Catalytic domain of the Serine/Threonine Kinase, Cell Division Cycle 7 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Cdc7 kinase (or Hsk1 in fission yeast) is a critical regulator in the initiation of DNA replication. It forms a complex with a Dbf4-related regulatory subunit, a cyclin-like molecule that activates the kinase in late G1 phase, and is also referred to as Dbf4-dependent kinase (DDK). Its main targets are mini-chromosome maintenance (MCM) proteins. Cdc7 kinase may also have additional roles in meiosis, checkpoint responses, the maintenance and repair of chromosome structures, and cancer progression. The Cdc7 kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4502715   56 NVFKIEDKIGEGTFSSVYLATAQLQV----GPEEKIALKHLIPTSHPIRIAAELQCLTVAGGQDNVMGVKYCFRKNDHVV 131
Cdd:cd14019   1 NKYRIIEKIGEGTFSSVYKAEDKLHDlydrNKGRLVALKHIYPTSSPSRILNELECLERLGGSNNVSGLITAFRNEDQVV 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4502715  132 IAMPYLEHESFLDILNSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRLKKYALVDFGLAQGTHDtkiell 211
Cdd:cd14019  81 AVLPYIEHDDFRDFYRKMSLTDIRIYLRNLFKALKHVHSFGIIHRDVKPGNFLYNRETGKGVLVDFGLAQREED------ 154

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4502715  212 kfvqseaqqercsqnkshiitgnkiplsgpvpkeldqqsttkasvkrpytnaqiqikqgkdgkegsvglsvqrsvfgern 291
Cdd:cd14019     --------------------------------------------------------------------------------

                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4502715  292 fnihssishespavklmkqsktvdvlsrklatkkkaistkvmnsavmrktasscpasltcdcyatdkvcsiclsRRQQVA 371
Cdd:cd14019 155 --------------------------------------------------------------------------RPEQRA 160

                       330       340       350       360       370       380
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 4502715  372 PRAGTPGFRAPEVLTKCPNQTTAIDMWSAGVIFLSLLSGRYPFYKASDDLTALAQIMTIRGSRETIQ 438
Cdd:cd14019 161 PRAGTRGFRAPEVLFKCPHQTTAIDIWSAGVILLSILSGRFPFFFSSDDIDALAEIATIFGSDEAYD 227

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 4502715  358 KVCSICLSRRQQVAPRAG-------TPGFRAPEVLTKCPNQTTAIDMWSAGVIFLSLLSGRyPFYKASDDLTALAQIMTI 430
Cdd:cd07834 143 KICDFGLARGVDPDEDKGflteyvvTRWYRAPELLLSSKKYTKAIDIWSVGCIFAELLTRK-PLFPGRDYIDQLNLIVEV 221

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4502715  431 RGSRetiqaaktfgksilcskevPAQDLRKLC-----ERLRGMDSSTPKLTSDIQGHASHQpAIsektDHKASCLVqtpp 505
Cdd:cd07834 222 LGTP-------------------SEEDLKFISsekarNYLKSLPKKPKKPLSEVFPGASPE-AI----DLLEKMLV---- 273

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 4502715  506 gqysgnsfkkgdsnscehcFdeyntnlegwnevpdeaydlldklldlNPASRITAEEALLHPFFKD 571
Cdd:cd07834 274 -------------------F---------------------------NPKKRITADEALAHPYLAQ 293

