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 767977141   1 MGFARLFNSPLKPLADLDPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEPIFHCRQEDIKTSNPYHHDQLD 80
Cdd:cd07868  172 MGFARLFNSPLKPLADLDPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEPIFHCRQEDIKTSNPYHHDQLD 251

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767977141  81 RIFNVMGFPADKDWEDIKKMPEHSTLMKDFRRNTYTNCSLIKYMEKHKVKPDSKAFHLLQKLLTMDPIKRITSEQAMQDP 160
Cdd:cd07868  252 RIFNVMGFPADKDWEDIKKMPEHSTLMKDFRRNTYTNCSLIKYMEKHKVKPDSKAFHLLQKLLTMDPIKRITSEQAMQDP 331

                 ..
gi 767977141 161 YF 162
Cdd:cd07868  332 YF 333

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 8; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK8 can act as a negative or positive regulator of transcription, depending on the scenario. Together with its regulator, cyclin C, it reversibly associates with the multi-subunit core Mediator complex, a cofactor that is involved in regulating RNA polymerase II (RNAP II)-dependent transcription. CDK8 phosphorylates cyclin H, a subunit of the general transcription factor TFIIH, which results in the inhibition of TFIIH-dependent phosphorylation of the C-terminal domain of RNAP II, facilitating the inhibition of transcription. It has also been shown to promote transcription by a mechanism that is likely to involve RNAP II phosphorylation. CDK8 also functions as a stimulus-specific positive coregulator of p53 transcriptional responses. 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 CDK8 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 767977141   1 MGFARLFNSPLKPLADLDPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEPIFHCRQEDIKTSNPYHHDQLD 80
Cdd:cd07868  172 MGFARLFNSPLKPLADLDPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEPIFHCRQEDIKTSNPYHHDQLD 251

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767977141  81 RIFNVMGFPADKDWEDIKKMPEHSTLMKDFRRNTYTNCSLIKYMEKHKVKPDSKAFHLLQKLLTMDPIKRITSEQAMQDP 160
Cdd:cd07868  252 RIFNVMGFPADKDWEDIKKMPEHSTLMKDFRRNTYTNCSLIKYMEKHKVKPDSKAFHLLQKLLTMDPIKRITSEQAMQDP 331

                 ..
gi 767977141 161 YF 162
Cdd:cd07868  332 YF 333

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767977141     2 GFARLFNSPLKpladLDPVVVTFWYRAPELLLGaRHYTKAIDIWAIGCIFAELLTSEPIFhcrqediktsnpYHHDQLDR 81
Cdd:smart00220 142 GLARQLDPGEK----LTTFVGTPEYMAPEVLLG-KGYGKAVDIWSLGVILYELLTGKPPF------------PGDDQLLE 204

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767977141    82 IFNVMGFPADKDWEDIKKMPEhstlmkdfrrntytncslikymekhkvkpdsKAFHLLQKLLTMDPIKRITSEQAMQDPY 161
Cdd:smart00220 205 LFKKIGKPKPPFPPPEWDISP-------------------------------EAKDLIRKLLVKDPEKRLTAEEALQHPF 253

                   .
gi 767977141   162 F 162
Cdd:smart00220 254 F 254

Serine/threonine protein kinase [Signal transduction mechanisms];

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 767977141   2 GFARLFNSPlkPLADLDPVVVTFWYRAPELLLGARhYTKAIDIWAIGCIFAELLTSEPIFH 62
Cdd:COG0515  152 GIARALGGA--TLTQTGTVVGTPGYMAPEQARGEP-VDPRSDVYSLGVTLYELLTGRPPFD 209

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 8; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK8 can act as a negative or positive regulator of transcription, depending on the scenario. Together with its regulator, cyclin C, it reversibly associates with the multi-subunit core Mediator complex, a cofactor that is involved in regulating RNA polymerase II (RNAP II)-dependent transcription. CDK8 phosphorylates cyclin H, a subunit of the general transcription factor TFIIH, which results in the inhibition of TFIIH-dependent phosphorylation of the C-terminal domain of RNAP II, facilitating the inhibition of transcription. It has also been shown to promote transcription by a mechanism that is likely to involve RNAP II phosphorylation. CDK8 also functions as a stimulus-specific positive coregulator of p53 transcriptional responses. 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 CDK8 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 767977141   1 MGFARLFNSPLKPLADLDPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEPIFHCRQEDIKTSNPYHHDQLD 80
Cdd:cd07868  172 MGFARLFNSPLKPLADLDPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEPIFHCRQEDIKTSNPYHHDQLD 251

