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 1958783850   1 MDLWSAGCVFYEIASLQPLFPGVNELDQISKIHDVIGTPCQKTLTKFKQSRAMSFDFPFKKGSGIPLLTTNLTPQCLSLL 80
Cdd:cd07831   180 MDIWAVGCVFFEILSLFPLFPGTNELDQIAKIHDVLGTPDAEVLKKFRKSRHMNYNFPSKKGTGLRKLLPNASAEGLDLL 259

                          90       100
                  ....*....|....*....|...
gi 1958783850  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 1958783850   1 MDLWSAGCVFYEIASLQPLFPGVNELDQISKIHDVIGTPCQKTLTKFKQSRAMSFDFPFKKGSGIPLLTTNLTPQCLSLL 80
Cdd:cd07831   180 MDIWAVGCVFFEILSLFPLFPGTNELDQIAKIHDVLGTPDAEVLKKFRKSRHMNYNFPSKKGTGLRKLLPNASAEGLDLL 259

                          90       100
                  ....*....|....*....|...
gi 1958783850  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 1958783850    2 DLWSAGCVFYEIASLQPLFPGVNELDQISKIhdvIGTPcqktltkfkqsramSFDFPFKKgsgiplltTNLTPQCLSLLH 81
Cdd:smart00220 178 DIWSLGVILYELLTGKPPFPGDDQLLELFKK---IGKP--------------KPPFPPPE--------WDISPEAKDLIR 232

                           90       100
                   ....*....|....*....|..
gi 1958783850   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 1958783850   1 MDLWSAGCVFYEIASLQPLFPGVNELDQISKIHDVIGTPCQKTLTKFKQSRAMSFDFPFKKGSGIPLLTTNLTPQCLSLL 80
Cdd:cd07831   180 MDIWAVGCVFFEILSLFPLFPGTNELDQIAKIHDVLGTPDAEVLKKFRKSRHMNYNFPSKKGTGLRKLLPNASAEGLDLL 259

                          90       100
                  ....*....|....*....|...
gi 1958783850  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 1958783850   2 DLWSAGCVFYEIASLQPLFPGVNELDQISKIHDVIGTPCQKT---LTKFKQsramsFDFPFKKGSGIPLLTT--NLTPQC 76
Cdd:cd07829   181 DIWSVGCIFAELITGKPLFPGDSEIDQLFKIFQILGTPTEESwpgVTKLPD-----YKPTFPKWPKNDLEKVlpRLDPEG 255

                          90       100
                  ....*....|....*....|....*..
gi 1958783850  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 1958783850   1 MDLWSAGCVFYEIASLQPLFPGVNELDQISKIHDVIGtpcqktltkfkqsramsfdfpfkkgsgipllttnlTPQCLSLL 80
Cdd:cd05118   182 IDIWSLGCILAELLTGRPLFPGDSEVDQLAKIVRLLG-----------------------------------TPEALDLL 226

                          90       100
                  ....*....|....*....|...
gi 1958783850  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 1958783850   2 DLWSAGCVFYEIASLQPLFPGVNELDQISKIHDVIGTPCQ------KTLTKFKQSramsfdFPFKKGSGIPLLTTNLTPQ 75
Cdd:cd07835   182 DIWSVGCIFAEMVTRRPLFPGDSEIDQLFRIFRTLGTPDEdvwpgvTSLPDYKPT------FPKWARQDLSKVVPSLDED 255

                          90       100
                  ....*....|....*....|....*...
gi 1958783850  76 CLSLLHAMVAYDPDERIAAHQALQHPYF 103
Cdd:cd07835   256 GLDLLSQMLVYDPAKRISAKAALQHPYF 283

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 1958783850   1 MDLWSAGCVFYEIASLQPLFPGVNELDQISKIHDVIGTPCQKTLTKFKQSRAMSFDFPFKKGSGIPLLTTNLTPQCLSLL 80
Cdd:cd07836   182 IDIWSVGCIMAEMITGRPLFPGTNNEDQLLKIFRIMGTPTESTWPGISQLPEYKPTFPRYPPQDLQQLFPHADPLGIDLL 261

                          90       100
                  ....*....|....*....|...
gi 1958783850  81 HAMVAYDPDERIAAHQALQHPYF 103
Cdd:cd07836   262 HRLLQLNPELRISAHDALQHPWF 284

