ID MK07_RAT Reviewed; 806 AA. AC P0C865; DT 02-SEP-2008, integrated into UniProtKB/Swiss-Prot. DT 02-SEP-2008, sequence version 1. DT 27-MAR-2024, entry version 82. DE RecName: Full=Mitogen-activated protein kinase 7; DE Short=MAP kinase 7; DE Short=MAPK 7; DE EC=2.7.11.24; DE AltName: Full=Big MAP kinase 1; DE Short=BMK-1; DE AltName: Full=Extracellular signal-regulated kinase 5; DE Short=ERK-5; GN Name=Mapk7; Synonyms=Bmk1, Erk5; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Brown Norway; RX PubMed=15057822; DOI=10.1038/nature02426; RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J., RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G., RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G., RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G., RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S., RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T., RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D., RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L., RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D., RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M., RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C., RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J., RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H., RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X., RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q., RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P., RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A., RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C., RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J., RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J., RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F., RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A., RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A., RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J., RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E., RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M., RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C., RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L., RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W., RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y., RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V., RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M., RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S., RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B., RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R., RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J., RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D., RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S., RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S., RA Mockrin S., Collins F.S.; RT "Genome sequence of the Brown Norway rat yields insights into mammalian RT evolution."; RL Nature 428:493-521(2004). RN [2] RP FUNCTION, AND INTERACTION WITH MEF2A; MEF2C AND MEF2D. RX PubMed=9753748; DOI=10.1093/nar/26.20.4771; RA Yang C.-C., Ornatsky O.I., McDermott J.C., Cruz T.F., Prody C.A.; RT "Interaction of myocyte enhancer factor 2 (MEF2) with a mitogen-activated RT protein kinase, ERK5/BMK1."; RL Nucleic Acids Res. 26:4771-4777(1998). RN [3] RP FUNCTION. RX PubMed=20724525; DOI=10.1096/fj.10-162636; RA Woo C.H., Le N.T., Shishido T., Chang E., Lee H., Heo K.S., Mickelsen D.M., RA Lu Y., McClain C., Spangenberg T., Yan C., Molina C.A., Yang J., RA Patterson C., Abe J.; RT "Novel role of C terminus of Hsc70-interacting protein (CHIP) ubiquitin RT ligase on inhibiting cardiac apoptosis and dysfunction via regulating ERK5- RT mediated degradation of inducible cAMP early repressor."; RL FASEB J. 24:4917-4928(2010). RN [4] RP INTERACTION WITH HSP90AB1. RX PubMed=23428871; DOI=10.1128/mcb.01246-12; RA Erazo T., Moreno A., Ruiz-Babot G., Rodriguez-Asiain A., Morrice N.A., RA Espadamala J., Bayascas J.R., Gomez N., Lizcano J.M.; RT "Canonical and kinase activity-independent mechanisms for extracellular RT signal-regulated kinase 5 (ERK5) nuclear translocation require dissociation RT of Hsp90 from the ERK5-Cdc37 complex."; RL Mol. Cell. Biol. 33:1671-1686(2013). CC -!