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 1972244210  18 KYKVTKLLGGGSYGCVHEVIELKTGDRYAMKSEYSSMKKPILLNELKVMKAIYtfSSQHVLKVRDMGVHGSTKFIIMQML 97
Cdd:cd14017     1 RWKVVKKIGGGGFGEIYKVRDVVDGEEVAMKVESKSQPKQVLKMEVAVLKKLQ--GKPHFCRLIGCGRTERYNYIVMTLL 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972244210  98 EKNMDEVFELLG-GSMTLNTAVATSYQCLEGLEFMHWAGFLHRDIKPNNYCLDANSGQgLRTIYIIDYGICKRFVD-NNN 175
Cdd:cd14017    79 GPNLAELRRSQPrGKFSVSTTLRLGIQILKAIEDIHEVGFLHRDVKPSNFAIGRGPSD-ERTVYILDFGLARQYTNkDGE 157

                         170       180       190
                  ....*....|....*....|....*....|....*.
gi 1972244210 176 VIRQPRKITKFRGTLDFAPIVSHELREHSRGSDLES 211
Cdd:cd14017   158 VERPPRNAAGFRGTVRYASVNAHRNKEQGRRDDLWS 193

Catalytic domain of the Serine/Threonine protein kinase, Tau-Tubulin Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TTBK is a neuron-specific kinase that phosphorylates the microtubule-associated protein tau and promotes its aggregation. Higher vertebrates contain two TTBK proteins, TTBK1 and TTBK2, both of which have been implicated in neurodegeneration. TTBK1 has been linked to Alzheimer's disease (AD) while TTBK2 is associated with spinocerebellar ataxia type 11 (SCA11). Both AD and SCA11 patients show the presence of neurofibrillary tangles in the brain. The Drosophila TTBK homolog, Asator, is an essential protein that localizes to the mitotic spindle during mitosis and may be involved in regulating microtubule dynamics and function. The TTBK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972244210  18 KYKVTKLLGGGSYGCVHEVIELKTGDRYAMKSEYSSMKKPILLNELKVMKAIYtfSSQHVLKVRDMGVHGSTKFIIMQML 97
Cdd:cd14017     1 RWKVVKKIGGGGFGEIYKVRDVVDGEEVAMKVESKSQPKQVLKMEVAVLKKLQ--GKPHFCRLIGCGRTERYNYIVMTLL 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972244210  98 EKNMDEVFELLG-GSMTLNTAVATSYQCLEGLEFMHWAGFLHRDIKPNNYCLDANSGQgLRTIYIIDYGICKRFVD-NNN 175
Cdd:cd14017    79 GPNLAELRRSQPrGKFSVSTTLRLGIQILKAIEDIHEVGFLHRDVKPSNFAIGRGPSD-ERTVYILDFGLARQYTNkDGE 157

                         170       180       190
                  ....*....|....*....|....*....|....*.
gi 1972244210 176 VIRQPRKITKFRGTLDFAPIVSHELREHSRGSDLES 211
Cdd:cd14017   158 VERPPRNAAGFRGTVRYASVNAHRNKEQGRRDDLWS 193

Serine/threonine protein kinase [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972244210  17 NKYKVTKLLGGGSYGCVHEVIELKTGDRYAMK---SEYSSMKKPI--LLNELKVMKAIytfSSQHVLKVRDMGVHGSTKF 91
Cdd:COG0515     7 GRYRILRLLGRGGMGVVYLARDLRLGRPVALKvlrPELAADPEARerFRREARALARL---NHPNIVRVYDVGEEDGRPY 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972244210  92 IIMQMLE-KNMDEVFELlGGSMTLNTAVATSYQCLEGLEFMHWAGFLHRDIKPNNYCLDANsGQglrtIYIIDYGICKRF 170
Cdd:COG0515    84 LVMEYVEgESLADLLRR-RGPLPPAEALRILAQLAEALAAAHAAGIVHRDIKPANILLTPD-GR----VKLIDFGIARAL 157

cyclin-dependent protein kinase; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972244210  21 VTKLLGGGSYGCVHEVIELKTGDRYAMK----SEYSSMKKP------------ILLNELKVMKAIytfSSQHVLKVRDMG 84
Cdd:PTZ00024   13 KGAHLGEGTYGKVEKAYDTLTGKIVAIKkvkiIEISNDVTKdrqlvgmcgihfTTLRELKIMNEI---KHENIMGLVDVY 89

