic activity against exogenous substrates but is still able to bind ATP and autophosphorylate. HER3 binds the neuregulin ligands, NRG1 and NRG2, and it relies on its heterodimerization partners for activity following ligand binding. The HER2-HER3 heterodimer constitutes a high affinity co-receptor capable of potent mitogenic signaling. HER3 participates in a signaling pathway involved in the proliferation, survival, adhesion, and motility of tumor cells. The HER3 subfamily is part of a larger superfamily that includes other pseudokinases and the the catalytic domains of active kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173656 [Multi-domain]  Cd Length: 279  Bit Score: 48.80  E-value: 4.63e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 345 MNKLGELRHPNLVPLLGYCVVEDERLlVYKHMVNGTLFSQL--HNGGLC-DAVLDWptrraiGVGAAKGLAWLHHGCQpp 421
Cdd:cd05111  60 MLAIGSLDHAYIVRLLGICPGASLQL-VTQLLPLGSLLDHVrqHRGSLGpQLLLNW------CVQIAKGMYYLEEHRM-- 130
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 422 yLHQFISSNVILLDDDFDARITDYGLAKLVGSRDSNdsSFNNGDLGELGYVAPEYSSTMVASLKGDVYGFGIVLLELVT- 500
Cdd:cd05111 131 -VHRNLAARNVLLKSPSQVQVADFGVADLLYPDDKK--YFYSEAKTPIKWMALESIHFGKYTHQSDVWSYGVTVWEMMTf 207

                ....*...
gi 15223445 501 GQKPLSVI 508
Cdd:cd05111 208 GAEPYAGM 215
STKc_GRK6 cd05630
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 6; STKs ...
312-505 5.28e-06

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: 48.48  E-value: 5.28e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 312 TGVSYKADLPDGSALAVKRLSACGFGEKQFRSEMNKlgelrhpNLVPLLGYCV-VEDERLLVYKHMVNGTL-FSQLHNGg 389
Cdd:cd05630  24 TGKMYACKKLEKKRIKKRKGEAMALNEKQILEKVNS-------RFVVSLAYAYeTKDALCLVLTLMNGGDLkFHIYHMG- 95
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 390 lcDAvlDWPTRRAIGVGA--AKGLAWLHhgcQPPYLHQFISSNVILLDDDFDARITDYGLAKLVgsrdsNDSSFNNGDLG 467
Cdd:cd05630  96 --QA--GFPEARAVFYAAeiCCGLEDLH---RERIVYRDLKPENILLDDHGHIRISDLGLAVHV-----PEGQTIKGRVG 163
                       170       180       190
                ....*....|....*....|....*....|....*...
gi 15223445 468 ELGYVAPEYSSTMVASLKGDVYGFGIVLLELVTGQKPL 505
Cdd:cd05630 164 TVGYMAPEVVKNERYTFSPDWWALGCLLYEMIAGQSPF 201
PTKc_Fes cd05084
Catalytic domain of the Protein Tyrosine Kinase, Fes; PTKs catalyze the transfer of the ...
340-576 5.33e-06

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: 48.39  E-value: 5.33e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 340 QFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHNGGlcdAVLDWPTRRAIGVGAAKGLAWLHHGCq 419
Cdd:cd05084  40 KFLQEARILKQYSHPNIVRLIGVCTQKQPIYIVMELVQGGDFLTFLRTEG---PRLKVKELIRMVENAAAGMEYLESKH- 115
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 420 ppYLHQFISSNVILLDDDFDARITDYGLaklvgSRDSNDSSFN-NGDLGEL--GYVAPEYSSTMVASLKGDVYGFGIVLL 496
Cdd:cd05084 116 --CIHRDLAARNCLVTEKNVLKISDFGM-----SREEEDGVYAaTGGMKQIpvKWTAPEALNYGRYSSESDVWSFGILLW 188
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 497 ELVT-GQKPLSVingvegfkgslvdwvsqyLGTGRSKDAIDRSI---CDKGHDEEILQFLkiaCSCVVSRPKERPTMIQV 572
Cdd:cd05084 189 ETFSlGAVPYAN------------------LSNQQTREAVEQGVrlpCPENCPDEVYRLM---EQCWEYDPRKRPSFSTV 247

                ....
gi 15223445 573 YESL 576
Cdd:cd05084 248 HQDL 251
PTKc_Syk cd05116
Catalytic domain of the Protein Tyrosine Kinase, Spleen tyrosine kinase; PTKs catalyze the ...
422-578 5.66e-06

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: 48.04  E-value: 5.66e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 422 YLHQFISSNVILLDDDFDARITDYGLAKLVGSrDSNDSSFNNGDLGELGYVAPEYSSTMVASLKGDVYGFGIVLLELVT- 500
Cdd:cd05116 116 FVHRDLAARNVLLVTQHYAKISDFGLSKALRA-DENYYKAQTHGKWPVKWYAPECMNYYKFSSKSDVWSFGVLMWEAFSy 194
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 15223445 501 GQKPLsvingvEGFKGSLvdwVSQYLGTGRskdaidRSICDKGHDEEILQFLKIacsCVVSRPKERPTMIQVYESLKN 578
Cdd:cd05116 195 GQKPY------KGMKGNE---VTQMIEKGE------RMECPAGCPPEMYDLMKL---CWTYDVDERPGFAAVELRLRN 254
STKc_MAP4K3_like cd06613
Catalytic domain of Mitogen-activated protein kinase kinase kinase kinase (MAP4K) 3-like ...
313-506 8.02e-06

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: 47.69  E-value: 8.02e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 313 GVSYKA-DLPDGSALAVKRLS-ACGFGEKQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLH-NGG 389
Cdd:cd06613  14 GDVYKArNIATGELAAVKVIKlEPGDDFEIIQQEISMLKECRHPNIVAYFGSYLRRDKLWIVMEYCGGGSLQDIYQvTGP 93
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 390 LCDAVLDWPTRRAIgvgaaKGLAWLHHGCQppyLHQFISSNVILLDDDFDARITDYGLAKLVGSRDSNDSSFnngdLGEL 469
Cdd:cd06613  94 LSELQIAYVCRETL-----KGLAYLHSTGK---IHRDIKGANILLTEDGDVKLADFGVSAQLTATIAKRKSF----IGTP 161
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*
gi 15223445 470 GYVAPEysstmVAS--------LKGDVYGFGIVLLELVTGQKPLS 506
Cdd:cd06613 162 YWMAPE-----VAAverkggydGKCDIWALGITAIELAELQPPMF 201
PTKc_EGFR cd05108
Catalytic domain of the Protein Tyrosine Kinase, Epidermal Growth Factor Receptor; PTKs ...
313-512 9.80e-06

Catalytic domain of the Protein Tyrosine Kinase, Epidermal Growth Factor Receptor; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EGFR (HER1, ErbB1) is a receptor PTK (RTK) 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, leading to the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. Ligands for EGFR include EGF, heparin binding EGF-like growth factor (HBEGF), epiregulin, amphiregulin, TGFalpha, and betacellulin. Upon ligand binding, EGFR can form homo- or heterodimers with other EGFR subfamily members. The EGFR signaling pathway is one of the most important pathways regulating cell proliferation, differentiation, survival, and growth. Overexpression and mutation in the kinase domain of EGFR have been implicated in the development and progression of a variety of cancers. A number of monoclonal antibodies and small molecule inhibitors have been developed that target EGFR, including the antibodies Cetuximab and Panitumumab, which are used in combination with other therapies for the treatment of colorectal cancer and non-small cell lung carcinoma (NSCLC). The small molecule inhibitors Gefitinib (Iressa) and Erlotinib (Tarceva), already used for NSCLC, are undergoing clinical trials for other types of cancer including gastrointestinal, breast, head and neck, and bladder. 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: 270683 [Multi-domain]  Cd Length: 313  Bit Score: 47.71  E-value: 9.80e-06
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 313 GVSYKAD-LPDGS------ALAVKRLSACGFGEKQFRSEMNKLGELRHPNLVPLLGYCVVEDERLlVYKHMVNGTL--FS 383
Cdd:cd05108  21 GTVYKGLwIPEGEkvkipvAIKELREATSPKANKEILDEAYVMASVDNPHVCRLLGICLTSTVQL-ITQLMPFGCLldYV 99
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 384 QLHNGGLCDA-VLDWptrraiGVGAAKGLAWLHhgcQPPYLHQFISSNVILLDDDFDARITDYGLAKLVGSrDSNDSSFN 462
Cdd:cd05108 100 REHKDNIGSQyLLNW------CVQIAKGMNYLE---DRRLVHRDLAARNVLVKTPQHVKITDFGLAKLLGA-EEKEYHAE 169
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|.
gi 15223445 463 NGDLgELGYVAPEYSSTMVASLKGDVYGFGIVLLELVT-GQKPLSVINGVE 512
Cdd:cd05108 170 GGKV-PIKWMALESILHRIYTHQSDVWSYGVTVWELMTfGSKPYDGIPASE 219
PK_KSR2 cd14153
Pseudokinase domain of Kinase Suppressor of Ras 2; The pseudokinase domain shows similarity to ...
339-582 1.11e-05

Pseudokinase domain of Kinase Suppressor of Ras 2; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. KSR2 interacts with the protein phosphatase calcineurin and functions in calcium-mediated ERK signaling. It also functions in energy metabolism by regulating AMP kinase and AMPK-dependent processes such as glucose uptake and fatty acid oxidation. KSR proteins act as scaffold proteins that function 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. The KSR2 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: 271055 [Multi-domain]  Cd Length: 270  Bit Score: 47.31  E-value: 1.11e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 339 KQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHNGGLcdaVLDWPTRRAIGVGAAKGLAWLHhgc 418
Cdd:cd14153  41 KAFKREVMAYRQTRHENVVLFMGACMSPPHLAIITSLCKGRTLYSVVRDAKV---VLDVNKTRQIAQEIVKGMGYLH--- 114
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 419 QPPYLHQFISSNVILLDDDfDARITDYGLAKLVG----SRDSNDSSFNNgdlGELGYVAPEY---------SSTMVASLK 485
Cdd:cd14153 115 AKGILHKDLKSKNVFYDNG-KVVITDFGLFTISGvlqaGRREDKLRIQS---GWLCHLAPEIirqlspeteEDKLPFSKH 190
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 486 GDVYGFGIVLLELVTGQKPlsvingvegFKGSLVDWVSQYLGTGR----SKDAIDRSICDkghdeeILQFlkiacsCVVS 561
Cdd:cd14153 191 SDVFAFGTIWYELHAREWP---------FKTQPAEAIIWQVGSGMkpnlSQIGMGKEISD------ILLF------CWAY 249
                       250       260
                ....*....|....*....|.
gi 15223445 562 RPKERPTMIQVYESLKNMADK 582
Cdd:cd14153 250 EQEERPTFSKLMEMLEKLPKR 270
STKc_TAO2 cd06634
Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 2; STKs catalyze ...
313-568 1.39e-05

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: 47.32  E-value: 1.39e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 313 GVSYKADLPDGSALAVKRLSACG--FGEK--QFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMV-NGTLFSQLHN 387
Cdd:cd06634  30 AVYFARDVRNNEVVAIKKMSYSGkqSNEKwqDIIKEVKFLQKLRHPNTIEYRGCYLREHTAWLVMEYCLgSASDLLEVHK 109
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 388 GGLCDAVLdwptrRAIGVGAAKGLAWLHhgcQPPYLHQFISSNVILLDDDFDARITDYGLAKLVGSRdsndssfnNGDLG 467
Cdd:cd06634 110 KPLQEVEI-----AAITHGALQGLAYLH---SHNMIHRDVKAGNILLTEPGLVKLGDFGSASIMAPA--------NSFVG 173
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 468 ELGYVAPEYSSTMVASL---KGDVYGFGIVLLELVTGQKPLSVINGVegfkgSLVDWVSQYlgtgrskdaiDRSICDKGH 544
Cdd:cd06634 174 TPYWMAPEVILAMDEGQydgKVDVWSLGITCIELAERKPPLFNMNAM-----SALYHIAQN----------ESPALQSGH 238
                       250       260
                ....*....|....*....|....
gi 15223445 545 DEEilQFLKIACSCVVSRPKERPT 568
Cdd:cd06634 239 WSE--YFRNFVDSCLQKIPQDRPT 260
STKc_YSK4 cd06631
Catalytic domain of the Serine/Threonine Kinase, Yeast Sps1/Ste20-related Kinase 4; STKs ...
338-509 1.47e-05

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: 47.05  E-value: 1.47e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 338 EKQF---RSEMNKLGELRHPNLVPLLGYCVvEDERLLVYKHMVNGTLFSQLHN--GGLCDAVLDWPTRRAIgvgaaKGLA 412
Cdd:cd06631  44 EKEYeklQEEVDLLKTLKHVNIVGYLGTCL-EDNVVSIFMEFVPGGSIASILArfGALEEPVFCRYTKQIL-----EGVA 117
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 413 WLHHGCqppYLHQFISSNVILLDDDFDARITDYGLAKLVGSRDSNDSsfnNGDL-----GELGYVAPEYSSTMVASLKGD 487
Cdd:cd06631 118 YLHNNN---VIHRDIKGNNIMLMPNGVIKLIDFGCAKRLCINLSSGS---QSQLlksmrGTPYWMAPEVINETGHGRKSD 191
                       170       180
                ....*....|....*....|..
gi 15223445 488 VYGFGIVLLELVTGQKPLSVIN 509
Cdd:cd06631 192 IWSIGCTVFEMATGKPPWADMN 213
STKc_GRK4 cd05631
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 4; STKs ...
432-566 1.93e-05

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: 46.91  E-value: 1.93e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 432 ILLDDDFDARITDYGLAKLVGSRDSNdssfnNGDLGELGYVAPEYSSTMVASLKGDVYGFGIVLLELVTGQKPLSVingv 511
Cdd:cd05631 133 ILLDDRGHIRISDLGLAVQIPEGETV-----RGRVGTVGYMAPEVINNEKYTFSPDWWGLGCLIYEMIQGQSPFRK---- 203
                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 15223445 512 egfKGSLVDWvsqylgtgrskDAIDRSICD--KGHDEEILQFLKIACSCVVSR-PKER 566
Cdd:cd05631 204 ---RKERVKR-----------EEVDRRVKEdqEEYSEKFSEDAKSICRMLLTKnPKER 247
STKc_KSR1 cd14152
Catalytic domain of the Serine/Threonine Kinase, Kinase Suppressor of Ras 1; STKs catalyze the ...
339-579 2.53e-05

Catalytic domain of the Serine/Threonine Kinase, Kinase Suppressor of Ras 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. KSR1 functions as a transducer of TNFalpha-stimulated C-Raf activation of ERK1/2 and NF-kB. Detected activity of KSR1 is cell type specific and context dependent. It is inactive in normal colon epithelial cells and becomes activated at the onset of inflammatory bowel disease (IBD). Similarly, KSR1 activity is undetectable prior to stimulation by EGF or ceramide in COS-7 or YAMC cells, respectively. KSR proteins are widely regarded as pseudokinases, however, this matter is up for debate as catalytic activity has been detected for KSR1 in some systems. The KSR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271054 [Multi-domain]  Cd Length: 279  Bit Score: 46.50  E-value: 2.53e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 339 KQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHNGglcDAVLDWPTRRAIGVGAAKGLAWLHhgc 418
Cdd:cd14152  41 KLFKKEVMNYRQTRHENVVLFMGACMHPPHLAIITSFCKGRTLYSFVRDP---KTSLDINKTRQIAQEIIKGMGYLH--- 114
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 419 QPPYLHQFISSNVILLDDDfDARITDYGLAKLVG----SRDSNDSSFNNgdlGELGYVAPEYSSTMVA---------SLK 485
Cdd:cd14152 115 AKGIVHKDLKSKNVFYDNG-KVVITDFGLFGISGvvqeGRRENELKLPH---DWLCYLAPEIVREMTPgkdedclpfSKA 190
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 486 GDVYGFGIVLLELVTGQKPlsvingvegFKGSLVDWVSQYLGTGRSKDAIDRSICDKGHDEEILQflkiACSCVvsRPKE 565
Cdd:cd14152 191 ADVYAFGTIWYELQARDWP---------LKNQPAEALIWQIGSGEGMKQVLTTISLGKEVTEILS----ACWAF--DLEE 255
                       250
                ....*....|....
gi 15223445 566 RPTMIQVYESLKNM 579
Cdd:cd14152 256 RPSFTLLMDMLEKL 269
STKc_PAK5 cd06658
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 5; STKs catalyze the ...
323-504 2.76e-05