- FUNCTION: Plays a role in various cellular processes such as CC proliferation, differentiation and cell survival. The upstream CC activator of MAPK7 is the MAPK kinase MAP2K5. Upon activation, it CC translocates to the nucleus and phosphorylates various downstream CC targets including MEF2C. EGF activates MAPK7 through a Ras-independent CC and MAP2K5-dependent pathway. As part of the MAPK/ERK signaling CC pathway, acts as a negative regulator of apoptosis in cardiomyocytes CC via interaction with STUB1/CHIP and promotion of STUB1-mediated CC ubiquitination and degradation of ICER-type isoforms of CREM CC (PubMed:20724525). May have a role in muscle cell differentiation. May CC be important for endothelial function and maintenance of blood vessel CC integrity. MAP2K5 and MAPK7 interact specifically with one another and CC not with MEK1/ERK1 or MEK2/ERK2 pathways. Phosphorylates SGK1 at Ser-78 CC and this is required for growth factor-induced cell cycle progression CC (By similarity). Involved in the regulation of p53/TP53 by disrupting CC the PML-MDM2 interaction (By similarity). {ECO:0000250, CC ECO:0000269|PubMed:20724525, ECO:0000269|PubMed:9753748}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl- CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA- CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.24; CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L- CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; CC EC=2.7.11.24; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; CC -!- ACTIVITY REGULATION: Activated by tyrosine and threonine CC phosphorylation. Activated in response to hyperosmolarity, hydrogen CC peroxide, and epidermal growth factor (EGF) (By similarity). CC {ECO:0000250}. CC -!- SUBUNIT: Interacts with MAP2K5. Forms oligomers (By similarity). CC Interacts with MEF2A, MEF2C and MEF2D; the interaction phosphorylates CC the MEF2s and enhances transcriptional activity of MEF2A, MEF2C but not CC MEF2D. Interacts with SGK1 (By similarity). Interacts with PML (By CC similarity). Interacts (via N-terminal half) with HSP90AB1-CDC37 CC chaperone complex in resting cells; the interaction is MAP2K5- CC independent and prevents MAPK7 from ubiquitination and proteasomal CC degradation (PubMed:23428871). Interacts with STUB1/CHIP; the CC interaction is enhanced in the presence of IGF1 or MAP2K5 and promotes CC STUB1/CHIP E3 ligase activity (By similarity). {ECO:0000250, CC ECO:0000250|UniProtKB:Q13164, ECO:0000269|PubMed:23428871}. CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Nucleus, PML body CC {ECO:0000250}. Note=Translocates to the nucleus upon activation. CC {ECO:0000250}. CC -!- DOMAIN: The second proline-rich region may interact with actin CC targeting the kinase to a specific location in the cell. CC -!- DOMAIN: The TXY motif contains the threonine and tyrosine residues CC whose phosphorylation activates the MAP kinases. CC -!- PTM: Dually phosphorylated on Thr-219 and Tyr-221, which activates the CC enzyme. {ECO:0000250}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr CC protein kinase family. MAP kinase subfamily. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AABR03073216; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR AlphaFoldDB; P0C865; -. DR SMR; P0C865; -. DR STRING; 10116.ENSRNOP00000054673; -. DR iPTMnet; P0C865; -. DR PhosphoSitePlus; P0C865; -. DR jPOST; P0C865; -. DR PaxDb; 10116-ENSRNOP00000054673; -. DR UCSC; RGD:621505; rat. DR AGR; RGD:621505; -. DR RGD; 621505; Mapk7. DR eggNOG; KOG0660; Eukaryota. DR InParanoid; P0C865; -. DR PhylomeDB; P0C865; -. DR Reactome; R-RNO-198753; ERK/MAPK targets. DR Reactome; R-RNO-198765; Signalling to ERK5. DR Reactome; R-RNO-202670; ERKs are inactivated. DR Reactome; R-RNO-2559582; Senescence-Associated Secretory Phenotype (SASP). DR Reactome; R-RNO-881907; Gastrin-CREB signalling pathway via PKC and MAPK. DR Reactome; R-RNO-8853659; RET signaling. DR PRO; PR:P0C865; -. DR Proteomes; UP000002494; Unplaced. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0005829; C:cytosol; ISO:RGD. DR GO; GO:0005634; C:nucleus; ISO:RGD. DR GO; GO:0016605; C:PML body; ISS:UniProtKB. DR GO; GO:0005524; F:ATP binding; IDA:RGD. DR GO; GO:0004707; F:MAP kinase activity; IDA:RGD. DR GO; GO:0051019; F:mitogen-activated protein kinase binding; ISO:RGD. DR GO; GO:0004672; F:protein kinase activity; ISO:RGD. DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISO:RGD. DR GO; GO:0033173; P:calcineurin-NFAT signaling cascade; ISO:RGD. DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW. DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW. DR GO; GO:0071363; P:cellular response to growth factor stimulus; ISO:RGD. DR GO; GO:0070301; P:cellular response to hydrogen peroxide; ISO:RGD. DR GO; GO:0071499; P:cellular response to laminar fluid shear stress; ISO:RGD. DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; ISO:RGD. DR GO; GO:0070375; P:ERK5 