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 755519450   1 MAELHLGWPLYPGNNEYDQVRYICETQGLPKPHLLHAARKAHHFFKRNPHPDAtNPWQLKSSADYLAETKVRPLERRKYM 80
Cdd:cd14211  193 IAELFLGWPLYPGSSEYDQIRYISQTQGLPAEHLLNAATKTSRFFNRDPDSPY-PLWRLKTPEEHEAETGIKSKEARKYI 271

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 755519450  81 LKSLDQIETVNGGgavsrLSFPDREALAEHADLKSMVELIKRMLTWESHERISPSAALRHPFV 143
Cdd:cd14211  272 FNCLDDMAQVNGP-----SDLEGSELLAEKADRREFIDLLKRMLTIDQERRITPGEALNHPFV 329

Catalytic domain of the Serine/Threonine Kinase, Homeodomain-Interacting Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HIPKs, originally identified by their ability to bind homeobox factors, are nuclear proteins containing catalytic kinase and homeobox-interacting domains as well as a PEST region overlapping with the speckle-retention signal (SRS). They show speckled localization in the nucleus, apart from the nucleoles. They play roles in the regulation of many nuclear pathways including gene transcription, cell survival, proliferation, differentiation, development, and DNA damage response. Vertebrates contain three HIPKs (HIPK1-3) and mammals harbor an additional family member HIPK4, which does not contain a homeobox-interacting domain and is localized in the cytoplasm. HIPK2, the most studied HIPK, is a coregulator of many transcription factors and cofactors and it regulates gene transcription during development and in DNA damage response. The HIPK 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 755519450   1 MAELHLGWPLYPGNNEYDQVRYICETQGLPKPHLLHAARKAHHFFKRNPHPDAtNPWQLKSSADYLAETKVRPLERRKYM 80
Cdd:cd14211  193 IAELFLGWPLYPGSSEYDQIRYISQTQGLPAEHLLNAATKTSRFFNRDPDSPY-PLWRLKTPEEHEAETGIKSKEARKYI 271

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 755519450  81 LKSLDQIETVNGGgavsrLSFPDREALAEHADLKSMVELIKRMLTWESHERISPSAALRHPFV 143
Cdd:cd14211  272 FNCLDDMAQVNGP-----SDLEGSELLAEKADRREFIDLLKRMLTIDQERRITPGEALNHPFV 329

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

                           10        20        30
                   ....*....|....*....|....*....|
gi 755519450   114 KSMVELIKRMLTWESHERISPSAALRHPFV 143
Cdd:smart00220 225 PEAKDLIRKLLVKDPEKRLTAEEALQHPFF 254

Catalytic domain of the Serine/Threonine Kinase, Homeodomain-Interacting Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HIPKs, originally identified by their ability to bind homeobox factors, are nuclear proteins containing catalytic kinase and homeobox-interacting domains as well as a PEST region overlapping with the speckle-retention signal (SRS). They show speckled localization in the nucleus, apart from the nucleoles. They play roles in the regulation of many nuclear pathways including gene transcription, cell survival, proliferation, differentiation, development, and DNA damage response. Vertebrates contain three HIPKs (HIPK1-3) and mammals harbor an additional family member HIPK4, which does not contain a homeobox-interacting domain and is localized in the cytoplasm. HIPK2, the most studied HIPK, is a coregulator of many transcription factors and cofactors and it regulates gene transcription during development and in DNA damage response. The HIPK 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 755519450   1 MAELHLGWPLYPGNNEYDQVRYICETQGLPKPHLLHAARKAHHFFKRNPHPDAtNPWQLKSSADYLAETKVRPLERRKYM 80
Cdd:cd14211  193 IAELFLGWPLYPGSSEYDQIRYISQTQGLPAEHLLNAATKTSRFFNRDPDSPY-PLWRLKTPEEHEAETGIKSKEARKYI 271

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 755519450  81 LKSLDQIETVNGGgavsrLSFPDREALAEHADLKSMVELIKRMLTWESHERISPSAALRHPFV 143
Cdd:cd14211  272 FNCLDDMAQVNGP-----SDLEGSELLAEKADRREFIDLLKRMLTIDQERRITPGEALNHPFV 329

Catalytic domain of the Serine/Threonine Kinase, Homeodomain-Interacting Protein Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HIPK2, the most studied HIPK, is a coregulator of many transcription factors and cofactors including homeodomain proteins (Nkx and HOX families), Smad1-4, Pax6, c-Myb, AML1, the histone acetyltransferase p300, and the tumor repressor p53, among others. It regulates gene transcription during development and in DNA damage response (DDR), and mediates cell processes such as apoptosis, survival, differentiation, and proliferation. HIPK2 mediates apoptosis by phosphorylating and activating p53 during DDR, resulting in the activation of apoptotic genes. In the absence of p53, HIPK2 targets the anti-apoptotic corepressor C-terminal binding protein (CtBP), leading to CtBP's degradation and the promotion of apoptosis. HIPKs, originally identified by their ability to bind homeobox factors, are nuclear proteins containing catalytic kinase and homeobox-interacting domains as well as a PEST region overlapping with the speckle-retention signal (SRS). The HIPK2 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 755519450   1 MAELHLGWPLYPGNNEYDQVRYICETQGLPKPHLLHAARKAHHFFKRNphPDATNP-WQLKSSADYLAETKVRPLERRKY 79
Cdd:cd14227  209 IAELFLGWPLYPGASEYDQIRYISQTQGLPAEYLLSAGTKTTRFFNRD--TDSPYPlWRLKTPEDHEAETGIKSKEARKY 286