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767977141  81 RIFNVMGFPADKDWEDIKKMPEHSTLMKDFRRNTYTNCSLIKYMEKHKVKPDSKAFHLLQKLLTMDPIKRITSEQAMQDP 160
Cdd:cd07868  252 RIFNVMGFPADKDWEDIKKMPEHSTLMKDFRRNTYTNCSLIKYMEKHKVKPDSKAFHLLQKLLTMDPIKRITSEQAMQDP 331

                 ..
gi 767977141 161 YF 162
Cdd:cd07868  332 YF 333

Catalytic domain of Serine/Threonine Kinase, Cell Division Cycle 2-like 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDC2L6 is also called CDK8-like and was previously referred to as CDK11. However, this is a confusing nomenclature as CDC2L6 is distinct from CDC2L1, which is represented by the two protein products from its gene, called CDK11(p110) and CDK11(p58), as well as the caspase-processed CDK11(p46). CDK11(p110), CDK11(p58), and CDK11(p46)do not belong to this subfamily. CDC2L6 is an associated protein of Mediator, a multiprotein complex that provides a platform to connect transcriptional and chromatin regulators and cofactors, in order to activate and mediate RNA polymerase II transcription. CDC2L6 is localized mainly in the nucleus amd exerts an opposing effect to CDK8 in VP16-dependent transcriptional activation by being a negative regulator. 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 CDC2L6 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 767977141   1 MGFARLFNSPLKPLADLDPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEPIFHCRQEDIKTSNPYHHDQLD 80
Cdd:cd07867  157 MGFARLFNSPLKPLADLDPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEPIFHCRQEDIKTSNPFHHDQLD 236

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767977141  81 RIFNVMGFPADKDWEDIKKMPEHSTLMKDFRRNTYTNCSLIKYMEKHKVKPDSKAFHLLQKLLTMDPIKRITSEQAMQDP 160
Cdd:cd07867  237 RIFSVMGFPADKDWEDIRKMPEYPTLQKDFRRTTYANSSLIKYMEKHKVKPDSKVFLLLQKLLTMDPTKRITSEQALQDP 316

                 ..
gi 767977141 161 YF 162
Cdd:cd07867  317 YF 318

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 767977141   2 GFARLFNSPLKPLAdldPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEPIFHCRQEdiktsnpyhHDQLDR 81
Cdd:cd07843  151 GLAREYGSPLKPYT---QLVVTLWYRAPELLLGAKEYSTAIDMWSVGCIFAELLTKKPLFPGKSE---------IDQLNK 218

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767977141  82 IFNVMGFPADKDWEDIKKMPehstLMKDFRRNTYTNCSLikymeKHKVKPDS---KAFHLLQKLLTMDPIKRITSEQAMQ 158
Cdd:cd07843  219 IFKLLGTPTEKIWPGFSELP----GAKKKTFTKYPYNQL-----RKKFPALSlsdNGFDLLNRLLTYDPAKRISAEDALK 289

                 ....
gi 767977141 159 DPYF 162
Cdd:cd07843  290 HPYF 293

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 767977141   2 GFARLFNSPLKPLAdldPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEPIFHcRQEDIktsnpyhhDQLDR 81
Cdd:cd07841  147 GLARSFGSPNRKMT---HQVVTRWYRAPELLFGARHYGVGVDMWSVGCIFAELLLRVPFLP-GDSDI--------DQLGK 214

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767977141  82 IFNVMGFPADKDWEDIKKMPEHSTlMKDF----RRNTYTNCSlikymekhkvkpdSKAFHLLQKLLTMDPIKRITSEQAM 157
Cdd:cd07841  215 IFEALGTPTEENWPGVTSLPDYVE-FKPFpptpLKQIFPAAS-------------DDALDLLQRLLTLNPNKRITARQAL 280

                        170
                 ....*....|..
gi 767977141 158 QDPYFLEDPLPT 169
Cdd:cd07841  281 EHPYFSNDPAPT 292

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 767977141   2 GFARLFNSPLKPLaDLDPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEPIFhcrqediKTSNPYHhdQLDR 81
Cdd:cd07834  148 GLARGVDPDEDKG-FLTEYVVTRWYRAPELLLSSKKYTKAIDIWSVGCIFAELLTRKPLF-------PGRDYID--QLNL 217

