MK07_HUMAN
ID MK07_HUMAN Reviewed; 816 AA.
AC Q13164; Q16634; Q59F50; Q6QLU7; Q7L4P4; Q969G1; Q96G51;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 02-SEP-2008, sequence version 2.
DT 03-AUG-2022, entry version 207.
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, PRKM7;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RC TISSUE=Placenta;
RX PubMed=7646528; DOI=10.1006/bbrc.1995.2189;
RA Lee J.-D., Ulevitch R.J., Han J.;
RT "Primary structure of BMK1: a new mammalian map kinase.";
RL Biochem. Biophys. Res. Commun. 213:715-724(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH MAP2K5, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Fetal brain;
RX PubMed=7759517; DOI=10.1074/jbc.270.21.12665;
RA Zhou G., Bao Z.Q., Dixon J.E.;
RT "Components of a new human protein kinase signal transduction pathway.";
RL J. Biol. Chem. 270:12665-12669(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RC TISSUE=Placenta;
RX PubMed=15716121; DOI=10.1016/j.gene.2004.11.011;
RA McCaw B.J., Chow S.Y., Wong E.S.M., Tan K.L., Guo H., Guy G.R.;
RT "Identification and characterization of mErk5-T, a novel Erk5/Bmk1 splice
RT variant.";
RL Gene 345:183-190(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
RC TISSUE=Spleen;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.,
RA Ohara O., Nagase T., Kikuno R.F.;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Muscle, and Pancreas;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PROTEIN SEQUENCE OF 2-35; 75-98; 119-131; 198-205; 296-343; 377-392;
RP 468-485; 489-505; 544-571; 720-735 AND 798-816, CLEAVAGE OF INITIATOR
RP METHIONINE, ACETYLATION AT ALA-2, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Hepatoma;
RA Bienvenut W.V., Fleming J., Leug H.Y.;
RL Submitted (JAN-2010) to UniProtKB.
RN [8]
RP FUNCTION, ACTIVITY REGULATION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF
RP 219-THR--TYR-221.
RX PubMed=9384584; DOI=10.1093/emboj/16.23.7054;
RA Kato Y., Kravchenko V.V., Tapping R.I., Han J., Ulevitch R.J., Lee J.-D.;
RT "BMK1/ERK5 regulates serum-induced early gene expression through
RT transcription factor MEF2C.";
RL EMBO J. 16:7054-7066(1997).
RN [9]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=9790194; DOI=10.1038/27234;
RA Kato Y., Tapping R.I., Huang S., Watson M.H., Ulevitch R.J., Lee J.-D.;
RT "Bmk1/Erk5 is required for cell proliferation induced by epidermal growth
RT factor.";
RL Nature 395:713-716(1998).
RN [10]
RP FUNCTION, AND INTERACTION WITH SGK1.
RX PubMed=11254654; DOI=10.1074/jbc.c000838200;
RA Hayashi M., Tapping R.I., Chao T.H., Lo J.F., King C.C., Yang Y., Lee J.D.;
RT "BMK1 mediates growth factor-induced cell proliferation through direct
RT cellular activation of serum and glucocorticoid-inducible kinase.";
RL J. Biol. Chem. 276:8631-8634(2001).
RN [11]
RP FUNCTION.
RX PubMed=11278431; DOI=10.1074/jbc.m008748200;
RA Dong F., Gutkind J.S., Larner A.C.;
RT "Granulocyte colony-stimulating factor induces ERK5 activation, which is
RT differentially regulated by protein-tyrosine kinases and protein kinase C.
RT Regulation of cell proliferation and survival.";
RL J. Biol. Chem. 276:10811-10816(2001).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-720 AND THR-733, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [14]
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).
RN [15]
RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION, AND INTERACTION WITH PML.
RX PubMed=22869143; DOI=10.1038/onc.2012.332;
RA Yang Q., Liao L., Deng X., Chen R., Gray N.S., Yates J.R. III, Lee J.D.;
RT "BMK1 is involved in the regulation of p53 through disrupting the PML-MDM2
RT interaction.";
RL Oncogene 32:3156-3164(2013).