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: 46.18  E-value: 2.76e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 323 GSALAVKRLSAcgfgEKQFRSEM--NKLGELR---HPNLVPLLGYCVVEDERLLVYKHmvngtlfsqLHNGGLCDAV--- 394
Cdd:cd06658  47 GKQVAVKKMDL----RKQQRRELlfNEVVIMRdyhHENVVDMYNSYLVGDELWVVMEF---------LEGGALTDIVtht 113
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 395 -LDWPTRRAIGVGAAKGLAWLHHgcqPPYLHQFISSNVILLDDDFDARITDYGLAKLVGSRDSNDSSFnngdLGELGYVA 473
Cdd:cd06658 114 rMNEEQIATVCLSVLRALSYLHN---QGVIHRDIKSDSILLTSDGRIKLSDFGFCAQVSKEVPKRKSL----VGTPYWMA 186
                       170       180       190
                ....*....|....*....|....*....|.
gi 15223445 474 PEYSSTMVASLKGDVYGFGIVLLELVTGQKP 504
Cdd:cd06658 187 PEVISRLPYGTEVDIWSLGIMVIEMIDGEPP 217
STKc_PAK4 cd06657
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 4; STKs catalyze the ...
323-504 2.87e-05

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: 46.17  E-value: 2.87e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 323 GSALAVKRLSAcgfgEKQFRSEM--NKLGELR---HPNLVPLLGYCVVEDERLLVYKHMVNGTL--------FSQLHNGG 389
Cdd:cd06657  45 GKLVAVKKMDL----RKQQRRELlfNEVVIMRdyqHENVVEMYNSYLVGDELWVVMEFLEGGALtdivthtrMNEEQIAA 120
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 390 LCDAVLdwptrRAIGVGAAKGLawlhhgcqppyLHQFISSNVILLDDDFDARITDYGLAKLVGSRDSNDSSFnngdLGEL 469
Cdd:cd06657 121 VCLAVL-----KALSVLHAQGV-----------IHRDIKSDSILLTHDGRVKLSDFGFCAQVSKEVPRRKSL----VGTP 180
                       170       180       190
                ....*....|....*....|....*....|....*
gi 15223445 470 GYVAPEYSSTMVASLKGDVYGFGIVLLELVTGQKP 504
Cdd:cd06657 181 YWMAPELISRLPYGPEVDIWSLGIMVIEMVDGEPP 215
PTKc_VEGFR1 cd14207
Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; ...
423-579 2.92e-05

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: 46.53  E-value: 2.92e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 423 LHQFISSNVILLDDDFDARITDYGLAklvgsRD--SNDSSFNNGDLG-ELGYVAPEYSSTMVASLKGDVYGFGIVLLELV 499
Cdd:cd14207 202 IHRDLAARNILLSENNVVKICDFGLA-----RDiyKNPDYVRKGDARlPLKWMAPESIFDKIYSTKSDVWSYGVLLWEIF 276
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 500 T-GQKPLSVINGVEGFKGSLVDwvsqylgtGRSKDAIDRSIcdkghdEEILQflkIACSCVVSRPKERPTMIQVYESLKN 578
Cdd:cd14207 277 SlGASPYPGVQIDEDFCSKLKE--------GIRMRAPEFAT------SEIYQ---IMLDCWQGDPNERPRFSELVERLGD 339

                .
gi 15223445 579 M 579
Cdd:cd14207 340 L 340
PTKc_Trk cd05049
Catalytic domain of the Protein Tyrosine Kinases, Tropomyosin Related Kinases; PTKs catalyze ...
322-504 3.10e-05

Catalytic domain of the Protein Tyrosine Kinases, Tropomyosin Related Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Trk subfamily consists of TrkA, TrkB, TrkC, and similar proteins. They are receptor PTKs (RTKs) containing an extracellular region with arrays of leucine-rich motifs flanked by two cysteine-rich clusters followed by two immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands, the nerve growth factor (NGF) family of neutrotrophins, leads to Trk receptor oligomerization and activation of the catalytic domain. Trk receptors are mainly expressed in the peripheral and central nervous systems. They play important roles in cell fate determination, neuronal survival and differentiation, as well as in the regulation of synaptic plasticity. Altered expression of Trk receptors is associated with many human diseases. The Trk 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: 270643 [Multi-domain]  Cd Length: 280  Bit Score: 45.92  E-value: 3.10e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 322 DGSALAVKRL--SACGFGEKQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHNGGlCDAVL---- 395
Cdd:cd05049  34 DKMLVAVKTLkdASSPDARKDFEREAELLTNLQHENIVKFYGVCTEGDPLLMVFEYMEHGDLNKFLRSHG-PDAAFlase 112
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 396 DWPTRR-------AIGVGAAKGLAWL--HHgcqppYLHQFISSNVILLDDDFDARITDYGLaklvgSRD--SNDSSFNNG 464
Cdd:cd05049 113 DSAPGEltlsqllHIAVQIASGMVYLasQH-----FVHRDLATRNCLVGTNLVVKIGDFGM-----SRDiySTDYYRVGG 182
                       170       180       190       200
                ....*....|....*....|....*....|....*....|..
gi 15223445 465 D-LGELGYVAPEYSSTMVASLKGDVYGFGIVLLELVT-GQKP 504
Cdd:cd05049 183 HtMLPIRWMPPESILYRKFTTESDVWSFGVVLWEIFTyGKQP 224
STKc_LKB1_CaMKK cd14008
Catalytic domain of the Serine/Threonine kinases, Liver Kinase B1, Calmodulin Dependent ...
351-574 3.15e-05

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: 46.01  E-value: 3.15e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 351 LRHPNLVPLlgYCVVEDER----LLVYKHMVNGTLFSQlhNGGLCDAVLDWPTRRAIGVGAAKGLAWLH-----HGCQPP 421
Cdd:cd14008  61 LDHPNIVRL--YEVIDDPEsdklYLVLEYCEGGPVMEL--DSGDRVPPLPEETARKYFRDLVLGLEYLHengivHRDIKP 136
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 422 ylhqfisSNvILLDDDFDARITDYGLAKLVGsrDSNDSSFNNgdLGELGYVAPEYSSTMVASLKG---DVYGFGIVLLEL 498
Cdd:cd14008 137 -------EN-LLLTADGTVKISDFGVSEMFE--DGNDTLQKT--AGTPAFLAPELCDGDSKTYSGkaaDIWALGVTLYCL 204
                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 15223445 499 VTGQKPlsvingvegFKGSLVdwVSQYLGTGRSKDAIDRSicdKGHDEEILQFLKiacSCVVSRPKERPTMIQVYE 574
Cdd:cd14008 205 VFGRLP---------FNGDNI--LELYEAIQNQNDEFPIP---PELSPELKDLLR---RMLEKDPEKRITLKEIKE 263
PknB_PASTA_kin NF033483
Stk1 family PASTA domain-containing Ser/Thr kinase;
341-504 3.17e-05

Stk1 family PASTA domain-containing Ser/Thr kinase;


Pssm-ID: 468045 [Multi-domain]  Cd Length: 563  Bit Score: 46.71  E-value: 3.17e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445  341 FRSEMNKLGELRHPNLVPLlgYCVVEDERLlVYKHM--VNG-TLFSQLHNGG--LCDAVLDWptrrAIGVGAAKGLAwlH 415
Cdd:NF033483  54 FRREAQSAASLSHPNIVSV--YDVGEDGGI-PYIVMeyVDGrTLKDYIREHGplSPEEAVEI----MIQILSALEHA--H 124
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445  416 HgcqppylHQFISSNV----ILLDDDFDARITDYGLAKLVGSrdsndSS--FNNGDLGELGYVAPEYSSTMVASLKGDVY 489
Cdd:NF033483 125 R-------NGIVHRDIkpqnILITKDGRVKVTDFGIARALSS-----TTmtQTNSVLGTVHYLSPEQARGGTVDARSDIY 192
                        170
                 ....*....|....*
gi 15223445  490 GFGIVLLELVTGQKP 504
Cdd:NF033483 193 SLGIVLYEMLTGRPP 207
PTKc_FGFR3 cd05100
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 3; PTKs ...
343-590 3.38e-05

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: 46.17  E-value: 3.38e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 343 SEMNKLGEL-RHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLH------------NGGLCDAVLDWPTRRAIGVGAAK 409
Cdd:cd05100  66 SEMEMMKMIgKHKNIINLLGACTQDGPLYVLVEYASKGNLREYLRarrppgmdysfdTCKLPEEQLTFKDLVSCAYQVAR 145
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 410 GLAWLhhgCQPPYLHQFISSNVILLDDDFDARITDYGLAKLVGSRDSNDSSfNNGDLgELGYVAPEYSSTMVASLKGDVY 489
Cdd:cd05100 146 GMEYL---ASQKCIHRDLAARNVLVTEDNVMKIADFGLARDVHNIDYYKKT-TNGRL-PVKWMAPEALFDRVYTHQSDVW 220
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 490 GFGIVLLELVT-GQKPlsvingvegFKGSLVDWVSQYLGTGRSKDaiDRSICDkgHDeeilqFLKIACSCVVSRPKERPT 568
Cdd:cd05100 221 SFGVLLWEIFTlGGSP---------YPGIPVEELFKLLKEGHRMD--KPANCT--HE-----LYMIMRECWHAVPSQRPT 282
                       250       260
                ....*....|....*....|..
gi 15223445 569 MIQVYESLKNMADKHGVSEHYD 590
Cdd:cd05100 283 FKQLVEDLDRVLTVTSTDEYLD 304
PTKc_Aatyk cd05042
Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinases; PTKs ...
328-576 4.13e-05

Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Aatyk subfamily is also referred to as the lemur tyrosine kinase (Lmtk) subfamily. It consists of Aatyk1 (Lmtk1), Aatyk2 (Lmtk2, Brek), Aatyk3 (Lmtk3), and similar proteins. Aatyk proteins are mostly receptor PTKs (RTKs) containing a transmembrane segment and a long C-terminal cytoplasmic tail with a catalytic domain. Aatyk1 does not contain a transmembrane segment and is a cytoplasmic (or nonreceptor) kinase. Aatyk proteins are classified as PTKs based on overall sequence similarity and the phylogenetic tree. However, analysis of catalytic residues suggests that Aatyk proteins may be multispecific kinases, functioning also as serine/threonine kinases. They are involved in neural differentiation, nerve growth factor (NGF) signaling, apoptosis, and spermatogenesis. The Aatyk 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: 270638 [Multi-domain]  Cd Length: 269  Bit Score: 45.66  E-value: 4.13e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 328 VKRL--SACGFGEKQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQL-----HNGGLCDAVldwpTR 400
Cdd:cd05042  27 VKELkaSANPKEQDTFLKEGQPYRILQHPNILQCLGQCVEAIPYLLVMEFCDLGDLKAYLrsereHERGDSDTR----TL 102
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 401 RAIGVGAAKGLAWLHhgcQPPYLHQFISSNVILLDDDFDARITDYGLAKlvgSRDSNDSSFNNGDLG-ELGYVAPE---- 475
Cdd:cd05042 103 QRMACEVAAGLAHLH---KLNFVHSDLALRNCLLTSDLTVKIGDYGLAH---SRYKEDYIETDDKLWfPLRWTAPElvte 176
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 476 -YSSTMVA--SLKGDVYGFGIVLLELVT-GQKPLSVINGVEgfkgsLVDWVSQYLGTGRSKDAIDRSICDKGHdeEILQF 551
Cdd:cd05042 177 fHDRLLVVdqTKYSNIWSLGVTLWELFEnGAQPYSNLSDLD-----VLAQVVREQDTKLPKPQLELPYSDRWY--EVLQF 249
                       250       260
                ....*....|....*....|....*
gi 15223445 552 lkiacsCVVSrPKERPTMIQVYESL 576
Cdd:cd05042 250 ------CWLS-PEQRPAAEDVHLLL 267
PK_GC-C cd14044
Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-C; The pseudokinase domain ...
336-499 4.60e-05

Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-C; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity and/or ATP binding. GC-C binds and is activated by the intestinal hormones, guanylin (GN) and uroguanylin (UGN), which are secreted after salty meals to inhibit sodium absorption and induce the secretion of chloride, bicarbonate, and water. GN and UGN are also present in the kidney, where they induce increased salt and water secretion. This prevents the development of hypernatremia and hypervolemia after ingestion of high amounts of salt. 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 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-C 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: 270946 [Multi-domain]  Cd Length: 271  Bit Score: 45.65  E-value: 4.60e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 336 FGEKQfRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLhNGGLC---DAVLDWPTRRAIGVGAAKGLA 412
Cdd:cd14044  46 FTEKQ-KIELNKLLQIDYYNLTKFYGTVKLDTMIFGVIEYCERGSLRDVL-NDKISypdGTFMDWEFKISVMYDIAKGMS 123
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 413 WLHhgCQPPYLHQFISSNVILLDDDFDARITDYGLAKLVGSRDsndssfnngDLgelgYVAPEYSSTMVASLKGDVYGFG 492
Cdd:cd14044 124 YLH--SSKTEVHGRLKSTNCVVDSRMVVKITDFGCNSILPPSK---------DL----WTAPEHLRQAGTSQKGDVYSYG 188

                ....*..
gi 15223445 493 IVLLELV 499
Cdd:cd14044 189 IIAQEII 195
PTKc_Ack_like cd05040
Catalytic domain of the Protein Tyrosine Kinase, Activated Cdc42-associated kinase; PTKs ...
341-578 4.66e-05

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: 45.41  E-value: 4.66e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 341 FRSEMNKLGELRHPNLVPLlgYCVVEDERLLvykhMVN-----GTLFSQLHNGG-------LCDavldwptrraIGVGAA 408
Cdd:cd05040  45 FLKEVNAMHSLDHPNLIRL--YGVVLSSPLM----MVTelaplGSLLDRLRKDQghflistLCD----------YAVQIA 108
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 409 KGLAWLHhgcQPPYLHQFISSNVILLDDDFDARITDYGLAKLVGSRDSNDSSFNNGDLgELGYVAPEYSSTMVASLKGDV 488
Cdd:cd05040 109 NGMAYLE---SKRFIHRDLAARNILLASKDKVKIGDFGLMRALPQNEDHYVMQEHRKV-PFAWCAPESLKTRKFSHASDV 184
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 489 YGFGIVLLELVT-GQKPLSVINGvegfkgslvdwvSQYLgtgrskDAIDR--------SICdkghDEEILQFLKiacSCV 559
Cdd:cd05040 185 WMFGVTLWEMFTyGEEPWLGLNG------------SQIL------EKIDKegerlerpDDC----PQDIYNVML---QCW 239
                       250
                ....*....|....*....
gi 15223445 560 VSRPKERPTMIQVYESLKN 578
Cdd:cd05040 240 AHKPADRPTFVALRDFLPE 258
STKc_myosinIIIA_N cd06638
N-terminal Catalytic domain of the Serine/Threonine Kinase, Class IIIA myosin; STKs catalyze ...
322-506 4.68e-05