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767977141  82 IFNVMGFPadkDWEDIKKMpehstlmkdfrrntyTNCSLIKYMEKHKVKP-----------DSKAFHLLQKLLTMDPIKR 150
Cdd:cd07834  218 IVEVLGTP---SEEDLKFI---------------SSEKARNYLKSLPKKPkkplsevfpgaSPEAIDLLEKMLVFNPKKR 279

                        170
                 ....*....|..
gi 767977141 151 ITSEQAMQDPYF 162
Cdd:cd07834  280 ITADEALAHPYL 291

cyclin-dependent protein kinase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767977141  12 KPLADLDPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEPIFHCRQEdiktsnpyhHDQLDRIFNVMGFPAD 91
Cdd:PTZ00024 185 QRREEMTSKVVTLWYRAPELLMGAEKYHFAVDMWSVGCIFAELLTGKPLFPGENE---------IDQLGRIFELLGTPNE 255

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767977141  92 KDWEDIKKMP---EHSTLMKDFRRNTYTNCslikymekhkvkpDSKAFHLLQKLLTMDPIKRITSEQAMQDPYFLEDPLP 168
Cdd:PTZ00024 256 DNWPQAKKLPlytEFTPRKPKDLKTIFPNA-------------SDDAIDLLQSLLKLNPLERISAKEALKHEYFKSDPLP 322

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 767977141  26 YRAPELLLGARHYTKAIDIWAIGCIFAELLTSEPIFHCRqedikTSNpyhhDQLDRIFNVMGFPADkdwEDIKKMPEHST 105
Cdd:cd14137  172 YRAPELIFGATDYTTAIDIWSAGCVLAELLLGQPLFPGE-----SSV----DQLVEIIKVLGTPTR---EQIKAMNPNYT 239

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 767977141 106 lmkDFRRNTYTNCSLIKYMEKHkvkPDSKAFHLLQKLLTMDPIKRITSEQAMQDPYF 162
Cdd:cd14137  240 ---EFKFPQIKPHPWEKVFPKR---TPPDAIDLLSKILVYNPSKRLTALEALAHPFF 290

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 1 from higher eukaryotes; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK1 is also called Cell division control protein 2 (Cdc2) or p34 protein kinase, and is regulated by cyclins A, B, and E. The CDK1/cyclin A complex controls G2 phase entry and progression. CDK1/cyclin A2 has also been implicated as an important regulator of S phase events. The CDK1/cyclin B complex is critical for G2 to M phase transition. It induces mitosis by activating nuclear enzymes that regulate chromatin condensation, nuclear membrane degradation, mitosis-specific microtubule and cytoskeletal reorganization. CDK1 also associates with cyclin E and plays a role in the entry into S phase. CDK1 transcription is stable throughout the cell cycle but is modulated in some pathological conditions. It may play a role in regulating apoptosis under these conditions. In breast cancer cells, HER2 can mediate apoptosis by inactivating CDK1. Activation of CDK1 may contribute to HIV-1 induced apoptosis as well as neuronal apoptosis in neurodegenerative diseases. 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 CDK1 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 767977141   2 GFARLFNSPLKPLADldpVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEPIFHCRQEDiktsnpyhhDQLDR 81
Cdd:cd07861  146 GLARAFGIPVRVYTH---EVVTLWYRAPEVLLGSPRYSTPVDIWSIGTIFAEMATKKPLFHGDSEI---------DQLFR 213

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767977141  82 IFNVMGFPADKDWEDIKKMPEHSTLMKDFRRNTYTncSLIKYMekhkvkpDSKAFHLLQKLLTMDPIKRITSEQAMQDPY 161
Cdd:cd07861  214 IFRILGTPTEDIWPGVTSLPDYKNTFPKWKKGSLR--TAVKNL-------DEDGLDLLEKMLIYDPAKRISAKKALVHPY 284

                 .
gi 767977141 162 F 162
Cdd:cd07861  285 F 285

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 767977141   2 GFARLFNSPLKPLADLDPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEPIFHCRQediktsnpYHHdQLDR 81
Cdd:cd07849  151 GLARIADPEHDHTGFLTEYVATRWYRAPEIMLNSKGYTKAIDIWSVGCILAEMLSNRPLFPGKD--------YLH-QLNL 221

