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 409168308  50 NVFKIKDKIGEGTFSSVYLATAQLQEGH----EEKIALKHLIPTSHPMRIAAELQCLTVAGGQDNVMGLKYCFRKNDHVV 125
Cdd:cd14019    1 NKYRIIEKIGEGTFSSVYKAEDKLHDLYdrnkGRLVALKHIYPTSSPSRILNELECLERLGGSNNVSGLITAFRNEDQVV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 409168308 126 IAMPYLEHESFLDILNSLSFQEVREYMYNLFVALKRIHQFGIVHRDVKPSNFLYNRRLKKYALVDFGLAQGTRDtkiell 205
Cdd:cd14019   81 AVLPYIEHDDFRDFYRKMSLTDIRIYLRNLFKALKHVHSFGIIHRDVKPGNFLYNRETGKGVLVDFGLAQREED------ 154

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 409168308 206 kfvqseaqqedcsrnkyhgvvghkgllsrpapktvdqqctpktsvkrsytqvhikqgkdgkersvglsvqrsvfgernfn 285
Cdd:cd14019      --------------------------------------------------------------------------------

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 409168308 286 ihssishespaeklikqsktvdiisrklatkktaistkamnsvmretarscpavltcdcygsdrvcsvclsRRQQVAPRA 365
Cdd:cd14019  155 -----------------------------------------------------------------------RPEQRAPRA 163

                        330       340       350       360       370       380
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 409168308 366 GTPGFRAPEVLTKCPDQTTAIDMWSAGVIFLSLLSGRYPFYKASDDLTALAQIMTIRGSRETIQ 429
Cdd:cd14019  164 GTRGFRAPEVLFKCPHQTTAIDIWSAGVILLSILSGRFPFFFSSDDIDALAEIATIFGSDEAYD 227

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 409168308  50 NVFKIKDKIGEGTFSSVYLATAQLQEGH----EEKIALKHLIPTSHPMRIAAELQCLTVAGGQDNVMGLKYCFRKNDHVV 125
Cdd:cd14019    1 NKYRIIEKIGEGTFSSVYKAEDKLHDLYdrnkGRLVALKHIYPTSSPSRILNELECLERLGGSNNVSGLITAFRNEDQVV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 409168308 126 IAMPYLEHESFLDILNSLSFQEVREYMYNLFVALKRIHQFGIVHRDVKPSNFLYNRRLKKYALVDFGLAQGTRDtkiell 205
Cdd:cd14019   81 AVLPYIEHDDFRDFYRKMSLTDIRIYLRNLFKALKHVHSFGIIHRDVKPGNFLYNRETGKGVLVDFGLAQREED------ 154

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 409168308 206 kfvqseaqqedcsrnkyhgvvghkgllsrpapktvdqqctpktsvkrsytqvhikqgkdgkersvglsvqrsvfgernfn 285
Cdd:cd14019      --------------------------------------------------------------------------------

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 409168308 286 ihssishespaeklikqsktvdiisrklatkktaistkamnsvmretarscpavltcdcygsdrvcsvclsRRQQVAPRA 365
Cdd:cd14019  155 -----------------------------------------------------------------------RPEQRAPRA 163

                        330       340       350       360       370       380
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 409168308 366 GTPGFRAPEVLTKCPDQTTAIDMWSAGVIFLSLLSGRYPFYKASDDLTALAQIMTIRGSRETIQ 429
Cdd:cd14019  164 GTRGFRAPEVLFKCPHQTTAIDIWSAGVILLSILSGRFPFFFSSDDIDALAEIATIFGSDEAYD 227

Serine/threonine protein kinase [Signal transduction mechanisms];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 409168308  52 FKIKDKIGEGTFSSVYLATaqlQEGHEEKIALKHLIPTSHP-----------MRIAAELQcltvaggQDNVMGLKYCFRK 120
Cdd:COG0515    9 YRILRLLGRGGMGVVYLAR---DLRLGRPVALKVLRPELAAdpearerfrreARALARLN-------HPNIVRVYDVGEE 78