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: 45.77  E-value: 4.68e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 322 DGSALAVKRLSACGFGEKQFRSEMNKLGELR-HPNLVPLLGYCVVED----ERLLVYKHMVNGTLFSQLHNGGLCDA-VL 395
Cdd:cd06638  42 NGSKAAVKILDPIHDIDEEIEAEYNILKALSdHPNVVKFYGMYYKKDvkngDQLWLVLELCNGGSVTDLVKGFLKRGeRM 121
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 396 DWPTRRAIGVGAAKGLAWLHHGcqpPYLHQFISSNVILLDDDFDARITDYGL-AKLVGSRDSNDSSfnngdLGELGYVAP 474
Cdd:cd06638 122 EEPIIAYILHEALMGLQHLHVN---KTIHRDVKGNNILLTTEGGVKLVDFGVsAQLTSTRLRRNTS-----VGTPFWMAP 193
                       170       180       190
                ....*....|....*....|....*....|....*....
gi 15223445 475 E-------YSSTMVAslKGDVYGFGIVLLELVTGQKPLS 506
Cdd:cd06638 194 EviaceqqLDSTYDA--RCDVWSLGITAIELGDGDPPLA 230
PK_STRAD_alpha cd08227
Pseudokinase domain of STE20-related kinase adapter protein alpha; The pseudokinase domain ...
321-505 4.70e-05

Pseudokinase domain of STE20-related kinase adapter protein alpha; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. 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. A mutation which results in a truncation of a C-terminal part of the human STRAD-alpha pseudokinase domain and disrupts its association with LKB1, leads to PMSE (polyhydramnios, megalencephaly, symptomatic epilepsy) syndrome. Several splice variants of STRAD-alpha exist which exhibit different effects on the localization and activation of LKB1. 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. The STRAD alpha 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: 173767 [Multi-domain]  Cd Length: 327  Bit Score: 45.70  E-value: 4.70e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 321 PDGSALAVKR--LSACGFGEKQF-RSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLfsqlhNGGLCDAVLDW 397
Cdd:cd08227  23 PTGEYVTVRRinLEACTNEMVTFlQGELHVSKLFNHPNIVPYRATFIADNELWVVTSFMAYGSA-----KDLICTHFMDG 97
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 398 PTRRAIG---VGAAKGLAWLHHgcqPPYLHQFISSNVILLDDDfdaritdyGLAKLVGSRdSNDSSFNNGDLGELGYVAP 474
Cdd:cd08227  98 MSELAIAyilQGVLKALDYIHH---MGYVHRSVKASHILISVD--------GKVYLSGLR-SNLSMINHGQRLRVVHDFP 165
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*
gi 15223445 475 EYSSTMVASL--------------KGDVYGFGIVLLELVTGQKPL 505
Cdd:cd08227 166 KYSVKVLPWLspevlqqnlqgydaKSDIYSVGITACELANGHVPF 210
STKc_PKB_gamma cd05593
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B gamma (also called Akt3); ...
343-505 5.19e-05

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: 45.84  E-value: 5.19e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 343 SEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHNgglcDAVLDWPTRRAIGVGAAKGLAWLHHGcqpPY 422
Cdd:cd05593  64 TESRVLKNTRHPFLTSLKYSFQTKDRLCFVMEYVNGGELFFHLSR----ERVFSEDRTRFYGAEIVSALDYLHSG---KI 136
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 423 LHQFISSNVILLDDDFDARITDYGLAKlvgsRDSNDSSFNNGDLGELGYVAPEYSSTMVASLKGDVYGFGIVLLELVTGQ 502
Cdd:cd05593 137 VYRDLKLENLMLDKDGHIKITDFGLCK----EGITDAATMKTFCGTPEYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGR 212

                ...
gi 15223445 503 KPL 505
Cdd:cd05593 213 LPF 215
STKc_TAO1 cd06635
Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 1; STKs catalyze ...
313-514 6.23e-05

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: 45.43  E-value: 6.23e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 313 GVSYKADLPDGSALAVKRLSACGFGEKQ----FRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTL-FSQLHN 387
Cdd:cd06635  40 AVYFARDVRTSEVVAIKKMSYSGKQSNEkwqdIIKEVKFLQRIKHPNSIEYKGCYLREHTAWLVMEYCLGSASdLLEVHK 119
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 388 GGLCDAVLdwptrRAIGVGAAKGLAWLHhgcQPPYLHQFISSNVILLDDDFDARITDYGLAKLVgsrdSNDSSFnngdLG 467
Cdd:cd06635 120 KPLQEIEI-----AAITHGALQGLAYLH---SHNMIHRDIKAGNILLTEPGQVKLADFGSASIA----SPANSF----VG 183
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|
gi 15223445 468 ELGYVAPEYSSTMVASL---KGDVYGFGIVLLELVTGQKPLSVINGVEGF 514
Cdd:cd06635 184 TPYWMAPEVILAMDEGQydgKVDVWSLGITCIELAERKPPLFNMNAMSAL 233
STKc_GRK4_like cd05605
Catalytic domain of G protein-coupled Receptor Kinase 4-like Serine/Threonine Kinases; STKs ...
432-504 7.54e-05

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: 45.04  E-value: 7.54e-05
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 15223445 432 ILLDDDFDARITDYGLAKLVGSRDSndssfNNGDLGELGYVAPEYSSTMVASLKGDVYGFGIVLLELVTGQKP 504
Cdd:cd05605 133 ILLDDHGHVRISDLGLAVEIPEGET-----IRGRVGTVGYMAPEVVKNERYTFSPDWWGLGCLIYEMIEGQAP 200
PTKc_TrkA cd05092
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase A; PTKs catalyze ...
322-504 8.01e-05

Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase A; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. TrkA is a receptor PTK (RTK) containing an extracellular region with arrays of leucine-rich motifs flanked by two cysteine-rich clusters followed by two immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. Binding of TrkA to its ligand, nerve growth factor (NGF), results in receptor oligomerization and activation of the catalytic domain. TrkA is expressed mainly in neural-crest-derived sensory and sympathetic neurons of the peripheral nervous system, and in basal forebrain cholinergic neurons of the central nervous system. It is critical for neuronal growth, differentiation and survival. Alternative TrkA splicing has been implicated as a pivotal regulator of neuroblastoma (NB) behavior. Normal TrkA expression is associated with better NB prognosis, while the hypoxia-regulated TrkAIII splice variant promotes NB pathogenesis and progression. Aberrant TrkA expression has also been demonstrated in non-neural tumors including prostate, breast, lung, and pancreatic cancers. The TrkA 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: 270674 [Multi-domain]  Cd Length: 280  Bit Score: 44.96  E-value: 8.01e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 322 DGSALAVKRLSACGFGEKQ-FRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHNGGLCDAVLD---- 396
Cdd:cd05092  34 DKMLVAVKALKEATESARQdFQREAELLTVLQHQHIVRFYGVCTEGEPLIMVFEYMRHGDLNRFLRSHGPDAKILDggeg 113
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 397 -------WPTRRAIGVGAAKG---LAWLHhgcqppYLHQFISSNVILLDDDFDARITDYGLAKLVGSRDSndSSFNNGDL 466
Cdd:cd05092 114 qapgqltLGQMLQIASQIASGmvyLASLH------FVHRDLATRNCLVGQGLVVKIGDFGMSRDIYSTDY--YRVGGRTM 185
                       170       180       190
                ....*....|....*....|....*....|....*....
gi 15223445 467 GELGYVAPEYSSTMVASLKGDVYGFGIVLLELVT-GQKP 504
Cdd:cd05092 186 LPIRWMPPESILYRKFTTESDIWSFGVVLWEIFTyGKQP 224
STKc_Chk2 cd14084
Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2; STKs catalyze ...
342-506 8.07e-05

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: 44.69  E-value: 8.07e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 342 RSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHNGGLcdavLDWPTRRAIGVGAAKGLAWLH-HGCqp 420
Cdd:cd14084  59 ETEIEILKKLSHPCIIKIEDFFDAEDDYYIVLELMEGGELFDRVVSNKR----LKEAICKLYFYQMLLAVKYLHsNGI-- 132
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 421 pyLHQFIS-SNVILLDDDFDAR--ITDYGLAKLVGsrdsnDSSFNNGDLGELGYVAPE---YSSTMVASLKGDVYGFGIV 494
Cdd:cd14084 133 --IHRDLKpENVLLSSQEEECLikITDFGLSKILG-----ETSLMKTLCGTPTYLAPEvlrSFGTEGYTRAVDCWSLGVI 205
                       170
                ....*....|..
gi 15223445 495 LLELVTGQKPLS 506
Cdd:cd14084 206 LFICLSGYPPFS 217
PTKc_TrkC cd05094
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase C; PTKs catalyze ...
322-504 8.47e-05

Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase C; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. TrkC is a receptor PTK (RTK) containing an extracellular region with arrays of leucine-rich motifs flanked by two cysteine-rich clusters followed by two immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. Binding of TrkC to its ligand, neurotrophin 3 (NT3), results in receptor oligomerization and activation of the catalytic domain. TrkC is broadly expressed in the nervous system and in some non-neural tissues including the developing heart. NT3/TrkC signaling plays an important role in the innervation of the cardiac conducting system and the development of smooth muscle cells. Mice deficient with NT3 and TrkC have multiple heart defects. NT3/TrkC signaling is also critical for the development and maintenance of enteric neurons that are important for the control of gut peristalsis. The TrkC 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: 270676 [Multi-domain]  Cd Length: 287  Bit Score: 44.62  E-value: 8.47e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 322 DGSALAVKRLSACGF-GEKQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHNGGLCDAVL-DWPT 399
Cdd:cd05094  34 DKMLVAVKTLKDPTLaARKDFQREAELLTNLQHDHIVKFYGVCGDGDPLIMVFEYMKHGDLNKFLRAHGPDAMILvDGQP 113
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 400 RRA-----------IGVGAAKGLAWLhhgCQPPYLHQFISSNVILLDDDFDARITDYGLAKLVGSRDSndSSFNNGDLGE 468
Cdd:cd05094 114 RQAkgelglsqmlhIATQIASGMVYL---ASQHFVHRDLATRNCLVGANLLVKIGDFGMSRDVYSTDY--YRVGGHTMLP 188
                       170       180       190
                ....*....|....*....|....*....|....*..
gi 15223445 469 LGYVAPEYSSTMVASLKGDVYGFGIVLLELVT-GQKP 504
Cdd:cd05094 189 IRWMPPESIMYRKFTTESDVWSFGVILWEIFTyGKQP 225
STKc_MAK_like cd07830
Catalytic domain of Male germ cell-Associated Kinase-like Serine/Threonine Kinases; STKs ...
313-505 9.51e-05

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: 44.45  E-value: 9.51e-05
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 313 GVSYKA-DLPDGSALAVKRLsacgfgEKQFRS--EMNKLGELR-------HPNLVPLLGYCVVEDERLLVYKHMvNGTLF 382
Cdd:cd07830  13 GSVYLArNKETGELVAIKKM------KKKFYSweECMNLREVKslrklneHPNIVKLKEVFRENDELYFVFEYM-EGNLY 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 383 sQL---HNGGLcdavLDWPTRRAIGVGAAKGLAWLH-HGcqppYLHQFISSNVILLDDDFDARITDYGLAKLVGSRDsnd 458
Cdd:cd07830  86 -QLmkdRKGKP----FSESVIRSIIYQILQGLAHIHkHG----FFHRDLKPENLLVSGPEVVKIADFGLAREIRSRP--- 153
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 459 ssfnngDLGElgYV------APE-------YSSTMvaslkgDVYGFGIVLLELVTGqKPL 505
Cdd:cd07830 154 ------PYTD--YVstrwyrAPEillrstsYSSPV------DIWALGCIMAELYTL-RPL 198
STKc_MAP4K5 cd06646
Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase ...
342-505 1.00e-04

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: 44.25  E-value: 1.00e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 342 RSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLH-NGGLCDAVLDWPTRRAIgvgaaKGLAWLHHGCQp 420
Cdd:cd06646  54 QQEIFMVKECKHCNIVAYFGSYLSREKLWICMEYCGGGSLQDIYHvTGPLSELQIAYVCRETL-----QGLAYLHSKGK- 127
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 421 pyLHQFISSNVILLDDDFDARITDYGLAKLVGSRDSNDSSFnngdLGELGYVAPEYSStmVASLKG-----DVYGFGIVL 495
Cdd:cd06646 128 --MHRDIKGANILLTDNGDVKLADFGVAAKITATIAKRKSF----IGTPYWMAPEVAA--VEKNGGynqlcDIWAVGITA 199
                       170
                ....*....|
gi 15223445 496 LELVTGQKPL 505
Cdd:cd06646 200 IELAELQPPM 209
PTKc_Ror2 cd05091
Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor ...
311-504 1.03e-04

Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Ror2 plays important roles in skeletal and heart formation. Ror2-deficient mice show widespread bone abnormalities, ventricular defects in the heart, and respiratory dysfunction. Mutations in human Ror2 result in two different bone development genetic disorders, recessive Robinow syndrome and brachydactyly type B. Ror2 is also implicated in neural development. Ror proteins are orphan receptor PTKs (RTKs) containing an extracellular region with immunoglobulin-like, cysteine-rich, and kringle domains, a transmembrane segment, and an intracellular catalytic domain. Ror RTKs are unrelated to the nuclear receptor subfamily called retinoid-related orphan receptors (RORs). RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain. The Ror2 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: 270673 [Multi-domain]  Cd Length: 284  Bit Score: 44.62  E-value: 1.03e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 311 RTGVSYKADL------PDGSALAVKRLS--ACGFGEKQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLF 382
Cdd:cd05091  18 RFGKVYKGHLfgtapgEQTQAVAIKTLKdkAEGPLREEFRHEAMLRSRLQHPNIVCLLGVVTKEQPMSMIFSYCSHGDLH 97
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 383 SQL-----HNG-GLCD------AVLDWPTRRAIGVGAAKGLAWL--HHgcqppYLHQFISSNVILLDDDFDARITDYGLA 448
Cdd:cd05091  98 EFLvmrspHSDvGSTDddktvkSTLEPADFLHIVTQIAAGMEYLssHH-----VVHKDLATRNVLVFDKLNVKISDLGLF 172
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*..
gi 15223445 449 KLVGSRDSNDSSFNNgdLGELGYVAPEYSSTMVASLKGDVYGFGIVLLELVT-GQKP 504
Cdd:cd05091 173 REVYAADYYKLMGNS--LLPIRWMSPEAIMYGKFSIDSDIWSYGVVLWEVFSyGLQP 227
STKc_Yank1 cd05578
Catalytic domain of the Serine/Threonine Kinase, Yank1; STKs catalyze the transfer of the ...
423-504 1.14e-04

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: 44.17  E-value: 1.14e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 423 LHQFISSNVILLDDDFDARITDYGLAKLVgsrdsNDSSFNNGDLGELGYVAPEYSSTMVASLKGDVYGFGIVLLELVTGQ 502
Cdd:cd05578 122 IHRDIKPDNILLDEQGHVHITDFNIATKL-----TDGTLATSTSGTKPYMAPEVFMRAGYSFAVDWWSLGVTAYEMLRGK 196

                ..
gi 15223445 503 KP 504
Cdd:cd05578 197 RP 198
PK_STRAD_beta cd08226
Pseudokinase domain of STE20-related kinase adapter protein beta; The pseudokinase domain ...
310-504 1.17e-04