RN [16]
RP VARIANTS [LARGE SCALE ANALYSIS] HIS-535 AND ALA-550.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
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. Involved in the regulation of
CC p53/TP53 by disrupting the PML-MDM2 interaction.
CC {ECO:0000269|PubMed:11254654, ECO:0000269|PubMed:11278431,
CC ECO:0000269|PubMed:22869143, ECO:0000269|PubMed:9384584,
CC ECO:0000269|PubMed:9790194}.
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 (By similarity). Activated in response to
CC hyperosmolarity, hydrogen peroxide, and epidermal growth factor (EGF).
CC {ECO:0000250, ECO:0000269|PubMed:9384584, ECO:0000269|PubMed:9790194}.
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 (By similarity). Interacts with SGK1. Preferentially interacts
CC with PML isoform PML-4 but shows interaction also with its other
CC isoforms: isoform PML-1, isoform PML-2, isoform PML-3 and isoform PML-
CC 6. Interacts (via N-terminal half) with HSP90AB1-CDC37 chaperone
CC complex in resting cells; the interaction is MAP2K5-independent and
CC prevents MAPK7 from ubiquitination and proteasomal degradation
CC (PubMed:23428871). {ECO:0000250, ECO:0000269|PubMed:11254654,
CC ECO:0000269|PubMed:22869143, ECO:0000269|PubMed:23428871,
CC ECO:0000269|PubMed:7759517}.
CC -!- INTERACTION:
CC Q13164; O95816: BAG2; NbExp=3; IntAct=EBI-1213983, EBI-355275;
CC Q13164; Q16204: CCDC6; NbExp=3; IntAct=EBI-1213983, EBI-1045350;
CC Q13164; Q13163: MAP2K5; NbExp=7; IntAct=EBI-1213983, EBI-307294;
CC Q13164; Q02078-6: MEF2A; NbExp=3; IntAct=EBI-1213983, EBI-16437973;
CC Q13164; P29590: PML; NbExp=6; IntAct=EBI-1213983, EBI-295890;
CC Q13164; O00762: UBE2C; NbExp=3; IntAct=EBI-1213983, EBI-719691;
CC Q13164; Q5TZN3: UBE2C; NbExp=3; IntAct=EBI-1213983, EBI-10247554;
CC Q13164; P17029: ZKSCAN1; NbExp=3; IntAct=EBI-1213983, EBI-10199654;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Nucleus, PML body.
CC Note=Translocates to the nucleus upon activation.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q13164-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q13164-2; Sequence=VSP_035198;
CC Name=3;
CC IsoId=Q13164-3; Sequence=VSP_035200;
CC Name=4;
CC IsoId=Q13164-4; Sequence=VSP_035199, VSP_035200;
CC -!- TISSUE SPECIFICITY: Expressed in many adult tissues. Abundant in heart,
CC placenta, lung, kidney and skeletal muscle. Not detectable in liver.
CC {ECO:0000269|PubMed:7759517}.
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 (By similarity). Autophosphorylated in vitro on threonine and
CC tyrosine residues when the C-terminal part of the kinase, which could
CC have a regulatory role, is absent. {ECO:0000250,
CC ECO:0000269|PubMed:22869143}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC protein kinase family. MAP kinase subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA81381.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=BAD92848.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/MAPK7ID41294ch17p11.html";
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; U29725; AAA82931.1; -; mRNA.
DR EMBL; U29726; AAA82932.1; -; mRNA.
DR EMBL; U29727; AAA82933.1; -; Genomic_DNA.
DR EMBL; U25278; AAA81381.1; ALT_FRAME; mRNA.
DR EMBL; AY534741; AAS38577.1; -; mRNA.
DR EMBL; AB209611; BAD92848.1; ALT_INIT; mRNA.
DR EMBL; CH471212; EAW50883.1; -; Genomic_DNA.
DR EMBL; CH471212; EAW50886.1; -; Genomic_DNA.
DR EMBL; BC007404; AAH07404.1; -; mRNA.
DR EMBL; BC007992; AAH07992.1; -; mRNA.
DR EMBL; BC009963; AAH09963.1; -; mRNA.