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 409168308 121 NDHVVIAMPYLEHESFLDILNS---LSFQEVREYMYNLFVALKRIHQFGIVHRDVKPSNFLYNR--RLKkyaLVDFGLA 194
Cdd:COG0515   79 DGRPYLVMEYVEGESLADLLRRrgpLPPAEALRILAQLAEALAAAHAAGIVHRDIKPANILLTPdgRVK---LIDFGIA 154

cyclin-dependent kinase A; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 409168308  56 DKIGEGTFSSVYLATAQLQEgheEKIALKHL--------IPTSHPMRIA--AELQcltvaggQDNVMGLKYCFRKNDHVV 125
Cdd:PLN00009   8 EKIGEGTYGVVYKARDRVTN---ETIALKKIrleqedegVPSTAIREISllKEMQ-------HGNIVRLQDVVHSEKRLY 77

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 409168308 126 IAMPYLEHESFLDILNSLSFQE----VREYMYNLFVALKRIHQFGIVHRDVKPSNFLYNRRLKKYALVDFGLAQ 195
Cdd:PLN00009  78 LVFEYLDLDLKKHMDSSPDFAKnprlIKTYLYQILRGIAYCHSHRVLHRDLKPQNLLIDRRTNALKLADFGLAR 151

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 409168308  125 VIAMPYLEHESFLDILNSLSFqevrEYMYNLFVALKRIHQFGIVHRDVKPSNFLYNRRlKKYaLVDFGLAQGTR---DTK 201
Cdd:TIGR03724  73 TIVMEYIEGKPLKDVIEENGD----ELAREIGRLVGKLHKAGIVHGDLTTSNIIVRDD-KVY-LIDFGLGKYSDeieDKA 146

                  ....*....
gi 409168308  202 IELLKFVQS 210
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 409168308  50 NVFKIKDKIGEGTFSSVYLATAQLQEGH----EEKIALKHLIPTSHPMRIAAELQCLTVAGGQDNVMGLKYCFRKNDHVV 125
Cdd:cd14019    1 NKYRIIEKIGEGTFSSVYKAEDKLHDLYdrnkGRLVALKHIYPTSSPSRILNELECLERLGGSNNVSGLITAFRNEDQVV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 409168308 126 IAMPYLEHESFLDILNSLSFQEVREYMYNLFVALKRIHQFGIVHRDVKPSNFLYNRRLKKYALVDFGLAQGTRDtkiell 205
Cdd:cd14019   81 AVLPYIEHDDFRDFYRKMSLTDIRIYLRNLFKALKHVHSFGIIHRDVKPGNFLYNRETGKGVLVDFGLAQREED------ 154

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 409168308 206 kfvqseaqqedcsrnkyhgvvghkgllsrpapktvdqqctpktsvkrsytqvhikqgkdgkersvglsvqrsvfgernfn 285
Cdd:cd14019      --------------------------------------------------------------------------------

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 409168308 286 ihssishespaeklikqsktvdiisrklatkktaistkamnsvmretarscpavltcdcygsdrvcsvclsRRQQVAPRA 365
Cdd:cd14019  155 -----------------------------------------------------------------------RPEQRAPRA 163

                        330       340       350       360       370       380
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 409168308 366 GTPGFRAPEVLTKCPDQTTAIDMWSAGVIFLSLLSGRYPFYKASDDLTALAQIMTIRGSRETIQ 429
Cdd:cd14019  164 GTRGFRAPEVLFKCPHQTTAIDIWSAGVILLSILSGRFPFFFSSDDIDALAEIATIFGSDEAYD 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 409168308  58 IGEGTFSSVYLATaqlQEGHEEKIALKHLIPTSH---PMRIAAELQCLTVAGGQdNVMGLKYCFRKNDHVVIAMPYLEHE 134
Cdd:cd00180    1 LGKGSFGKVYKAR---DKETGKKVAVKVIPKEKLkklLEELLREIEILKKLNHP-NIVKLYDVFETENFLYLVMEYCEGG 76