Pseudokinase domain of STE20-related kinase adapter protein beta; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity.STRAD-beta is also referred to as ALS2CR2 (Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 2 protein), since the human gene encoding it is located within the juvenile ALS2 critical region on chromosome 2q33-q34. It is not linked to the development of ALS2. 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. The STRAD-beta 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: 270864 [Multi-domain]  Cd Length: 328  Bit Score: 44.48  E-value: 1.17e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 310 SRTGVSYKADLPDGSALAVKRLSACGFGEKQFRSEMNKL---GELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLH 386
Cdd:cd08226  12 NLTSVYLARHTPTGTLVTVKITNLDNCSEEHLKALQNEVvlsHFFRHPNIMTHWTVFTEGSWLWVISPFMAYGSARGLLK 91
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 387 N---GGLCDAVLdwptrRAIGVGAAKGLAWLHhgcQPPYLHQFISSNVILLDDDfdARITDYGLAKLVgsrdsndSSFNN 463
Cdd:cd08226  92 TyfpEGMNEALI-----GNILYGAIKALNYLH---QNGCIHRSVKASHILISGD--GLVSLSGLSHLY-------SMVTN 154
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*
gi 15223445 464 GDLGELGYVAPEYSSTMVASL--------------KGDVYGFGIVLLELVTGQKP 504
Cdd:cd08226 155 GQRSKVVYDFPQFSTSVLPWLspellrqdlhgynvKSDIYSVGITACELARGQVP 209
STKc_CaMKI_alpha cd14167
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
338-505 1.24e-04

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: 44.25  E-value: 1.24e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 338 EKQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHNGG---------LCDAVLDwptrraiGVGAA 408
Cdd:cd14167  45 ETSIENEIAVLHKIKHPNIVALDDIYESGGHLYLIMQLVSGGELFDRIVEKGfyterdaskLIFQILD-------AVKYL 117
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 409 KGLAWLHHGCQPPYLHQFIssnvilLDDDFDARITDYGLAKLVGSrdsndSSFNNGDLGELGYVAPEYSSTMVASLKGDV 488
Cdd:cd14167 118 HDMGIVHRDLKPENLLYYS------LDEDSKIMISDFGLSKIEGS-----GSVMSTACGTPGYVAPEVLAQKPYSKAVDC 186
                       170
                ....*....|....*..
gi 15223445 489 YGFGIVLLELVTGQKPL 505
Cdd:cd14167 187 WSIGVIAYILLCGYPPF 203
STKc_cGK cd05572
Catalytic domain of the Serine/Threonine Kinase, cGMP-dependent protein kinase (cGK or PKG); ...
338-506 1.24e-04

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: 44.14  E-value: 1.24e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 338 EKQFRSEMNKLGELRHPNLVPLlgYCVVEDER----LLVYkhMVNGTLFSQLHNGGLCDavlDWPTRRAIG--VGAakgL 411
Cdd:cd05572  37 QEHIFSEKEILEECNSPFIVKL--YRTFKDKKylymLMEY--CLGGELWTILRDRGLFD---EYTARFYTAcvVLA---F 106
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 412 AWLHHgcqppylHQFISSNV----ILLDDDFDARITDYGLAKLVGSRdSNDSSFnngdLGELGYVAPEysstmVASLKG- 486
Cdd:cd05572 107 EYLHS-------RGIIYRDLkpenLLLDSNGYVKLVDFGFAKKLGSG-RKTWTF----CGTPEYVAPE-----IILNKGy 169
                       170       180
                ....*....|....*....|....
gi 15223445 487 ----DVYGFGIVLLELVTGQKPLS 506
Cdd:cd05572 170 dfsvDYWSLGILLYELLTGRPPFG 193
STKc_MST3_like cd06609
Catalytic domain of Mammalian Ste20-like protein kinase 3-like Serine/Threonine Kinases; STKs ...
344-506 1.35e-04

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: 44.16  E-value: 1.35e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 344 EMNKLGELRHPNLVPLLGyCVVEDERL-LVYKHMVNGTLFSQLHNGGLCDAVLDWPTRRAIgvgaaKGLAWLHHGCQppy 422
Cdd:cd06609  49 EIQFLSQCDSPYITKYYG-SFLKGSKLwIIMEYCGGGSVLDLLKPGPLDETYIAFILREVL-----LGLEYLHSEGK--- 119
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 423 LHQFISSNVILLDDDFDARITDYGLAKLVGSRDSNDSSFnngdLGELGYVAPEYSSTMVASLKGDVYGFGIVLLELVTGQ 502
Cdd:cd06609 120 IHRDIKAANILLSEEGDVKLADFGVSGQLTSTMSKRNTF----VGTPFWMAPEVIKQSGYDEKADIWSLGITAIELAKGE 195

                ....
gi 15223445 503 KPLS 506
Cdd:cd06609 196 PPLS 199
STKc_MSK2_N cd05614
N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
317-517 1.36e-04

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: 44.52  E-value: 1.36e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 317 KADLPDGSAL-AVKRLSACGFGEK-----QFRSEMNKLGELRHPNLVPLLGYCVVEDERL-LVYKHMVNGTLFSQLHNgg 389
Cdd:cd05614  21 KVSGHDANKLyAMKVLRKAALVQKaktveHTRTERNVLEHVRQSPFLVTLHYAFQTDAKLhLILDYVSGGELFTHLYQ-- 98
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 390 lcdavLDWPTRRAIGVGAAKGLAWLHHGCQPPYLHQFISSNVILLDDDFDARITDYGLAKLVGSRDSNDS-SFnngdLGE 468
Cdd:cd05614  99 -----RDHFSEDEVRFYSGEIILALEHLHKLGIVYRDIKLENILLDSEGHVVLTDFGLSKEFLTEEKERTySF----CGT 169
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|
gi 15223445 469 LGYVAPEYSSTMVASLKG-DVYGFGIVLLELVTGQKPLSvingVEGFKGS 517
Cdd:cd05614 170 IEYMAPEIIRGKSGHGKAvDWWSLGILMFELLTGASPFT----LEGEKNT 215
STKc_ACVR1_ALK1 cd14142
Catalytic domain of the Serine/Threonine Kinases, Activin Type I Receptor and Activin ...
351-576 1.43e-04

Catalytic domain of the Serine/Threonine Kinases, Activin Type I Receptor and Activin receptor-Like Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ACVR1, also called Activin receptor-Like Kinase 2 (ALK2), and ALK1 act as receptors for bone morphogenetic proteins (BMPs) and they activate SMAD1/5/8. ACVR1 is widely expressed while ALK1 is limited mainly to endothelial cells. The specificity of BMP binding to type I receptors is affected by type II receptors. ACVR1 binds BMP6/7/9/10 and can also bind anti-Mullerian hormone (AMH) in the presence of AMHR2. ALK1 binds BMP9/10 as well as TGFbeta in endothelial cells. A missense mutation in the GS domain of ACVR1 causes fibrodysplasia ossificans progressiva, a complex and disabling disease characterized by congenital skeletal malformations and extraskeletal bone formation. ACVR1 belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, BMPs, activins, growth and differentiation factors, and AMH, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. Type I receptors, like ACVR1 and ALK1, are low-affinity receptors that bind ligands only after they are recruited by the ligand/type II high-affinity receptor complex. Following activation, they start intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. The ACVR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271044 [Multi-domain]  Cd Length: 298  Bit Score: 43.97  E-value: 1.43e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 351 LRHPNLvplLGYcVVED--------ERLLVYKHMVNGTLFSQLHNgglcdAVLDWPTRRAIGVGAAKGLAWLH------H 416
Cdd:cd14142  56 LRHENI---LGF-IASDmtsrnsctQLWLITHYHENGSLYDYLQR-----TTLDHQEMLRLALSAASGLVHLHteifgtQ 126
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 417 GcQPPYLHQFISSNVILLDDDFDARITDYGLAKLVGSRDSNDSSFNNGDLGELGYVAPEY------SSTMVASLKGDVYG 490
Cdd:cd14142 127 G-KPAIAHRDLKSKNILVKSNGQCCIADLGLAVTHSQETNQLDVGNNPRVGTKRYMAPEVldetinTDCFESYKRVDIYA 205
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 491 FGIVLLELVTgqkpLSVING-VEGFKGSLVDwvsqYLGTGRSKDAIDRSICDKGH----------DEEILQFLKIACSCV 559
Cdd:cd14142 206 FGLVLWEVAR----RCVSGGiVEEYKPPFYD----VVPSDPSFEDMRKVVCVDQQrpnipnrwssDPTLTAMAKLMKECW 277
                       250
                ....*....|....*..
gi 15223445 560 VSRPKERPTMIQVYESL 576
Cdd:cd14142 278 YQNPSARLTALRIKKTL 294
STKc_TSSK1_2-like cd14165
Catalytic domain of testis-specific serine/threonine kinase 1, TSSK2, and similar proteins; ...
329-540 1.48e-04

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: 44.00  E-value: 1.48e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 329 KRLSACGFGEKQFRSEMNKLGELRHPNLVPLlgYCVVEDERLLVYKHM---VNGTLFSQLHNGGlcdaVLDWPTRRAIGV 405
Cdd:cd14165  36 KKKAPDDFVEKFLPRELEILARLNHKSIIKT--YEIFETSDGKVYIVMelgVQGDLLEFIKLRG----ALPEDVARKMFH 109
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 406 GAAKGLAWLHhgcQPPYLHQFISSNVILLDDDFDARITDYGLAKLVgSRDSN-----DSSFnngdLGELGYVAPE-YSST 479
Cdd:cd14165 110 QLSSAIKYCH---ELDIVHRDLKCENLLLDKDFNIKLTDFGFSKRC-LRDENgrivlSKTF----CGSAAYAAPEvLQGI 181
                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 15223445 480 MVASLKGDVYGFGIVLLELVTGQKPLSVINGVEGFKGSL---VDWVSQYLGTGRSKDAIDRSIC 540
Cdd:cd14165 182 PYDPRIYDIWSLGVILYIMVCGSMPYDDSNVKKMLKIQKehrVRFPRSKNLTSECKDLIYRLLQ 245
PTKc_Tie2 cd05088
Catalytic domain of the Protein Tyrosine Kinase, Tie2; PTKs catalyze the transfer of the ...
327-582 1.58e-04

Catalytic domain of the Protein Tyrosine Kinase, Tie2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tie2 is a receptor PTK (RTK) containing an extracellular region, a transmembrane segment, and an intracellular catalytic domain. The extracellular region contains an immunoglobulin (Ig)-like domain, three epidermal growth factor (EGF)-like domains, a second Ig-like domain, and three fibronectin type III repeats. Tie2 is expressed mainly in endothelial cells and hematopoietic stem cells. It is also found in a subset of tumor-associated monocytes and eosinophils. The angiopoietins (Ang-1 to Ang-4) serve as ligands for Tie2. The binding of Ang-1 to Tie2 leads to receptor autophosphorylation and activation, promoting cell migration and survival. In contrast, Ang-2 binding to Tie2 does not result in the same response, suggesting that Ang-2 may function as an antagonist. Tie2 signaling plays key regulatory roles in vascular integrity and quiescence, and in inflammation. The Tie2 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: 133219 [Multi-domain]  Cd Length: 303  Bit Score: 44.22  E-value: 1.58e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 327 AVKRLS--ACGFGEKQFRSEMNKLGEL-RHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHNGGLCD----------- 392
Cdd:cd05088  38 AIKRMKeyASKDDHRDFAGELEVLCKLgHHPNIINLLGACEHRGYLYLAIEYAPHGNLLDFLRKSRVLEtdpafaianst 117
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 393 -AVLDWPTRRAIGVGAAKGLAWLhhgCQPPYLHQFISSNVILLDDDFDARITDYGLAKlvgsrdsNDSSFNNGDLGELG- 470
Cdd:cd05088 118 aSTLSSQQLLHFAADVARGMDYL---SQKQFIHRDLAARNILVGENYVAKIADFGLSR-------GQEVYVKKTMGRLPv 187
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 471 -YVAPEYSSTMVASLKGDVYGFGIVLLELVT-GQKPLSVINGVEGFkgslvdwvsQYLGTG-RSKDAIDrsiCdkghDEE 547
Cdd:cd05088 188 rWMAIESLNYSVYTTNSDVWSYGVLLWEIVSlGGTPYCGMTCAELY---------EKLPQGyRLEKPLN---C----DDE 251
                       250       260       270
                ....*....|....*....|....*....|....*
gi 15223445 548 ILQFLKiacSCVVSRPKERPTMIQVYESLKNMADK 582
Cdd:cd05088 252 VYDLMR---QCWREKPYERPSFAQILVSLNRMLEE 283
PKc_Dusty cd13975
Catalytic domain of the Dual-specificity Protein Kinase, Dusty; Dual-specificity PKs catalyze ...
393-582 1.62e-04

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: 43.63  E-value: 1.62e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 393 AVLDWPTRRAIGVGAAKGLAWLHhgcQPPYLHQFISSNVILLDDDFDARITDYGLAKlvgsrdsNDSSFNNGDLGELGYV 472
Cdd:cd13975  97 AGLSLEERLQIALDVVEGIRFLH---SQGLVHRDIKLKNVLLDKKNRAKITDLGFCK-------PEAMMSGSIVGTPIHM 166
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 473 APE-----YSSTMvaslkgDVYGFGIVLLELVTGQKPLSviNGVEGFKgslvdwvsqylgtgrSKDAIDRSIcDKGHDEE 547
Cdd:cd13975 167 APElfsgkYDNSV------DVYAFGILFWYLCAGHVKLP--EAFEQCA---------------SKDHLWNNV-RKGVRPE 222
                       170       180       190       200
                ....*....|....*....|....*....|....*....|
gi 15223445 548 ILQFLKIAC-----SCVVSRPKERPTMIQVYESLKNMADK 582
Cdd:cd13975 223 RLPVFDEECwnlmeACWSGDPSQRPLLGIVQPKLQGIMDR 262
PKc_MKK7 cd06618
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase ...
313-504 1.66e-04

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: 43.90  E-value: 1.66e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 313 GVSYKAD-LPDGSALAVKRLSACGFGEKQFRSEMN-KLGELRH--PNLVPLLGYCVVEDERLLVYKHMvnGTLFSQLH-- 386
Cdd:cd06618  29 GQVYKMRhKKTGHVMAVKQMRRSGNKEENKRILMDlDVVLKSHdcPYIVKCYGYFITDSDVFICMELM--STCLDKLLkr 106
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 387 -NGGLCDAVLDwptrrAIGVGAAKGLAWL--HHGCqppyLHQFISSNVILLDDDFDARITDYGLA-KLVGSRDSNDSSfn 462
Cdd:cd06618 107 iQGPIPEDILG-----KMTVSIVKALHYLkeKHGV----IHRDVKPSNILLDESGNVKLCDFGISgRLVDSKAKTRSA-- 175
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*
gi 15223445 463 ngdlGELGYVAPEY---SSTMVASLKGDVYGFGIVLLELVTGQKP 504
Cdd:cd06618 176 ----GCAAYMAPERidpPDNPKYDIRADVWSLGISLVELATGQFP 216
PTKc_FGFR1 cd05098
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 1; PTKs ...
343-576 1.68e-04

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: 43.85  E-value: 1.68e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 343 SEMNKLGEL-RHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQL------------HNGGLCDAVLDWPTRRAIGVGAAK 409
Cdd:cd05098  67 SEMEMMKMIgKHKNIINLLGACTQDGPLYVIVEYASKGNLREYLqarrppgmeycyNPSHNPEEQLSSKDLVSCAYQVAR 146
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 410 GLAWLhhgCQPPYLHQFISSNVILLDDDFDARITDYGLAKLVGSRDSNDSSfNNGDLgELGYVAPEYSSTMVASLKGDVY 489
Cdd:cd05098 147 GMEYL---ASKKCIHRDLAARNVLVTEDNVMKIADFGLARDIHHIDYYKKT-TNGRL-PVKWMAPEALFDRIYTHQSDVW 221
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 490 GFGIVLLELVT-GQKPlsvingvegFKGSLVDWVSQYLGTGRSKDAidRSICdkghDEEILQFLKiacSCVVSRPKERPT 568
Cdd:cd05098 222 SFGVLLWEIFTlGGSP---------YPGVPVEELFKLLKEGHRMDK--PSNC----TNELYMMMR---DCWHAVPSQRPT 283

                ....*...
gi 15223445 569 MIQVYESL 576
Cdd:cd05098 284 FKQLVEDL 291
STKc_EIF2AK1_HRI cd14049
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
322-575 1.80e-04

