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 1231802378   1 MDLWSAGCVFYEIASLQPLFPGVNELDQISKIHDVIGTPAQKILTKFKQSRAMNFDFPFKKGSGIPLLTTNLSPQCLSLL 80
Cdd:cd07831   180 MDIWAVGCVFFEILSLFPLFPGTNELDQIAKIHDVLGTPDAEVLKKFRKSRHMNYNFPSKKGTGLRKLLPNASAEGLDLL 259

                          90       100
                  ....*....|....*....|...
gi 1231802378  81 HAMVAYDPDERIAAHQALQHPYF 103
Cdd:cd07831   260 KKLLAYDPDERITAKQALRHPYF 282

Catalytic domain of the Serine/Threonine Kinase, MAPK/MAK/MRK Overlapping Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MOK, also called Renal tumor antigen 1 (RAGE-1), is widely expressed and is enriched in testis, kidney, lung, and brain. It is expressed in approximately 50% of renal cell carcinomas (RCC) and is a potential target for immunotherapy. MOK is stabilized by its association with the HSP90 molecular chaperone. It is induced by the transcription factor Cdx2 and may be involved in regulating intestinal epithelial development and differentiation. The MOK 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 1231802378   1 MDLWSAGCVFYEIASLQPLFPGVNELDQISKIHDVIGTPAQKILTKFKQSRAMNFDFPFKKGSGIPLLTTNLSPQCLSLL 80
Cdd:cd07831   180 MDIWAVGCVFFEILSLFPLFPGTNELDQIAKIHDVLGTPDAEVLKKFRKSRHMNYNFPSKKGTGLRKLLPNASAEGLDLL 259

                          90       100
                  ....*....|....*....|...
gi 1231802378  81 HAMVAYDPDERIAAHQALQHPYF 103
Cdd:cd07831   260 KKLLAYDPDERITAKQALRHPYF 282

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1231802378    2 DLWSAGCVFYEIASLQPLFPGVNELDQISKIhdvIGTPaqkiltkfkqsramNFDFPFKKgsgiplltTNLSPQCLSLLH 81
Cdd:smart00220 178 DIWSLGVILYELLTGKPPFPGDDQLLELFKK---IGKP--------------KPPFPPPE--------WDISPEAKDLIR 232

                           90       100
                   ....*....|....*....|..
gi 1231802378   82 AMVAYDPDERIAAHQALQHPYF 103
Cdd:smart00220 233 KLLVKDPEKRLTAEEALQHPFF 254

Catalytic domain of the Serine/Threonine Kinase, MAPK/MAK/MRK Overlapping Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MOK, also called Renal tumor antigen 1 (RAGE-1), is widely expressed and is enriched in testis, kidney, lung, and brain. It is expressed in approximately 50% of renal cell carcinomas (RCC) and is a potential target for immunotherapy. MOK is stabilized by its association with the HSP90 molecular chaperone. It is induced by the transcription factor Cdx2 and may be involved in regulating intestinal epithelial development and differentiation. The MOK 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 1231802378   1 MDLWSAGCVFYEIASLQPLFPGVNELDQISKIHDVIGTPAQKILTKFKQSRAMNFDFPFKKGSGIPLLTTNLSPQCLSLL 80
Cdd:cd07831   180 MDIWAVGCVFFEILSLFPLFPGTNELDQIAKIHDVLGTPDAEVLKKFRKSRHMNYNFPSKKGTGLRKLLPNASAEGLDLL 259

                          90       100
                  ....*....|....*....|...
gi 1231802378  81 HAMVAYDPDERIAAHQALQHPYF 103
Cdd:cd07831   260 KKLLAYDPDERITAKQALRHPYF 282

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 1231802378   2 DLWSAGCVFYEIASLQPLFPGVNELDQISKIHDVIGTPAQKI---LTKFKqsramNFDFPFKKGSGIPLLTT--NLSPQC 76
Cdd:cd07829   181 DIWSVGCIFAELITGKPLFPGDSEIDQLFKIFQILGTPTEESwpgVTKLP-----DYKPTFPKWPKNDLEKVlpRLDPEG 255