DR EMBL; BC030134; AAH30134.1; -; mRNA.
DR CCDS; CCDS11206.1; -. [Q13164-1]
DR CCDS; CCDS11207.1; -. [Q13164-2]
DR PIR; B56708; B56708.
DR RefSeq; NP_002740.2; NM_002749.3. [Q13164-1]
DR RefSeq; NP_620601.1; NM_139032.2. [Q13164-2]
DR RefSeq; NP_620602.2; NM_139033.2. [Q13164-1]
DR RefSeq; NP_620603.2; NM_139034.2. [Q13164-1]
DR RefSeq; XP_011522259.1; XM_011523957.2. [Q13164-2]
DR PDB; 2Q8Y; X-ray; 2.00 A; B=215-223.
DR PDB; 4B99; X-ray; 2.80 A; A=1-397.
DR PDB; 4IC7; X-ray; 2.60 A; A/D=1-431.
DR PDB; 4IC8; X-ray; 2.80 A; A/B=1-431.
DR PDB; 4ZSG; X-ray; 1.79 A; A=47-393.
DR PDB; 4ZSJ; X-ray; 2.48 A; A=50-393.
DR PDB; 4ZSL; X-ray; 2.25 A; A=53-393.
DR PDB; 5BYY; X-ray; 2.79 A; A=49-394.
DR PDB; 5BYZ; X-ray; 1.65 A; A=48-395.
DR PDB; 5O7I; X-ray; 2.38 A; A=46-402.
DR PDB; 6HKM; X-ray; 2.47 A; A=49-395.
DR PDB; 6HKN; X-ray; 2.33 A; A=54-393.
DR PDBsum; 2Q8Y; -.
DR PDBsum; 4B99; -.
DR PDBsum; 4IC7; -.
DR PDBsum; 4IC8; -.
DR PDBsum; 4ZSG; -.
DR PDBsum; 4ZSJ; -.
DR PDBsum; 4ZSL; -.
DR PDBsum; 5BYY; -.
DR PDBsum; 5BYZ; -.
DR PDBsum; 5O7I; -.
DR PDBsum; 6HKM; -.
DR PDBsum; 6HKN; -.
DR AlphaFoldDB; Q13164; -.
DR SMR; Q13164; -.
DR BioGRID; 111584; 133.
DR IntAct; Q13164; 108.
DR MINT; Q13164; -.
DR STRING; 9606.ENSP00000311005; -.
DR BindingDB; Q13164; -.
DR ChEMBL; CHEMBL5332; -.
DR DrugBank; DB00945; Acetylsalicylic acid.
DR DrugBank; DB12010; Fostamatinib.
DR DrugBank; DB01017; Minocycline.
DR DrugCentral; Q13164; -.
DR GuidetoPHARMACOLOGY; 2093; -.
DR GlyGen; Q13164; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q13164; -.
DR PhosphoSitePlus; Q13164; -.
DR BioMuta; MAPK7; -.
DR DMDM; 205371766; -.
DR CPTAC; CPTAC-887; -.
DR CPTAC; CPTAC-888; -.
DR EPD; Q13164; -.
DR jPOST; Q13164; -.
DR MassIVE; Q13164; -.
DR MaxQB; Q13164; -.
DR PaxDb; Q13164; -.
DR PeptideAtlas; Q13164; -.
DR PRIDE; Q13164; -.
DR ProteomicsDB; 59203; -. [Q13164-1]
DR ProteomicsDB; 59204; -. [Q13164-2]
DR ProteomicsDB; 59205; -. [Q13164-3]
DR ProteomicsDB; 59206; -. [Q13164-4]
DR Antibodypedia; 4345; 675 antibodies from 41 providers.
DR DNASU; 5598; -.
DR Ensembl; ENST00000299612.11; ENSP00000299612.7; ENSG00000166484.20. [Q13164-2]
DR Ensembl; ENST00000308406.9; ENSP00000311005.5; ENSG00000166484.20. [Q13164-1]
DR Ensembl; ENST00000395602.8; ENSP00000378966.4; ENSG00000166484.20. [Q13164-1]
DR Ensembl; ENST00000395604.8; ENSP00000378968.3; ENSG00000166484.20. [Q13164-1]
DR GeneID; 5598; -.
