Protein Kinases, catalytic domain; The protein kinase superfamily is mainly composed of the catalytic domains of serine/threonine-specific and tyrosine-specific protein kinases. It also includes RIO kinases, which are atypical serine protein kinases, aminoglycoside phosphotransferases, and choline kinases. These proteins catalyze the transfer of the gamma-phosphoryl group from ATP to hydroxyl groups in specific substrates such as serine, threonine, or tyrosine residues of proteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 808355033    9 QIKIIDFGLSREIEPGAVVKDMVGTPEFVAPEVVNYEALSPATDMWAVGVVTYILLSGGSPFLGDNRDETFSNITRVRYH 88
Cdd:cd14103   131 QIKIIDFGLARKYDPDKKLKVLFGTPEFVAPEVVNYEPISYATDMWSVGVICYVLLSGLSPFMGDNDAETLANVTRAKWD 210

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 808355033   89 FSDRYFKNTSKHAKDFIYRLFVRDVDQRATVEECLQHPWI 128
Cdd:cd14103   211 FDDEAFDDISDEAKDFISKLLVKDPRKRMSAAQCLQHPWL 250

Death domain found in death-associated protein kinase 1; Death domain (DD) found in death-associated protein kinase 1 (DAPK1). DAPK1 is composed of several functional domains, including a kinase domain, a CaM regulatory domain, ankyrin repeats, a cytoskeletal-binding domain and a C-terminal DD. It plays important roles in a diverse range of signal transduction pathways including apoptosis, growth factor signalling, and autophagy. Loss of DAPK1 expression, usually because of DNA methylation, is implicated in many tumor types. DAPK1 is highly abundant in the brain and has also been associated with neurodegeneration. In general, DDs are protein-protein interaction domains found in a variety of domain architectures. Their common feature is that they form homodimers by self-association or heterodimers by associating with other members of the DD superfamily including CARD (Caspase activation and recruitment domain), DED (Death Effector Domain), and PYRIN. They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 808355033 1143 ASRCELACLLDPPHAMGRDWSILAVKLQLTDQVPDVDSTGQSL-SRTDQLLNEWAIHHPeqASVGNLCRILVELGRCDAR 1221
Cdd:cd08782     1 LTRRKLARLLDPPDPMGRDWCLLAVNLGLTDLVAKLDSTSSPLpSPTDRLLQEWTARPP--STIGALLRKLRELGRRDAA 78

                  ....
gi 808355033 1222 DALY 1225
Cdd:cd08782    79 DFLL 82

P-loop containing Nucleoside Triphosphate Hydrolases; Members of the P-loop NTPase domain superfamily are characterized by a conserved nucleotide phosphate-binding motif, also referred to as the Walker A motif (GxxxxGK[S/T], where x is any residue), and the Walker B motif (hhhh[D/E], where h is a hydrophobic residue). The Walker A and B motifs bind the beta-gamma phosphate moiety of the bound nucleotide (typically ATP or GTP) and the Mg2+ cation, respectively. The P-loop NTPases are involved in diverse cellular functions, and they can be divided into two major structural classes: the KG (kinase-GTPase) class which includes Ras-like GTPases and its circularly permutated YlqF-like; and the ASCE (additional strand catalytic E) class which includes ATPase Binding Cassette (ABC), DExD/H-like helicases, 4Fe-4S iron sulfur cluster binding proteins of NifH family, RecA-like F1-ATPases, and ATPases Associated with a wide variety of Activities (AAA). Also included are a diverse set of nucleotide/nucleoside kinase families.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 808355033  616 GSKYaPPHSQYTRGIDVQTVNI----NGCGEFSVWEFGGYEPMHTCYDHFVGNAdCIHLILYRTSDPTEVQykQILYWMN 691
Cdd:cd09914    23 GEKF-DGDESSTHGINVQDWKIpapeRKKIRLNVWDFGGQEIYHATHQFFLTSR-SLYLLVFDLRTGDEVS--RVPYWLR 98

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 808355033  692 FLKGRvtpfepighcgfsSRRSKVIIVGTHATSSLFPQMNQEG 734
Cdd:cd09914    99 QIKAF-------------GGVSPVILVGTHIDESCDEDILKKA 128