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 755519450  80 MLKSLDQIETVNgggavSRLSFPDREALAEHADLKSMVELIKRMLTWESHERISPSAALRHPFVSMQQL 148
Cdd:cd14227  287 IFNCLDDMAQVN-----MTTDLEGSDMLVEKADRREFIDLLKKMLTIDADKRITPIETLNHPFVTMTHL 350

Catalytic domain of the Dual-specificity protein kinase, YAK1; 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 proteins with similarity to Saccharomyces cerevisiae YAK1 (or Yak1p), a dual-specificity kinase that autophosphorylates at tyrosine residues and phosphorylates substrates on S/T residues. YAK1 phosphorylates and activates the transcription factors Hsf1 and Msn2, which play important roles in cellular homeostasis during stress conditions including heat shock, oxidative stress, and nutrient deficiency. It also phosphorylates the protein POP2, a component of a complex that regulates transcription, under glucose-deprived conditions. It functions as a part of a glucose-sensing system that is involved in controlling growth in yeast. The YAK1 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 755519450   2 AELHLGWPLYPGNNEYDQVRYICETQGLPKPHLLHAARKAHHFFKRNPHPDATNPWQLKSSADYLAETKVRPLERRKYM- 80
Cdd:cd14212  193 AELFLGLPLFPGNSEYNQLSRIIEMLGMPPDWMLEKGKNTNKFFKKVAKSGGRSTYRLKTPEEFEAENNCKLEPGKRYFk 272

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 755519450  81 LKSLDQIETVNGggavSRLSFPDrEALAEHADLKSMVELIKRMLTWESHERISPSAALRHPFV 143
Cdd:cd14212  273 YKTLEDIIMNYP----MKKSKKE-QIDKEMETRLAFIDFLKGLLEYDPKKRWTPDQALNHPFI 330

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 755519450   1 MAELHLGWPLYPGNNEYDQVRYICETQGLPKPHLLHAARKAHHFFKRNPHPdatnpwqlkssadylaetKVRPLERRKYM 80
Cdd:cd14210  205 LAELYTGYPLFPGENEEEQLACIMEVLGVPPKSLIDKASRRKKFFDSNGKP------------------RPTTNSKGKKR 266

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 755519450  81 L---KSLDQIETvngggaVSRLSFpdrealaehadlksmVELIKRMLTWESHERISPSAALRHPFV 143
Cdd:cd14210  267 RpgsKSLAQVLK------CDDPSF---------------LDFLKKCLRWDPSERMTPEEALQHPWI 311

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 755519450   1 MAELHLGWPLYPGNNEYDQVRYICETQGLPKPHLLhaarkahhffkrnphpdatnpwqlkssadylaetkvrplerrkym 80
Cdd:cd14133  191 LAELYTGEPLFPGASEVDQLARIIGTIGIPPAHML--------------------------------------------- 225

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 755519450  81 lksldqietvNGGGAvsrlsfpDREALaehadlksmVELIKRMLTWESHERISPSAALRHPFV 143
Cdd:cd14133  226 ----------DQGKA-------DDELF---------VDFLKKLLEIDPKERPTASQALSHPWL 262

Catalytic domain of Male germ cell-Associated Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of human MAK and MAK-related kinase (MRK), Saccharomyces cerevisiae Ime2p, Schizosaccharomyces pombe Mei4-dependent protein 3 (Mde3) and Pit1, Caenorhabditis elegans dyf-5, Arabidopsis thaliana MHK, and similar proteins. These proteins play important roles during meiosis. MAK is highly expressed in testicular cells specifically in the meiotic phase, but is not essential for spermatogenesis and fertility. It functions as a coactivator of the androgen receptor in prostate cells. MRK, also called Intestinal Cell Kinase (ICK), is expressed ubiquitously, with highest expression in the ovary and uterus. A missense mutation in MRK causes endocrine-cerebro-osteodysplasia, suggesting that this protein plays an important role in the development of many organs. MAK and MRK may be involved in regulating cell cycle and cell fate. Ime2p is a meiosis-specific kinase that is important during meiotic initiation and during the later stages of meiosis. Mde3 functions downstream of the transcription factor Mei-4 which is essential for meiotic prophase I. The MAK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755519450   1 MAELHLGWPLYPGNNEYDQVRYICETQGLPKPhllhaarkahhffkrNPHPDATNpwqlkssadyLAETkvrpLERR--K 78
Cdd:cd07830  189 MAELYTLRPLFPGSSEIDQLYKICSVLGTPTK---------------QDWPEGYK----------LASK----LGFRfpQ 239

