MK06_HUMAN
ID MK06_HUMAN Reviewed; 721 AA.
AC Q16659; B2R945; B5BU65; Q68DH4; Q8IYN8;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 196.
DE RecName: Full=Mitogen-activated protein kinase 6;
DE Short=MAP kinase 6;
DE Short=MAPK 6;
DE EC=2.7.11.24;
DE AltName: Full=Extracellular signal-regulated kinase 3;
DE Short=ERK-3;
DE AltName: Full=MAP kinase isoform p97;
DE Short=p97-MAPK;
GN Name=MAPK6; Synonyms=ERK3, PRKM6;
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 [MRNA].
RC TISSUE=Fetal skeletal muscle;
RX PubMed=7969157; DOI=10.1128/mcb.14.12.8202-8211.1994;
RA Zhu A.X., Zhao Y., Moller D.E., Flier J.S.;
RT "Cloning and characterization of p97MAPK, a novel human homolog of rat ERK-
RT 3.";
RL Mol. Cell. Biol. 14:8202-8211(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Smooth muscle;
RX PubMed=8875998;
RA Meloche S., Beatty B.G., Pellerin J.;
RT "Primary structure, expression and chromosomal locus of a human homolog of
RT rat ERK3.";
RL Oncogene 13:1575-1579(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Oral cancer;
RA Saranath D., Mahale A., Rai R., Dedhia P.;
RT "ERK-3 cDNA clone isolated from human oral cancer.";
RL Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Trachea;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Esophageal carcinoma;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=19054851; DOI=10.1038/nmeth.1273;
RA Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R.,
RA Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y.,
RA Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B.,
RA Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y.,
RA Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A.,
RA Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y.,
RA Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T.,
RA Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y.,
RA Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S.,
RA Nomura N.;
RT "Human protein factory for converting the transcriptome into an in vitro-
RT expressed proteome.";
RL Nat. Methods 5:1011-1017(2008).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-290.
RC TISSUE=Placenta;
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 [8]
RP UBIQUITINATION AT MET-1.
RX PubMed=15226418; DOI=10.1128/mcb.24.14.6140-6150.2004;
RA Coulombe P., Rodier G., Bonneil E., Thibault P., Meloche S.;
RT "N-Terminal ubiquitination of extracellular signal-regulated kinase 3 and
RT p21 directs their degradation by the proteasome.";
RL Mol. Cell. Biol. 24:6140-6150(2004).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-189, AND IDENTIFICATION BY
RP 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 [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-189, AND IDENTIFICATION BY
RP 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 [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [12]
RP PHOSPHORYLATION AT SER-189.
RX PubMed=21177870; DOI=10.1074/jbc.m110.181529;
RA Deleris P., Trost M., Topisirovic I., Tanguay P.L., Borden K.L.,
RA Thibault P., Meloche S.;
RT "Activation loop phosphorylation of ERK3/ERK4 by group I p21-activated
RT kinases (PAKs) defines a novel PAK-ERK3/4-MAPK-activated protein kinase 5
RT signaling pathway.";
RL J. Biol. Chem. 286:6470-6478(2011).
RN [13]
RP INTERACTION WITH UBE3A AND NEURL4.
RX PubMed=22645313; DOI=10.1128/mcb.00201-12;
RA Martinez-Noel G., Galligan J.T., Sowa M.E., Arndt V., Overton T.M.,
RA Harper J.W., Howley P.M.;
RT "Identification and proteomic analysis of distinct UBE3A/E6AP protein
RT complexes.";
RL Mol. Cell. Biol. 32:3095-3106(2012).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-189; SER-386; SER-452;
RP SER-556; SER-558; SER-665 AND SER-684, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [15]
RP VARIANT [LARGE SCALE ANALYSIS] VAL-290.