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972244210  85 VHGSTKFIIMQMLEKNMDEVFELlggsmtlNTAVATSY------QCLEGLEFMHWAGFLHRDIKPNNycldansgqglrt 158
Cdd:PTZ00024   90 VEGDFINLVMDIMASDLKKVVDR-------KIRLTESQvkcillQILNGLNVLHKWYFMHRDLSPAN------------- 149

                         170
                  ....*....|
gi 1972244210 159 IYIIDYGICK 168
Cdd:PTZ00024  150 IFINSKGICK 159

Catalytic domain of the Serine/Threonine protein kinase, Tau-Tubulin Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TTBK is a neuron-specific kinase that phosphorylates the microtubule-associated protein tau and promotes its aggregation. Higher vertebrates contain two TTBK proteins, TTBK1 and TTBK2, both of which have been implicated in neurodegeneration. TTBK1 has been linked to Alzheimer's disease (AD) while TTBK2 is associated with spinocerebellar ataxia type 11 (SCA11). Both AD and SCA11 patients show the presence of neurofibrillary tangles in the brain. The Drosophila TTBK homolog, Asator, is an essential protein that localizes to the mitotic spindle during mitosis and may be involved in regulating microtubule dynamics and function. The TTBK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972244210  18 KYKVTKLLGGGSYGCVHEVIELKTGDRYAMKSEYSSMKKPILLNELKVMKAIYtfSSQHVLKVRDMGVHGSTKFIIMQML 97
Cdd:cd14017     1 RWKVVKKIGGGGFGEIYKVRDVVDGEEVAMKVESKSQPKQVLKMEVAVLKKLQ--GKPHFCRLIGCGRTERYNYIVMTLL 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972244210  98 EKNMDEVFELLG-GSMTLNTAVATSYQCLEGLEFMHWAGFLHRDIKPNNYCLDANSGQgLRTIYIIDYGICKRFVD-NNN 175
Cdd:cd14017    79 GPNLAELRRSQPrGKFSVSTTLRLGIQILKAIEDIHEVGFLHRDVKPSNFAIGRGPSD-ERTVYILDFGLARQYTNkDGE 157

                         170       180       190
                  ....*....|....*....|....*....|....*.
gi 1972244210 176 VIRQPRKITKFRGTLDFAPIVSHELREHSRGSDLES 211
Cdd:cd14017   158 VERPPRNAAGFRGTVRYASVNAHRNKEQGRRDDLWS 193

Catalytic domain of the Serine/Threonine protein kinase, Tau-Tubulin Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TTBK is a neuron-specific kinase that phosphorylates the microtubule-associated protein tau and promotes its aggregation. Higher vertebrates contain two TTBK proteins, TTBK1 and TTBK2, both of which have been implicated in neurodegeneration. Mutations in TTBK2 is associated with the development of spinocerebellar ataxia type 11, belonging to a group of neurodegenerative disorders characterized by progressive incoordination, dysarthria and impairment of eye movements. Brain tissues of SCA11 patients show the presence of neurofibrillary tangles and tau deposition in the brain, similar to Alzheimer's disease (AD) patients. The TTBK2 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 1972244210  18 KYKVTKLLGGGSYGCVHEVIELKTGDRYAMKSEYSSMKKPILLNELKVMKAIYtfSSQHVLKVRDMGVHGSTKFIIMQML 97
Cdd:cd14129     1 RWKVLRKIGGGGFGEIYDALDLLTRENVALKVESAQQPKQVLKMEVAVLKKLQ--GKDHVCRFIGCGRNDRFNYVVMQLQ 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972244210  98 EKNMDEVFELLG-GSMTLNTAVATSYQCLEGLEFMHWAGFLHRDIKPNNYCLdANSGQGLRTIYIIDYGICKRFVDNNNV 176
Cdd:cd14129    79 GRNLADLRRSQSrGTFTISTTLRLGRQILESIESIHSVGFLHRDIKPSNFAM-GRFPSTCRKCYMLDFGLARQFTNSCGD 157

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 1972244210 177 IRQPRKITKFRGTLDFAPIVSHELREHSRGSDLES 211
Cdd:cd14129   158 VRPPRAVAGFRGTVRYASINAHRNREMGRHDDLWS 192