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 409168308 135 SFLDILNS----LSFQEVREYMYNLFVALKRIHQFGIVHRDVKPSNFLYNRRLkKYALVDFGLA 194
Cdd:cd00180   77 SLKDLLKEnkgpLSEEEALSILRQLLSALEYLHSNGIIHRDLKPENILLDSDG-TVKLADFGLA 139

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 409168308  52 FKIKDKIGEGTFSSVYLAtaqLQEGHEEKIALKHLIPTsHPMRIAAELQCLTVAGGQDNVMGLKYCFR--KNDHVVIAMP 129
Cdd:cd14132   20 YEIIRKIGRGKYSEVFEG---INIGNNEKVVIKVLKPV-KKKKIKREIKILQNLRGGPNIVKLLDVVKdpQSKTPSLIFE 95

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 409168308 130 YLEHESFLDILNSLSFQEVREYMYNLFVALKRIHQFGIVHRDVKPSNFLYNRRLKKYALVDFGLA 194
Cdd:cd14132   96 YVNNTDFKTLYPTLTDYDIRYYMYELLKALDYCHSKGIMHRDVKPHNIMIDHEKRKLRLIDWGLA 160

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 409168308  52 FKIKDKIGEGTFSSVYLATaqlQEGHEEKIALK--HLIPTSHP---------MRIAAELQCltvaggqDNVMGLKYCFRK 120
Cdd:cd14014    2 YRLVRLLGRGGMGEVYRAR---DTLLGRPVAIKvlRPELAEDEefrerflreARALARLSH-------PNIVRVYDVGED 71

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 409168308 121 NDHVVIAMPYLEHESFLDILN---SLSFQEVREYMYNLFVALKRIHQFGIVHRDVKPSNFLYNR--RLKkyaLVDFGLAQ 195
Cdd:cd14014   72 DGRPYIVMEYVEGGSLADLLRergPLPPREALRILAQIADALAAAHRAGIVHRDIKPANILLTEdgRVK---LTDFGIAR 148

                 ....*..
gi 409168308 196 GTRDTKI 202
Cdd:cd14014  149 ALGDSGL 155

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 409168308  52 FKIKDKIGEGTFSSVYLATAQ----------------LQEGHE-----EKIALKHLiptSHPmriaaelqcltvaggqdN 110
Cdd:cd05581    3 FKFGKPLGEGSYSTVVLAKEKetgkeyaikvldkrhiIKEKKVkyvtiEKEVLSRL---AHP-----------------G 62

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 409168308 111 VMGLKYCFRKNDHVVIAMPYLEHESFLDILN---SLSFQEVREYMYNLFVALKRIHQFGIVHRDVKPSNFL--YNRRLKk 185
Cdd:cd05581   63 IVKLYYTFQDESKLYFVLEYAPNGDLLEYIRkygSLDEKCTRFYTAEIVLALEYLHSKGIIHRDLKPENILldEDMHIK- 141

                        170       180       190
                 ....*....|....*....|....*....|....*
gi 409168308 186 yaLVDFGLAQ-GTRDTKIELLKFVQSEAQQEDCSR 219
Cdd:cd05581  142 --ITDFGTAKvLGPDSSPESTKGDADSQIAYNQAR 174

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 409168308  52 FKIKDKIGEGTFSSVYLATaQLQEGheEKIALKHL--------IPTShPMR-IAA--ELQCltvaggqDNVMGLKYCFRK 120
Cdd:cd07829    1 YEKLEKLGEGTYGVVYKAK-DKKTG--EIVALKKIrldneeegIPST-ALReISLlkELKH-------PNIVKLLDVIHT 69