DR KEGG; hsa:5598; -.
DR MANE-Select; ENST00000395604.8; ENSP00000378968.3; NM_002749.4; NP_002740.2.
DR UCSC; uc002gvn.4; human. [Q13164-1]
DR CTD; 5598; -.
DR DisGeNET; 5598; -.
DR GeneCards; MAPK7; -.
DR HGNC; HGNC:6880; MAPK7.
DR HPA; ENSG00000166484; Low tissue specificity.
DR MalaCards; MAPK7; -.
DR MIM; 602521; gene.
DR neXtProt; NX_Q13164; -.
DR OpenTargets; ENSG00000166484; -.
DR PharmGKB; PA30625; -.
DR VEuPathDB; HostDB:ENSG00000166484; -.
DR eggNOG; KOG0660; Eukaryota.
DR GeneTree; ENSGT00940000160215; -.
DR HOGENOM; CLU_008789_1_0_1; -.
DR InParanoid; Q13164; -.
DR OMA; NWSGQQL; -.
DR OrthoDB; 741207at2759; -.
DR PhylomeDB; Q13164; -.
DR TreeFam; TF105099; -.
DR BRENDA; 2.7.11.24; 2681.
DR PathwayCommons; Q13164; -.
DR Reactome; R-HSA-198753; ERK/MAPK targets.
DR Reactome; R-HSA-198765; Signalling to ERK5.
DR Reactome; R-HSA-202670; ERKs are inactivated.
DR Reactome; R-HSA-2559582; Senescence-Associated Secretory Phenotype (SASP).
DR Reactome; R-HSA-881907; Gastrin-CREB signalling pathway via PKC and MAPK.
DR Reactome; R-HSA-8853659; RET signaling.
DR SignaLink; Q13164; -.
DR SIGNOR; Q13164; -.
DR BioGRID-ORCS; 5598; 16 hits in 1115 CRISPR screens.
DR ChiTaRS; MAPK7; human.
DR GeneWiki; MAPK7; -.
DR GenomeRNAi; 5598; -.
DR Pharos; Q13164; Tchem.
DR PRO; PR:Q13164; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q13164; protein.
DR Bgee; ENSG00000166484; Expressed in lower esophagus mucosa and 137 other tissues.
DR ExpressionAtlas; Q13164; baseline and differential.
DR Genevisible; Q13164; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:BHF-UCL.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0016605; C:PML body; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004707; F:MAP kinase activity; IBA:GO_Central.
DR GO; GO:0051019; F:mitogen-activated protein kinase binding; IPI:BHF-UCL.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0033173; P:calcineurin-NFAT signaling cascade; IEA:Ensembl.
DR GO; GO:0019933; P:cAMP-mediated signaling; NAS:BHF-UCL.
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; IGI:BHF-UCL.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IMP:BHF-UCL.
DR GO; GO:0071499; P:cellular response to laminar fluid shear stress; IMP:BHF-UCL.
DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IDA:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0070885; P:negative regulation of calcineurin-NFAT signaling cascade; IEA:Ensembl.
DR GO; GO:0051344; P:negative regulation of cyclic-nucleotide phosphodiesterase activity; NAS:BHF-UCL.
DR GO; GO:2000352; P:negative regulation of endothelial cell apoptotic process; IMP:BHF-UCL.
DR GO; GO:2001240; P:negative regulation of extrinsic apoptotic signaling pathway in absence of ligand; IGI:BHF-UCL.
DR GO; GO:0034115; P:negative regulation of heterotypic cell-cell adhesion; IGI:BHF-UCL.
DR GO; GO:0050728; P:negative regulation of inflammatory response; TAS:BHF-UCL.
DR GO; GO:1902176; P:negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway; IMP:BHF-UCL.
DR GO; GO:0060761; P:negative regulation of response to cytokine stimulus; IGI:BHF-UCL.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IEA:Ensembl.
DR GO; GO:0051247; P:positive regulation of protein metabolic process; IGI:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IGI:BHF-UCL.