Catalytic domain of Cyclin-Dependent protein Kinase 9-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 CDK9 and CDK12 from higher eukaryotes, yeast BUR1, C-type plant CDKs (CdkC), and similar proteins. CDK9, BUR1, and CdkC are functionally equivalent. They act as a kinase for the C-terminal domain of RNA polymerase II and participate in regulating mutliple steps of gene expression including transcription elongation and RNA processing. CDK9 and CdkC associate with T-type cyclins while BUR1 associates with the cyclin BUR2. CDK12 is a unique CDK that contains an arginine/serine-rich (RS) domain, which is predominantly found in splicing factors. CDK12 interacts with cyclins L1 and L2, and participates in regulating transcription and alternative splicing. 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 CDK9-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 1958783850   2 DLWSAGCVFYEIASLQPLFPGVNELDQISKIHDVIGTPCQKT---LTKFKQSRAMSFDFPFKKgsgipLLTTN----LTP 74
Cdd:cd07840   188 DMWSVGCILAELFTGKPIFQGKTELEQLEKIFELCGSPTEENwpgVSDLPWFENLKPKKPYKR-----RLREVfknvIDP 262

                          90       100
                  ....*....|....*....|....*....
gi 1958783850  75 QCLSLLHAMVAYDPDERIAAHQALQHPYF 103
Cdd:cd07840   263 SALDLLDKLLTLDPKKRISADQALQHEYF 291

Catalytic domain of the Serine/Threonine Kinase, Fungal Mitogen-Activated Protein Kinase MPK1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the MAPKs MPK1 from Saccharomyces cerevisiae, Pmk1 from Schizosaccharomyces pombe, and similar proteins. MPK1 (also called Slt2) and Pmk1 (also called Spm1) are stress-activated MAPKs that regulate the cell wall integrity pathway, and are therefore important in the maintainance of cell shape, cell wall construction, morphogenesis, and ion homeostasis. MPK1 is activated in response to cell wall stress including heat stimulation, osmotic shock, UV irradiation, and any agents that interfere with cell wall biogenesis such as chitin antagonists, caffeine, or zymolase. MPK1 is regulated by the MAP2Ks Mkk1/2, which are regulated by the MAP3K Bck1. Pmk1 is also activated by multiple stresses including elevated temperatures, hyper- or hypotonic stress, glucose deprivation, exposure to cell-wall damaging compounds, and oxidative stress. It is regulated by the MAP2K Pek1, which is regulated by the MAP3K Mkh1. MAPKs are important mediators of cellular responses to extracellular signals. The MPK1 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 1958783850   1 MDLWSAGCVFYEIASLQPLFPGVNELDQISKIHDVIGTPCQKTLTKFKQSRAMSF--DFPFKKGSGIPLLTTNLTPQCLS 78
Cdd:cd07857   191 IDVWSVGCILAELLGRKPVFKGKDYVDQLNQILQVLGTPDEETLSRIGSPKAQNYirSLPNIPKKPFESIFPNANPLALD 270

                          90       100
                  ....*....|....*....|....*..
gi 1958783850  79 LLHAMVAYDPDERIAAHQALQHPYFQV 105
Cdd:cd07857   271 LLEKLLAFDPTKRISVEEALEHPYLAI 297

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958783850   2 DLWSAGCVFYEIASLQPLFPGVNELDQISKIHDVIGTPCQKTLTKFKQSRAMSF--DFPFKKGSGIPLLTTNLTPQCLSL 79
Cdd:cd07855   196 DMWSVGCIFAEMLGRRQLFPGKNYVHQLQLILTVLGTPSQAVINAIGADRVRRYiqNLPNKQPVPWETLYPKADQQALDL 275

                          90       100
                  ....*....|....*....|....*
gi 1958783850  80 LHAMVAYDPDERIAAHQALQHPYFQ 104
Cdd:cd07855   276 LSQMLRFDPSERITVAEALQHPFLA 300