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972244210   19 YKVTKLLGGGSYGCVHEVIELKTGDRYAMKS---EYSSMKKPILLNELKVMKAIytfSSQHVLKVRDMGVHGSTKFIIMQ 95
Cdd:smart00220   1 YEILEKLGEGSFGKVYLARDKKTGKLVAIKVikkKKIKKDRERILREIKILKKL---KHPNIVRLYDVFEDEDKLYLVME 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972244210   96 MLEknMDEVFELL--GGSMTLNTAVATSYQCLEGLEFMHWAGFLHRDIKPNNYCLDANSgqglrTIYIIDYGICKRFvdn 173
Cdd:smart00220  78 YCE--GGDLFDLLkkRGRLSEDEARFYLRQILSALEYLHSKGIVHRDLKPENILLDEDG-----HVKLADFGLARQL--- 147

                          170       180
                   ....*....|....*....|..
gi 1972244210  174 nnviRQPRKITKFRGTLDF-AP 194
Cdd:smart00220 148 ----DPGEKLTTFVGTPEYmAP 165

Catalytic domain of the Serine/Threonine protein kinases, Casein Kinase 1 delta and epsilon; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CK1 phosphorylates a variety of substrates including enzymes, transcription and splice factors, cytoskeletal proteins, viral oncogenes, receptors, and membrane-associated proteins. There are mutliple isoforms of CK1 and in mammals, seven isoforms (alpha, beta, gamma1-3, delta, and epsilon) have been characterized. These isoforms differ mainly in the length and structure of their C-terminal non-catalytic region. The delta and epsilon isoforms of CK1 play important roles in circadian rhythm and cell growth. They phosphorylate PERIOD proteins (PER1-3), which are circadian clock proteins that fulfill negative regulatory functions. PER phosphorylation leads to its degradation. However, CRY proteins form a complex with PER and CK1delta/epsilon that protects PER from degradation and leads to nuclear accummulation of the complex, which inhibits BMAL1-CLOCK dependent transcription activation. CK1delta/epsilon also phosphorylate the tumor suppressor p53 and the cellular oncogene Mdm2, which are key regulators of cell growth, genome integrity, and the development of cancer. This subfamily also includes the CK1 fungal proteins Saccharomyces cerevisiae HRR25 and Schizosaccharomyces pombe HHP1. These fungal proteins are involved in DNA repair. The CK1 delta/epsilon 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 1972244210  18 KYKVTKLLGGGSYGCVHEVIELKTGDRYAMKSEYSSMKKPILLNELKVMKAIYtfSSQHVLKVRDMGVHGSTKFIIMQML 97
Cdd:cd14125     1 KYRLGRKIGSGSFGDIYLGTNIQTGEEVAIKLESVKTKHPQLLYESKLYKILQ--GGVGIPNVRWYGVEGDYNVMVMDLL 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972244210  98 EKNMDEVFELLGGSMTLNTAVATSYQCLEGLEFMHWAGFLHRDIKPNNYCLdansGQGLRT--IYIIDYGICKRFVDNNN 175
Cdd:cd14125    79 GPSLEDLFNFCSRKFSLKTVLMLADQMISRIEYVHSKNFIHRDIKPDNFLM----GLGKKGnlVYIIDFGLAKKYRDPRT 154

                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 1972244210 176 VIRQPRKITK-FRGTLDFAPIVSHELREHSRGSDLES 211
Cdd:cd14125   155 HQHIPYRENKnLTGTARYASINTHLGIEQSRRDDLES 191

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 1972244210  18 KYKVTKLLGGGSYGCVHEVIELKTGDRYAMK----SEYSSMKKPILLNELKVMKAIytfSSQHVLKVRDMGVHGSTKFII 93
Cdd:cd05117     1 KYELGKVLGRGSFGVVRLAVHKKTGEEYAVKiidkKKLKSEDEEMLRREIEILKRL---DHPNIVKLYEVFEDDKNLYLV 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972244210  94 MQMLEKNmdEVFELL--GGSMTLNTAVATSYQCLEGLEFMHWAGFLHRDIKPNNYCLDANSGQGlrTIYIIDYGICKRFV 171
Cdd:cd05117    78 MELCTGG--ELFDRIvkKGSFSEREAAKIMKQILSAVAYLHSQGIVHRDLKPENILLASKDPDS--PIKIIDFGLAKIFE 153

                         170       180
                  ....*....|....*....|....*.
gi 1972244210 172 DNNnvirqprKITKFRGTLDF-APIV 196
Cdd:cd05117   154 EGE-------KLKTVCGTPYYvAPEV 172