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 755519450  79 YMLKSLDQIetvngggavsrlsFPDreALAEHADlksmveLIKRMLTWESHERISPSAALRHPF 142
Cdd:cd07830  240 FAPTSLHQL-------------IPN--ASPEAID------LIKDMLRWDPKKRPTASQALQHPY 282

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPKs serve as important mediators of cellular responses to extracellular signals. They control critical cellular functions including differentiation, proliferation, migration, and apoptosis. They are also implicated in the pathogenesis of many diseases including multiple types of cancer, stroke, diabetes, and chronic inflammation. Typical MAPK pathways involve a triple kinase core cascade comprising of the MAPK, which is phosphorylated and activated by a MAPK kinase (MAP2K or MKK), which itself is phosphorylated and activated by a MAPK kinase kinase (MAP3K or MKKK). Each cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. There are three typical MAPK subfamilies: Extracellular signal-Regulated Kinase (ERK), c-Jun N-terminal Kinase (JNK), and p38. Some MAPKs are atypical in that they are not regulated by MAP2Ks. These include MAPK4, MAPK6, NLK, and ERK7. The MAPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755519450   1 MAELHLGWPLYPGNNEYDQVRYICETQGLPKPHllhaarkahhFFKRNPHPDATNpwqlkssadYLAETKVRPLerrkym 80
Cdd:cd07834  196 FAELLTRKPLFPGRDYIDQLNLIVEVLGTPSEE----------DLKFISSEKARN---------YLKSLPKKPK------ 250

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 755519450  81 lKSLDQIetvngggavsrLSFPDREALaehadlksmvELIKRMLTWESHERISPSAALRHPFvsMQQLRSAHEAT 155
Cdd:cd07834  251 -KPLSEV-----------FPGASPEAI----------DLLEKMLVFNPKKRITADEALAHPY--LAQLHDPEDEP 301

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 755519450   1 MAELHLGWPLYPGNNEYDQVRYICETQGLPKPHLLH--AARKAHHFFKRNPHPDATNPWQLKSSADYLAetkvrplerrk 78
Cdd:cd07878  206 MAELLKGKALFPGNDYIDQLKRIMEVVGTPSPEVLKkiSSEHARKYIQSLPHMPQQDLKKIFRGANPLA----------- 274

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 755519450  79 ymlksldqietvngggavsrlsfpdrealaehadlksmVELIKRMLTWESHERISPSAALRHPFVS 144
Cdd:cd07878  275 --------------------------------------IDLLEKMLVLDSDKRISASEALAHPYFS 302

cyclin-dependent protein kinase; Provisional

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 755519450   1 MAELHLGWPLYPGNNEYDQVRYICETQGLPKPhllhaarkahhffkrNPHPDATNpwqLKSSADYlaeTKVRPlerrkym 80
Cdd:PTZ00024 224 FAELLTGKPLFPGENEIDQLGRIFELLGTPNE---------------DNWPQAKK---LPLYTEF---TPRKP------- 275

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 755519450  81 lKSLDQIetvngggavsrlsFPDREALAehadlksmVELIKRMLTWESHERISPSAALRHPFVSMQQL 148
Cdd:PTZ00024 276 -KDLKTI-------------FPNASDDA--------IDLLQSLLKLNPLERISAKEALKHEYFKSDPL 321

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 755519450   9 PLYPGNNEYDQVRYICETQGLPKPHLLhaaRKAHHFFKRNPHpdatnpwqlkssadylaetkvrplerrkymlksldqie 88
Cdd:cd07831  197 PLFPGTNELDQIAKIHDVLGTPDAEVL---KKFRKSRHMNYN-------------------------------------- 235

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 755519450  89 tvngggavsrlsFPDREA-----LAEHADLKSMvELIKRMLTWESHERISPSAALRHPF 142
Cdd:cd07831  236 ------------FPSKKGtglrkLLPNASAEGL-DLLKKLLAYDPDERITAKQALRHPY 281

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
                 ....*....|....*....|....*..
gi 755519450 116 MVELIKRMLTWESHERISPSAALRHPF 142
Cdd:cd05118  222 ALDLLSKMLKYDPAKRITASQALAHPY 248

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 755519450   1 MAELHLGWPLYPGNNEYDQVRYICETQGLPKPHLLH--AARKAHHFFKRNPHPDAtnpwqlkssadylaetkvRPLERrk 78
Cdd:cd07857  200 LAELLGRKPVFKGKDYVDQLNQILQVLGTPDEETLSriGSPKAQNYIRSLPNIPK------------------KPFES-- 259

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 755519450  79 ymlksldqietvngggavsrlSFPDREALAehadlksmVELIKRMLTWESHERISPSAALRHPFVSM 145
Cdd:cd07857  260 ---------------------IFPNANPLA--------LDLLEKLLAFDPTKRISVEEALEHPYLAI 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
                 ....*....|....*....|....*....|....*....|....*....|
gi 755519450 100 SFPDREALAEH-----ADlKSMVELIKRMLTWESHERISPSAALRHPFVS 144
Cdd:cd07855  252 NLPNKQPVPWEtlypkAD-QQALDLLSQMLRFDPSERITVAEALQHPFLA 300