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767977141  82 IFNVMGFPADKDWEDIKkmpehSTLMKDFRRNT--YTNCSLIKYMEKHkvkpDSKAFHLLQKLLTMDPIKRITSEQAMQD 159
Cdd:cd07849  222 ILGILGTPSQEDLNCII-----SLKARNYIKSLpfKPKVPWNKLFPNA----DPKALDLLDKMLTFNPHKRITVEEALAH 292

                        170
                 ....*....|....*...
gi 767977141 160 PYfLE---DPL--PTSDV 172
Cdd:cd07849  293 PY-LEqyhDPSdePVAEE 309

Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase (CDK), Bypass UAS Requirement 1, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BUR1, also called SGV1, is a yeast CDK that is functionally equivalent to mammalian CDK9. It associates with the cyclin BUR2. BUR genes were orginally identified in a genetic screen as factors involved in general transcription. The BUR1/BUR2 complex phosphorylates the C-terminal domain of RNA polymerase II. In addition, this complex regulates histone modification by phosporylating Rad6 and mediating the association of the Paf1 complex with chromatin. 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 BUR1 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 767977141   2 GFARLFNSPLKPL--------ADLDPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEPIFHcRQEDIktsnp 73
Cdd:cd07866  160 GLARPYDGPPPNPkggggggtRKYTNLVVTRWYRPPELLLGERRYTTAVDIWGIGCVFAEMFTRRPILQ-GKSDI----- 233

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767977141  74 yhhDQLDRIFNVMGFPADKDWEDIKKMPEHSTLmkdfrrNTYTNCslIKYMEKHKVKPDSKAFHLLQKLLTMDPIKRITS 153
Cdd:cd07866  234 ---DQLHLIFKLCGTPTEETWPGWRSLPGCEGV------HSFTNY--PRTLEERFGKLGPEGLDLLSKLLSLDPYKRLTA 302

                 ....*....
gi 767977141 154 EQAMQDPYF 162
Cdd:cd07866  303 SDALEHPYF 311

Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase Pho85; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Pho85 is a multifunctional CDK in yeast. It is regulated by 10 different cyclins (Pcls) and plays a role in G1 progression, cell polarity, phosphate and glycogen metabolism, gene expression, and in signaling changes in the environment. It is not essential for yeast viability and is the functional homolog of mammalian CDK5, which plays a role in central nervous system development. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The Pho85 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767977141   2 GFARLFNSPLKPLADldpVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEPIFHCRQEDiktsnpyhhDQLDR 81
Cdd:cd07836  145 GLARAFGIPVNTFSN---EVVTLWYRAPDVLLGSRTYSTSIDIWSVGCIMAEMITGRPLFPGTNNE---------DQLLK 212

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767977141  82 IFNVMGFPADKDWEDIKKMPEHstlmkdfrRNTYTNCSLIKyMEKHKVKPDSKAFHLLQKLLTMDPIKRITSEQAMQDPY 161
Cdd:cd07836  213 IFRIMGTPTESTWPGISQLPEY--------KPTFPRYPPQD-LQQLFPHADPLGIDLLHRLLQLNPELRISAHDALQHPW 283

                 .
gi 767977141 162 F 162
Cdd:cd07836  284 F 284

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 767977141  21 VVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEPIFHCRQEdiktsnpyhHDQLDRIFNVMGFPADKDWedikkm 100
Cdd:cd07830  159 VSTRWYRAPEILLRSTSYSSPVDIWALGCIMAELYTLRPLFPGSSE---------IDQLYKICSVLGTPTKQDW------ 223

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 767977141 101 PEHSTLMKD--FRRNTYTNCSLikymekHKVKPDS--KAFHLLQKLLTMDPIKRITSEQAMQDPYF 162
Cdd:cd07830  224 PEGYKLASKlgFRFPQFAPTSL------HQLIPNAspEAIDLIKDMLRWDPKKRPTASQALQHPYF 283