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: Atypical MAPK protein. Phosphorylates microtubule-associated
CC protein 2 (MAP2) and MAPKAPK5. The precise role of the complex formed
CC with MAPKAPK5 is still unclear, but the complex follows a complex set
CC of phosphorylation events: upon interaction with atypical MAPKAPK5,
CC ERK3/MAPK6 is phosphorylated at Ser-189 and then mediates
CC phosphorylation and activation of MAPKAPK5, which in turn
CC phosphorylates ERK3/MAPK6. May promote entry in the cell cycle (By
CC similarity). {ECO:0000250}.
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 phosphorylation at Ser-189.
CC -!- SUBUNIT: Heterodimer with ERK4/MAPK4. Interacts with (via FRIEDE motif)
CC MAPKAPK5 (By similarity). Interacts with UBE3A; this interaction may be
CC indirect and mediated by HERC2, possibly via HERC2 interaction with
CC NEURL4. {ECO:0000250, ECO:0000269|PubMed:22645313}.
CC -!- INTERACTION:
CC Q16659; Q9GZV1: ANKRD2; NbExp=7; IntAct=EBI-1384105, EBI-12111292;
CC Q16659; Q9H6Z9: EGLN3; NbExp=6; IntAct=EBI-1384105, EBI-1175354;
CC Q16659; Q8IW41: MAPKAPK5; NbExp=9; IntAct=EBI-1384105, EBI-1201460;
CC Q16659; Q8IW41-2: MAPKAPK5; NbExp=6; IntAct=EBI-1384105, EBI-11958803;
CC Q16659; P12504: vif; Xeno; NbExp=2; IntAct=EBI-1384105, EBI-779991;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC Note=Translocates to the cytoplasm following interaction with MAPKAPK5.
CC {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Highest expression in the skeletal muscle, followed
CC by the brain. Also found in heart, placenta, lung, liver, pancreas,
CC kidney and skin fibroblasts.
CC -!- DOMAIN: In contrast to classical MAPKs, the TXY motif within the
CC activation loop is replaced by the SEG motif, whose phosphorylation
CC activates the MAP kinases. {ECO:0000250}.
CC -!- PTM: Phosphorylated at Ser-189 by PAK1, PAK2 and PAK3 resulting in
CC catalytic activation. Phosphorylated by MAPKAPK5 at other sites.
CC {ECO:0000269|PubMed:21177870}.
CC -!- PTM: Ubiquitination at Met-1 leads to degradation by the proteasome
CC pathway. {ECO:0000269|PubMed:15226418}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC protein kinase family. MAP kinase subfamily. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/MAPK6ID43349ch15q21.html";
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DR EMBL; X80692; CAA56709.1; -; mRNA.
DR EMBL; L77964; AAA98769.1; -; mRNA.
DR EMBL; AF420474; AAL17605.1; -; mRNA.
DR EMBL; AK313633; BAG36392.1; -; mRNA.
DR EMBL; CR749401; CAH18246.1; -; mRNA.
DR EMBL; AB451301; BAG70115.1; -; mRNA.
DR EMBL; BC035492; AAH35492.1; -; mRNA.
DR CCDS; CCDS10147.1; -.
DR PIR; A56352; A56352.
DR RefSeq; NP_002739.1; NM_002748.3.
DR RefSeq; XP_005254594.1; XM_005254537.2.
DR RefSeq; XP_005254595.1; XM_005254538.2.
DR RefSeq; XP_005254596.1; XM_005254539.3.
DR RefSeq; XP_011520084.1; XM_011521782.1.
DR PDB; 6YKY; X-ray; 2.52 A; A/B/C/D=9-327.
DR PDB; 6YLC; X-ray; 2.43 A; A/B/C/D=9-327.
DR PDB; 6YLL; X-ray; 2.89 A; A/B=9-327.
DR PDB; 7AQB; X-ray; 2.25 A; A/B=9-327.
DR PDBsum; 6YKY; -.
DR PDBsum; 6YLC; -.
DR PDBsum; 6YLL; -.