Catalytic domain of the Serine/Threonine Kinase, Cell Division Cycle 7 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Cdc7 kinase (or Hsk1 in fission yeast) is a critical regulator in the initiation of DNA replication. It forms a complex with a Dbf4-related regulatory subunit, a cyclin-like molecule that activates the kinase in late G1 phase, and is also referred to as Dbf4-dependent kinase (DDK). Its main targets are mini-chromosome maintenance (MCM) proteins. Cdc7 kinase may also have additional roles in meiosis, checkpoint responses, the maintenance and repair of chromosome structures, and cancer progression. The Cdc7 kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4502715   56 NVFKIEDKIGEGTFSSVYLATAQLQV----GPEEKIALKHLIPTSHPIRIAAELQCLTVAGGQDNVMGVKYCFRKNDHVV 131
Cdd:cd14019   1 NKYRIIEKIGEGTFSSVYKAEDKLHDlydrNKGRLVALKHIYPTSSPSRILNELECLERLGGSNNVSGLITAFRNEDQVV 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4502715  132 IAMPYLEHESFLDILNSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRLKKYALVDFGLAQGTHDtkiell 211
Cdd:cd14019  81 AVLPYIEHDDFRDFYRKMSLTDIRIYLRNLFKALKHVHSFGIIHRDVKPGNFLYNRETGKGVLVDFGLAQREED------ 154

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4502715  212 kfvqseaqqercsqnkshiitgnkiplsgpvpkeldqqsttkasvkrpytnaqiqikqgkdgkegsvglsvqrsvfgern 291
Cdd:cd14019     --------------------------------------------------------------------------------

                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4502715  292 fnihssishespavklmkqsktvdvlsrklatkkkaistkvmnsavmrktasscpasltcdcyatdkvcsiclsRRQQVA 371
Cdd:cd14019 155 --------------------------------------------------------------------------RPEQRA 160

                       330       340       350       360       370       380
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 4502715  372 PRAGTPGFRAPEVLTKCPNQTTAIDMWSAGVIFLSLLSGRYPFYKASDDLTALAQIMTIRGSRETIQ 438
Cdd:cd14019 161 PRAGTRGFRAPEVLFKCPHQTTAIDIWSAGVILLSILSGRFPFFFSSDDIDALAEIATIFGSDEAYD 227

Serine/threonine protein kinase [Signal transduction mechanisms];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4502715   58 FKIEDKIGEGTFSSVYLATaqlQVGPEEKIALKHLIPTSHP-----------IRIAAELQcltvaggQDNVMGVKYCFRK 126
Cdd:COG0515   9 YRILRLLGRGGMGVVYLAR---DLRLGRPVALKVLRPELAAdpearerfrreARALARLN-------HPNIVRVYDVGEE 78

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 4502715  127 NDHVVIAMPYLEHESFLDILNS---LSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNR--RLKkyaLVDFGLA 200
Cdd:COG0515  79 DGRPYLVMEYVEGESLADLLRRrgpLPPAEALRILAQLAEALAAAHAAGIVHRDIKPANILLTPdgRVK---LIDFGIA 154

Serine/threonine-protein kinase SNT7; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4502715    58 FKIEDKIGEGTFSSVYLAT-AQLQVGPEEKIALKHL-------IPTSHPIRIAAELQCLTVAGGQDNVMGVKycfrKNDH 129
Cdd:PLN03225 134 FVLGKKLGEGAFGVVYKASlVNKQSKKEGKYVLKKAteygaveIWMNERVRRACPNSCADFVYGFLEPVSSK----KEDE 209

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4502715   130 VVIAMPYLEHESFLDILNSLSFQ-EVREYML----------------------NLFKALKRIHQFGIVHRDVKPSNFLYN 186
Cdd:PLN03225 210 YWLVWRYEGESTLADLMQSKEFPyNVEPYLLgkvqdlpkglerenkiiqtimrQILFALDGLHSTGIVHRDVKPQNIIFS 289

                        170
                 ....*....|....
gi 4502715   187 RRLKKYALVDFGLA 200
Cdd:PLN03225 290 EGSGSFKIIDLGAA 303

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 4502715  358 KVCSICLSRRQQVAPRAG-------TPGFRAPEVLTKCPNQTTAIDMWSAGVIFLSLLSGRyPFYKASDDLTALAQIMTI 430
Cdd:cd07834 143 KICDFGLARGVDPDEDKGflteyvvTRWYRAPELLLSSKKYTKAIDIWSVGCIFAELLTRK-PLFPGRDYIDQLNLIVEV 221