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: 43.65  E-value: 1.80e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 322 DGSALAVKRLSACGFGEKQFR---SEMNKLGELRHPNLVpllGYCV--VEDERLLVYKHMV-------------NGTLFS 383
Cdd:cd14049  30 DGQYYAIKKILIKKVTKRDCMkvlREVKVLAGLQHPNIV---GYHTawMEHVQLMLYIQMQlcelslwdwiverNKRPCE 106
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 384 QLHNGGLCDAV-LDWPTR--RAI--GVGAAKGLAWLHHGCQPpylhqfisSNVILLDDDFDARITDYGLA---KLVGSRD 455
Cdd:cd14049 107 EEFKSAPYTPVdVDVTTKilQQLleGVTYIHSMGIVHRDLKP--------RNIFLHGSDIHVRIGDFGLAcpdILQDGND 178
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 456 SNDSSFNNG-----DLGELGYVAPEYSSTMVASLKGDVYGFGIVLLELVtgqKPLsvinGVEGFKGSLVdwvsqylgTGR 530
Cdd:cd14049 179 STTMSRLNGlthtsGVGTCLYAAPEQLEGSHYDFKSDMYSIGVILLELF---QPF----GTEMERAEVL--------TQL 243
                       250       260       270       280
                ....*....|....*....|....*....|....*....|....*
gi 15223445 531 SKDAIDRSICDKGhdEEILQFLKIACScvvSRPKERPTMIQVYES 575
Cdd:cd14049 244 RNGQIPKSLCKRW--PVQAKYIKLLTS---TEPSERPSASQLLES 283
PKc_Byr1_like cd06620
Catalytic domain of fungal Byr1-like dual-specificity Mitogen-activated protein Kinase Kinases; ...
339-573 1.84e-04

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: 43.58  E-value: 1.84e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 339 KQFRSEMNKLGELRHPNLVPLLGYCVVED-ERLLVYKHMVNGTLFSQLHNGG-LCDAVLdwptrRAIGVGAAKGLAWL-- 414
Cdd:cd06620  48 KQILRELQILHECHSPYIVSFYGAFLNENnNIIICMEYMDCGSLDKILKKKGpFPEEVL-----GKIAVAVLEGLTYLyn 122
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 415 -HHgcqppYLHQFISSNVILLDDDFDARITDYGLA-KLVgsrdsndSSFNNGDLGELGYVAPEYSSTMVASLKGDVYGFG 492
Cdd:cd06620 123 vHR-----IIHRDIKPSNILVNSKGQIKLCDFGVSgELI-------NSIADTFVGTSTYMSPERIQGGKYSVKSDVWSLG 190
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 493 IVLLELVTGQKPLSVINgvegfkgslvDWVSQYLGTGRSKDAIDRSI--------CDKGHDEEILQFLKIacsCVVSRPK 564
Cdd:cd06620 191 LSIIELALGEFPFAGSN----------DDDDGYNGPMGILDLLQRIVneppprlpKDRIFPKDLRDFVDR---CLLKDPR 257

                ....*....
gi 15223445 565 ERPTMIQVY 573
Cdd:cd06620 258 ERPSPQLLL 266
PTKc_DDR_like cd05097
Catalytic domain of Discoidin Domain Receptor-like Protein Tyrosine Kinases; PTKs catalyze the ...
319-509 1.85e-04

Catalytic domain of Discoidin Domain Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. DDR-like proteins are members of the DDR subfamily, which are receptor PTKs (RTKs) containing an extracellular discoidin homology domain, a transmembrane segment, an extended juxtamembrane region, and an intracellular catalytic domain. The binding of the ligand, collagen, to DDRs results in a slow but sustained receptor activation. DDRs regulate cell adhesion, proliferation, and extracellular matrix remodeling. They have been linked to a variety of human cancers including breast, colon, ovarian, brain, and lung. There is no evidence showing that DDRs act as transforming oncogenes. They are more likely to play a role in the regulation of tumor growth and metastasis. The DDR-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: 133228 [Multi-domain]  Cd Length: 295  Bit Score: 43.81  E-value: 1.85e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 319 DLPDGSALAVKRLSACGFGEKQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTL---------FSQLHNGG 389
Cdd:cd05097  42 GQPVLVAVKMLRADVTKTARNDFLKEIKIMSRLKNPNIIRLLGVCVSDDPLCMITEYMENGDLnqflsqreiESTFTHAN 121
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 390 LCDAV-----LDWPTRRAIGVgaaKGLAWLHhgcqppYLHQFISSNVILLDDDFDARITDYGLAKLVGSRDSndSSFNNG 464
Cdd:cd05097 122 NIPSVsianlLYMAVQIASGM---KYLASLN------FVHRDLATRNCLVGNHYTIKIADFGMSRNLYSGDY--YRIQGR 190
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*..
gi 15223445 465 DLGELGYVAPEYSSTMVASLKGDVYGFGIVLLELVT--GQKPLSVIN 509
Cdd:cd05097 191 AVLPIRWMAWESILLGKFTTASDVWAFGVTLWEMFTlcKEQPYSLLS 237
STKc_nPKC_delta cd05620
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C delta; STKs catalyze ...
432-537 1.85e-04

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: 43.78  E-value: 1.85e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 432 ILLDDDFDARITDYGLAKLVGSRDSNDSSFnngdLGELGYVAPEYSSTMVASLKGDVYGFGIVLLELVTGQKPLSVINGV 511
Cdd:cd05620 127 VMLDRDGHIKIADFGMCKENVFGDNRASTF----CGTPDYIAPEILQGLKYTFSVDWWSFGVLLYEMLIGQSPFHGDDED 202
                        90       100       110
                ....*....|....*....|....*....|..
gi 15223445 512 EGFKGSLVD------WVsqylgTGRSKDAIDR 537
Cdd:cd05620 203 ELFESIRVDtphyprWI-----TKESKDILEK 229
STKc_Pho85 cd07836
Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase Pho85; ...
344-505 2.16e-04

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: 43.62  E-value: 2.16e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 344 EMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMvNGTLFSQLHNGGLCDAvLDWPTRRAIGVGAAKGLAWLHhgcQPPYL 423
Cdd:cd07836  48 EISLMKELKHENIVRLHDVIHTENKLMLVFEYM-DKDLKKYMDTHGVRGA-LDPNTVKSFTYQLLKGIAFCH---ENRVL 122
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 424 HQFISSNVILLDDDFDARITDYGLAKLVGsrdSNDSSFNNgDLGELGYVAPEY---SSTMVASLkgDVYGFGIVLLELVT 500
Cdd:cd07836 123 HRDLKPQNLLINKRGELKLADFGLARAFG---IPVNTFSN-EVVTLWYRAPDVllgSRTYSTSI--DIWSVGCIMAEMIT 196

                ....*
gi 15223445 501 GqKPL 505
Cdd:cd07836 197 G-RPL 200
PKc_MKK5 cd06619
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase ...
313-568 2.33e-04

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: 43.33  E-value: 2.33e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 313 GVSYKA-DLPDGSALAVK--RLSACGFGEKQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQlhnGG 389
Cdd:cd06619  15 GTVYKAyHLLTRRILAVKviPLDITVELQKQIMSELEILYKCDSPYIIGFYGAFFVENRISICTEFMDGGSLDVY---RK 91
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 390 LCDAVLDwptrrAIGVGAAKGLAWLhhgCQPPYLHQFISSNVILLDDDFDARITDYGLA-KLVgsrdsndSSFNNGDLGE 468
Cdd:cd06619  92 IPEHVLG-----RIAVAVVKGLTYL---WSLKILHRDVKPSNMLVNTRGQVKLCDFGVStQLV-------NSIAKTYVGT 156
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 469 LGYVAPEYSSTMVASLKGDVYGFGIVLLELVTGQKPLSVINGVEGFKGSL------VDWVSQYLGTGRSKDaidrsicdk 542
Cdd:cd06619 157 NAYMAPERISGEQYGIHSDVWSLGISFMELALGRFPYPQIQKNQGSLMPLqllqciVDEDPPVLPVGQFSE--------- 227
                       250       260
                ....*....|....*....|....*.
gi 15223445 543 ghdeeilQFLKIACSCVVSRPKERPT 568
Cdd:cd06619 228 -------KFVHFITQCMRKQPKERPA 246
PTZ00263 PTZ00263
protein kinase A catalytic subunit; Provisional
343-504 2.42e-04

protein kinase A catalytic subunit; Provisional


Pssm-ID: 140289 [Multi-domain]  Cd Length: 329  Bit Score: 43.65  E-value: 2.42e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445  343 SEMNKLGELRHPNLVPLlgYCVVEDERLL--VYKHMVNGTLFSQLHNGGlcdavlDWPTRRAIGVGAAKGLAWlhhgcqp 420
Cdd:PTZ00263  67 QEKSILMELSHPFIVNM--MCSFQDENRVyfLLEFVVGGELFTHLRKAG------RFPNDVAKFYHAELVLAF------- 131
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445  421 PYLHqfiSSNVI---------LLDDDFDARITDYGLAKLVGSRdsndsSFNNgdLGELGYVAPEysstmVASLKG----- 486
Cdd:PTZ00263 132 EYLH---SKDIIyrdlkpenlLLDNKGHVKVTDFGFAKKVPDR-----TFTL--CGTPEYLAPE-----VIQSKGhgkav 196
                        170
                 ....*....|....*...
gi 15223445  487 DVYGFGIVLLELVTGQKP 504
Cdd:PTZ00263 197 DWWTMGVLLYEFIAGYPP 214
STKc_CDK9_like cd07840
Catalytic domain of Cyclin-Dependent protein Kinase 9-like Serine/Threonine Kinases; STKs ...
316-505 2.76e-04

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: 43.32  E-value: 2.76e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 316 YKA-DLPDGSALAVKRLS----ACGFGEKQFRsEMNKLGELRHPNLVPLLGYCVVEDERL------LVYKHM---VNGTL 381
Cdd:cd07840  16 YKArNKKTGELVALKKIRmeneKEGFPITAIR-EIKLLQKLDHPNVVRLKEIVTSKGSAKykgsiyMVFEYMdhdLTGLL 94
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 382 ------FSQLHNGGLCDAVLdwptrraigvgaaKGLAWLHhgcQPPYLHQFI-SSNvILLDDDFDARITDYGLAKLVGSR 454
Cdd:cd07840  95 dnpevkFTESQIKCYMKQLL-------------EGLQYLH---SNGILHRDIkGSN-ILINNDGVLKLADFGLARPYTKE 157
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 15223445 455 DSNDssFNNGDLgELGYVAPE-------YSSTMvaslkgDVYGFGIVLLELVTGqKPL 505
Cdd:cd07840 158 NNAD--YTNRVI-TLWYRPPElllgatrYGPEV------DMWSVGCILAELFTG-KPI 205
LRR COG4886
Leucine-rich repeat (LRR) protein [Transcription];
76-209 3.23e-04

Leucine-rich repeat (LRR) protein [Transcription];


Pssm-ID: 443914 [Multi-domain]  Cd Length: 414  Bit Score: 43.38  E-value: 3.23e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445  76 SLQLQSMQLAgEIPESLKLCRSLQSLDLSGNDLSgSIPS---------------QI-----CSWLPYLVTLDLSGNKLGG 135
Cdd:COG4886 209 ELDLSGNQLT-DLPEPLANLTNLETLDLSNNQLT-DLPElgnltnleeldlsnnQLtdlppLANLTNLKTLDLSNNQLTD 286
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 15223445 136 SIPTQIVECKFLNALILSDNKLSGSIPSQLSRLDRLRRLSLAGNDLSGTIPSELARFGGDDFSGNNGLCGKPLS 209
Cdd:COG4886 287 LKLKELELLLGLNSLLLLLLLLNLLELLILLLLLTTLLLLLLLLKGLLVTLTTLALSLSLLALLTLLLLLNLLS 360
PTKc_IGF-1R cd05062
Catalytic domain of the Protein Tyrosine Kinase, Insulin-like Growth Factor-1 Receptor; PTKs ...
340-578 3.38e-04

Catalytic domain of the Protein Tyrosine Kinase, Insulin-like Growth Factor-1 Receptor; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. IGF-1R is a receptor PTK (RTK) that is composed of two alphabeta heterodimers. Binding of the ligand (IGF-1 or IGF-2) to the extracellular alpha subunit activates the intracellular tyr kinase domain of the transmembrane beta subunit. Receptor activation leads to autophosphorylation, which stimulates downstream kinase activities and biological function. IGF-1R signaling is important in the differentiation, growth, and survival of normal cells. In cancer cells, where it is frequently overexpressed, IGF-1R is implicated in proliferation, the suppression of apoptosis, invasion, and metastasis. IGF-1R is being developed as a therapeutic target in cancer treatment. The IGF-1R 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: 133193 [Multi-domain]  Cd Length: 277  Bit Score: 42.71  E-value: 3.38e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 340 QFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHN---GGLCDAVLDWPT-RRAIGVGA--AKGLAW 413
Cdd:cd05062  55 EFLNEASVMKEFNCHHVVRLLGVVSQGQPTLVIMELMTRGDLKSYLRSlrpEMENNPVQAPPSlKKMIQMAGeiADGMAY 134
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 414 LHHGcqpPYLHQFISSNVILLDDDFDARITDYGLAKLVGSRDSndssFNNGDLGELG--YVAPEYSSTMVASLKGDVYGF 491
Cdd:cd05062 135 LNAN---KFVHRDLAARNCMVAEDFTVKIGDFGMTRDIYETDY----YRKGGKGLLPvrWMSPESLKDGVFTTYSDVWSF 207
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 492 GIVLLELVT-GQKPlsvingvegFKGSLVDWVSQYLGTGRSKDAIDRSicdkghDEEILQFLKIacsCVVSRPKERPTMI 570
Cdd:cd05062 208 GVVLWEIATlAEQP---------YQGMSNEQVLRFVMEGGLLDKPDNC------PDMLFELMRM---CWQYNPKMRPSFL 269

                ....*...
gi 15223445 571 QVYESLKN 578
Cdd:cd05062 270 EIISSIKE 277
STKc_PKB_beta cd05595
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B beta (also called Akt2); ...
343-505 4.41e-04

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: 42.69  E-value: 4.41e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 343 SEMNKLGELRHPNLVPLlGYCVVEDERL-LVYKHMVNGTLFSQLHNgglcDAVLDWPTRRAIGVGAAKGLAWLHhgcQPP 421
Cdd:cd05595  44 TESRVLQNTRHPFLTAL-KYAFQTHDRLcFVMEYANGGELFFHLSR----ERVFTEDRARFYGAEIVSALEYLH---SRD 115
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 422 YLHQFISSNVILLDDDFDARITDYGLAKLVGSRDSNDSSFnngdLGELGYVAPEYSSTMVASLKGDVYGFGIVLLELVTG 501
Cdd:cd05595 116 VVYRDIKLENLMLDKDGHIKITDFGLCKEGITDGATMKTF----CGTPEYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCG 191

                ....
gi 15223445 502 QKPL 505
Cdd:cd05595 192 RLPF 195
STKc_nPKC_theta_like cd05592
Catalytic domain of the Serine/Threonine Kinases, Novel Protein Kinase C theta, delta, and ...
432-506 4.51e-04

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: 42.76  E-value: 4.51e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 432 ILLDDDFDARITDYGLAKLVGSRDSNDSSFnngdLGELGYVAPEYsstmvasLKG-------DVYGFGIVLLELVTGQKP 504
Cdd:cd05592 127 VLLDREGHIKIADFGMCKENIYGENKASTF----CGTPDYIAPEI-------LKGqkynqsvDWWSFGVLLYEMLIGQSP 195

                ..
gi 15223445 505 LS 506
Cdd:cd05592 196 FH 197
STKc_Chk1 cd14069
Catalytic domain of the Serine/Threonine kinase, Checkpoint kinase 1; STKs catalyze the ...
410-504 4.88e-04