Catalytic domain of the Serine/Threonine Kinases, Plant TEY Mitogen-Activated Protein Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Plant MAPKs are typed based on the conserved phosphorylation motif present in the activation loop, TEY and TDY. This subfamily represents the TEY subtype of plant MAPKs and is further subdivided into three groups (A, B, and C). Group A is represented by AtMPK3, AtMPK6, Nicotiana tabacum BTF4 (NtNTF4), among others. They are mostly involved in environmental and hormonal responses. AtMPK3 and AtMPK6 are also key regulators for stomatal development and patterning. Group B is represented by AtMPK4, AtMPK13, and NtNTF6, among others. They may be involved in both cell division and environmental stress response. AtMPK4 also participates in regulating innate immunity. Group C is represented by AtMPK1, AtMPK2, NtNTF3, Oryza sativa MAPK4 (OsMAPK4), among others. They may also be involved in stress responses. AtMPK1 and AtMPK2 are activated following mechanical injury and in the presence of stress chemicals such as jasmonic acid, hydrogen peroxide and abscisic acid. OsMAPK4 is also called OsMSRMK3 for Multiple Stress-Responsive MAPK3. In plants, MAPKs are associated with physiological, developmental, hormonal, and stress responses. Some plants show numerous gene duplications of MAPKs; Arabidopsis thaliana harbors at least 20 MAPKs, named AtMPK1-20. The TEY MAPK 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 767977141  21 VVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEPIFHCRQediktsnpYHHdQLDRIFNVMGFPADKDWEDIkkm 100
Cdd:cd07858  169 VVTRWYRAPELLLNCSEYTTAIDVWSVGCIFAELLGRKPLFPGKD--------YVH-QLKLITELLGSPSEEDLGFI--- 236

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767977141 101 peHSTLMKDFRRN--TYTNCSLIKYMEkhKVKPDskAFHLLQKLLTMDPIKRITSEQAMQDPYF--LEDP 166
Cdd:cd07858  237 --RNEKARRYIRSlpYTPRQSFARLFP--HANPL--AIDLLEKMLVFDPSKRITVEEALAHPYLasLHDP 300

cyclin-dependent kinase A; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767977141   2 GFARLFNSPLKPLADldpVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEPIFHCRQEDiktsnpyhhDQLDR 81
Cdd:PLN00009 148 GLARAFGIPVRTFTH---EVVTLWYRAPEILLGSRHYSTPVDIWSVGCIFAEMVNQKPLFPGDSEI---------DELFK 215

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767977141  82 IFNVMGFPADKDWEDIKKMPEH-STLMKDFRRNTYTncslikymekhkVKP--DSKAFHLLQKLLTMDPIKRITSEQAMQ 158
Cdd:PLN00009 216 IFRILGTPNEETWPGVTSLPDYkSAFPKWPPKDLAT------------VVPtlEPAGVDLLSKMLRLDPSKRITARAALE 283

                 ....
gi 767977141 159 DPYF 162
Cdd:PLN00009 284 HEYF 287

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 767977141   1 MGFARLFNSPLkpladLDPVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEPIFhcrqediktSNPYHHDQLD 80
Cdd:cd05118  146 FGLARSFTSPP-----YTPYVATRWYRAPEVLLGAKPYGSSIDIWSLGCILAELLTGRPLF---------PGDSEVDQLA 211

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767977141  81 RIFNVMGfpadkdwedikkmpehstlmkdfrrntytncslikymekhkvkpDSKAFHLLQKLLTMDPIKRITSEQAMQDP 160
Cdd:cd05118  212 KIVRLLG--------------------------------------------TPEALDLLSKMLKYDPAKRITASQALAHP 247

                 ..
gi 767977141 161 YF 162
Cdd:cd05118  248 YF 249

Catalytic domain of PCTAIRE-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PCTAIRE-like proteins show unusual expression patterns with high levels in post-mitotic tissues, suggesting that they may be involved in regulating post-mitotic cellular events. They share sequence similarity with Cyclin-Dependent Kinases (CDKs), which belong to a large family of STKs that are regulated by their cognate cyclins. Together, CDKs and cyclins are involved in the control of cell-cycle progression, transcription, and neuronal function. The association of PCTAIRE-like proteins with cyclins has not been widely studied, although PFTAIRE-1 has been shown to function as a CDK which is regulated by cyclin D3 as well as the membrane-associated cyclin Y. The PCTAIRE-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 767977141  21 VVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEPIFHcrqediKTSNPYhhDQLDRIFNVMGFPADKDWEDIKKM 100
Cdd:cd07844  159 VVTLWYRPPDVLLGSTEYSTSLDMWGVGCIFYEMATGRPLFP------GSTDVE--DQLHKIFRVLGTPTEETWPGVSSN 230

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 767977141 101 PEHstlmKDFRRNTYTNCSLIKYMEKHKVKPDskAFHLLQKLLTMDPIKRITSEQAMQDPYF 162
Cdd:cd07844  231 PEF----KPYSFPFYPPRPLINHAPRLDRIPH--GEELALKFLQYEPKKRISAAEAMKHPYF 286