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972244210  18 KYKVTKLLGGGSYGCVHEVIELKTGDRYAMK---SEYSSMKKPI--LLNELKVMKAIytfSSQHVLKVRDMGVHGSTKFI 92
Cdd:cd14014     1 RYRLVRLLGRGGMGEVYRARDTLLGRPVAIKvlrPELAEDEEFRerFLREARALARL---SHPNIVRVYDVGEDDGRPYI 77

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1972244210  93 IMQMLE-KNMDEVFELlGGSMTLNTAVATSYQCLEGLEFMHWAGFLHRDIKPNNYCLDANSgqglrTIYIIDYGICK 168
Cdd:cd14014    78 VMEYVEgGSLADLLRE-RGPLPPREALRILAQIADALAAAHRAGIVHRDIKPANILLTEDG-----RVKLTDFGIAR 148

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972244210  18 KYKVTKLLGGGSYGCVHEVIELKTGDRYAMKSEYSSMKKPI----LLNELKVMKaiyTFSSQHVLKVRDMGVHGSTKFII 93
Cdd:cd06606     1 RWKKGELLGKGSFGSVYLALNLDTGELMAVKEVELSGDSEEeleaLEREIRILS---SLKHPNIVRYLGTERTENTLNIF 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972244210  94 M---------QMLEKNmdevfellGGsmtLNTAVATSY--QCLEGLEFMHWAGFLHRDIKPNNYCLDANSgqglrTIYII 162
Cdd:cd06606    78 LeyvpggslaSLLKKF--------GK---LPEPVVRKYtrQILEGLEYLHSNGIVHRDIKGANILVDSDG-----VVKLA 141

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*....
gi 1972244210 163 DYGICKRFVDNNNVIRqprkITKFRGTLDF-AP-IVSHElrEHSRGSDL 209
Cdd:cd06606   142 DFGCAKRLAEIATGEG----TKSLRGTPYWmAPeVIRGE--GYGRAADI 184

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972244210  19 YKVTKLLGGGSYGCVHEVIELKTGDRYAMK--SEYSSMKKPILlNELKVMKAIYTFSSQ-HVLKVRD--MGVHGSTKFII 93
Cdd:cd05118     1 YEVLRKIGEGAFGTVWLARDKVTGEKVAIKkiKNDFRHPKAAL-REIKLLKHLNDVEGHpNIVKLLDvfEHRGGNHLCLV 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972244210  94 MQMLEKNMDEVFELLGGSMTLNTAVATSYQCLEGLEFMHWAGFLHRDIKPNNYCLDANSGQglrtIYIIDYGICKRFVDN 173
Cdd:cd05118    80 FELMGMNLYELIKDYPRGLPLDLIKSYLYQLLQALDFLHSNGIIHRDLKPENILINLELGQ----LKLADFGLARSFTSP 155

                  ....*....
gi 1972244210 174 NNVIR-QPR 181
Cdd:cd05118   156 PYTPYvATR 164

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972244210  17 NKYKVTKLLGGGSYGCVHEVIELKTGDRYAMKSEYSSMKKPILLNELKvmKAIY---TFSSQHVLKVRDMGVHGSTKFII 93
Cdd:cd14069     1 EDWDLVQTLGEGAFGEVFLAVNRNTEEAVAVKFVDMKRAPGDCPENIK--KEVCiqkMLSHKNVVRFYGHRREGEFQYLF 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972244210  94 MQMLEKNmdEVFELLGGSMTLNTAVATSY--QCLEGLEFMHWAGFLHRDIKPNNYCLDANSgqglrTIYIIDYGICKRFV 171
Cdd:cd14069    79 LEYASGG--ELFDKIEPDVGMPEDVAQFYfqQLMAGLKYLHSCGITHRDIKPENLLLDEND-----NLKISDFGLATVFR 151

                         170       180
                  ....*....|....*....|....
gi 1972244210 172 DNNnvirQPRKITKFRGTLDF-AP 194
Cdd:cd14069   152 YKG----KERLLNKMCGTLPYvAP 171