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: 42.32  E-value: 4.88e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 410 GLAWLHhGCQppYLHQFISSNVILLDDDFDARITDYGLAKLVgsRDSNDSSFNNGDLGELGYVAPE--YSSTMVASlKGD 487
Cdd:cd14069 112 GLKYLH-SCG--ITHRDIKPENLLLDENDNLKISDFGLATVF--RYKGKERLLNKMCGTLPYVAPEllAKKKYRAE-PVD 185
                        90
                ....*....|....*..
gi 15223445 488 VYGFGIVLLELVTGQKP 504
Cdd:cd14069 186 VWSCGIVLFAMLAGELP 202
STKc_PAK6 cd06659
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 6; STKs catalyze the ...
323-504 5.41e-04

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: 42.28  E-value: 5.41e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 323 GSALAVKRLSAcgfgEKQFRSEM--NK---LGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFS----------QLHN 387
Cdd:cd06659  46 GRQVAVKMMDL----RKQQRRELlfNEvviMRDYQHPNVVEMYKSYLVGEELWVLMEYLQGGALTDivsqtrlneeQIAT 121
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 388 ggLCDAVLdwptrraigvgaaKGLAWLHhgcQPPYLHQFISSNVILLDDDFDARITDYGLAKLVgsrdSNDSSFNNGDLG 467
Cdd:cd06659 122 --VCEAVL-------------QALAYLH---SQGVIHRDIKSDSILLTLDGRVKLSDFGFCAQI----SKDVPKRKSLVG 179
                       170       180       190
                ....*....|....*....|....*....|....*..
gi 15223445 468 ELGYVAPEYSSTMVASLKGDVYGFGIVLLELVTGQKP 504
Cdd:cd06659 180 TPYWMAPEVISRCPYGTEVDIWSLGIMVIEMVDGEPP 216
STKc_CAMKK cd14118
Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase; ...
344-504 5.85e-04

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: 41.96  E-value: 5.85e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 344 EMNKLGELRHPNLVPLLGycvVEDERLLVYKHMVngtlFSQLHNGglcdAVLDWPTRRAIGVGAAK--------GLAWLH 415
Cdd:cd14118  64 EIAILKKLDHPNVVKLVE---VLDDPNEDNLYMV----FELVDKG----AVMEVPTDNPLSEETARsyfrdivlGIEYLH 132
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 416 HgcqPPYLHQFISSNVILLDDDFDARITDYGLAKLVgsrdSNDSSFNNGDLGELGYVAPEYSSTMVASLKG---DVYGFG 492
Cdd:cd14118 133 Y---QKIIHRDIKPSNLLLGDDGHVKIADFGVSNEF----EGDDALLSSTAGTPAFMAPEALSESRKKFSGkalDIWAMG 205
                       170
                ....*....|..
gi 15223445 493 IVLLELVTGQKP 504
Cdd:cd14118 206 VTLYCFVFGRCP 217
STKc_PLK4 cd14186
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 4; STKs catalyze the ...
409-505 6.15e-04

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: 41.77  E-value: 6.15e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 409 KGLAWLH-HGCqppyLHQFISSNVILLDDDFDARITDYGLAKLVGSRDSNDSSFnngdLGELGYVAPEYSSTMVASLKGD 487
Cdd:cd14186 113 TGMLYLHsHGI----LHRDLTLSNLLLTRNMNIKIADFGLATQLKMPHEKHFTM----CGTPNYISPEIATRSAHGLESD 184
                        90
                ....*....|....*...
gi 15223445 488 VYGFGIVLLELVTGQKPL 505
Cdd:cd14186 185 VWSLGCMFYTLLVGRPPF 202
STKc_TSSK-like cd14080
Catalytic domain of testis-specific serine/threonine kinases and similar proteins; STKs ...
432-504 6.27e-04

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: 41.79  E-value: 6.27e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 432 ILLDDDFDARITDYGLAKLVGSRDSNDSS--FnngdLGELGYVAPE------YSSTMvaslkGDVYGFGIVLLELVTGQK 503
Cdd:cd14080 133 ILLDSNNNVKLSDFGFARLCPDDDGDVLSktF----CGSAAYAAPEilqgipYDPKK-----YDIWSLGVILYIMLCGSM 203

                .
gi 15223445 504 P 504
Cdd:cd14080 204 P 204
PTK_Jak2_rpt1 cd05078
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 2; Jak2 is widely ...
336-509 6.71e-04

Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 2; Jak2 is widely expressed in many tissues. It 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 cytoplasmic (or nonreceptor) PTK containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. The pseudokinase domain shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. Despite this, the presumed pseudokinase (repeat 1) domain of Jak2 exhibits dual-specificity kinase activity, phosphorylating two negative regulatory sites in Jak2: Ser523 and Tyr570. Inactivation of the repeat 1 domain increased Jak2 basal activity, suggesting that it modulates the kinase activity of the C-terminal catalytic (repeat 2) domain. The Jak2 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: 270663 [Multi-domain]  Cd Length: 262  Bit Score: 41.86  E-value: 6.71e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 336 FGEKQFRSEmNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHNGGLCDAVLdWPtrraigVGAAKGLAW-L 414
Cdd:cd05078  46 YSESFFEAA-SMMSQLSHKHLVLNYGVCVCGDENILVQEYVKFGSLDTYLKKNKNCINIL-WK------LEVAKQLAWaM 117
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 415 HHGCQPPYLHQFISSNVILLDDDFD--------ARITDYGLAKLVGSRDSNdssfnngdLGELGYVAPE-YSSTMVASLK 485
Cdd:cd05078 118 HFLEEKTLVHGNVCAKNILLIREEDrktgnppfIKLSDPGISITVLPKDIL--------LERIPWVPPEcIENPKNLSLA 189
                       170       180
                ....*....|....*....|....*
gi 15223445 486 GDVYGFGIVLLELVT-GQKPLSVIN 509
Cdd:cd05078 190 TDKWSFGTTLWEICSgGDKPLSALD 214
PTKc_VEGFR cd05054
Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; ...
423-579 6.75e-04

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: 42.09  E-value: 6.75e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 423 LHQFISSNVILLDDDFDARITDYGLAklvgsRD--SNDSSFNNGDLG-ELGYVAPEYSSTMVASLKGDVYGFGIVLLELV 499
Cdd:cd05054 160 IHRDLAARNILLSENNVVKICDFGLA-----RDiyKDPDYVRKGDARlPLKWMAPESIFDKVYTTQSDVWSFGVLLWEIF 234
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 500 T-GQKPLSVINGVEGFkgslvdwvSQYLGTGRSKDAIDRSIcdkghdEEILQflkIACSCVVSRPKERPTMIQVYESLKN 578
Cdd:cd05054 235 SlGASPYPGVQMDEEF--------CRRLKEGTRMRAPEYTT------PEIYQ---IMLDCWHGEPKERPTFSELVEKLGD 297

                .
gi 15223445 579 M 579
Cdd:cd05054 298 L 298
STKc_Nek9 cd08221
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
423-575 6.83e-04

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: 41.65  E-value: 6.83e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 423 LHQFISSNVILLDDDFDARITDYGLAKLVGSRDSNDSSFnngdLGELGYVAPEYSSTMVASLKGDVYGFGIVLLELVTGQ 502
Cdd:cd08221 123 LHRDIKTLNIFLTKADLVKLGDFGISKVLDSESSMAESI----VGTPYYMSPELVQGVKYNFKSDIWAVGCVLYELLTLK 198
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 15223445 503 KPLSVIN----GVEGFKGSLVDWVSQYlgtgrskdaidrsicdkghDEEILQFLKiacSCVVSRPKERPTMIQVYES 575
Cdd:cd08221 199 RTFDATNplrlAVKIVQGEYEDIDEQY-------------------SEEIIQLVH---DCLHQDPEDRPTAEELLER 253
PTKc_InsR cd05061
Catalytic domain of the Protein Tyrosine Kinase, Insulin Receptor; PTKs catalyze the transfer ...
408-578 7.15e-04

Catalytic domain of the Protein Tyrosine Kinase, Insulin Receptor; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. InsR is a receptor PTK (RTK) that is composed of two alphabeta heterodimers. Binding of the insulin ligand to the extracellular alpha subunit activates the intracellular tyr kinase domain of the transmembrane beta subunit. Receptor activation leads to autophosphorylation, stimulating downstream kinase activities, which initiate signaling cascades and biological function. InsR signaling plays an important role in many cellular processes including glucose homeostasis, glycogen synthesis, lipid and protein metabolism, ion and amino acid transport, cell cycle and proliferation, cell differentiation, gene transcription, and nitric oxide synthesis. Insulin resistance, caused by abnormalities in InsR signaling, has been described in diabetes, hypertension, cardiovascular disease, metabolic syndrome, heart failure, and female infertility. The InsR 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: 133192 [Multi-domain]  Cd Length: 288  Bit Score: 41.88  E-value: 7.15e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 408 AKGLAWLHhgcQPPYLHQFISSNVILLDDDFDARITDYGLAKLVGSRDSndssFNNGDLGEL--GYVAPEYSSTMVASLK 485
Cdd:cd05061 129 ADGMAYLN---AKKFVHRDLAARNCMVAHDFTVKIGDFGMTRDIYETDY----YRKGGKGLLpvRWMAPESLKDGVFTTS 201
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 486 GDVYGFGIVLLELVT-GQKPlsvingvegFKGSLVDWVSQYLGTGRSKDAIDRsiCdkghDEEILQFLKIacsCVVSRPK 564
Cdd:cd05061 202 SDMWSFGVVLWEITSlAEQP---------YQGLSNEQVLKFVMDGGYLDQPDN--C----PERVTDLMRM---CWQFNPK 263
                       170
                ....*....|....
gi 15223445 565 ERPTMIQVYESLKN 578
Cdd:cd05061 264 MRPTFLEIVNLLKD 277
PTZ00283 PTZ00283
serine/threonine protein kinase; Provisional
414-568 9.46e-04

serine/threonine protein kinase; Provisional


Pssm-ID: 240344 [Multi-domain]  Cd Length: 496  Bit Score: 42.16  E-value: 9.46e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445  414 LHHGCQPPYLHQFISSNVILLDDDFDARITDYGLAKLVGSRDSND--SSFnngdLGELGYVAPEYSSTMVASLKGDVYGF 491
Cdd:PTZ00283 156 VHHVHSKHMIHRDIKSANILLCSNGLVKLGDFGFSKMYAATVSDDvgRTF----CGTPYYVAPEIWRRKPYSKKADMFSL 231
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 15223445  492 GIVLLELVTGQKPlsvingvegFKGSLVDWVSQYLGTGRSkDAIDRSICDKGHDeeilqflkIACSCVVSRPKERPT 568
Cdd:PTZ00283 232 GVLLYELLTLKRP---------FDGENMEEVMHKTLAGRY-DPLPPSISPEMQE--------IVTALLSSDPKRRPS 290
STKc_MLCK3 cd14192
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 3; STKs catalyze ...
318-505 9.63e-04

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: 41.49  E-value: 9.63e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 318 ADLPDGSALAVKRLSACGFGEK-QFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQL----HNGGLCD 392
Cdd:cd14192  24 TELSTGLTLAAKIIKVKGAKEReEVKNEINIMNQLNHVNLIQLYDAFESKTNLTLIMEYVDGGELFDRItdesYQLTELD 103
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 393 AVLDwpTRRaigvgAAKGLAWLHhgcQPPYLHQFISSNVILLDDDF--DARITDYGLAKLVGSRDSNDSSFnngdlGELG 470
Cdd:cd14192 104 AILF--TRQ-----ICEGVHYLH---QHYILHLDLKPENILCVNSTgnQIKIIDFGLARRYKPREKLKVNF-----GTPE 168
                       170       180       190
                ....*....|....*....|....*....|....*
gi 15223445 471 YVAPEYSSTMVASLKGDVYGFGIVLLELVTGQKPL 505
Cdd:cd14192 169 FLAPEVVNYDFVSFPTDMWSVGVITYMLLSGLSPF 203
STKc_RSK_N cd05582
N-terminal catalytic domain of the Serine/Threonine Kinase, 90 kDa ribosomal protein S6 kinase; ...
432-504 1.00e-03

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: 41.62  E-value: 1.00e-03
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 15223445 432 ILLDDDFDARITDYGLAKLVGSRDSNDSSFnngdLGELGYVAPEYSSTMVASLKGDVYGFGIVLLELVTGQKP 504
Cdd:cd05582 128 ILLDEDGHIKLTDFGLSKESIDHEKKAYSF----CGTVEYMAPEVVNRRGHTQSADWWSFGVLMFEMLTGSLP 196
STKc_aPKC_zeta cd05617
Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C zeta; STKs catalyze ...
432-508 1.05e-03

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: 41.55  E-value: 1.05e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 432 ILLDDDFDARITDYGLAKLVGSRDSNDSSFnngdLGELGYVAPEYsstmvasLKGDVYGF-------GIVLLELVTGQKP 504
Cdd:cd05617 147 VLLDADGHIKLTDYGMCKEGLGPGDTTSTF----CGTPNYIAPEI-------LRGEEYGFsvdwwalGVLMFEMMAGRSP 215

                ....
gi 15223445 505 LSVI 508
Cdd:cd05617 216 FDII 219
STKc_Nek1 cd08218
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
322-500 1.06e-03

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: 41.33  E-value: 1.06e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 322 DGSALAVKRLSACGFGEKQ---FRSEMNKLGELRHPNLVP-------------LLGYCVVEDerllVYKHM--VNGTLFS 383
Cdd:cd08218  24 DGKQYVIKEINISKMSPKEreeSRKEVAVLSKMKHPNIVQyqesfeengnlyiVMDYCDGGD----LYKRInaQRGVLFP 99
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 384 QlhngglcDAVLDWPTRRAIGvgaakglawLHHGCQPPYLHQFISSNVILLDDDFDARITDYGLAKLVGSRDSNDSSFnn 463
Cdd:cd08218 100 E-------DQILDWFVQLCLA---------LKHVHDRKILHRDIKSQNIFLTKDGIIKLGDFGIARVLNSTVELARTC-- 161
                       170       180       190
                ....*....|....*....|....*....|....*..
gi 15223445 464 gdLGELGYVAPEYSSTMVASLKGDVYGFGIVLLELVT 500
Cdd:cd08218 162 --IGTPYYLSPEICENKPYNNKSDIWALGCVLYEMCT 196
PTKc_VEGFR3 cd05102
Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 3; ...
423-579 1.08e-03

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: 41.50  E-value: 1.08e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 423 LHQFISSNVILLDDDFDARITDYGLAKLVgSRDSNDSSFNNGDLgELGYVAPEYSSTMVASLKGDVYGFGIVLLELVT-G 501
Cdd:cd05102 194 IHRDLAARNILLSENNVVKICDFGLARDI-YKDPDYVRKGSARL-PLKWMAPESIFDKVYTTQSDVWSFGVLLWEIFSlG 271
                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 15223445 502 QKPLSVINGVEGFKGSLVDwvsqylGTG-RSKDAIDRSIcdkghdeeilqfLKIACSCVVSRPKERPTMIQVYESLKNM 579
Cdd:cd05102 272 ASPYPGVQINEEFCQRLKD------GTRmRAPEYATPEI------------YRIMLSCWHGDPKERPTFSDLVEILGDL 332
STKc_SGK1 cd05602
Catalytic domain of the Protein Serine/Threonine Kinase, Serum- and Glucocorticoid-induced ...
338-518 1.17e-03