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 409168308 121 NDHVVIAMPYLEH--ESFLDILNS-LSFQEVREYMYNLFVALKRIHQFGIVHRDVKPSNFLYNRR--LKkyaLVDFGLA 194
Cdd:cd07829   70 ENKLYLVFEYCDQdlKKYLDKRPGpLPPNLIKSIMYQLLRGLAYCHSHRILHRDLKPQNLLINRDgvLK---LADFGLA 145

Catalytic domain of Fungal Sid2p-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This group contains fungal kinases including Schizosaccharomyces pombe Sid2p and Saccharomyces cerevisiae Dbf2p. Group members show similarity to NDR kinases in that they contain an N-terminal regulatory (NTR) domain and an insert within the catalytic domain that contains an auto-inhibitory sequence. Sid2p plays a crucial role in the septum initiation network (SIN) and in the initiation of cytokinesis. Dbf2p is important in regulating the mitotic exit network (MEN) and in cytokinesis. The Sid2p-like group is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 409168308  52 FKIKDKIGEGTFSSVYLAtaQLQEGHE-------EKIALKHLIPTSHpmrIAAELQCLTVAGgQDNVMGLKYCFRKNDHV 124
Cdd:cd05600   13 FQILTQVGQGGYGSVFLA--RKKDTGEicalkimKKKVLFKLNEVNH---VLTERDILTTTN-SPWLVKLLYAFQDPENV 86

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 409168308 125 VIAMPYLEHESFLDILNS---LSFQEVREYMYNLFVALKRIHQFGIVHRDVKPSNFLYNRR--LKkyaLVDFGLAQGTRD 199
Cdd:cd05600   87 YLAMEYVPGGDFRTLLNNsgiLSEEHARFYIAEMFAAISSLHQLGYIHRDLKPENFLIDSSghIK---LTDFGLASGTLS 163

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*..
gi 409168308 200 TKI---------ELLKFVQSEAQQED----------CSRNKYHGVVG 227
Cdd:cd05600  164 PKKiesmkirleEVKNTAFLELTAKErrniyramrkEDQNYANSVVG 210

Catalytic domain of the Serine/Threonine protein kinase, Casein Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CK1 phosphorylates a variety of substrates including enzymes, transcription and splice factors, cytoskeletal proteins, viral oncogenes, receptors, and membrane-associated proteins. There are mutliple isoforms of CK1 and in mammals, seven isoforms (alpha, beta, gamma1-3, delta, and epsilon) have been characterized. These isoforms differ mainly in the length and structure of their C-terminal non-catalytic region. Some isoforms have several splice variants such as the long (L) and short (S) variants of CK1alpha. CK1 proteins are involved in the regulation of many cellular processes including membrane transport processes, circadian rhythm, cell division, apoptosis, and the development of cancer and neurodegenerative diseases. The CK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 409168308  52 FKIKDKIGEGTFSSVYLATaQLQEGheEKIALKHLIPTSHPMRIAAELQCLTVAGGQDNVMGLKYCFRKNDHVVIAMPYL 131
Cdd:cd14016    2 YKLVKKIGSGSFGEVYLGI-DLKTG--EEVAIKIEKKDSKHPQLEYEAKVYKLLQGGPGIPRLYWFGQEGDYNVMVMDLL 78

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 409168308 132 EHeSFLDILN----SLSFQEVREYMYNLFVALKRIHQFGIVHRDVKPSNFL--YNRRLKKYALVDFGLA 194
Cdd:cd14016   79 GP-SLEDLFNkcgrKFSLKTVLMLADQMISRLEYLHSKGYIHRDIKPENFLmgLGKNSNKVYLIDFGLA 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 409168308  52 FKIKDKIGEGTFSSVYLATAQlQEGheEKIALKHLIPTSH------PMRiaaELQCLTVAGGQDNVMGLKYCFRKNDHVV 125
Cdd:cd07830    1 YKVIKQLGDGTFGSVYLARNK-ETG--ELVAIKKMKKKFYsweecmNLR---EVKSLRKLNEHPNIVKLKEVFRENDELY 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 409168308 126 IAMPYLEhESFLDILNS-----LSFQEVREYMYNLFVALKRIHQFGIVHRDVKPSNFLYNRR--LKkyaLVDFGLAQGTR 198
Cdd:cd07830   75 FVFEYME-GNLYQLMKDrkgkpFSESVIRSIIYQILQGLAHIHKHGFFHRDLKPENLLVSGPevVK---IADFGLAREIR 150