Catalytic domain of the Serine/Threonine Kinase, p38 Mitogen-Activated Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38 kinases are mitogen-activated protein kinases (MAPKs), serving as important mediators of cellular responses to extracellular signals. They function in the regulation of the cell cycle, cell development, cell differentiation, senescence, tumorigenesis, apoptosis, pain development and pain progression, and immune responses. p38 kinases 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. p38 substrates include other protein kinases and factors that regulate transcription, nuclear export, mRNA stability and translation. p38 kinases are drug targets for the inflammatory diseases psoriasis, rheumatoid arthritis, and chronic pulmonary disease. Vertebrates contain four isoforms of p38, named alpha, beta, gamma, and delta, which show varying substrate specificity and expression patterns. p38alpha and p38beta are ubiquitously expressed, p38gamma is predominantly found in skeletal muscle, and p38delta is found in the heart, lung, testis, pancreas, and small intestine. The p38 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 1958783850   2 DLWSAGCVFYEIASLQPLFPGVNELDQISKIHDVIGTPCQKTLTKFKQSRAMSF--DFPFKKGSGIPLLTTNLTPQCLSL 79
Cdd:cd07851   198 DIWSVGCIMAELLTGKTLFPGSDHIDQLKRIMNLVGTPDEELLKKISSESARNYiqSLPQMPKKDFKEVFSGANPLAIDL 277

                          90       100
                  ....*....|....*....|....
gi 1958783850  80 LHAMVAYDPDERIAAHQALQHPYF 103
Cdd:cd07851   278 LEKMLVLDPDKRITAAEALAHPYL 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 1958783850   1 MDLWSAGCVFYEIASLQPLFPGV-NELDQISKIHDVIGTPCQKT---LTKFKQSRAMSFDF--PFKKGSGIPLLttNLTP 74
Cdd:cd07844   180 LDMWGVGCIFYEMATGRPLFPGStDVEDQLHKIFRVLGTPTEETwpgVSSNPEFKPYSFPFypPRPLINHAPRL--DRIP 257

                          90       100
                  ....*....|....*....|....*....
gi 1958783850  75 QCLSLLHAMVAYDPDERIAAHQALQHPYF 103
Cdd:cd07844   258 HGEELALKFLQYEPKKRISAAEAMKHPYF 286

cyclin-dependent kinase A; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958783850   1 MDLWSAGCVFYEIASLQPLFPGVNELDQISKIHDVIGTPCQKT------LTKFKQSramsfdFPFKKGSGIPLLTTNLTP 74
Cdd:PLN00009  185 VDIWSVGCIFAEMVNQKPLFPGDSEIDELFKIFRILGTPNEETwpgvtsLPDYKSA------FPKWPPKDLATVVPTLEP 258

                          90       100       110
                  ....*....|....*....|....*....|
gi 1958783850  75 QCLSLLHAMVAYDPDERIAAHQALQHPYFQ 104
Cdd:PLN00009  259 AGVDLLSKMLRLDPSKRITARAALEHEYFK 288

Catalytic domain of Cyclin-Dependent protein Kinase 8-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 CDK8, CDC2L6, and similar proteins. CDK8 functions 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-dependent transcription. CDC2L6 also associates with Mediator in complexes lacking CDK8. In VP16-dependent transcriptional activation, CDK8 and CDC2L6 exerts opposing effects by positive and negative regulation, respectively, in similar conditions. 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-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 1958783850   2 DLWSAGCVFYEIASLQPLFPGVNE---------LDQISKIHDVIGTPCQK---TLTKFKQSRAMSFDF---PFKKGSGIP 66
Cdd:cd07842   198 DIWAIGCIFAELLTLEPIFKGREAkikksnpfqRDQLERIFEVLGTPTEKdwpDIKKMPEYDTLKSDTkasTYPNSLLAK 277

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1958783850  67 LLTT--NLTPQCLSLLHAMVAYDPDERIAAHQALQHPYF 103
Cdd:cd07842   278 WMHKhkKPDSQGFDLLRKLLEYDPTKRITAEEALEHPYF 316

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 1958783850   1 MDLWSAGCVFYEIASLQPLFPGVNELDQISKIHDVIGTPCQKTLTKFKQSRAMSF--DFPFKKGSGIPLLTTNLTPQCLS 78
Cdd:cd07880   197 VDIWSVGCIMAEMLTGKPLFKGHDHLDQLMEIMKVTGTPSKEFVQKLQSEDAKNYvkKLPRFRKKDFRSLLPNANPLAVN 276