                          90       100
                  ....*....|....*....|....*..
gi 1231802378  77 LSLLHAMVAYDPDERIAAHQALQHPYF 103
Cdd:cd07829   256 IDLLSKMLQYNPAKRISAKEALKHPYF 282

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 1231802378   1 MDLWSAGCVFYEIASLQPLFPGVNELDQISKIHDVIGTpaqkiltkfkqsramnfdfpfkkgsgipllttnlsPQCLSLL 80
Cdd:cd05118   182 IDIWSLGCILAELLTGRPLFPGDSEVDQLAKIVRLLGT-----------------------------------PEALDLL 226

                          90       100
                  ....*....|....*....|...
gi 1231802378  81 HAMVAYDPDERIAAHQALQHPYF 103
Cdd:cd05118   227 SKMLKYDPAKRITASQALAHPYF 249

Catalytic domain of Cyclin-Dependent protein Kinase 1-like Serine/Threonine Kinases and of 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. This subfamily is composed of CDK, CDK2, and CDK3. 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 while the CDK1/cyclin B complex is critical for G2 to M phase transition. CDK2 is regulated by cyclin E or cyclin A. Upon activation by cyclin E, it phosphorylates the retinoblastoma (pRb) protein which activates E2F mediated transcription and allows cells to move into S phase. The CDK2/cyclin A complex plays a role in regulating DNA replication. Studies in knockout mice revealed that CDK1 can compensate for the loss of the cdk2 gene as it can also bind cyclin E and drive G1 to S phase transition. CDK3 is regulated by cyclin C and it phosphorylates pRB specifically during the G0/G1 transition. This phosphorylation is required for cells to exit G0 efficiently and enter the G1 phase. 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 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 1231802378   2 DLWSAGCVFYEIASLQPLFPGVNELDQISKIHDVIGTPAQKI------LTKFKQSramnfdFPFKKGSGIPLLTTNLSPQ 75
Cdd:cd07835   182 DIWSVGCIFAEMVTRRPLFPGDSEIDQLFRIFRTLGTPDEDVwpgvtsLPDYKPT------FPKWARQDLSKVVPSLDED 255

                          90       100
                  ....*....|....*....|....*...
gi 1231802378  76 CLSLLHAMVAYDPDERIAAHQALQHPYF 103
Cdd:cd07835   256 GLDLLSQMLVYDPAKRISAKAALQHPYF 283

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 1231802378   2 DLWSAGCVFYEIASLQPLFPGVNELDQISKIHDVIGTPAQKILTKFKQ-SRAMNFDFPFKKGSGIP--LLTTNLSPQCLS 78
Cdd:cd07843   189 DMWSVGCIFAELLTKKPLFPGKSEIDQLNKIFKLLGTPTEKIWPGFSElPGAKKKTFTKYPYNQLRkkFPALSLSDNGFD 268

                          90       100
                  ....*....|....*....|....*
gi 1231802378  79 LLHAMVAYDPDERIAAHQALQHPYF 103
Cdd:cd07843   269 LLNRLLTYDPAKRISAEDALKHPYF 293

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 1231802378   1 MDLWSAGCVFYEIASLQPLFPGVNELDQISKIHDVIGTPAQKILTKFKQSRAMNFDFPFKKGSGIPLLTTNLSPQCLSLL 80
Cdd:cd07836   182 IDIWSVGCIMAEMITGRPLFPGTNNEDQLLKIFRIMGTPTESTWPGISQLPEYKPTFPRYPPQDLQQLFPHADPLGIDLL 261

                          90       100
                  ....*....|....*....|...
gi 1231802378  81 HAMVAYDPDERIAAHQALQHPYF 103
Cdd:cd07836   262 HRLLQLNPELRISAHDALQHPWF 284

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 1231802378   1 MDLWSAGCVFYEIASLQPLFPGVNELDQISKIHDVIGTPAQKILTKFKQSRAMNF--DFPFKKGSGIPLLTTNLSPQCLS 78
Cdd:cd07849   191 IDIWSVGCILAEMLSNRPLFPGKDYLHQLNLILGILGTPSQEDLNCIISLKARNYikSLPFKPKVPWNKLFPNADPKALD 270