Catalytic domain of the Serine/Threonine Kinase, Nemo-Like Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NLK is an atypical mitogen-activated protein kinase (MAPK) that is not regulated by a MAPK kinase. It functions downstream of the MAPK kinase kinase Tak1, which also plays a role in activating the JNK and p38 MAPKs. The Tak1/NLK pathways are regulated by Wnts, a family of secreted proteins that is critical in the control of asymmetric division and cell polarity. NLK can phosphorylate transcription factors from the TCF/LEF family, inhibiting their ability to activate the transcription of target genes. In prostate cancer cells, NLK is involved in regulating androgen receptor-mediated transcription and its expression is altered during cancer progression. MAPKs are important mediators of cellular responses to extracellular signals. The NLK 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 767977141  21 VVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEPIFhcrqediKTSNPYhhDQLDRIFNVMGFPAdkdwedikkm 100
Cdd:cd07853  165 VVTQYYRAPEILMGSRHYTSAVDIWSVGCIFAELLGRRILF-------QAQSPI--QQLDLITDLLGTPS---------- 225

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767977141 101 pehstlMKDFRrntyTNCS-LIKYMEKHKVKPDS-------------KAFHLLQKLLTMDPIKRITSEQAMQDPYFLEDP 166
Cdd:cd07853  226 ------LEAMR----SACEgARAHILRGPHKPPSlpvlytlssqathEAVHLLCRMLVFDPDKRISAADALAHPYLDEGR 295

                        170       180
                 ....*....|....*....|....*.
gi 767977141 167 LP-TSDVFAGCQIPYPKREFLTEEEP 191
Cdd:cd07853  296 LRyHTCMCKCCYTTSGGRVYTSDFEP 321

Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 1 and 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKL1, also called p42 KKIALRE, is a glial protein that is upregulated in gliosis. It is present in neuroblastoma and A431 human carcinoma cells, and may be implicated in neoplastic transformation. The function of CDKL4 is unknown. 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 CDKL1/4 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 767977141   2 GFARLFNSPLKPLADLdpvVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEPIFHCRQeDIktsnpyhhDQLDR 81
Cdd:cd07847  145 GFARILTGPGDDYTDY---VATRWYRAPELLVGDTQYGPPVDVWAIGCVFAELLTGQPLWPGKS-DV--------DQLYL 212

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767977141  82 IFNVMGfpadkdwediKKMPEHSTLmkdFRRNTY------TNCSLIKYMEKHKVKPDSKAFHLLQKLLTMDPIKRITSEQ 155
Cdd:cd07847  213 IRKTLG----------DLIPRHQQI---FSTNQFfkglsiPEPETREPLESKFPNISSPALSFLKGCLQMDPTERLSCEE 279

                 ....*..
gi 767977141 156 AMQDPYF 162
Cdd:cd07847  280 LLEHPYF 286

Catalytic domain of the Serine/Threonine Kinase, Plant B-type Cyclin-Dependent protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The plant-specific B-type CDKs are expressed from the late S to the M phase of the cell cycle. They are characterized by the cyclin binding motif PPT[A/T]LRE. They play a role in controlling mitosis and integrating developmental pathways, such as stomata and leaf development. CdkB has been shown to associate with both cyclin B, which controls G2/M transition, and cyclin D, which acts as a mediator in linking extracellular signals to the cell cycle. 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 CdkB 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 767977141   1 MGFARLFNSPLKPLADldpVVVTFWYRAPELLLGARHYTKAIDIWAIGCIFAELLTSEPIFHCRQEdiktsnpyhHDQLD 80
Cdd:cd07837  154 LGLGRAFTIPIKSYTH---EIVTLWYRAPEVLLGSTHYSTPVDMWSVGCIFAEMSRKQPLFPGDSE---------LQQLL 221

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767977141  81 RIFNVMGFPADKDWEDIKKMPEHSTLMKDFRRNTytnCSLIKYMEKHKVKpdskafhLLQKLLTMDPIKRITSEQAMQDP 160
Cdd:cd07837  222 HIFRLLGTPNEEVWPGVSKLRDWHEYPQWKPQDL---SRAVPDLEPEGVD-------LLTKMLAYDPAKRISAKAALQHP 291

                 ..
gi 767977141 161 YF 162
Cdd:cd07837  292 YF 293