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 409168308  52 FKIKDKIGEGTFSSVYLATaqlqegHE---EKIALKHL----IPTSHPMRIAAELQCLTVAGgQDNVMGLKYCFRKNDHV 124
Cdd:cd14003    2 YELGKTLGEGSFGKVKLAR------HKltgEKVAIKIIdkskLKEEIEEKIKREIEIMKLLN-HPNIIKLYEVIETENKI 74

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 409168308 125 VIAMPYLEHESFLDILNS---LSFQEVREYMYNLFVALKRIHQFGIVHRDVKPSNFLY--NRRLKkyaLVDFGLA 194
Cdd:cd14003   75 YLVMEYASGGELFDYIVNngrLSEDEARRFFQQLISAVDYCHSNGIVHRDLKLENILLdkNGNLK---IIDFGLS 146

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 409168308  52 FKIKDKIGEGTFSSVYLAT---------------AQLQEGHEEK-----IAL-KHLiptSHPmriaaelqcltvaggqdN 110
Cdd:cd14007    2 FEIGKPLGKGKFGNVYLARekksgfivalkviskSQLQKSGLEHqlrreIEIqSHL---RHP-----------------N 61

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 409168308 111 VMGLKYCFRKNDHVVIAMPYLEHESFLDILNS---LSFQEVREYMYNLFVALKRIHQFGIVHRDVKPSNFL--YNRRLKk 185
Cdd:cd14007   62 ILRLYGYFEDKKRIYLILEYAPNGELYKELKKqkrFDEKEAAKYIYQLALALDYLHSKNIIHRDIKPENILlgSNGELK- 140

                 ....*....
gi 409168308 186 yaLVDFGLA 194
Cdd:cd14007  141 --LADFGWS 147

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 409168308  58 IGEGTFSSVYLATAQLQEgheEKIALK-----HLIPTSHPMRIAAELQCLTVAGGqDNVMGLKYCFRKNDHVVIAMPYLE 132
Cdd:cd05579    1 ISRGAYGRVYLAKKKSTG---DLYAIKvikkrDMIRKNQVDSVLAERNILSQAQN-PFVVKLYYSFQGKKNLYLVMEYLP 76

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 409168308 133 H---ESFLDILNSLSFQEVREYMYNLFVALKRIHQFGIVHRDVKPSNFLYNR--RLKkyaLVDFGL 193
Cdd:cd05579   77 GgdlYSLLENVGALDEDVARIYIAEIVLALEYLHSHGIIHRDLKPDNILIDAngHLK---LTDFGL 139

Catalytic domain of the Serine/Threonine Kinase, Cell Cycle-Related Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CCRK was previously called p42. It is a Cyclin-Dependent Kinase (CDK)-Activating Kinase (CAK) which is essential for the activation of CDK2. It is indispensable for cell growth and has been implicated in the progression of glioblastoma multiforme. In the heart, a splice variant of CCRK with a different C-terminal half is expressed; this variant promotes cardiac cell growth and survival and is significantly down-regulated during the development of heart failure. The CCRK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 409168308  52 FKIKDKIGEGTFSSVYLATaQLQEGheEKIALKHL--------IPTShPMRiaaELQCLTVAGGQDNVMGLKYCFRKNDH 123
Cdd:cd07832    2 YKILGRIGEGAHGIVFKAK-DRETG--ETVALKKValrkleggIPNQ-ALR---EIKALQACQGHPYVVKLRDVFPHGTG 74