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 808355033    9 QIKIIDFGLSREIEPGAVVKDMVGTPEFVAPEVVNYEALSPATDMWAVGVVTYILLSGGSPFLGDNRDETFSNITRVRYH 88
Cdd:cd14103   131 QIKIIDFGLARKYDPDKKLKVLFGTPEFVAPEVVNYEPISYATDMWSVGVICYVLLSGLSPFMGDNDAETLANVTRAKWD 210

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 808355033   89 FSDRYFKNTSKHAKDFIYRLFVRDVDQRATVEECLQHPWI 128
Cdd:cd14103   211 FDDEAFDDISDEAKDFISKLLVKDPRKRMSAAQCLQHPWL 250

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

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 808355033      7 DSQIKIIDFGLSREIEPGAVVKDMVGTPEFVAPEVVNYEALSPATDMWAVGVVTYILLSGGSPFLGDNRDETFSNITRVR 86
Cdd:smart00220  133 DGHVKLADFGLARQLDPGEKLTTFVGTPEYMAPEVLLGKGYGKAVDIWSLGVILYELLTGKPPFPGDDQLLELFKKIGKP 212

                            90       100       110       120
                    ....*....|....*....|....*....|....*....|..
gi 808355033     87 YHFSDRYFKNTSKHAKDFIYRLFVRDVDQRATVEECLQHPWI 128
Cdd:smart00220  213 KPPFPPPEWDISPEAKDLIRKLLVKDPEKRLTAEEALQHPFF 254

Protein kinase domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 808355033     1 MLKQRG---DSQIKIIDFGLSREIEPGAVVKDMVGTPEFVAPEVVNYEALSPATDMWAVGVVTYILLSGGSPFLGDNRDE 77
Cdd:pfam00069   88 LLSEKGafsEREAKFIMKQILEGLESGSSLTTFVGTPWYMAPEVLGGNPYGPKVDVWSLGCILYELLTGKPPFPGINGNE 167

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 808355033    78 TFSNITRVRYHFSDRyFKNTSKHAKDFIYRLFVRDVDQRATVEECLQHPWI 128
Cdd:pfam00069  168 IYELIIDQPYAFPEL-PSNLSEEAKDLLKKLLKKDPSKRLTATQALQHPWF 217

ankyrin-like protein; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 808355033  245 AEVFNYFHMKGGNICARDDNGDTPLHVACRFAQHTVAGYVA---NEKIDVDSINKTGETALHCAVESADT-RVVRLLLQL 320
Cdd:PHA03095   27 VEEVRRLLAAGADVNFRGEYGKTPLHLYLHYSSEKVKDIVRlllEAGADVNAPERCGFTPLHLYLYNATTlDVIKLLIKA 106

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 808355033  321 RPRLDLPNASGDTVLH--LAADSINPRIVPLLVCLAPPLHLRNIREETPLHV--AAARGHVDCVQALLDANSPIDAVEQD 396
Cdd:PHA03095  107 GADVNAKDKVGRTPLHvyLSGFNINPKVIRLLLRKGADVNALDLYGMTPLAVllKSRNANVELLRLLIDAGADVYAVDDR 186

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 808355033  397 GKTALIIALEN--GNVDIASILITNGCDINHADHHGDTALHIASKHGLLQA--VQTLCHCAVTVDSVNANKKTALHLAAH 472
Cdd:PHA03095  187 FRSLLHHHLQSfkPRARIVRELIRAGCDPAATDMLGNTPLHSMATGSSCKRslVLPLLIAGISINARNRYGQTPLHYAAV 266

                         250       260       270
                  ....*....|....*....|....*....|...
gi 808355033  473 YGHVDIIRVLLLARADVTLRGDDGLTAELVAVA 505
Cdd:PHA03095  267 FNNPRACRRLIALGADINAVSSDGNTPLSLMVR 299

DEATH domain, found in proteins involved in cell death (apoptosis); Alpha-helical domain present in a variety of proteins with apoptotic functions. Some (but not all) of these domains form homotypic and heterotypic dimers.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 808355033   1141 QMASRCELACLLDPPhaMGRDWSILAVKLQLTDQVPDVDSTGQS---LSRTDQLLNEWAIHHPEQASVGNLCRILVELGR 1217
Cdd:smart00005    1 PELTRQKLAKLLDHP--LGLDWRELARKLGLSEADIDQIRTEAPrdlAEQSVQLLRLWEQREGKNATLGTLLEALRKMGR 78