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4502715  431 RGSRetiqaaktfgksilcskevPAQDLRKLC-----ERLRGMDSSTPKLTSDIQGHASHQpAIsektDHKASCLVqtpp 505
Cdd:cd07834 222 LGTP-------------------SEEDLKFISsekarNYLKSLPKKPKKPLSEVFPGASPE-AI----DLLEKMLV---- 273

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 4502715  506 gqysgnsfkkgdsnscehcFdeyntnlegwnevpdeaydlldklldlNPASRITAEEALLHPFFKD 571
Cdd:cd07834 274 -------------------F---------------------------NPKKRITADEALAHPYLAQ 293

Kae1-associated kinase Bud32; Members of this protein family are the Bud32 protein associated with Kae1 (kinase-associated endopeptidase 1) in the Archaea. In many Archaeal genomes, Kae1 and Bud32 are fused. The complex is homologous to the Kae1 and Bud32 subunits of the eukaryotic KEOPS complex, an apparently ancient protein kinase-containing molecular machine. [Unknown function, General]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4502715    131 VIAMPYLEHESFLDILNSLSFqevrEYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRlKKYaLVDFGLAQGTH---DTK 207
Cdd:TIGR03724  73 TIVMEYIEGKPLKDVIEENGD----ELAREIGRLVGKLHKAGIVHGDLTTSNIIVRDD-KVY-LIDFGLGKYSDeieDKA 146

                  ....*....
gi 4502715    208 IELLKFVQS 216
Cdd:TIGR03724 147 VDLHVLKRS 155

Catalytic domain of the Serine/Threonine Kinase, Cell Division Cycle 7 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Cdc7 kinase (or Hsk1 in fission yeast) is a critical regulator in the initiation of DNA replication. It forms a complex with a Dbf4-related regulatory subunit, a cyclin-like molecule that activates the kinase in late G1 phase, and is also referred to as Dbf4-dependent kinase (DDK). Its main targets are mini-chromosome maintenance (MCM) proteins. Cdc7 kinase may also have additional roles in meiosis, checkpoint responses, the maintenance and repair of chromosome structures, and cancer progression. The Cdc7 kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4502715   56 NVFKIEDKIGEGTFSSVYLATAQLQV----GPEEKIALKHLIPTSHPIRIAAELQCLTVAGGQDNVMGVKYCFRKNDHVV 131
Cdd:cd14019   1 NKYRIIEKIGEGTFSSVYKAEDKLHDlydrNKGRLVALKHIYPTSSPSRILNELECLERLGGSNNVSGLITAFRNEDQVV 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4502715  132 IAMPYLEHESFLDILNSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRLKKYALVDFGLAQGTHDtkiell 211
Cdd:cd14019  81 AVLPYIEHDDFRDFYRKMSLTDIRIYLRNLFKALKHVHSFGIIHRDVKPGNFLYNRETGKGVLVDFGLAQREED------ 154

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4502715  212 kfvqseaqqercsqnkshiitgnkiplsgpvpkeldqqsttkasvkrpytnaqiqikqgkdgkegsvglsvqrsvfgern 291
Cdd:cd14019     --------------------------------------------------------------------------------

                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4502715  292 fnihssishespavklmkqsktvdvlsrklatkkkaistkvmnsavmrktasscpasltcdcyatdkvcsiclsRRQQVA 371
Cdd:cd14019 155 --------------------------------------------------------------------------RPEQRA 160

                       330       340       350       360       370       380
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 4502715  372 PRAGTPGFRAPEVLTKCPNQTTAIDMWSAGVIFLSLLSGRYPFYKASDDLTALAQIMTIRGSRETIQ 438
Cdd:cd14019 161 PRAGTRGFRAPEVLFKCPHQTTAIDIWSAGVILLSILSGRFPFFFSSDDIDALAEIATIFGSDEAYD 227