                          90       100
                  ....*....|....*....|....*..
gi 1231802378  79 LLHAMVAYDPDERIAAHQALQHPYFQE 105
Cdd:cd07849   271 LLDKMLTFNPHKRITVEEALAHPYLEQ 297

Catalytic domain of the Serine/Threonine Kinase, p38gamma Mitogen-Activated Protein Kinase (also called MAPK12); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38gamma/MAPK12 is predominantly expressed in skeletal muscle. Unlike p38alpha and p38beta, p38gamma is insensitive to pyridinylimidazoles. It displays an antagonizing function compared to p38alpha. p38gamma inhibits, while p38alpha stimulates, c-Jun phosphorylation and AP-1 mediated transcription. p38gamma also plays a role in the signaling between Ras and the estrogen receptor and has been implicated to increase cell invasion and breast cancer progression. In Xenopus, p38gamma is critical in the meiotic maturation of oocytes. p38 kinases are MAPKs, serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38gamma 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 1231802378   1 MDLWSAGCVFYEIASLQPLFPGVNELDQISKIHDVIGTPAQKILTKFKQSRAMNF--DFPFKKGSGIPLLTTNLSPQCLS 78
Cdd:cd07880   197 VDIWSVGCIMAEMLTGKPLFKGHDHLDQLMEIMKVTGTPSKEFVQKLQSEDAKNYvkKLPRFRKKDFRSLLPNANPLAVN 276

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1231802378  79 LLHAMVAYDPDERIAAHQALQHPYFQEQRKTE 110
Cdd:cd07880   277 VLEKMLVLDAESRITAAEALAHPYFEEFHDPE 308

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 1231802378   2 DLWSAGCVFYEIASLQPLFPGVNELDQISKIHDVIGTPAQkilTKFKQSRAMNFDFPFKKGSGIPL--LTTNLSPQCLSL 79
Cdd:cd07841   185 DMWSVGCIFAELLLRVPFLPGDSDIDQLGKIFEALGTPTE---ENWPGVTSLPDYVEFKPFPPTPLkqIFPAASDDALDL 261

                          90       100
                  ....*....|....*....|....*..
gi 1231802378  80 LHAMVAYDPDERIAAHQALQHPYFQEQ 106
Cdd:cd07841   262 LQRLLTLNPNKRITARQALEHPYFSND 288

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 1231802378   1 MDLWSAGCVFYEIASLQPLFPGVNELDQISKIHDVIGTPAQKILTKFKQSRAMNfDFPFKKGSGIPLLTTNLSPQCLSLL 80
Cdd:cd07837   192 VDMWSVGCIFAEMSRKQPLFPGDSELQQLLHIFRLLGTPNEEVWPGVSKLRDWH-EYPQWKPQDLSRAVPDLEPEGVDLL 270

                          90       100
                  ....*....|....*....|...
gi 1231802378  81 HAMVAYDPDERIAAHQALQHPYF 103
Cdd:cd07837   271 TKMLAYDPAKRISAKAALQHPYF 293

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK5 is unusual in that it is regulated by non-cyclin proteins, p35 and p39. It is highly expressed in the nervous system and is critical in normal neural development and function. It plays a role in neuronal migration and differentiation, and is also important in synaptic plasticity and learning. CDK5 also participates in protecting against cell death and promoting angiogenesis. Impaired CDK5 activity is implicated in Alzheimer's disease, amyotrophic lateral sclerosis, Parkinson's disease, Huntington's disease and acute neuronal injury. 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 CDK5 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 1231802378   1 MDLWSAGCVFYEIASL-QPLFPGVNELDQISKIHDVIGTPAQKILTKFkqSRAMNF-DFPFKKGSGIPL-LTTNLSPQCL 77
Cdd:cd07839   181 IDMWSAGCIFAELANAgRPLFPGNDVDDQLKRIFRLLGTPTEESWPGV--SKLPDYkPYPMYPATTSLVnVVPKLNSTGR 258

                          90       100
                  ....*....|....*....|....*.
gi 1231802378  78 SLLHAMVAYDPDERIAAHQALQHPYF 103
Cdd:cd07839   259 DLLQNLLVCNPVQRISAEEALQHPYF 284