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1958783850  79 LLHAMVAYDPDERIAAHQALQHPYFQVQRAAETQTLAK 116
Cdd:cd07880   277 VLEKMLVLDAESRITAAEALAHPYFEEFHDPEDETEAP 314

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 1958783850   1 MDLWSAGCVFYEIASLQPLFPGVNELDQISKIHDVIGTPCQKTLTKFKQSRAMSFDFPFKKGSGIPLLTTNLTPQCLSLL 80
Cdd:cd07860   182 VDIWSLGCIFAEMVTRRALFPGDSEIDQLFRIFRTLGTPDEVVWPGVTSMPDYKPSFPKWARQDFSKVVPPLDEDGRDLL 261

                          90       100
                  ....*....|....*....|...
gi 1958783850  81 HAMVAYDPDERIAAHQALQHPYF 103
Cdd:cd07860   262 SQMLHYDPNKRISAKAALAHPFF 284

Catalytic domain of the protein kinase, Dual-specificity tYrosine-phosphorylated and -Regulated Kinase; Protein Kinases (PKs), Dual-specificity tYrosine-phosphorylated and -Regulated Kinase (DYRK) subfamily, catalytic (c) domain. 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. The DYRK subfamily is part of a larger superfamily that includes the catalytic domains of other protein S/T PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K). DYRKs autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. They play important roles in cell proliferation, differentiation, survival, and development. Vertebrates contain multiple DYRKs (DYRK1-4) and mammals contain two types of DYRK1 proteins, DYRK1A and DYRK1B. DYRK1A is involved in neuronal differentiation and is implicated in the pathogenesis of DS (Down syndrome). DYRK1B 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. DYRK2 promotes apoptosis in response to DNA damage by phosphorylating the tumor suppressor p53, while DYRK3 promotes cell survival by phosphorylating SIRT1 and promoting p53 deacetylation. DYRK4 is a testis-specific kinase that may function during spermiogenesis.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958783850   1 MDLWSAGCVFYEIASLQPLFPGVNELDQISKIHDVIGTPCQKTLTKFKqSRAMSFDfpfkkGSGIPLLTTNLT------- 73
Cdd:cd14210   196 IDMWSLGCILAELYTGYPLFPGENEEEQLACIMEVLGVPPKSLIDKAS-RRKKFFD-----SNGKPRPTTNSKgkkrrpg 269

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1958783850  74 ------------PQCLSLLHAMVAYDPDERIAAHQALQHPYF 103
Cdd:cd14210   270 skslaqvlkcddPSFLDFLKKCLRWDPSERMTPEEALQHPWI 311

Catalytic domain of the Serine/Threonine Kinases, Fungal Mitogen-Activated Protein Kinases Sty1 and Hog1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the MAPKs Sty1 from Schizosaccharomyces pombe, Hog1 from Saccharomyces cerevisiae, and similar proteins. Sty1 and Hog1 are stress-activated MAPKs that partipate in transcriptional regulation in response to stress. Sty1 is activated in response to oxidative stress, osmotic stress, and UV radiation. It is regulated by the MAP2K Wis1, which is activated by the MAP3Ks Wis4 and Win1, which receive signals of the stress condition from membrane-spanning histidine kinases Mak1-3. Activated Sty1 stabilizes the Atf1 transcription factor and induces transcription of Atf1-dependent genes of the core environmetal stress response. Hog1 is the key element in the high osmolarity glycerol (HOG) pathway and is activated upon hyperosmotic stress. Activated Hog1 accumulates in the nucleus and regulates stress-induced transcription. The HOG pathway is mediated by two transmembrane osmosensors, Sln1 and Sho1. MAPKs are important mediators of cellular responses to extracellular signals. The Sty1/Hog1 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 1958783850   1 MDLWSAGCVFYEIASLQPLFPGVNELDQISKIHDVIGTPCQKTLTKFKQSRAMSFDFPFKKGSGIPL--LTTNLTPQCLS 78
Cdd:cd07856   187 VDIWSAGCIFAEMLEGKPLFPGKDHVNQFSIITELLGTPPDDVINTICSENTLRFVQSLPKRERVPFseKFKNADPDAID 266

                          90       100
                  ....*....|....*....|....
gi 1958783850  79 LLHAMVAYDPDERIAAHQALQHPY 102
Cdd:cd07856   267 LLEKMLVFDPKKRISAAEALAHPY 290