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4502715   64 IGEGTFSSVYLATaqlQVGPEEKIALKHLIPTSH---PIRIAAELQCLTVAGGQdNVMGVKYCFRKNDHVVIAMPYLEHE 140
Cdd:cd00180   1 LGKGSFGKVYKAR---DKETGKKVAVKVIPKEKLkklLEELLREIEILKKLNHP-NIVKLYDVFETENFLYLVMEYCEGG 76

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 4502715  141 SFLDILNS----LSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRLkKYALVDFGLA 200
Cdd:cd00180  77 SLKDLLKEnkgpLSEEEALSILRQLLSALEYLHSNGIIHRDLKPENILLDSDG-TVKLADFGLA 139

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 4502715   58 FKIEDKIGEGTFSSVYLATAQLqvgPEEKIALK--HLIPTSHP---------IRIAAELQCltvaggqDNVMGVKYCFRK 126
Cdd:cd14014   2 YRLVRLLGRGGMGEVYRARDTL---LGRPVAIKvlRPELAEDEefrerflreARALARLSH-------PNIVRVYDVGED 71

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4502715  127 NDHVVIAMPYLEHESFLDILN---SLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNR--RLKkyaLVDFGLAQ 201
Cdd:cd14014  72 DGRPYIVMEYVEGGSLADLLRergPLPPREALRILAQIADALAAAHRAGIVHRDIKPANILLTEdgRVK---LTDFGIAR 148

                ....*..
gi 4502715  202 GTHDTKI 208
Cdd:cd14014 149 ALGDSGL 155

Catalytic subunit (alpha) of the Serine/Threonine Kinase, Casein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CK2 is a tetrameric protein with two catalytic (alpha) and two regulatory (beta) subunits. It is constitutively active and ubiquitously expressed, and is found in the cytoplasm, nucleus, as well as in the plasma membrane. It phosphorylates a wide variety of substrates including gylcogen synthase, cell cycle proteins, nuclear proteins (e.g. DNA topoisomerase II), and ion channels (e.g. ENaC), among others. It may be considered a master kinase controlling the activity or lifespan of many other kinases and exerting its effect over cell fate, gene expression, protein synthesis and degradation, and viral infection. CK2 is implicated in every stage of the cell cycle and is required for cell cycle progression. It plays crucial roles in cell differentiation, proliferation, and survival, and is thus implicated in cancer. CK2 is not an oncogene by itself but elevated CK2 levels create an environment that enhances the survival of tumor cells. The CK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4502715   58 FKIEDKIGEGTFSSVYLAtaqLQVGPEEKIALKHLIPTSHPiRIAAELQCLTVAGGQDNVMG----VKYcfRKNDHVVIA 133
Cdd:cd14132  20 YEIIRKIGRGKYSEVFEG---INIGNNEKVVIKVLKPVKKK-KIKREIKILQNLRGGPNIVKlldvVKD--PQSKTPSLI 93

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 4502715  134 MPYLEHESFLDILNSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRLKKYALVDFGLA 200
Cdd:cd14132  94 FEYVNNTDFKTLYPTLTDYDIRYYMYELLKALDYCHSKGIMHRDVKPHNIMIDHEKRKLRLIDWGLA 160

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4502715   57 VFKIEDKIGEGTFSSVYLAtaqLQVGPEEKIALKHLIPTSHPIR--IAAELQCLTvaggQ---DNVmgVKY--CFRKNDH 129
Cdd:cd05122   1 LFEILEKIGKGGFGVVYKA---RHKKTGQIVAIKKINLESKEKKesILNEIAILK----KckhPNI--VKYygSYLKKDE 71

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 4502715  130 VVIAMPYLEHESFLDILNSL--SFQE--VREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRR--LKkyaLVDFGLA 200
Cdd:cd05122  72 LWIVMEFCSGGSLKDLLKNTnkTLTEqqIAYVCKEVLKGLEYLHSHGIIHRDIKAANILLTSDgeVK---LIDFGLS 145