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase 15 and similar MAPKs; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Human MAPK15 is also called Extracellular signal Regulated Kinase 8 (ERK8) while the rat protein is called ERK7. ERK7 and ERK8 display both similar and different biochemical properties. They autophosphorylate and activate themselves and do not require upstream activating kinases. ERK7 is constitutively active and is not affected by extracellular stimuli whereas ERK8 shows low basal activity and is activated by DNA-damaging agents. ERK7 and ERK8 also have different substrate profiles. Genome analysis shows that they are orthologs with similar gene structures. ERK7 and ERK 8 may be involved in the signaling of some nuclear receptor transcription factors. ERK7 regulates hormone-dependent degradation of estrogen receptor alpha while ERK8 down-regulates the transcriptional co-activation androgen and glucocorticoid receptors. MAPKs are important mediators of cellular responses to extracellular signals. The MAPK15 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 1231802378   1 MDLWSAGCVFYEIASLQPLFPGVNELDQISKIHDVIGTPAQKILTKFKQSRAMN--FDFPFKKGSGIPLLTTNLSPQCLS 78
Cdd:cd07852   194 VDMWSVGCILGEMLLGKPLFPGTSTLNQLEKIIEVIGRPSAEDIESIQSPFAATmlESLPPSRPKSLDELFPKASPDALD 273

                          90       100
                  ....*....|....*....|....*..
gi 1231802378  79 LLHAMVAYDPDERIAAHQALQHPYFQE 105
Cdd:cd07852   274 LLKKLLVFNPNKRLTAEEALRHPYVAQ 300

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 1231802378   1 MDLWSAGCVFYEIASLQPLFPGVNELDQISKIHDVIGTPAQKI------LTKFKQSramnfdFPFKKGSGIPLLTTNLSP 74
Cdd:cd07861   183 VDIWSIGTIFAEMATKKPLFHGDSEIDQLFRIFRILGTPTEDIwpgvtsLPDYKNT------FPKWKKGSLRTAVKNLDE 256

                          90       100
                  ....*....|....*....|....*....
gi 1231802378  75 QCLSLLHAMVAYDPDERIAAHQALQHPYF 103
Cdd:cd07861   257 DGLDLLEKMLIYDPAKRISAKKALVHPYF 285

Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase 2 and 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK2 is regulated by cyclin E or cyclin A. Upon activation by cyclin E, it phosphorylates the retinoblastoma (pRb) protein which activates E2F mediated transcription and allows cells to move into S phase. The CDK2/cyclin A complex plays a role in regulating DNA replication. CDK2, together with CDK4, also regulates embryonic cell proliferation. Despite these important roles, mice deleted for the cdk2 gene are viable and normal except for being sterile. This may be due to compensation provided by CDK1 (also called Cdc2), which can also bind cyclin E and drive the G1 to S phase transition. CDK3 is regulated by cyclin C and it phosphorylates pRB specifically during the G0/G1 transition. This phosphorylation is required for cells to exit G0 efficiently and enter the G1 phase. 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 CDK2/3 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 1231802378   1 MDLWSAGCVFYEIASLQPLFPGVNELDQISKIHDVIGTPAQKILTKFKQSRAMNFDFPFKKGSGIPLLTTNLSPQCLSLL 80
Cdd:cd07860   182 VDIWSLGCIFAEMVTRRALFPGDSEIDQLFRIFRTLGTPDEVVWPGVTSMPDYKPSFPKWARQDFSKVVPPLDEDGRDLL 261

                          90       100
                  ....*....|....*....|...
gi 1231802378  81 HAMVAYDPDERIAAHQALQHPYF 103
Cdd:cd07860   262 SQMLHYDPNKRISAKAALAHPFF 284

