MK07_RAT
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 03-AUG-2022, entry version 75.
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 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. May have a role in muscle cell
CC differentiation. May be important for endothelial function and
CC maintenance of blood vessel integrity. MAP2K5 and MAPK7 interact
CC specifically with one another and not with MEK1/ERK1 or MEK2/ERK2
CC pathways. Phosphorylates SGK1 at Ser-78 and this is required for growth
CC factor-induced cell cycle progression (By similarity). Involved in the
CC regulation of p53/TP53 by disrupting the PML-MDM2 interaction (By
CC similarity). {ECO:0000250, 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). {ECO:0000250,
CC 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}.
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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; P0C865; -.
DR UCSC; RGD:621505; rat.
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-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; IDA: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: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:RGD.
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:0018105; P:peptidyl-serine phosphorylation; ISO:RGD.
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:0036003; P:positive regulation of transcription from RNA polymerase II promoter in response to stress; ISO:RGD.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:RGD.
DR GO; GO:0006468; P:protein phosphorylation; IDA:RGD.
DR GO; GO:0045765; P:regulation of angiogenesis; ISO:RGD.
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 Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 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