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: 41.54  E-value: 1.17e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 338 EKQFRSEMNKL-GELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHNgglcDAVLDWPTRRAIGVGAAKGLAWLHh 416
Cdd:cd05602  51 EKHIMSERNVLlKNVKHPFLVGLHFSFQTTDKLYFVLDYINGGELFYHLQR----ERCFLEPRARFYAAEIASALGYLH- 125
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 417 gcQPPYLHQFISSNVILLDDDFDARITDYGLAKLVGSRDSNDSSFnngdLGELGYVAPEYSSTMVASLKGDVYGFGIVLL 496
Cdd:cd05602 126 --SLNIVYRDLKPENILLDSQGHIVLTDFGLCKENIEPNGTTSTF----CGTPEYLAPEVLHKQPYDRTVDWWCLGAVLY 199
                       170       180
                ....*....|....*....|..
gi 15223445 497 ELVTGQKPLSVINGVEGFKGSL 518
Cdd:cd05602 200 EMLYGLPPFYSRNTAEMYDNIL 221
STKc_TAO cd06607
Catalytic domain of the Serine/Threonine Kinases, Thousand-and-One Amino acids proteins; STKs ...
314-509 1.25e-03

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: 40.90  E-value: 1.25e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 314 VSYKADLPDGSALAVKRLSACGfgeKQFRS-------EMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVngtlfsqlh 386
Cdd:cd06607  17 VYYARNKRTSEVVAIKKMSYSG---KQSTEkwqdiikEVKFLRQLRHPNTIEYKGCYLREHTAWLVMEYCL--------- 84
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 387 nGGLCD--AVLDWPTRR----AIGVGAAKGLAWLHHGCQppyLHQFISSNVILLDDDFDARITDYGLAKLVgsrdSNDSS 460
Cdd:cd06607  85 -GSASDivEVHKKPLQEveiaAICHGALQGLAYLHSHNR---IHRDVKAGNILLTEPGTVKLADFGSASLV----CPANS 156
                       170       180       190       200       210
                ....*....|....*....|....*....|....*....|....*....|..
gi 15223445 461 FnngdLGELGYVAPEYSSTMVASL---KGDVYGFGIVLLELVTGQKPLSVIN 509
Cdd:cd06607 157 F----VGTPYWMAPEVILAMDEGQydgKVDVWSLGITCIELAERKPPLFNMN 204
STKc_GRK cd05577
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase; STKs ...
432-504 1.32e-03

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: 40.97  E-value: 1.32e-03
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 15223445 432 ILLDDDFDARITDYGLAKlvgsrDSNDSSFNNGDLGELGYVAPEYSSTMVA-SLKGDVYGFGIVLLELVTGQKP 504
Cdd:cd05577 126 ILLDDHGHVRISDLGLAV-----EFKGGKKIKGRVGTHGYMAPEVLQKEVAyDFSVDWFALGCMLYEMIAGRSP 194
PTKc_DDR1 cd05096
Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 1; PTKs catalyze ...
325-449 1.33e-03

Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. DDR1 is a receptor PTK (RTK) containing an extracellular discoidin homology domain, a transmembrane segment, an extended juxtamembrane region, and an intracellular catalytic domain. The binding of the ligand, collagen, to DDR1 results in a slow but sustained receptor activation. DDR1 binds to all collagens tested to date (types I-IV). It is widely expressed in many tissues. It is abundant in the brain and is also found in keratinocytes, colonic mucosa epithelium, lung epithelium, thyroid follicles, and the islets of Langerhans. During embryonic development, it is found in the developing neuroectoderm. DDR1 is a key regulator of cell morphogenesis, differentiation and proliferation. It is important in the development of the mammary gland, the vasculator and the kidney. DDR1 is also found in human leukocytes, where it facilitates cell adhesion, migration, maturation, and cytokine production. The DDR1 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: 133227 [Multi-domain]  Cd Length: 304  Bit Score: 41.07  E-value: 1.33e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 325 ALAVKRLSACGFGEKQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHNGGL-------------- 390
Cdd:cd05096  50 AVKILRPDANKNARNDFLKEVKILSRLKDPNIIRLLGVCVDEDPLCMITEYMENGDLNQFLSSHHLddkeengndavppa 129
                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 391 -CDAVLDWPTRRAIGVGAAKGLAWLhhgCQPPYLHQFISSNVILLDDDFDARITDYGLAK 449
Cdd:cd05096 130 hCLPAISYSSLLHVALQIASGMKYL---SSLNFVHRDLATRNCLVGENLTIKIADFGMSR 186
PTKc_VEGFR2 cd05103
Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 2; ...
408-579 1.35e-03

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: 41.12  E-value: 1.35e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 408 AKGLAWL-HHGCqppyLHQFISSNVILLDDDFDARITDYGLAKLVgSRDSNDSSFNNGDLgELGYVAPEYSSTMVASLKG 486
Cdd:cd05103 189 AKGMEFLaSRKC----IHRDLAARNILLSENNVVKICDFGLARDI-YKDPDYVRKGDARL-PLKWMAPETIFDRVYTIQS 262
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 487 DVYGFGIVLLELVT-GQKPLSVINGVEGFkgslvdwvSQYLGTGRSKDAIDRSicdkghDEEILQFLkiaCSCVVSRPKE 565
Cdd:cd05103 263 DVWSFGVLLWEIFSlGASPYPGVKIDEEF--------CRRLKEGTRMRAPDYT------TPEMYQTM---LDCWHGEPSQ 325
                       170
                ....*....|....
gi 15223445 566 RPTMIQVYESLKNM 579
Cdd:cd05103 326 RPTFSELVEHLGNL 339
PTKc_DDR cd05051
Catalytic domain of the Protein Tyrosine Kinases, Discoidin Domain Receptors; PTKs catalyze ...
321-381 1.35e-03

Catalytic domain of the Protein Tyrosine Kinases, Discoidin Domain Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The DDR subfamily consists of homologs of mammalian DDR1, DDR2, and similar proteins. They are receptor PTKs (RTKs) containing an extracellular discoidin homology domain, a transmembrane segment, an extended juxtamembrane region, and an intracellular catalytic domain. The binding of the ligand, collagen, to DDRs results in a slow but sustained receptor activation. DDRs regulate cell adhesion, proliferation, and extracellular matrix remodeling. They have been linked to a variety of human cancers including breast, colon, ovarian, brain, and lung. There is no evidence showing that DDRs act as transforming oncogenes. They are more likely to play a role in the regulation of tumor growth and metastasis. The DDR 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: 270644 [Multi-domain]  Cd Length: 297  Bit Score: 41.17  E-value: 1.35e-03
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 15223445 321 PDGSAL-AVKRL--SACGFGEKQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTL 381
Cdd:cd05051  43 KDEPVLvAVKMLrpDASKNAREDFLKEVKIMSQLKDPNIVRLLGVCTRDEPLCMIVEYMENGDL 106
STKc_BMPR1 cd14144
Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type I Receptor; ...
381-498 1.36e-03

Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type I Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BMPR1 functions as a receptor for morphogenetic proteins (BMPs), which are involved in the regulation of cell proliferation, survival, differentiation, and apoptosis. BMPs are able to induce bone, cartilage, ligament, and tendon formation, and may play roles in bone diseases and tumors. Vertebrates contain two type I BMP receptors, BMPR1a and BMPR1b. BMPR1 belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that also includes TGFbeta, activins, growth and differentiation factors, and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. Type I receptors, like BMPR1, are low-affinity receptors that bind ligands only after they are recruited by the ligand/type II high-affinity receptor complex. Following activation, they start intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. The BMPR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271046 [Multi-domain]  Cd Length: 287  Bit Score: 40.92  E-value: 1.36e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 381 LFSQLH-NGGLCD----AVLDWPTRRAIGVGAAKGLAWLH---HGCQ--PPYLHQFISSNVILLDDDFDARITDYGLA-K 449
Cdd:cd14144  70 LITDYHeNGSLYDflrgNTLDTQSMLKLAYSAACGLAHLHteiFGTQgkPAIAHRDIKSKNILVKKNGTCCIADLGLAvK 149
                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*
gi 15223445 450 LVGSRDSNDSSFNNgDLGELGYVAPE-YSSTMV-----ASLKGDVYGFGIVLLEL 498
Cdd:cd14144 150 FISETNEVDLPPNT-RVGTKRYMAPEvLDESLNrnhfdAYKMADMYSFGLVLWEI 203
PTKc_Jak1_rpt2 cd05079
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 1; PTKs catalyze the ...
323-500 1.55e-03

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: 40.68  E-value: 1.55e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 323 GSALAVKRLSACGFGEK--QFRSEMNKLGELRHPNLVPLLGYCVVEDER--LLVYKHMVNGTLFSQLHNGglcDAVLDWP 398
Cdd:cd05079  33 GEQVAVKSLKPESGGNHiaDLKKEIEILRNLYHENIVKYKGICTEDGGNgiKLIMEFLPSGSLKEYLPRN---KNKINLK 109
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 399 TRRAIGVGAAKGLAWLhhGCQPpYLHQFISSNVILLDDDFDARITDYGLAKLVGSRDSNDSSFNNGDLGELGYvAPE--- 475
Cdd:cd05079 110 QQLKYAVQICKGMDYL--GSRQ-YVHRDLAARNVLVESEHQVKIGDFGLTKAIETDKEYYTVKDDLDSPVFWY-APEcli 185
                       170       180
                ....*....|....*....|....*
gi 15223445 476 YSSTMVASlkgDVYGFGIVLLELVT 500
Cdd:cd05079 186 QSKFYIAS---DVWSFGVTLYELLT 207
STKc_nPKC_theta cd05619
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C theta; STKs catalyze ...
432-520 1.59e-03

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: 41.06  E-value: 1.59e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 432 ILLDDDFDARITDYGLAKLVGSRDSNDSSFnngdLGELGYVAPEYSSTMVASLKGDVYGFGIVLLELVTGQKPLSVINGV 511
Cdd:cd05619 137 ILLDKDGHIKIADFGMCKENMLGDAKTSTF----CGTPDYIAPEILLGQKYNTSVDWWSFGVLLYEMLIGQSPFHGQDEE 212

                ....*....
gi 15223445 512 EGFKGSLVD 520
Cdd:cd05619 213 ELFQSIRMD 221
STKc_ULK4 cd14010
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 4; STKs catalyze the ...
401-504 1.92e-03

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: 40.35  E-value: 1.92e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 401 RAIGVGAAKGLAWLH-HG---C--QPpylhqfisSNvILLDDDFDARITDYGLAKLVG------------SRDSNDSSFN 462
Cdd:cd14010  97 RKFGRDLVRGLHYIHsKGiiyCdlKP--------SN-ILLDGNGTLKLSDFGLARREGeilkelfgqfsdEGNVNKVSKK 167
                        90       100       110       120
                ....*....|....*....|....*....|....*....|..
gi 15223445 463 NGDLGELGYVAPEYSSTMVASLKGDVYGFGIVLLELVTGQKP 504
Cdd:cd14010 168 QAKRGTPYYMAPELFQGGVHSFASDLWALGCVLYEMFTGKPP 209
PTKc_HER2 cd05109
Catalytic domain of the Protein Tyrosine Kinase, HER2; PTKs catalyze the transfer of the ...
313-504 2.11e-03

Catalytic domain of the Protein Tyrosine Kinase, HER2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. HER2 (ErbB2, HER2/neu) is a member of the EGFR (HER, ErbB) subfamily of proteins, which 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, leading to the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. HER2 does not bind to any known EGFR subfamily ligands, but contributes to the kinase activity of all possible heterodimers. It acts as the preferred partner of other ligand-bound EGFR proteins and functions as a signal amplifier, with the HER2-HER3 heterodimer being the most potent pair in mitogenic signaling. HER2 plays an important role in cell development, proliferation, survival and motility. Overexpression of HER2 results in its activation and downstream signaling, even in the absence of ligand. HER2 overexpression, mainly due to gene amplification, has been shown in a variety of human cancers. Its role in breast cancer is especially well-documented. HER2 is up-regulated in about 25% of breast tumors and is associated with increases in tumor aggressiveness, recurrence and mortality. HER2 is a target for monoclonal antibodies and small molecule inhibitors, which are being developed as treatments for cancer. The first humanized antibody approved for clinical use is Trastuzumab (Herceptin), which is being used in combination with other therapies to improve the survival rates of patients with HER2-overexpressing breast cancer. The HER2 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: 270684 [Multi-domain]  Cd Length: 279  Bit Score: 40.39  E-value: 2.11e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 313 GVSYKAD-LPDGS------ALAVKRLSACGFGEKQFRSEMNKLGELRHPNLVPLLGYCVVEDERLlVYKHMVNGTLFSQL 385
Cdd:cd05109  21 GTVYKGIwIPDGEnvkipvAIKVLRENTSPKANKEILDEAYVMAGVGSPYVCRLLGICLTSTVQL-VTQLMPYGCLLDYV 99
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 386 -HNGGLCDA--VLDWptrraiGVGAAKGLAWLHhgcQPPYLHQFISSNVILLDDDFDARITDYGLAKLVgsrDSNDSSFN 462
Cdd:cd05109 100 rENKDRIGSqdLLNW------CVQIAKGMSYLE---EVRLVHRDLAARNVLVKSPNHVKITDFGLARLL---DIDETEYH 167
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....
gi 15223445 463 -NGDLGELGYVAPEYSSTMVASLKGDVYGFGIVLLELVT-GQKP 504
Cdd:cd05109 168 aDGGKVPIKWMALESILHRRFTHQSDVWSYGVTVWELMTfGAKP 211
STKc_HUNK cd14070
Catalytic domain of the Serine/Threonine Kinase, Hormonally up-regulated Neu-associated kinase ...
339-507 2.15e-03

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: 40.19  E-value: 2.15e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 339 KQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHNGGLCDavlDWPTRRAIGvGAAKGLAWLH-HG 417
Cdd:cd14070  48 KNLRREGRIQQMIRHPNITQLLDILETENSYYLVMELCPGGNLMHRIYDKKRLE---EREARRYIR-QLVSAVEHLHrAG 123
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 418 CqppyLHQFISSNVILLDDDFDARITDYGLAKLVGSRDSNDSSFNNgdLGELGYVAPEYSSTMVASLKGDVYGFGIVLLE 497
Cdd:cd14070 124 V----VHRDLKIENLLLDENDNIKLIDFGLSNCAGILGYSDPFSTQ--CGSPAYAAPELLARKKYGPKVDVWSIGVNMYA 197
                       170
                ....*....|
gi 15223445 498 LVTGQKPLSV 507
Cdd:cd14070 198 MLTGTLPFTV 207
pknD PRK13184
serine/threonine-protein kinase PknD;
339-500 2.47e-03

serine/threonine-protein kinase PknD;


Pssm-ID: 183880 [Multi-domain]  Cd Length: 932  Bit Score: 40.91  E-value: 2.47e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445  339 KQFRSEMNKLGELRHPNLVPLLGYCvveDERLLVYKHM--VNG-TLFSQLHNGGLCDAVldwPTRRAIGVGAAKGLAWLH 415
Cdd:PRK13184  47 KRFLREAKIAADLIHPGIVPVYSIC---SDGDPVYYTMpyIEGyTLKSLLKSVWQKESL---SKELAEKTSVGAFLSIFH 120
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445  416 HGCQP-PY------LHQFISSNVILLDDDFDARITDYGLAKLVGSR--DSNDSSFNNGD------------LGELGYVAP 474
Cdd:PRK13184 121 KICATiEYvhskgvLHRDLKPDNILLGLFGEVVILDWGAAIFKKLEeeDLLDIDVDERNicyssmtipgkiVGTPDYMAP 200
                        170       180
                 ....*....|....*....|....*.
gi 15223445  475 EYSSTMVASLKGDVYGFGIVLLELVT 500
Cdd:PRK13184 201 ERLLGVPASESTDIYALGVILYQMLT 226
STKc_MST1_2 cd06612
Catalytic domain of the Serine/Threonine Kinases, Mammalian STe20-like protein kinase 1 and 2; ...
313-509 2.48e-03