Catalytic domain of Dual-specificity tYrosine-phosphorylated and -Regulated Kinase-like protein kinases; 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. This subfamily is composed of the dual-specificity DYRKs and YAK1, as well as the S/T kinases (STKs), HIPKs. DYRKs and YAK1 autophosphorylate themselves on tyrosine residues and phosphorylate their substrates exclusively on S/T residues. Proteins in this subfamily play important roles in cell proliferation, differentiation, survival, growth, and development. The DYRK-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 1958783850   2 DLWSAGCVFYEIASLQPLFPGVNELDQISKIHDVIGTPCQKTLTKFKQSRAMSFDFpfkkgsgipllttnltpqclslLH 81
Cdd:cd14133   183 DMWSLGCILAELYTGEPLFPGASEVDQLARIIGTIGIPPAHMLDQGKADDELFVDF----------------------LK 240

                          90       100
                  ....*....|....*....|..
gi 1958783850  82 AMVAYDPDERIAAHQALQHPYF 103
Cdd:cd14133   241 KLLEIDPKERPTASQALSHPWL 262

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK4 partners with all three D-type cyclins (D1, D2, and D3) and is also regulated by INK4 inhibitors. It is active towards the retinoblastoma (pRb) protein and plays a role in regulating the early G1 phase of the cell cycle. It is expressed ubiquitously and is localized in the nucleus. CDK4 also shows kinase activity towards Smad3, a signal transducer of TGF-beta signaling which modulates transcription and plays a role in cell proliferation and apoptosis. CDK4 is inhibited by the p21 inhibitor and is specifically mutated in human melanoma. 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 CDK4 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 1958783850   1 MDLWSAGCVFYEIASLQPLFPGVNELDQISKIHDVIGTPCQKTL-TKFKQSRAmsfDFPFKKGSGIPLLTTNLTPQCLSL 79
Cdd:cd07863   188 VDMWSVGCIFAEMFRRKPLFCGNSEADQLGKIFDLIGLPPEDDWpRDVTLPRG---AFSPRGPRPVQSVVPEIEESGAQL 264

                          90       100
                  ....*....|....*....|....
gi 1958783850  80 LHAMVAYDPDERIAAHQALQHPYF 103
Cdd:cd07863   265 LLEMLTFNPHKRISAFRALQHPFF 288

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958783850   1 MDLWSAGCVFyeiASL----QPLFPGVNELDQISKIHDVIGT-PCQKTLTKFKQSRAMSFDFPFKKGSGIPLLT-TN--- 71
Cdd:cd14132   194 LDMWSLGCML---ASMifrkEPFFHGHDNYDQLVKIAKVLGTdDLYAYLDKYGIELPPRLNDILGRHSKKPWERfVNsen 270

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1958783850  72 ---LTPQCLSLLHAMVAYDPDERIAAHQALQHPYFQ 104
Cdd:cd14132   271 qhlVTPEALDLLDKLLRYDHQERITAKEAMQHPYFD 306

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 1958783850   2 DLWSAGCVFYEIASLQPLFPGVNELDQISKIHDVIGTPCQKTLTKFkqSRAMSFDFPFKKGSGIPLLTTN---LTPQCLS 78
Cdd:cd07866   209 DIWGIGCVFAEMFTRRPILQGKSDIDQLHLIFKLCGTPTEETWPGW--RSLPGCEGVHSFTNYPRTLEERfgkLGPEGLD 286

                          90       100
                  ....*....|....*....|....*
gi 1958783850  79 LLHAMVAYDPDERIAAHQALQHPYF 103
Cdd:cd07866   287 LLSKLLSLDPYKRLTASDALEHPYF 311

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

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958783850    2 DLWSAGCVFYEIASLQPLFPGVNELDQISKIhdvIGTPcqktltkfkqsramSFDFPFKKgsgiplltTNLTPQCLSLLH 81
Cdd:smart00220 178 DIWSLGVILYELLTGKPPFPGDDQLLELFKK---IGKP--------------KPPFPPPE--------WDISPEAKDLIR 232

                           90       100
                   ....*....|....*....|..
gi 1958783850   82 AMVAYDPDERIAAHQALQHPYF 103
Cdd:smart00220 233 KLLVKDPEKRLTAEEALQHPFF 254