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 409168308 124 VVIAMPYLE---HESFLDILNSLSFQEVREYMYNLFVALKRIHQFGIVHRDVKPSNFLYNRR--LKkyaLVDFGLA 194
Cdd:cd07832   75 FVLVFEYMLsslSEVLRDEERPLTEAQVKRYMRMLLKGVAYMHANRIMHRDLKPANLLISSTgvLK---IADFGLA 147

Catalytic domain of cyclin G-Associated Kinase-like proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes cyclin G-Associated Kinase (GAK), Drosophila melanogaster Numb-Associated Kinase (NAK)-like proteins, and similar protein kinases. GAK plays regulatory roles in clathrin-mediated membrane trafficking, the maintenance of centrosome integrity and chromosome congression, neural patterning, survival of neurons, and immune responses. NAK plays a role in asymmetric cell division through its association with Numb. It also regulates the localization of Dlg, a protein essential for septate junction formation. The GAK-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 409168308  58 IGEGTFSSVYLATAQlqeGHEEKIALKHLIPTSHP--MRIAAELQCLTVAGGQDNVMGLKYC--FRKNDH--VVIAMPYL 131
Cdd:cd13985    8 LGEGGFSYVYLAHDV---NTGRRYALKRMYFNDEEqlRVAIKEIEIMKRLCGHPNIVQYYDSaiLSSEGRkeVLLLMEYC 84

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 409168308 132 EhESFLDILNS-----LSFQEVREYMYNLFVALKRIHQFG--IVHRDVKPSNFLYNRRlKKYALVDFGLA 194
Cdd:cd13985   85 P-GSLVDILEKsppspLSEEEVLRIFYQICQAVGHLHSQSppIIHRDIKIENILFSNT-GRFKLCDFGSA 152

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 409168308 110 NVMGLKYCFRKNDHVVIAMPYLEHESFLDIL---NSLSFQEVREYMYNLFVALKRIHQFGIVHRDVKPSNFLYNR--RLK 184
Cdd:cd14099   62 NIVKFHDCFEDEENVYILLELCSNGSLMELLkrrKALTEPEVRYFMRQILSGVKYLHSNRIIHRDLKLGNLFLDEnmNVK 141

                         90
                 ....*....|
gi 409168308 185 kyaLVDFGLA 194
Cdd:cd14099  142 ---IGDFGLA 148

Catalytic domain of Extracellular signal-Regulated Kinase 1 and 2-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the mitogen-activated protein kinases (MAPKs) ERK1, ERK2, baker's yeast Fus3, and similar proteins. MAPK pathways are important mediators of cellular responses to extracellular signals. ERK1/2 activation is preferentially by mitogenic factors, differentiation stimuli, and cytokines, through a kinase cascade involving the MAPK kinases MEK1/2 and a MAPK kinase kinase from the Raf family. ERK1/2 have numerous substrates, many of which are nuclear and participate in transcriptional regulation of many cellular processes. They regulate cell growth, cell proliferation, and cell cycle progression from G1 to S phase. Although the distinct roles of ERK1 and ERK2 have not been fully determined, it is known that ERK2 can maintain most functions in the absence of ERK1, and that the deletion of ERK2 is embryonically lethal. The MAPK, Fus3, regulates yeast mating processes including mating-specific gene expression, G1 arrest, mating projection, and cell fusion. This ERK1/2-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 409168308  52 FKIKDKIGEGTFSSVYLATAQLqegHEEKIALKHLIPTSHPMriaaelqcltvaggqdnvmglkYCFRKNDHVVIaMPYL 131
Cdd:cd07849    7 YQNLSYIGEGAYGMVCSAVHKP---TGQKVAIKKISPFEHQT----------------------YCLRTLREIKI-LLRF 60