cascade; IMP:RGD. DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central. DR GO; GO:0000165; P:MAPK cascade; IMP:UniProtKB. DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:RGD. DR GO; GO:0070885; P:negative regulation of calcineurin-NFAT signaling cascade; ISO:RGD. DR GO; GO:2000352; P:negative regulation of endothelial cell apoptotic process; ISO:RGD. DR GO; GO:0070377; P:negative regulation of ERK5 cascade; ISO:RGD. DR GO; GO:2001240; P:negative regulation of extrinsic apoptotic signaling pathway in absence of ligand; ISO:RGD. DR GO; GO:0034115; P:negative regulation of heterotypic cell-cell adhesion; ISO:RGD. DR GO; GO:1902176; P:negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway; ISO:RGD. DR GO; GO:0060761; P:negative regulation of response to cytokine stimulus; ISO:RGD. DR GO; GO:0034392; P:negative regulation of smooth muscle cell apoptotic process; IMP:UniProtKB. DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW. DR GO; GO:0051247; P:positive regulation of protein metabolic process; ISO:RGD. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD. DR GO; GO:0045765; P:regulation of angiogenesis; ISO:RGD. DR CDD; cd07855; STKc_ERK5; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR003527; MAP_kinase_CS. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR008271; Ser/Thr_kinase_AS. DR PANTHER; PTHR24055; MITOGEN-ACTIVATED PROTEIN KINASE; 1. DR PANTHER; PTHR24055:SF588; MITOGEN-ACTIVATED PROTEIN KINASE 7; 1. DR Pfam; PF00069; Pkinase; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS01351; MAPK; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. PE 1: Evidence at protein level; KW Acetylation; ATP-binding; Cell cycle; Cytoplasm; Differentiation; Kinase; KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; KW Serine/threonine-protein kinase; Transferase. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000250|UniProtKB:Q13164" FT CHAIN 2..806 FT /note="Mitogen-activated protein kinase 7" FT /id="PRO_0000349105" FT DOMAIN 55..347 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT REGION 1..23 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2..77 FT /note="Required for cytoplasmic targeting" FT /evidence="ECO:0000250" FT REGION 78..139 FT /note="Required for binding to MAP2K5" FT /evidence="ECO:0000250" FT REGION 140..406 FT /note="Necessary for oligomerization" FT /evidence="ECO:0000250" FT REGION 407..806 FT /note="May not be required for kinase activity; required to FT stimulate MEF2C activity" FT /evidence="ECO:0000250" FT REGION 424..475 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 488..727 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 219..221 FT /note="TXY" FT /evidence="ECO:0000250" FT MOTIF 505..539 FT /note="Nuclear localization signal" FT /evidence="ECO:0000250" FT COMPBIAS 1..18 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 506..545 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 578..600 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 601..615 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 622..644 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 645..663 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 675..691 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 692..712 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 182 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10027" FT BINDING 61..69 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 84 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0000250|UniProtKB:Q13164" FT MOD_RES 710 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q13164" FT MOD_RES 723 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q13164" SQ SEQUENCE 806 AA; 87827 MW; 3CF236450A348C82 CRC64; MAEPLKEEDG EDGSGEPPGR VKAEPVHTAA SVVAKNLALL KARSFDVTFD VGDEYEIIET IGNGAYGVVS SARRRLTGQQ VAIKKIPNAF DVVTNAKRTL RELKILKHFK HDNIIAIKDI LRPTVPYGEF RSVYVVLDLM ESDLHQIIHS SQPLTLEHVR YFLYQLLRGL KYMHSAQVIH RDLKPSNLLV NENCELKIGD FGMARGLCTS PAEHQYFMTE YVATRWYRAP ELMLSLHEYT QAIDLWSVGC IFGEMLARRQ LFPGKNYVHQ LQLIMMVLGT PSPAVIQAVG AERVRAYIQS LPPRQPVPWE TVYPGADRQA LSLLGRMLRF EPSARISAAA ALRHPFLAKY HDPDDEPDCA PPFDFAFDRE ALTRERIKEA IVAEIEDFHA RREGIRQQIR FQPSLQPVAS EPVCPDVEMP SPWAPSGDCA MESPPPALPP CSGPAPDTVD LTLQPAPPAS ELAPPKREGA ISDNTKAALK AALLKSLRSR LRDGPSAPLE APEPRKPVTA QERQREREEK RRRRQERAKE REKRRQERER KERGAGTLGG PSTDPLAGLV LSDNDRSLLE RWTRMARPPV PAPAPAPAPT PKPSSAQPTS PPNGPVSQST APLQPAGSIP GPASQPVCPP PGPVPQPAGP VPAPLQTAPS TSLLASQSLV PPSGLPGSGA PEVLPYFPSG PPPPDPGLTP QPSTSESPDV NLVTQQLSKS QVEDPLPPVF SGTPKGSGAG YGVGFDLEEF LNQSFDMGVA DGPQDGQADS ASLSASLLAD WLEGHGMNPA DIESLQREIQ MDSPMLLSDL PDLQEP //