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 10; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK10, also called PISSLRE, is essential for cell growth and proliferation, and acts through the G2/M phase of the cell cycle. CDK10 has also been identified as an important factor in endocrine therapy resistance in breast cancer. CDK10 silencing increases the transcription of c-RAF and the activation of the p42/p44 MAPK pathway, which leads to antiestrogen resistance. Patients who express low levels of CDK10 relapse early on tamoxifen. 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 CDK10 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 1958783850   2 DLWSAGCVFYEIASLQPLFPGVNELDQISKIHDVIGTPCQKTLTKF-KQSRAMSFDFPFKKGSGIPLLTTNLTPQCLSLL 80
Cdd:cd07845   191 DMWAVGCILAELLAHKPLLPGKSEIEQLDLIIQLLGTPNESIWPGFsDLPLVGKFTLPKQPYNNLKHKFPWLSEAGLRLL 270

                          90       100
                  ....*....|....*....|....
gi 1958783850  81 HAMVAYDPDERIAAHQALQHPYFQ 104
Cdd:cd07845   271 NFLLMYDPKKRATAEEALESSYFK 294

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 1958783850   1 MDLWSAGCVFYEIASLQPLFPGVNELDQISKIHDVIGT-------PCQKTLTKFKQSRAMSFDFPFKKgsgiplLTTNLT 73
Cdd:cd07854   200 IDMWAAGCIFAEMLTGKPLFAGAHELEQMQLILESVPVvreedrnELLNVIPSFVRNDGGEPRRPLRD------LLPGVN 273

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1958783850  74 PQCLSLLHAMVAYDPDERIAAHQALQHPYFQVQRAAETQTLAKH 117
Cdd:cd07854   274 PEALDFLEQILTFNPMDRLTAEEALMHPYMSCYSCPFDEPVSLH 317

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 1958783850   2 DLWSAGCVFYEIASLQPLFPGVNELDQISKIHDVIGTPCQKTLTKFKQSRamsfdfpFKKGSGIP---------LLTTNL 72
Cdd:cd07847   183 DVWAIGCVFAELLTGQPLWPGKSDVDQLYLIRKTLGDLIPRHQQIFSTNQ-------FFKGLSIPepetrepleSKFPNI 255

                          90       100       110
                  ....*....|....*....|....*....|.
gi 1958783850  73 TPQCLSLLHAMVAYDPDERIAAHQALQHPYF 103
Cdd:cd07847   256 SSPALSFLKGCLQMDPTERLSCEELLEHPYF 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 1958783850   1 MDLWSAGCVFYEIASLQPLFPGVNELDQISKIHDVIGTPCQKTLTKFKQ-SRAMSFDFPFKKG--SGIPLLTTNLTPQCL 77
Cdd:cd07853   186 VDIWSVGCIFAELLGRRILFQAQSPIQQLDLITDLLGTPSLEAMRSACEgARAHILRGPHKPPslPVLYTLSSQATHEAV 265

                          90       100       110
                  ....*....|....*....|....*....|
gi 1958783850  78 SLLHAMVAYDPDERIAAHQALQHPYFQVQR 107
Cdd:cd07853   266 HLLCRMLVFDPDKRISAADALAHPYLDEGR 295

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNK3 is expressed primarily in the brain, and to a lesser extent in the heart and testis. Mice deficient in JNK3 are protected against kainic acid-induced seizures, stroke, sciatic axotomy neural death, and neuronal death due to NGF deprivation, oxidative stress, or exposure to beta-amyloid peptide. This suggests that JNK3 may play roles in the pathogenesis of these diseases. 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. The JNK3 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 1958783850   1 MDLWSAGCVFYEIASLQPLFPGVNELDQISKIHDVIGTPCQKTLTKFKQS-RAMSFDFPFKKGSGIP-LLTTNLTP---- 74
Cdd:cd07874   199 VDIWSVGCIMGEMVRHKILFPGRDYIDQWNKVIEQLGTPCPEFMKKLQPTvRNYVENRPKYAGLTFPkLFPDSLFPadse 278

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 1958783850  75 -------QCLSLLHAMVAYDPDERIAAHQALQHPYFQV 105
Cdd:cd07874   279 hnklkasQARDLLSKMLVIDPAKRISVDEALQHPYINV 316