                            90
                    ....*....|
gi 808355033   1218 CDARDALYRT 1227
Cdd:smart00005   79 DDAVELLRSE 88

serine/threonine-protein kinase 1; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 808355033    5 RGDSQIKIIDFGLSREI-EPGavVKDmvGTPEFVAPEVVNYEALSPATDMWAVGVVTYILLSGGSPFLGDNrDETFS-NI 82
Cdd:PHA03390  144 RAKDRIYLCDYGLCKIIgTPS--CYD--GTLDYFSPEKIKGHNYDVSFDWWAVGVLTYELLTGKHPFKEDE-DEELDlES 218

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 808355033   83 TRVRYHFSDRYFKNTSKHAKDFIYRLFVRDVDQRA-TVEECLQHPWI 128
Cdd:PHA03390  219 LLKRQQKKLPFIKNVSKNANDFVQSMLKYNINYRLtNYNEIIKHPFL 265

Ras of complex proteins (Roc) C-terminal of Roc (COR) domain family; RocCOR (or Roco) protein family is characterized by a superdomain containing a Ras-like GTPase domain, called Roc (Ras of complex proteins), and a characteristic second domain called COR (C-terminal of Roc). A kinase domain and diverse regulatory domains are also often found in Roco proteins. Their functions are diverse; in Dictyostelium discoideum, which encodes 11 Roco proteins, they are involved in cell division, chemotaxis and development, while in human, where 4 Roco proteins (LRRK1, LRRK2, DAPK1, and MFHAS1) are encoded, these proteins are involved in epilepsy and cancer. Mutations in LRRK2 (leucine-rich repeat kinase 2) are known to cause familial Parkinson's disease.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 808355033  616 GSKYaPPHSQYTRGIDVQTVNI----NGCGEFSVWEFGGYEPMHTCYDHFVGNAdCIHLILYRTSDPTEVQykQILYWMN 691
Cdd:cd09914    23 GEKF-DGDESSTHGINVQDWKIpapeRKKIRLNVWDFGGQEIYHATHQFFLTSR-SLYLLVFDLRTGDEVS--RVPYWLR 98

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 808355033  692 FLKGRvtpfepighcgfsSRRSKVIIVGTHATSSLFPQMNQEG 734
Cdd:cd09914    99 QIKAF-------------GGVSPVILVGTHIDESCDEDILKKA 128

transient-receptor-potential calcium channel protein; The Transient Receptor Potential Ca2+ Channel (TRP-CC) Family (TC. 1.A.4)The TRP-CC family has also been called the store-operated calcium channel (SOC) family. The prototypical members include the Drosophila retinal proteinsTRP and TRPL (Montell and Rubin, 1989; Hardie and Minke, 1993). SOC members of the family mediate the entry of extracellular Ca2+ into cells in responseto depletion of intracellular Ca2+ stores (Clapham, 1996) and agonist stimulated production of inositol-1,4,5 trisphosphate (IP3). One member of the TRP-CCfamily, mammalian Htrp3, has been shown to form a tight complex with the IP3 receptor (TC #1.A.3.2.1). This interaction is apparently required for IP3 tostimulate Ca2+ release via Htrp3. The vanilloid receptor subtype 1 (VR1), which is the receptor for capsaicin (the ?hot? ingredient in chili peppers) and servesas a heat-activated ion channel in the pain pathway (Caterina et al., 1997), is also a member of this family. The stretch-inhibitable non-selective cation channel(SIC) is identical to the vanilloid receptor throughout all of its first 700 residues, but it exhibits a different sequence in its last 100 residues. VR1 and SICtransport monovalent cations as well as Ca2+. VR1 is about 10x more permeable to Ca2+ than to monovalent ions. Ca2+ overload probably causes cell deathafter chronic exposure to capsaicin. (McCleskey and Gold, 1999). [Transport and binding proteins, Cations and iron carrying compounds]

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 808355033   371 AAARGHVDCVQALLDANSP--IDAVEQDGKTALI-IALENGNVDIASILITNGCDInhadHHGDTALHIASKhGLLQAVQ 447
Cdd:TIGR00870   24 AAERGDLASVYRDLEEPKKlnINCPDRLGRSALFvAAIENENLELTELLLNLSCRG----AVGDTLLHAISL-EYVDAVE 98