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 4502715   57 VFKIEDKIGEGTFSSVYLAT---------------AQLQVGPEEKI-----ALKHLiptSHPiriaaelqcltvaggqdN 116
Cdd:cd05117   1 KYELGKVLGRGSFGVVRLAVhkktgeeyavkiidkKKLKSEDEEMLrreieILKRL---DHP-----------------N 60

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4502715  117 VMGVKYCFRKNDHVVIAMPYLEH-ESFLDIL--NSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRRLKKYA 193
Cdd:cd05117  61 IVKLYEVFEDDKNLYLVMELCTGgELFDRIVkkGSFSEREAAKIMKQILSAVAYLHSQGIVHRDLKPENILLASKDPDSP 140

                ....*....
gi 4502715  194 --LVDFGLA 200
Cdd:cd05117 141 ikIIDFGLA 149

Catalytic domain of the Serine/Threonine Kinase, Cell Division Cycle 2-like 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDC2L1, also called PITSLRE, exists in different isoforms which are named using the alias CDK11(p). The CDC2L1 gene produces two protein products, CDK11(p110) and CDK11(p58). CDC2L1 is also represented by the caspase-processed CDK11(p46). CDK11(p110), the major isoform, associates with cyclin L and is expressed throughout the cell cycle. It is involved in RNA processing and the regulation of transcription. CDK11(p58) associates with cyclin D3 and is expressed during the G2/M phase of the cell cycle. It plays roles in spindle morphogenesis, centrosome maturation, sister chromatid cohesion, and the completion of mitosis. CDK11(p46) is formed from the larger isoforms by caspases during TNFalpha- and Fas-induced apoptosis. It functions as a downstream effector kinase in apoptotic signaling pathways and interacts with eukaryotic initiation factor 3f (eIF3f), p21-activated kinase (PAK1), and Ran-binding protein (RanBPM). CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDC2L1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4502715   58 FKIEDKIGEGTFSSVYLATAQLQvgpEEKIALKHLIPTSH----PIRIAAELQCLtVAGGQDNVMGVK-YCFRKN-DHVV 131
Cdd:cd07843   7 YEKLNRIEEGTYGVVYRARDKKT---GEIVALKKLKMEKEkegfPITSLREINIL-LKLQHPNIVTVKeVVVGSNlDKIY 82

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 4502715  132 IAMPYLEHE--SFLDILN-SLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRR--LKkyaLVDFGLA 200
Cdd:cd07843  83 MVMEYVEHDlkSLMETMKqPFLQSEVKCLMLQLLSGVAHLHDNWILHRDLKTSNLLLNNRgiLK---ICDFGLA 153

The catalytic domain of the Serine/Threonine Kinase, Glycogen Synthase Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GSK3 is a mutifunctional kinase involved in many cellular processes including cell division, proliferation, differentiation, adhesion, and apoptosis. In plants, GSK3 plays a role in the response to osmotic stress. In Caenorhabditis elegans, it plays a role in regulating normal oocyte-to-embryo transition and response to oxidative stress. In Chlamydomonas reinhardtii, GSK3 regulates flagellar length and assembly. In mammals, there are two isoforms, GSK3alpha and GSK3beta, which show both distinct and redundant functions. The two isoforms differ mainly in their N-termini. They are both involved in axon formation and in Wnt signaling.They play distinct roles in cardiogenesis, with GSKalpha being essential in cardiomyocyte survival, and GSKbeta regulating heart positioning and left-right symmetry. GSK3beta was first identified as a regulator of glycogen synthesis, but has since been determined to play other roles. It regulates the degradation of beta-catenin and IkB. Beta-catenin is the main effector of Wnt, which is involved in normal haematopoiesis and stem cell function. IkB is a central inhibitor of NF-kB, which is critical in maintaining leukemic cell growth. GSK3beta is enriched in the brain and is involved in regulating neuronal signaling pathways. It is implicated in the pathogenesis of many diseases including Type II diabetes, obesity, mood disorders, Alzheimer's disease, osteoporosis, and some types of cancer, among others. The GSK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4502715   58 FKIEDKIGEGTFSSVYLATAQlqvGPEEKIALKHLIPTSHPI-RiaaELQCLTVAGGQdNVMGVKYCF----RKNDHVV- 131
Cdd:cd14137   6 YTIEKVIGSGSFGVVYQAKLL---ETGEVVAIKKVLQDKRYKnR---ELQIMRRLKHP-NIVKLKYFFyssgEKKDEVYl 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4502715  132 -IAMPYL------EHESFLDILNSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNR---RLKkyaLVDFGLAQ 201
Cdd:cd14137  79 nLVMEYMpetlyrVIRHYSKNKQTIPIIYVKLYSYQLFRGLAYLHSLGICHRDIKPQNLLVDPetgVLK---LCDFGSAK 155