DR GO; GO:0036003; P:positive regulation of transcription from RNA polymerase II promoter in response to stress; IMP:BHF-UCL.
DR GO; GO:0045765; P:regulation of angiogenesis; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR DisProt; DP02831; -.
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 3D-structure; Acetylation; Alternative splicing; ATP-binding; Cell cycle;
KW Cytoplasm; Differentiation; Direct protein sequencing; Kinase;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.7"
FT CHAIN 2..816
FT /note="Mitogen-activated protein kinase 7"
FT /id="PRO_0000186260"
FT DOMAIN 55..347
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..26
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 406..737
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 407..806
FT /note="May not be required for kinase activity; required to
FT stimulate MEF2C activity"
FT /evidence="ECO:0000250"
FT MOTIF 219..221
FT /note="TXY"
FT MOTIF 505..539
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250"
FT COMPBIAS 1..15
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 429..464
FT /note="Pro 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 584..614
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 628..655
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 674..696
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 700..722
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:0000269|Ref.7"
FT MOD_RES 720
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 733
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT VAR_SEQ 1..139
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_035198"
FT VAR_SEQ 1..133
FT /note="MAEPLKEEDGEDGSAEPPGPVKAEPAHTAASVAAKNLALLKARSFDVTFDVG
FT DEYEIIETIGNGAYGVVSSARRRLTGQQVAIKKIPNAFDVVTNAKRTLRELKILKHFKH
FT DNIIAIKDILRPTVPYGEFKSV -> MLFFHTMPSAPMGSQGKAVTCLESEGCGEDGAC
FT PWSVIRPTHASLLPSPSS (in isoform 4)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_035199"
FT VAR_SEQ 493..816
FT /note="DGPSAPLEAPEPRKPVTAQERQREREEKRRRRQERAKEREKRRQERERKERG
FT AGASGGPSTDPLAGLVLSDNDRSLLERWTRMARPAAPALTSVPAPAPAPTPTPTPVQPT
FT SPPPGPVAQPTGPQPQSAGSTSGPVPQPACPPPGPAPHPTGPPGPIPVPAPPQIATSTS
FT LLAAQSLVPPPGLPGSSTPGVLPYFPPGLPPPDAGGAPQSSMSESPDVNLVTQQLSKSQ
FT VEDPLPPVFSGTPKGSGAGYGVGFDLEEFLNQSFDMGVADGPQDGQADSASLSASLLAD
FT WLEGHGMNPADIESLQREIQMDSPMLLADLPDLQDP -> GALWAGRVGRGETWTWTRL
FT QAFTFSPAQLPRKWPQRTPGGS (in isoform 3 and isoform 4)"
FT /evidence="ECO:0000303|PubMed:15716121, ECO:0000303|Ref.4"
FT /id="VSP_035200"
FT VARIANT 535
FT /note="R -> H"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_046225"
FT VARIANT 550
FT /note="G -> A (in dbSNP:rs56388327)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042257"
FT MUTAGEN 219..221
FT /note="TEY->AEF: Loss activation by MAP2K5."