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 808355033   448 -TLCH------CAVTVDSVNANKK-------TALHLAAHYGHVDIIRVLLLARADVTLR 492
Cdd:TIGR00870   99 aILLHllaafrKSGPLELANDQYTseftpgiTALHLAAHRQNYEIVKLLLERGASVPAR 157

C-terminal of Roc, COR, domain; The C-terminal of Roc domain, COR, along with Roc functions as the putative regulator of kinase activity. It functions as a proper GTP-binding protein with a low GTPase activity somehow stimulating the kinase activity.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 808355033   808 NLVRKKHANFPVITWPDFIQLVRNeiNPLTGDAHCRQIVQQLQLIGELVYLRNDLCDADYVVLNAEWfgthiLGQLLSAE 887
Cdd:pfam16095    9 EALEKERQKKPYISYEEYRKICAE--NGIDDEEDQDTLLEFLHDLGVLLYFQDDPGLRDIVILNPQW-----LTNAVYRV 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 808355033   888 FLSKASPN--GSYHTSSLAKIFPEIP----EQSDLMTILEVLQLC--APDARTGAHEFPVFIQTEAPDSIWRPYSlkeke 959
Cdd:pfam16095   82 LDSKHVLNnnGILTHEDLEQIWKDPGypreLHPYLLRLMEKFELCyeLPGDEEGTYLVPQLLPENPPELYDWDEE----- 156

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|
gi 808355033   960 rdtvyggvRILPMRGMERSLH-STFPRIQVALRRSINDYQ 998
Cdd:pfam16095  157 --------NNLELRYQYDFLPkGIFSRLIVRLHKFIDDEL 188

Ras of Complex, Roc, domain of DAPkinase; Roc, or Ras of Complex, proteins are mitochondrial Rho proteins (Miro-1, and Miro-2) and atypical Rho GTPases. Full-length proteins have a unique domain organization, with tandem GTP-binding domains and two EF hand domains (pfam00036) that may bind calcium. They are also larger than classical small GTPases. It has been proposed that they are involved in mitochondrial homeostasis and apoptosis.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 808355033   622 PHSQYTRGIDV---QTVNINGCGE---FSVWEFGGYEPMHTCYDHFVGNADCIhLILYrtsDPTEvqYKQILYWMNFLKg 695
Cdd:pfam08477   26 PKYKSTIGVDFktkTVLENDDNGKkikLNIWDTAGQERFRSLHPFYYRGAAAA-LLVY---DSRT--FSNLKYWLRELK- 98

                           90       100
                   ....*....|....*....|....*.
gi 808355033   696 rvtpfepiGHCGfssrRSKVIIVGTH 721
Cdd:pfam08477   99 --------KYAG----NSPVILVGNK 112

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 808355033    9 QIKIIDFGLSREIEPGAVVKDMVGTPEFVAPEVVNYEALSPATDMWAVGVVTYILLSGGSPFLGDNRDETFSNITRVRYH 88
Cdd:cd14103   131 QIKIIDFGLARKYDPDKKLKVLFGTPEFVAPEVVNYEPISYATDMWSVGVICYVLLSGLSPFMGDNDAETLANVTRAKWD 210

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 808355033   89 FSDRYFKNTSKHAKDFIYRLFVRDVDQRATVEECLQHPWI 128
Cdd:cd14103   211 FDDEAFDDISDEAKDFISKLLVKDPRKRMSAAQCLQHPWL 250

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 808355033    1 MLKQRGDSQIKIIDFGLSREIEPGAVVKDMVGTPEFVAPEVVNYEALSPATDMWAVGVVTYILLSGGSPFLGDNRDETFS 80
Cdd:cd14006   121 LLADRPSPQIKIIDFGLARKLNPGEELKEIFGTPEFVAPEIVNGEPVSLATDMWSIGVLTYVLLSGLSPFLGEDDQETLA 200

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 808355033   81 NITRVRYHFSDRYFKNTSKHAKDFIYRLFVRDVDQRATVEECLQHPW 127
Cdd:cd14006   201 NISACRVDFSEEYFSSVSQEAKDFIRKLLVKEPRKRPTAQEALQHPW 247