Catalytic domain of the Serine/Threonine Kinases, Plant TDY 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 TDY subtype and is composed of Group D plant MAPKs including Arabidopsis thaliana MPK18 (AtMPK18), Oryza sativa Blast- and Wound-induced MAPK1 (OsBWMK1), OsWJUMK1 (Wound- and JA-Uninducible MAPK1), Zea mays MPK6, and the Medicago sativa TDY1 gene product. OsBWMK1 enhances resistance to pathogenic infections. It mediates stress-activated defense responses by activating a transcription factor that affects the expression of stress-related genes. AtMPK18 is involved in microtubule-related functions. 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 while Oryza sativa contains at least 17 MAPKs. Arabidopsis thaliana contains more TEY-type MAPKs than TDY-type, whereas the reverse is true for Oryza sativa. The TDY 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 1231802378   1 MDLWSAGCVFYEIASLQPLFPGVNELDQISKIHDVIGTPAQKILTKFKQSRAMNFDFPFKKGSGIPLLTT--NLSPQCLS 78
Cdd:cd07859   189 IDIWSIGCIFAEVLTGKPLFPGKNVVHQLDLITDLLGTPSPETISRVRNEKARRYLSSMRKKQPVPFSQKfpNADPLALR 268

                          90       100       110
                  ....*....|....*....|....*....|...
gi 1231802378  79 LLHAMVAYDPDERIAAHQALQHPYFQEQRKTEK 111
Cdd:cd07859   269 LLERLLAFDPKDRPTAEEALADPYFKGLAKVER 301

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 1231802378   1 MDLWSAGCVFYEIASLQPLFPGV-NELDQISKIHDVIGTPAQKI---LTKFKQSRAMNFDF--PFKKGSGIPLLttNLSP 74
Cdd:cd07844   180 LDMWGVGCIFYEMATGRPLFPGStDVEDQLHKIFRVLGTPTEETwpgVSSNPEFKPYSFPFypPRPLINHAPRL--DRIP 257

                          90       100
                  ....*....|....*....|....*....
gi 1231802378  75 QCLSLLHAMVAYDPDERIAAHQALQHPYF 103
Cdd:cd07844   258 HGEELALKFLQYEPKKRISAAEAMKHPYF 286

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 1231802378   1 MDLWSAGCVFYEIASLQPLFPGVNELDQISKIHDVIGTPAQKILTKFKQSRAMNF--DFPFKKGSGIPLLTTNLSPQCLS 78
Cdd:cd07858   190 IDVWSVGCIFAELLGRKPLFPGKDYVHQLKLITELLGSPSEEDLGFIRNEKARRYirSLPYTPRQSFARLFPHANPLAID 269

                          90       100
                  ....*....|....*....|....*.
gi 1231802378  79 LLHAMVAYDPDERIAAHQALQHPYFQ 104
Cdd:cd07858   270 LLEKMLVFDPSKRITVEEALAHPYLA 295

Catalytic domain of the Serine/Threonine Kinase, p38beta Mitogen-Activated Protein Kinase (also called MAPK11); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38beta/MAPK11 is widely expressed in tissues and shows more similarity with p38alpha than with the other isoforms. Both are sensitive to pyridinylimidazoles and share some common substrates such as MAPK activated protein kinase 2 (MK2) and the transcription factors ATF2, c-Fos and, ELK-1. p38beta is involved in regulating the activation of the cyclooxygenase-2 promoter and the expression of TGFbeta-induced alpha-smooth muscle cell actin. p38 kinases are mitogen-activated protein kinases (MAPKs), serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38beta 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 1231802378   1 MDLWSAGCVFYEIASLQPLFPGVNELDQISKIHDVIGTPAQKILTKFKQSRAMNF--DFPFKKGSGIPLLTTNLSPQCLS 78
Cdd:cd07878   197 VDIWSVGCIMAELLKGKALFPGNDYIDQLKRIMEVVGTPSPEVLKKISSEHARKYiqSLPHMPQQDLKKIFRGANPLAID 276

                          90       100
                  ....*....|....*....|....*..
gi 1231802378  79 LLHAMVAYDPDERIAAHQALQHPYFQE 105
Cdd:cd07878   277 LLEKMLVLDSDKRISASEALAHPYFSQ 303

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 1231802378   2 DLWSAGCVFYEIASLQPLFPGVNELDQISKIHDVIGTPAQkilTKFKQSRAM-NFDFPFKKGSGIPLLTTN---LSPQCL 77
Cdd:cd07866   209 DIWGIGCVFAEMFTRRPILQGKSDIDQLHLIFKLCGTPTE---ETWPGWRSLpGCEGVHSFTNYPRTLEERfgkLGPEGL 285