Catalytic domain of fungal Rim15-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include Saccharomyces cerevisiae Rim15, Schizosaccharomyces pombe cek1, and similar fungal proteins. They contain a central catalytic domain, which contains an insert relative to MAST kinases. In addition, Rim15 contains a C-terminal signal receiver (REC) domain while cek1 contains an N-terminal PAS domain. Rim15 (or Rim15p) functions as a regulator of meiosis. It acts as a downstream effector of PKA and regulates entry into stationary phase (G0). Thus, it plays a crucial role in regulating yeast proliferation, differentiation, and aging. Cek1 may facilitate progression of mitotic anaphase. The Rim15-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4502715   64 IGEGTFSSVYLATAQLQvgpEEKIALK-----HLIPTSHPIRIAAELQCLTVAGGQDNVMGVKYCFRKNDHVVIAMPYL- 137
Cdd:cd05611   4 ISKGAFGSVYLAKKRST---GDYFAIKvlkksDMIAKNQVTNVKAERAIMMIQGESPYVAKLYYSFQSKDYLYLVMEYLn 80

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 4502715  138 --EHESFLDILNSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRR--LKkyaLVDFGLAQ 201
Cdd:cd05611  81 ggDCASLIKTLGGLPEDWAKQYIAEVVLGVEDLHQRGIIHRDIKPENLLIDQTghLK---LTDFGLSR 145

Catalytic domain of the Wee1-like Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. This subfamily is composed of the dual-specificity kinase Myt1, the protein tyrosine kinase Wee1, and similar proteins. These proteins are cell cycle checkpoint kinases that are involved in the regulation of cyclin-dependent kinase CDK1, the master engine for mitosis. CDK1 is kept inactivated through phosphorylation of N-terminal thr (T14 by Myt1) and tyr (Y15 by Myt1 and Wee1) residues. Mitosis progression is ensured through activation of CDK1 by dephoshorylation and inactivation of Myt1/Wee1. The Wee1-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4502715   58 FKIEDKIGEGTFSSVYLATAQLQvgpEEKIALKHLiptSHPI-------RIAAELQCLTVAGGQDNVMGVKYCFRKNDHV 130
Cdd:cd13997   2 FHELEQIGSGSFSEVFKVRSKVD---GCLYAVKKS---KKPFrgpkeraRALREVEAHAALGQHPNIVRYYSSWEEGGHL 75

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 4502715  131 VIAMPYLEHESFLDILNSLSFQ------EVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRR--LKkyaLVDFGLA 200
Cdd:cd13997  76 YIQMELCENGSLQDALEELSPIsklseaEVWDLLLQVALGLAFIHSKGIVHLDIKPDNIFISNKgtCK---IGDFGLA 150

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4502715   55 SNVFKIEDKIGEGTFSSVYLATaQLQVGpeEKIALKhLIPT-------SHPIRIAAELQCltvaggqDNVmgVKY--CFR 125
Cdd:cd06612   2 EEVFDILEKLGEGSYGSVYKAI-HKETG--QVVAIK-VVPVeedlqeiIKEISILKQCDS-------PYI--VKYygSYF 68

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4502715  126 KNDHVVIAMPYLEHESFLDILN----SLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRrlKKYA-LVDFGLA 200
Cdd:cd06612  69 KNTDLWIVMEYCGAGSVSDIMKitnkTLTEEEIAAILYQTLKGLEYLHSNKKIHRDIKAGNILLNE--EGQAkLADFGVS 146