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972244210  23 KLLGGGSYGCVHEVIELKTGDRYAMK------SEYSSMKKpiLLNELKVMKAIytfSSQHVLKVRDMGVHGSTKFIIMQM 96
Cdd:cd06626     6 NKIGEGTFGKVYTAVNLDTGELMAMKeirfqdNDPKTIKE--IADEMKVLEGL---DHPNLVRYYGVEVHREEVYIFMEY 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972244210  97 LEKNmdEVFELLGGSMTLNTAVATSY--QCLEGLEFMHWAGFLHRDIKPNNYCLDANSgqglrTIYIIDYGICKRFVDNN 174
Cdd:cd06626    81 CQEG--TLEELLRHGRILDEAVIRVYtlQLLEGLAYLHENGIVHRDIKPANIFLDSNG-----LIKLGDFGSAVKLKNNT 153

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|
gi 1972244210 175 NVIRQPRkITKFRGTLDF-AP--IVSHELREHSRGSDLES 211
Cdd:cd06626   154 TTMAPGE-VNSLVGTPAYmAPevITGNKGEGHGRAADIWS 192

Catalytic domain of the Serine/Threonine Kinase, Extracellular signal-Regulated Kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ERK5 (also called Big MAPK1 (BMK1) or MAPK7) has a unique C-terminal extension, making it approximately twice as big as other MAPKs. This extension contains transcriptional activation capability which is inhibited by the N-terminal half. ERK5 is activated in response to growth factors and stress by a cascade that leads to its phosphorylation by the MAP2K MEK5, which in turn is regulated by the MAP3Ks MEKK2 and MEKK3. Activated ERK5 phosphorylates its targets including myocyte enhancer factor 2 (MEF2), Sap1a, c-Myc, and RSK. It plays a role in EGF-induced cell proliferation during the G1/S phase transition. Studies on knockout mice revealed that ERK5 is essential for cardiovascular development and plays an important role in angiogenesis. It is also critical for neural differentiation and survival. The ERK5 pathway has been implicated in the pathogenesis of many diseases including cancer, cardiac hypertrophy, and atherosclerosis. MAPKs are important mediators of cellular responses to extracellular signals. The ERK5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972244210  14 KVCNKYKVTKLLGGGSYGCVHEVIELKTGDRYAMKSEYSSMKKPIL----LNELKVMKAiytFSSQHVLKVRDM----GV 85
Cdd:cd07855     2 DVGDRYEPIETIGSGAYGVVCSAIDTKSGQKVAIKKIPNAFDVVTTakrtLRELKILRH---FKHDNIIAIRDIlrpkVP 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972244210  86 HGSTK--FIIMQMLEKNMDEVFELlGGSMTLNTAVATSYQCLEGLEFMHWAGFLHRDIKPNNycLDANSGQGLRtiyIID 163
Cdd:cd07855    79 YADFKdvYVVLDLMESDLHHIIHS-DQPLTLEHIRYFLYQLLRGLKYIHSANVIHRDLKPSN--LLVNENCELK---IGD 152

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*....
gi 1972244210 164 YGICkRFVDNNNViRQPRKITKFRGTLDF-APIVSHELREHSRGSDLES 211
Cdd:cd07855   153 FGMA-RGLCTSPE-EHKYFMTEYVATRWYrAPELMLSLPEYTQAIDMWS 199

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972244210  17 NKYKVTKLLGGGSYGCVHEVIELKTGDRYAMK----SEYSSMKKPILLNELKVMKAIYtfsSQHVLKVRDMGVHGSTKFI 92
Cdd:cd07833     1 NKYEVLGVVGEGAYGVVLKCRNKATGEIVAIKkfkeSEDDEDVKKTALREVKVLRQLR---HENIVNLKEAFRRKGRLYL 77

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972244210  93 IMQMLEKNMDEVFELLGGSMTLNTAVATSYQCLEGLEFMHWAGFLHRDIKPNNYCLDANS 152
Cdd:cd07833    78 VFEYVERTLLELLEASPGGLPPDAVRSYIWQLLQAIAYCHSHNIIHRDIKPENILVSESG 137

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPKs serve as important mediators of cellular responses to extracellular signals. They control critical cellular functions including differentiation, proliferation, migration, and apoptosis. They are also implicated in the pathogenesis of many diseases including multiple types of cancer, stroke, diabetes, and chronic inflammation. Typical MAPK pathways involve a triple kinase core cascade comprising of the MAPK, which is phosphorylated and activated by a MAPK kinase (MAP2K or MKK), which itself is phosphorylated and activated by a MAPK kinase kinase (MAP3K or MKKK). Each cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. There are three typical MAPK subfamilies: Extracellular signal-Regulated Kinase (ERK), c-Jun N-terminal Kinase (JNK), and p38. Some MAPKs are atypical in that they are not regulated by MAP2Ks. These include MAPK4, MAPK6, NLK, and ERK7. The MAPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972244210  18 KYKVTKLLGGGSYGCVHEVIELKTGDRYAMKSEYSSMKKPIL----LNELKVMKAiytFSSQHVLKVRDMGVHGS-TKF- 91
Cdd:cd07834     1 RYELLKPIGSGAYGVVCSAYDKRTGRKVAIKKISNVFDDLIDakriLREIKILRH---LKHENIIGLLDILRPPSpEEFn 77