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: 39.94  E-value: 2.48e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 313 GVSYKA-DLPDGSALAVKRLSACGfGEKQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTlFSQLHNggLC 391
Cdd:cd06612  17 GSVYKAiHKETGQVVAIKVVPVEE-DLQEIIKEISILKQCDSPYIVKYYGSYFKNTDLWIVMEYCGAGS-VSDIMK--IT 92
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 392 DAVLDWPTRRAIGVGAAKGLAWLHhgcQPPYLHQFISSNVILLDDDFDARITDYGLA-KLVGSRDSNDSSfnngdLGELG 470
Cdd:cd06612  93 NKTLTEEEIAAILYQTLKGLEYLH---SNKKIHRDIKAGNILLNEEGQAKLADFGVSgQLTDTMAKRNTV-----IGTPF 164
                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*
gi 15223445 471 YVAPE------YSStmvaslKGDVYGFGIVLLELVTGQKPLSVIN 509
Cdd:cd06612 165 WMAPEviqeigYNN------KADIWSLGITAIEMAEGKPPYSDIH 203
STKc_PKB_alpha cd05594
Catalytic domain of the Serine/Threonine Kinase, Protein Kinase B alpha (also called Akt1); ...
343-505 3.14e-03

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: 40.01  E-value: 3.14e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 343 SEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHNgglcDAVLDWPTRRAIGVGAAKGLAWLHhgCQPPY 422
Cdd:cd05594  74 TENRVLQNSRHPFLTALKYSFQTHDRLCFVMEYANGGELFFHLSR----ERVFSEDRARFYGAEIVSALDYLH--SEKNV 147
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 423 LHQFISSNVILLDDDFDARITDYGLAKlvgsRDSNDSSFNNGDLGELGYVAPEYSSTMVASLKGDVYGFGIVLLELVTGQ 502
Cdd:cd05594 148 VYRDLKLENLMLDKDGHIKITDFGLCK----EGIKDGATMKTFCGTPEYLAPEVLEDNDYGRAVDWWGLGVVMYEMMCGR 223

                ...
gi 15223445 503 KPL 505
Cdd:cd05594 224 LPF 226
STKc_MARK cd14072
Catalytic domain of the Serine/Threonine Kinases, MAP/microtubule affinity-regulating kinases; ...
320-504 3.17e-03

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: 39.81  E-value: 3.17e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 320 LPDGSALAVK-----RLSACGFgEKQFRsEMNKLGELRHPNLVPLlgYCVVEDERLL--VYKHMVNGTLFSQLHNGGLCD 392
Cdd:cd14072  22 VLTGREVAIKiidktQLNPSSL-QKLFR-EVRIMKILNHPNIVKL--FEVIETEKTLylVMEYASGGEVFDYLVAHGRMK 97
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 393 AVLDWPTRRAIgVGAAKglaWLHhgcQPPYLHQFISSNVILLDDDFDARITDYGLaklvgsrdSNDSSFNNG-DL--GEL 469
Cdd:cd14072  98 EKEARAKFRQI-VSAVQ---YCH---QKRIVHRDLKAENLLLDADMNIKIADFGF--------SNEFTPGNKlDTfcGSP 162
                       170       180       190       200
                ....*....|....*....|....*....|....*....|.
gi 15223445 470 GYVAPE------YSSTMVaslkgDVYGFGIVLLELVTGQKP 504
Cdd:cd14072 163 PYAAPElfqgkkYDGPEV-----DVWSLGVILYTLVSGSLP 198
STKc_Kin4 cd14076
Catalytic domain of the yeast Serine/Threonine Kinase, Kin4; STKs catalyze the transfer of the ...
344-504 3.33e-03

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: 39.77  E-value: 3.33e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 344 EMNKLGELRHPNLVPLLGycVVEDERL--LVYKHMVNGTLFSQ-LHNGGLCDAVldwptRRAIGVGAAKGLAWLHhgcQP 420
Cdd:cd14076  56 EINILKGLTHPNIVRLLD--VLKTKKYigIVLEFVSGGELFDYiLARRRLKDSV-----ACRLFAQLISGVAYLH---KK 125
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 421 PYLHQFISSNVILLDDDFDARITDYGLAklvgsrdsNDSSFNNGDL-----GELGYVAPEY--SSTMVASLKGDVYGFGI 493
Cdd:cd14076 126 GVVHRDLKLENLLLDKNRNLVITDFGFA--------NTFDHFNGDLmstscGSPCYAAPELvvSDSMYAGRKADIWSCGV 197
                       170
                ....*....|.
gi 15223445 494 VLLELVTGQKP 504
Cdd:cd14076 198 ILYAMLAGYLP 208
STKc_MLCK4 cd14193
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 4; STKs catalyze ...
323-505 3.36e-03

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: 39.51  E-value: 3.36e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 323 GSALAVKRLSACGFGEKQ-FRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQL----HNGGLCDAVLdw 397
Cdd:cd14193  29 GLKLAAKIIKARSQKEKEeVKNEIEVMNQLNHANLIQLYDAFESRNDIVLVMEYVDGGELFDRIidenYNLTELDTIL-- 106
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 398 pTRRAIgvgaAKGLAWLHhgcQPPYLHQFISSNVILL--DDDFDARITDYGLAKLVGSRDSNDSSFnngdlGELGYVAPE 475
Cdd:cd14193 107 -FIKQI----CEGIQYMH---QMYILHLDLKPENILCvsREANQVKIIDFGLARRYKPREKLRVNF-----GTPEFLAPE 173
                       170       180       190
                ....*....|....*....|....*....|
gi 15223445 476 YSSTMVASLKGDVYGFGIVLLELVTGQKPL 505
Cdd:cd14193 174 VVNYEFVSFPTDMWSLGVIAYMLLSGLSPF 203
STKc_ATG1_ULK_like cd14009
Catalytic domain of the Serine/Threonine kinases, Autophagy-related protein 1 and Unc-51-like ...
343-512 3.79e-03

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: 39.51  E-value: 3.79e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 343 SEMNKLGELRHPNLVPLLGyCVVEDERL-LVYKHMVNGTLFSQLH-NGGLCDAVLdwptrRAIGVGAAKGLAWLHhgcqp 420
Cdd:cd14009  41 SEIAILKSIKHPNIVRLYD-VQKTEDFIyLVLEYCAGGDLSQYIRkRGRLPEAVA-----RHFMQQLASGLKFLR----- 109
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 421 pyLHQFI-----SSNVILLDDDFDA--RITDYGLAKlvgsrdsndsSFNNGDLGEL--G---YVAPE------YSStmva 482
Cdd:cd14009 110 --SKNIIhrdlkPQNLLLSTSGDDPvlKIADFGFAR----------SLQPASMAETlcGsplYMAPEilqfqkYDA---- 173
                       170       180       190
                ....*....|....*....|....*....|
gi 15223445 483 slKGDVYGFGIVLLELVTGQKPLSVINGVE 512
Cdd:cd14009 174 --KADLWSVGAILFEMLVGKPPFRGSNHVQ 201
STKc_CaMKI_delta cd14168
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
338-505 5.96e-03

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: 39.26  E-value: 5.96e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 338 EKQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHNGG---------LCDAVLDwptrraiGVGAA 408
Cdd:cd14168  52 ESSIENEIAVLRKIKHENIVALEDIYESPNHLYLVMQLVSGGELFDRIVEKGfytekdastLIRQVLD-------AVYYL 124
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 409 KGLAWLHHGCQPPYLHQFISsnvillDDDFDARITDYGLAKLVGSRDSNDSSfnngdLGELGYVAPEYSSTMVASLKGDV 488
Cdd:cd14168 125 HRMGIVHRDLKPENLLYFSQ------DEESKIMISDFGLSKMEGKGDVMSTA-----CGTPGYVAPEVLAQKPYSKAVDC 193
                       170
                ....*....|....*..
gi 15223445 489 YGFGIVLLELVTGQKPL 505
Cdd:cd14168 194 WSIGVIAYILLCGYPPF 210
PTKc_CSF-1R cd05106
Catalytic domain of the Protein Tyrosine Kinase, Colony-Stimulating Factor-1 Receptor; PTKs ...
408-581 6.22e-03

Catalytic domain of the Protein Tyrosine Kinase, Colony-Stimulating Factor-1 Receptor; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. CSF-1R, also called c-Fms, is a member of the Platelet Derived Growth Factor Receptor (PDGFR) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of CSF-1R to its ligand, CSF-1, leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. CSF-1R signaling is critical in the regulation of macrophages and osteoclasts. It leads to increases in gene transcription and protein translation, and induces cytoskeletal remodeling. CSF-1R signaling leads to a variety of cellular responses including survival, proliferation, and differentiation of target cells. It plays an important role in innate immunity, tissue development and function, and the pathogenesis of some diseases including atherosclerosis and cancer. CSF-1R signaling is also implicated in mammary gland development during pregnancy and lactation. Aberrant CSF-1/CSF-1R expression correlates with tumor cell invasiveness, poor clinical prognosis, and bone metastasis in breast cancer. Although the structure of the human CSF-1R catalytic domain is known, it is excluded from this specific alignment model because it contains a deletion in its sequence. The CSF-1R 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: 133237 [Multi-domain]  Cd Length: 374  Bit Score: 39.06  E-value: 6.22e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 408 AKGLAWL-HHGCqppyLHQFISSNVILLDDDFDARITDYGLAklvgsRD-SNDSSF---NNGDLgELGYVAPEYSSTMVA 482
Cdd:cd05106 222 AQGMDFLaSKNC----IHRDVAARNVLLTDGRVAKICDFGLA-----RDiMNDSNYvvkGNARL-PVKWMAPESIFDCVY 291
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 483 SLKGDVYGFGIVLLELVT-GQKPlsvingvegFKGSLVDwvSQYLGTGRSKDAIDRSicdkghDEEILQFLKIACSCVVS 561
Cdd:cd05106 292 TVQSDVWSYGILLWEIFSlGKSP---------YPGILVN--SKFYKMVKRGYQMSRP------DFAPPEIYSIMKMCWNL 354
                       170       180
                ....*....|....*....|
gi 15223445 562 RPKERPTMIQVYESLKNMAD 581
Cdd:cd05106 355 EPTERPTFSQISQLIQRQLG 374
PK_Unc-89_rpt1 cd14109
Pseudokinase domain, first repeat, of the Giant Serine/Threonine Kinase Uncoordinated protein ...
351-512 6.95e-03

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: 38.65  E-value: 6.95e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 351 LRHPNLVPLlgYCVVEDERLLVykhmvngTLFSQLHNGG--LCDAVL---DWPTRRAIGVGAAKGLAWLHHGCQPPYLHQ 425
Cdd:cd14109  53 LDHPNIVQM--HDAYDDEKLAV-------TVIDNLASTIelVRDNLLpgkDYYTERQVAVFVRQLLLALKHMHDLGIAHL 123
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 426 FISSNVILLDDDfDARITDYGLaklvgSRDSNDSSFNNGDLGELGYVAPEYSSTMVASLKGDVYGFGIVLLELVTGQKPL 505
Cdd:cd14109 124 DLRPEDILLQDD-KLKLADFGQ-----SRRLLRGKLTTLIYGSPEFVSPEIVNSYPVTLATDMWSVGVLTYVLLGGISPF 197

                ....*..
gi 15223445 506 SVINGVE 512
Cdd:cd14109 198 LGDNDRE 204
STKc_aPKC_iota cd05618
Catalytic domain of the Serine/Threonine Kinase, Atypical Protein Kinase C iota; STKs catalyze ...
353-526 7.68e-03

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: 38.86  E-value: 7.68e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 353 HPNLVPLLGyCVVEDERLLVYKHMVNG--TLFSQLHNGGLcdavldwPTRRAIGVGAAKGLA--WLH-HGCqppyLHQFI 427
Cdd:cd05618  80 HPFLVGLHS-CFQTESRLFFVIEYVNGgdLMFHMQRQRKL-------PEEHARFYSAEISLAlnYLHeRGI----IYRDL 147
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 428 SSNVILLDDDFDARITDYGLAKLVGSRDSNDSSFnngdLGELGYVAPEYsstmvasLKGDVYGF-------GIVLLELVT 500
Cdd:cd05618 148 KLDNVLLDSEGHIKLTDYGMCKEGLRPGDTTSTF----CGTPNYIAPEI-------LRGEDYGFsvdwwalGVLMFEMMA 216
                       170       180
                ....*....|....*....|....*.
gi 15223445 501 GQKPLSVINGVEGFKGSLVDWVSQYL 526
Cdd:cd05618 217 GRSPFDIVGSSDNPDQNTEDYLFQVI 242
STKc_PSKH1 cd14087
Catalytic domain of the Protein Serine/Threonine kinase H1; STKs catalyze the transfer of the ...
327-504 7.69e-03

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: 38.67  E-value: 7.69e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 327 AVKRLSACGFGEKQFRSEMNKLGELRHPNLVPLLGYCVVEDERLLVYKHMVNGTLFSQLHNGG---------LCDAVLDw 397
Cdd:cd14087  30 AIKMIETKCRGREVCESELNVLRRVRHTNIIQLIEVFETKERVYMVMELATGGELFDRIIAKGsfterdatrVLQMVLD- 108
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 398 ptrraiGVGAAKGLAWLHHGCQPpylhqfisSNVILLDDDFDAR--ITDYGLAKlvgSRDSNDSSFNNGDLGELGYVAPE 475
Cdd:cd14087 109 ------GVKYLHGLGITHRDLKP--------ENLLYYHPGPDSKimITDFGLAS---TRKKGPNCLMKTTCGTPEYIAPE 171
                       170       180
                ....*....|....*....|....*....
gi 15223445 476 YSSTMVASLKGDVYGFGIVLLELVTGQKP 504
Cdd:cd14087 172 ILLRKPYTQSVDMWAVGVIAYILLSGTMP 200
STKc_TSSK4-like cd14162
Catalytic domain of testis-specific serine/threonine kinase 4 and similar proteins; STKs ...
351-506 8.28e-03

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: 38.43  E-value: 8.28e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 351 LRHPNLVPLlgYCVVEDE-RllVYKHMV---NGTLFSQLHNGGLCDAvldwPTRRAIGVGAAKGLAWLHHgcqPPYLHQF 426
Cdd:cd14162  57 LKHPNLICF--YEAIETTsR--VYIIMElaeNGDLLDYIRKNGALPE----PQARRWFRQLVAGVEYCHS---KGVVHRD 125
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 427 ISSNVILLDDDFDARITDYGLAKLVGSRDSNDSSFNNGDLGELGYVAPE------YSSTMvaslkGDVYGFGIVLLELVT 500
Cdd:cd14162 126 LKCENLLLDKNNNLKITDFGFARGVMKTKDGKPKLSETYCGSYAYASPEilrgipYDPFL-----SDIWSMGVVLYTMVY 200

                ....*.
gi 15223445 501 GQKPLS 506
Cdd:cd14162 201 GRLPFD 206
STKc_TLK1 cd14040
Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase 1; STKs catalyze the ...
350-505 9.73e-03

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: 38.50  E-value: 9.73e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 350 ELRHPNLVPLLGYCVVEDERLLVYKHMVNGT---LFSQLHNgglcdaVLDWPTRRAIGVGAAKGLAWLHHgCQPPYLHQF 426
Cdd:cd14040  66 ELDHPRIVKLYDYFSLDTDTFCTVLEYCEGNdldFYLKQHK------LMSEKEARSIVMQIVNALRYLNE-IKPPIIHYD 138
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 15223445 427 ISSNVILLDDDF---DARITDYGLAKLVgsrDSNDSSFNNGDLGELG-----YVAPEY----SSTMVASLKGDVYGFGIV 494
Cdd:cd14040 139 LKPGNILLVDGTacgEIKITDFGLSKIM---DDDSYGVDGMDLTSQGagtywYLPPECfvvgKEPPKISNKVDVWSVGVI 215
                       170
                ....*....|.
gi 15223445 495 LLELVTGQKPL 505
Cdd:cd14040 216 FFQCLYGRKPF 226
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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