FT /evidence="ECO:0000269|PubMed:9384584"
FT CONFLICT 610
FT /note="V -> L (in Ref. 1; AAA81381)"
FT /evidence="ECO:0000305"
FT TURN 45..48
FT /evidence="ECO:0007829|PDB:4IC8"
FT STRAND 53..64
FT /evidence="ECO:0007829|PDB:5BYZ"
FT STRAND 67..74
FT /evidence="ECO:0007829|PDB:5BYZ"
FT TURN 75..77
FT /evidence="ECO:0007829|PDB:5BYZ"
FT STRAND 80..86
FT /evidence="ECO:0007829|PDB:5BYZ"
FT TURN 87..90
FT /evidence="ECO:0007829|PDB:5BYZ"
FT HELIX 93..108
FT /evidence="ECO:0007829|PDB:5BYZ"
FT STRAND 117..120
FT /evidence="ECO:0007829|PDB:5BYZ"
FT HELIX 127..129
FT /evidence="ECO:0007829|PDB:5BYZ"
FT STRAND 133..137
FT /evidence="ECO:0007829|PDB:5BYZ"
FT STRAND 141..143
FT /evidence="ECO:0007829|PDB:6HKN"
FT HELIX 144..148
FT /evidence="ECO:0007829|PDB:5BYZ"
FT STRAND 150..152
FT /evidence="ECO:0007829|PDB:5BYZ"
FT HELIX 156..175
FT /evidence="ECO:0007829|PDB:5BYZ"
FT HELIX 185..187
FT /evidence="ECO:0007829|PDB:5BYZ"
FT STRAND 188..190
FT /evidence="ECO:0007829|PDB:5BYZ"
FT STRAND 196..198
FT /evidence="ECO:0007829|PDB:5BYZ"
FT HELIX 201..203
FT /evidence="ECO:0007829|PDB:6HKN"
FT HELIX 214..216
FT /evidence="ECO:0007829|PDB:5BYZ"
FT HELIX 219..221
FT /evidence="ECO:0007829|PDB:5BYZ"
FT HELIX 225..227
FT /evidence="ECO:0007829|PDB:5BYZ"
FT HELIX 230..234
FT /evidence="ECO:0007829|PDB:5BYZ"
FT HELIX 242..257
FT /evidence="ECO:0007829|PDB:5BYZ"
FT HELIX 267..278
FT /evidence="ECO:0007829|PDB:5BYZ"
FT HELIX 283..287
FT /evidence="ECO:0007829|PDB:5BYZ"
FT STRAND 288..290
FT /evidence="ECO:0007829|PDB:4IC8"
FT HELIX 292..300
FT /evidence="ECO:0007829|PDB:5BYZ"
FT HELIX 309..312
FT /evidence="ECO:0007829|PDB:5BYZ"
FT STRAND 313..316
FT /evidence="ECO:0007829|PDB:5BYY"
FT HELIX 318..327
FT /evidence="ECO:0007829|PDB:5BYZ"
FT HELIX 332..334
FT /evidence="ECO:0007829|PDB:5BYZ"
FT HELIX 338..342
FT /evidence="ECO:0007829|PDB:5BYZ"
FT HELIX 345..347
FT /evidence="ECO:0007829|PDB:5BYZ"
FT TURN 348..350
FT /evidence="ECO:0007829|PDB:5BYZ"
FT HELIX 353..355
FT /evidence="ECO:0007829|PDB:5BYZ"
FT HELIX 366..369
FT /evidence="ECO:0007829|PDB:5BYZ"
FT STRAND 370..372
FT /evidence="ECO:0007829|PDB:4IC7"
FT HELIX 374..393
FT /evidence="ECO:0007829|PDB:5BYZ"
FT STRAND 396..398
FT /evidence="ECO:0007829|PDB:4IC7"
SQ SEQUENCE 816 AA; 88386 MW; 27729FE31658CE3B CRC64;
MAEPLKEEDG EDGSAEPPGP VKAEPAHTAA SVAAKNLALL KARSFDVTFD VGDEYEIIET
IGNGAYGVVS SARRRLTGQQ VAIKKIPNAF DVVTNAKRTL RELKILKHFK HDNIIAIKDI
LRPTVPYGEF KSVYVVLDLM 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 EPGCPDVEMP
SPWAPSGDCA MESPPPAPPP CPGPAPDTID LTLQPPPPVS EPAPPKKDGA ISDNTKAALK
AALLKSLRSR LRDGPSAPLE APEPRKPVTA QERQREREEK RRRRQERAKE REKRRQERER
KERGAGASGG PSTDPLAGLV LSDNDRSLLE RWTRMARPAA PALTSVPAPA PAPTPTPTPV
QPTSPPPGPV AQPTGPQPQS AGSTSGPVPQ PACPPPGPAP HPTGPPGPIP VPAPPQIATS
TSLLAAQSLV PPPGLPGSST PGVLPYFPPG LPPPDAGGAP QSSMSESPDV NLVTQQLSKS
QVEDPLPPVF SGTPKGSGAG YGVGFDLEEF LNQSFDMGVA DGPQDGQADS ASLSASLLAD
WLEGHGMNPA DIESLQREIQ MDSPMLLADL PDLQDP