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1972244210  92 ---IIMQMLEKNMDEVFEllGGSMTLNTAVAT-SYQCLEGLEFMHWAGFLHRDIKPNNYCLDANSgqglrTIYIIDYG 165
Cdd:cd07834    78 dvyIVTELMETDLHKVIK--SPQPLTDDHIQYfLYQILRGLKYLHSAGVIHRDLKPSNILVNSNC-----DLKICDFG 148

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 1972244210  25 LGGGSYGCVHEVIELKTGDRYAMK-SEYSSMKKPILLNELKVMKAIytfssQHVLKVRDMGVHGSTKFIIMqMLEKNMD- 102
Cdd:cd14006     1 LGRGRFGVVKRCIEKATGREFAAKfIPKRDKKKEAVLREISILNQL-----QHPRIIQLHEAYESPTELVL-ILELCSGg 74

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972244210 103 EVFELLGGSMTLNTAVATSY--QCLEGLEFMHWAGFLHRDIKPNN-YCLDANSGQglrtIYIIDYGICKRFvdnnnvirQ 179
Cdd:cd14006    75 ELLDRLAERGSLSEEEVRTYmrQLLEGLQYLHNHHILHLDLKPENiLLADRPSPQ----IKIIDFGLARKL--------N 142

                         170       180
                  ....*....|....*....|...
gi 1972244210 180 PRKITK-FRGTLDFAP--IVSHE 199
Cdd:cd14006   143 PGEELKeIFGTPEFVApeIVNGE 165

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972244210  18 KYKVTKLLGGGSYGCVHEVIELKTGDRYAMK---------SEYSSMKKPI-LLNELKVMKAiytFSSQHVLKVRDMGVHG 87
Cdd:cd14084     7 KYIMSRTLGSGACGEVKLAYDKSTCKKVAIKiinkrkftiGSRREINKPRnIETEIEILKK---LSHPCIIKIEDFFDAE 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972244210  88 STKFIIMQMLEKNmdEVFELLGGSMTLNTAVAT--SYQCLEGLEFMHWAGFLHRDIKPNNYCLDANSGQGLrtIYIIDYG 165
Cdd:cd14084    84 DDYYIVLELMEGG--ELFDRVVSNKRLKEAICKlyFYQMLLAVKYLHSNGIIHRDLKPENVLLSSQEEECL--IKITDFG 159

                         170
                  ....*....|...
gi 1972244210 166 ICKrFVDNNNVIR 178
Cdd:cd14084   160 LSK-ILGETSLMK 171

Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein kinase subfamily 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The SnRKs form three different subfamilies designated SnRK1-3. SnRK3 is represented in this cd. The SnRK3 group contains members also known as CBL-interacting protein kinase, salt overly sensitive 2, SOS3-interacting proteins and protein kinase S. These kinases interact with calcium-binding proteins such as SOS3, SCaBPs, and CBL proteins, and are involved in responses to salt stress and in sugar and ABA signaling. The SnRKs belong to a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1972244210  18 KYKVTKLLGGGSYGCVHEVIELKTGDRYAMK------SEYSSMKKPILlNELKVMKAIytfSSQHVLKVRDMgVHGSTK- 90
Cdd:cd14663     1 RYELGRTLGEGTFAKVKFARNTKTGESVAIKiidkeqVAREGMVEQIK-REIAIMKLL---RHPNIVELHEV-MATKTKi 75

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1972244210  91 FIIMQMLEKNmdEVFELLGGSMTLNTAVATSY--QCLEGLEFMHWAGFLHRDIKPNNYCLDANSgqglrTIYIIDYGI 166
Cdd:cd14663    76 FFVMELVTGG--ELFSKIAKNGRLKEDKARKYfqQLIDAVDYCHSRGVFHRDLKPENLLLDEDG-----NLKISDFGL 146