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 808355033   10 IKIIDFGLSREIEPGAVVKDMVGTPEFVAPEVVNYEALSPATDMWAVGVVTYILLSGGSPFLGDNRDETFSNITRVRYHF 89
Cdd:cd14106   150 IKLCDFGISRVIGEGEEIREILGTPDYVAPEILSYEPISLATDMWSIGVLTYVLLTGHSPFGGDDKQETFLNISQCNLDF 229

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 808355033   90 SDRYFKNTSKHAKDFIYRLFVRDVDQRATVEECLQHPWI 128
Cdd:cd14106   230 PEELFKDVSPLAIDFIKRLLVKDPEKRLTAKECLEHPWL 268

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 808355033    4 QRGDSQIKIIDFGLSREIEPGAVVKDMVGTPEFVAPEVVNYEALSPATDMWAVGVVTYILLSGGSPFLGDNRDETFSNIT 83
Cdd:cd05117   135 KDPDSPIKIIDFGLAKIFEEGEKLKTVCGTPYYVAPEVLKGKGYGKKCDIWSLGVILYILLCGYPPFYGETEQELFEKIL 214

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 808355033   84 RVRYHFSDRYFKNTSKHAKDFIYRLFVRDVDQRATVEECLQHPW 127
Cdd:cd05117   215 KGKYSFDSPEWKNVSEEAKDLIKRLLVVDPKKRLTAAEALNHPW 258

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 808355033    1 MLKQRGDSQIKIIDFGLSREIEPGAVVKDMVGTPEFVAPEVVNYEALSPATDMWAVGVVTYILLSGGSPFLGDNRDETFS 80
Cdd:cd14191   132 MCVNKTGTKIKLIDFGLARRLENAGSLKVLFGTPEFVAPEVINYEPIGYATDMWSIGVICYILVSGLSPFMGDNDNETLA 211

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 808355033   81 NITRVRYHFSDRYFKNTSKHAKDFIYRLFVRDVDQRATVEECLQHPWI 128
Cdd:cd14191   212 NVTSATWDFDDEAFDEISDDAKDFISNLLKKDMKARLTCTQCLQHPWL 259

Ankyrin repeat [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 808355033  252 HMKGGNICARDDNGDTPLHVACRFAQHTVAGYVANEKIDVDSINKTGETALHCAVESADTRVVRLLLQLRPRLDLPNASG 331
Cdd:COG0666     8 LLLLLAALLLLLLLALLLLAAALLLLLLLLLLLLLALLALALADALGALLLLAAALAGDLLVALLLLAAGADINAKDDGG 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 808355033  332 DTVLHLAADSINPRIVPLLVCLAPPLHLRNIREETPLHVAAARGHVDCVQALLDANSPIDAVEQDGKTALIIALENGNVD 411
Cdd:COG0666    88 NTLLHAAARNGDLEIVKLLLEAGADVNARDKDGETPLHLAAYNGNLEIVKLLLEAGADVNAQDNDGNTPLHLAAANGNLE 167

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 808355033  412 IASILITNGCDINHADHHGDTALHIASKHGLLQAVQTLCHCAVTVDSVNANKKTALHLAAHYGHVDIIRVLLLARADVTL 491
Cdd:COG0666   168 IVKLLLEAGADVNARDNDGETPLHLAAENGHLEIVKLLLEAGADVNAKDNDGKTALDLAAENGNLEIVKLLLEAGADLNA 247

                         250       260
                  ....*....|....*....|....*
gi 808355033  492 RGDDGLTAELVAVAAERLEAHSLLK 516
Cdd:COG0666   248 KDKDGLTALLLAAAAGAALIVKLLL 272

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 808355033    5 RGDSQIKIIDFGLSREIEPGAVVKDMVGTPEFVAPEVVNYEALSPATDMWAVGVVTYILLSGGSPFLGDNRDETFSNITR 84
Cdd:cd14193   138 REANQVKIIDFGLARRYKPREKLRVNFGTPEFLAPEVVNYEFVSFPTDMWSLGVIAYMLLSGLSPFLGEDDNETLNNILA 217

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 808355033   85 VRYHFSDRYFKNTSKHAKDFIYRLFVRDVDQRATVEECLQHPWI 128
Cdd:cd14193   218 CQWDFEDEEFADISEEAKDFISKLLIKEKSWRMSASEALKHPWL 261