                          90       100
                  ....*....|....*....|....*.
gi 1231802378  78 SLLHAMVAYDPDERIAAHQALQHPYF 103
Cdd:cd07866   286 DLLSKLLSLDPYKRLTASDALEHPYF 311

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNKs are mitogen-activated protein kinases (MAPKs) that are involved in many stress-activated responses including those during inflammation, neurodegeneration, apoptosis, and persistent pain sensitization, among others. They are also essential regulators of physiological and pathological processes and are involved in the pathogenesis of several diseases such as diabetes, atherosclerosis, stroke, Parkinson's and Alzheimer's. Vetebrates harbor three different JNK genes (Jnk1, Jnk2, and Jnk3) that are alternatively spliced to produce at least 10 isoforms. JNKs are specifically activated by the MAPK kinases MKK4 and MKK7, which are in turn activated by upstream MAPK kinase kinases as a result of different stimuli including stresses such as ultraviolet (UV) irradiation, hyperosmolarity, heat shock, or cytokines. JNKs activate a large number of different substrates based on specific stimulus, cell type, and cellular condition, and may be implicated in seemingly contradictory functions. The JNK 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 1231802378   2 DLWSAGCVFYEIASLQPLFPGVNELDQISKIHDVIGTPAQKILTKFKQSRAMNF-DFPFKKGSGIPLL------------ 68
Cdd:cd07850   183 DIWSVGCIMGEMIRGTVLFPGTDHIDQWNKIIEQLGTPSDEFMSRLQPTVRNYVeNRPKYAGYSFEELfpdvlfppdsee 262

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 1231802378  69 -TTNLSPQCLSLLHAMVAYDPDERIAAHQALQHPY 102
Cdd:cd07850   263 hNKLKASQARDLLSKMLVIDPEKRISVDDALQHPY 297

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1231802378    2 DLWSAGCVFYEIASLQPLFPGVNELDQISKIhdvIGTPaqkiltkfkqsramNFDFPFKKgsgiplltTNLSPQCLSLLH 81
Cdd:smart00220 178 DIWSLGVILYELLTGKPPFPGDDQLLELFKK---IGKP--------------KPPFPPPE--------WDISPEAKDLIR 232

                           90       100
                   ....*....|....*....|..
gi 1231802378   82 AMVAYDPDERIAAHQALQHPYF 103
Cdd:smart00220 233 KLLVKDPEKRLTAEEALQHPFF 254

Catalytic domain of the Serine/Threonine Kinase, PFTAIRE-2 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PFTAIRE-2 is also referred to as ALS2CR7 (amyotrophic lateral sclerosis 2 (juvenile) chromosome region candidate 7). It may be associated with amyotrophic lateral sclerosis 2 (ALS2), an autosomal recessive form of juvenile ALS. The function of PFTAIRE-2 is not yet known. It shares 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 PFTAIRE-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 1231802378   1 MDLWSAGCVFYEIASLQPLFPGV-NELDQISKIHDVIGTPAQKILTKFkqSRAMNFD---FPFKKGSGIPLLTTNLS--P 74
Cdd:cd07870   180 LDIWGAGCIFIEMLQGQPAFPGVsDVFEQLEKIWTVLGVPTEDTWPGV--SKLPNYKpewFLPCKPQQLRVVWKRLSrpP 257

                          90       100
                  ....*....|....*....|....*....
gi 1231802378  75 QCLSLLHAMVAYDPDERIAAHQALQHPYF 103
Cdd:cd07870   258 KAEDLASQMLMMFPKDRISAQDALLHPYF 286

Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinases 4 (also called ERK4) and 6 (also called ERK3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK4 (also called ERK4 or p63MAPK) and MAPK6 (also called ERK3 or p97MAPK) are atypical MAPKs that are not regulated by MAPK kinases. MAPK6 is expressed ubiquitously with highest amounts in brain and skeletal muscle. It may be involved in the control of cell differentiation by negatively regulating cell cycle progression in certain conditions. It may also play a role in glucose-induced insulin secretion. MAPK6 and MAPK4 cooperate to regulate the activity of MAPK-activated protein kinase 5 (MK5), leading to its relocation to the cytoplasm and exclusion from the nucleus. The MAPK6/MK5 and MAPK4/MK5 pathways may play critical roles in embryonic and post-natal development. MAPKs are important mediators of cellular responses to extracellular signals. The MAPK4/6 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 1231802378   1 MDLWSAGCVFYEIASLQPLFPGVNELDQISKIHDVIG----TPAQKILTKFKQSRAMNFDFPFKkgsgiPL--LTTNLSP 74
Cdd:cd07854   200 IDMWAAGCIFAEMLTGKPLFAGAHELEQMQLILESVPvvreEDRNELLNVIPSFVRNDGGEPRR-----PLrdLLPGVNP 274

                          90       100       110
                  ....*....|....*....|....*....|
gi 1231802378  75 QCLSLLHAMVAYDPDERIAAHQALQHPYFQ 104
Cdd:cd07854   275 EALDFLEQILTFNPMDRLTAEEALMHPYMS 304

Protein kinase domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1231802378   2 DLWSAGCVFYEIASLQPLFPGVNELDQISKIhdvigtpaqkiltkFKQSRAMNFDFPfkkgsgipllttNLSPQCLSLLH 81
Cdd:pfam00069 142 DVWSLGCILYELLTGKPPFPGINGNEIYELI--------------IDQPYAFPELPS------------NLSEEAKDLLK 195

                          90       100
                  ....*....|....*....|..
gi 1231802378  82 AMVAYDPDERIAAHQALQHPYF 103
Cdd:pfam00069 196 KLLKKDPSKRLTATQALQHPWF 217

Catalytic domain of the protein kinase, Dual-specificity tYrosine-phosphorylated and -Regulated Kinase 1; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (S/T) as well as tyrosine residues on protein substrates. Mammals contain two types of DYRK1 proteins, DYRK1A and DYRK1B. DYRK1A was previously called minibrain kinase homolog (MNBH) or dual-specificity YAK1-related kinase. It phosphorylates various substrates and is involved in many cellular events. It phosphorylates and inhibits the transcription factors, nuclear factor of activated T cells (NFAT) and forkhead in rhabdomyosarcoma (FKHR). It regulates neuronal differentiation by targetting CREB (cAMP response element-binding protein). It also targets many endocytic proteins including dynamin and amphiphysin and may play a role in the endocytic pathway. The gene encoding DYRK1A is located in the DSCR (Down syndrome critical region) of human chromosome 21 and DYRK1A has been implicated in the pathogenesis of DS. DYRK1B, also called minibrain-related kinase (MIRK), is highly expressed in muscle and plays a critical role in muscle differentiation by regulating transcription, cell motility, survival, and cell cycle progression. It is overexpressed in many solid tumors where it acts as a tumor survival factor. DYRKs autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. The DYRK1 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 1231802378   2 DLWSAGCVFYEIASLQPLFPGVNELDQISKIHDVIGTPAQKILTkfKQSRAMNFDFPFKKGSGIPLLT----TNLSP--- 74
Cdd:cd14226   199 DMWSLGCILVEMHTGEPLFSGANEVDQMNKIVEVLGMPPVHMLD--QAPKARKFFEKLPDGTYYLKKTkdgkKYKPPgsr 276

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1231802378  75 -----------------------------QCLSLLHAMVAYDPDERIAAHQALQHPYFQ 104
Cdd:cd14226   277 klheilgvetggpggrragepghtvedylKFKDLILRMLDYDPKTRITPAEALQHSFFK 335

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 1231802378   1 MDLWSAGCVFYEIASLQPLFPGVNELDQISKIHDVIGTPAQKILTKFKQ-SRAMNFDFPFKKG--SGIPLLTTNLSPQCL 77
Cdd:cd07853   186 VDIWSVGCIFAELLGRRILFQAQSPIQQLDLITDLLGTPSLEAMRSACEgARAHILRGPHKPPslPVLYTLSSQATHEAV 265

                          90       100       110
                  ....*....|....*....|....*....|
gi 1231802378  78 SLLHAMVAYDPDERIAAHQALQHPYFQEQR 107
Cdd:cd07853   266 HLLCRMLVFDPDKRISAADALAHPYLDEGR 295