                ....*.
gi 4502715  201 QGTHDT 206
Cdd:cd06612 147 GQLTDT 152

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4502715   58 FKIEDKIGEGTFSSVYLATAQLqvgPEEKIALKHL----IPTSHPIRIAAELQCLtvaggqdnvMGVKYC--------FR 125
Cdd:cd14003   2 YELGKTLGEGSFGKVKLARHKL---TGEKVAIKIIdkskLKEEIEEKIKREIEIM---------KLLNHPniiklyevIE 69

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4502715  126 KNDHVVIAMPYLEHESFLDILNS---LSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLY--NRRLKkyaLVDFGLA 200
Cdd:cd14003  70 TENKIYLVMEYASGGELFDYIVNngrLSEDEARRFFQQLISAVDYCHSNGIVHRDLKLENILLdkNGNLK---IIDFGLS 146

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4502715   58 FKIEDKIGEGTFSSVYLATAQLqvgPEEKIALKHLIPTSHPI------RiaaELQCLTVAGGQDNVMGVKYCFRKNDHVV 131
Cdd:cd07830   1 YKVIKQLGDGTFGSVYLARNKE---TGELVAIKKMKKKFYSWeecmnlR---EVKSLRKLNEHPNIVKLKEVFRENDELY 74

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 4502715  132 IAMPYLEhESFLDILNS-----LSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNRR--LKkyaLVDFGLA 200
Cdd:cd07830  75 FVFEYME-GNLYQLMKDrkgkpFSESVIRSIIYQILQGLAHIHKHGFFHRDLKPENLLVSGPevVK---IADFGLA 146

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4502715   64 IGEGTFSSVYLATaQLQVGpeEKIALKhLIPTSHPIR------IAAELQCLTVAggqDNVMGVK--YCFRKNDHVVIAMP 135
Cdd:cd05579   1 ISRGAYGRVYLAK-KKSTG--DLYAIK-VIKKRDMIRknqvdsVLAERNILSQA---QNPFVVKlyYSFQGKKNLYLVME 73

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 4502715  136 YLEH---ESFLDILNSLSFQEVREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNR--RLKkyaLVDFGL 199
Cdd:cd05579  74 YLPGgdlYSLLENVGALDEDVARIYIAEIVLALEYLHSHGIIHRDLKPDNILIDAngHLK---LTDFGL 139

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK7 plays essential roles in the cell cycle and in transcription. It associates with cyclin H and MAT1 and acts as a CDK-Activating Kinase (CAK) by phosphorylating and activating cell cycle CDKs (CDK1/2/4/6). In the brain, it activates CDK5. CDK7 is also a component of the general transcription factor TFIIH, which phosphorylates the C-terminal domain (CTD) of RNA polymerase II when it is bound with unphosphorylated DNA, as present in the pre-initiation complex. Following phosphorylation, the CTD dissociates from the DNA which allows transcription initiation. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK7 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4502715   58 FKIEDKIGEGTFSSVYLATaQLQVGpeEKIALKHlIPTSHP--------------IRIAAELQcltvaggQDNVMGVKYC 123
Cdd:cd07841   2 YEKGKKLGEGTYAVVYKAR-DKETG--RIVAIKK-IKLGERkeakdginftalreIKLLQELK-------HPNIIGLLDV 70

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4502715  124 FRKNDHVVIAMPYLEheSFLDIL---NSLSFQE--VREYMLNLFKALKRIHQFGIVHRDVKPSNFLYNR--RLKkyaLVD 196
Cdd:cd07841  71 FGHKSNINLVFEFME--TDLEKVikdKSIVLTPadIKSYMLMTLRGLEYLHSNWILHRDLKPNNLLIASdgVLK---LAD 145

                ....
gi 4502715  197 FGLA 200
Cdd:cd07841 146 FGLA 149