Ankyrin repeat [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 808355033  212 HKLLPNATRKSLKSSFSEPNGATAMHCAAKYGHAEVFNYFHMKGGNICARDDNGDTPLHVACRFAQHTVAGYVANEKIDV 291
Cdd:COG0666     1 LLLLLLLLLLLLAALLLLLLLALLLLAAALLLLLLLLLLLLLALLALALADALGALLLLAAALAGDLLVALLLLAAGADI 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 808355033  292 DSINKTGETALHCAVESADTRVVRLLLQLRPRLDLPNASGDTVLHLAADSINPRIVPLLVCLAPPLHLRNIREETPLHVA 371
Cdd:COG0666    81 NAKDDGGNTLLHAAARNGDLEIVKLLLEAGADVNARDKDGETPLHLAAYNGNLEIVKLLLEAGADVNAQDNDGNTPLHLA 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 808355033  372 AARGHVDCVQALLDANSPIDAVEQDGKTALIIALENGNVDIASILITNGCDINHADHHGDTALHIASKHGLLQAVQTLCH 451
Cdd:COG0666   161 AANGNLEIVKLLLEAGADVNARDNDGETPLHLAAENGHLEIVKLLLEAGADVNAKDNDGKTALDLAAENGNLEIVKLLLE 240

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*...
gi 808355033  452 CAVTVDSVNANKKTALHLAAHYGHVDIIRVLLLARADVTLRGDDGLTA 499
Cdd:COG0666   241 AGADLNAKDKDGLTALLLAAAAGAALIVKLLLLALLLLAAALLDLLTL 288

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 808355033    1 MLKQRGDSQIKIIDFGLSREIEPGAVVKDMVGTPEFVAPEVVNYEALSPATDMWAVGVVTYILLSGGSPFLGDNRDETFS 80
Cdd:cd14114   132 MCTTKRSNEVKLIDFGLATHLDPKESVKVTTGTAEFAAPEIVEREPVGFYTDMWAVGVLSYVLLSGLSPFAGENDDETLR 211

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 808355033   81 NITRVRYHFSDRYFKNTSKHAKDFIYRLFVRDVDQRATVEECLQHPWI 128
Cdd:cd14114   212 NVKSCDWNFDDSAFSGISEEAKDFIRKLLLADPNKRMTIHQALEHPWL 259

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

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 808355033      7 DSQIKIIDFGLSREIEPGAVVKDMVGTPEFVAPEVVNYEALSPATDMWAVGVVTYILLSGGSPFLGDNRDETFSNITRVR 86
Cdd:smart00220  133 DGHVKLADFGLARQLDPGEKLTTFVGTPEYMAPEVLLGKGYGKAVDIWSLGVILYELLTGKPPFPGDDQLLELFKKIGKP 212

                            90       100       110       120
                    ....*....|....*....|....*....|....*....|..
gi 808355033     87 YHFSDRYFKNTSKHAKDFIYRLFVRDVDQRATVEECLQHPWI 128
Cdd:smart00220  213 KPPFPPPEWDISPEAKDLIRKLLVKDPEKRLTAEEALQHPFF 254

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 808355033    7 DSQIKIIDFGLSREIEPGAVVKDMVGTPEFVAPEVVNYEALSPATDMWAVGVVTYILLSGGSPFLGDNRDETFSNITRVR 86
Cdd:cd14109   134 DDKLKLADFGQSRRLLRGKLTTLIYGSPEFVSPEIVNSYPVTLATDMWSVGVLTYVLLGGISPFLGDNDRETLTNVRSGK 213

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 808355033   87 YHFSDRYFKNTSKHAKDFIYRLFVRDVDQRATVEECLQHPWI 128
Cdd:cd14109   214 WSFDSSPLGNISDDARDFIKKLLVYIPESRLTVDEALNHPWF 255

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 808355033    7 DSQIKIIDFGLSREIEPGAVVKDMVGTPEFVAPEVVNYEALSPATDMWAVGVVTYILLSGGSPFLGDNRDE-TFSNITRV 85
Cdd:cd14085   137 DAPLKIADFGLSKIVDQQVTMKTVCGTPGYCAPEILRGCAYGPEVDMWSVGVITYILLCGFEPFYDERGDQyMFKRILNC 216