DR PDBsum; 7AQB; -.
DR AlphaFoldDB; Q16659; -.
DR SMR; Q16659; -.
DR BioGRID; 111583; 451.
DR CORUM; Q16659; -.
DR IntAct; Q16659; 403.
DR MINT; Q16659; -.
DR STRING; 9606.ENSP00000261845; -.
DR BindingDB; Q16659; -.
DR ChEMBL; CHEMBL5121; -.
DR DrugBank; DB00945; Acetylsalicylic acid.
DR DrugBank; DB01017; Minocycline.
DR DrugCentral; Q16659; -.
DR MoonDB; Q16659; Predicted.
DR iPTMnet; Q16659; -.
DR PhosphoSitePlus; Q16659; -.
DR BioMuta; MAPK6; -.
DR DMDM; 2499596; -.
DR CPTAC; CPTAC-885; -.
DR CPTAC; CPTAC-886; -.
DR EPD; Q16659; -.
DR jPOST; Q16659; -.
DR MassIVE; Q16659; -.
DR MaxQB; Q16659; -.
DR PaxDb; Q16659; -.
DR PeptideAtlas; Q16659; -.
DR PRIDE; Q16659; -.
DR ProteomicsDB; 61018; -.
DR Antibodypedia; 3920; 572 antibodies from 39 providers.
DR DNASU; 5597; -.
DR Ensembl; ENST00000261845.7; ENSP00000261845.5; ENSG00000069956.14.
DR Ensembl; ENST00000680066.1; ENSP00000505862.1; ENSG00000069956.14.
DR Ensembl; ENST00000680652.1; ENSP00000506184.1; ENSG00000069956.14.
DR Ensembl; ENST00000680777.1; ENSP00000505601.1; ENSG00000069956.14.
DR Ensembl; ENST00000681888.1; ENSP00000506036.1; ENSG00000069956.14.
DR Ensembl; ENST00000691380.1; ENSP00000509662.1; ENSG00000069956.14.
DR GeneID; 5597; -.
DR KEGG; hsa:5597; -.
DR MANE-Select; ENST00000261845.7; ENSP00000261845.5; NM_002748.4; NP_002739.1.
DR UCSC; uc002abp.4; human.
DR CTD; 5597; -.
DR DisGeNET; 5597; -.
DR GeneCards; MAPK6; -.
DR HGNC; HGNC:6879; MAPK6.
DR HPA; ENSG00000069956; Low tissue specificity.
DR MIM; 602904; gene.
DR neXtProt; NX_Q16659; -.
DR OpenTargets; ENSG00000069956; -.
DR PharmGKB; PA30624; -.
DR VEuPathDB; HostDB:ENSG00000069956; -.
DR eggNOG; KOG0660; Eukaryota.
DR GeneTree; ENSGT00940000154351; -.
DR HOGENOM; CLU_000288_181_15_1; -.
DR InParanoid; Q16659; -.
DR OMA; EADWQLH; -.
DR OrthoDB; 741207at2759; -.
DR PhylomeDB; Q16659; -.
DR TreeFam; TF105098; -.
DR BRENDA; 2.7.11.24; 2681.
DR PathwayCommons; Q16659; -.
DR Reactome; R-HSA-5687128; MAPK6/MAPK4 signaling.
DR SignaLink; Q16659; -.
DR SIGNOR; Q16659; -.
DR BioGRID-ORCS; 5597; 27 hits in 1074 CRISPR screens.
DR ChiTaRS; MAPK6; human.
DR EvolutionaryTrace; Q16659; -.
DR GeneWiki; MAPK6; -.
DR GenomeRNAi; 5597; -.
DR Pharos; Q16659; Tbio.
DR PRO; PR:Q16659; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q16659; protein.
DR Bgee; ENSG00000069956; Expressed in cartilage tissue and 213 other tissues.
DR Genevisible; Q16659; HS.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IEA:Ensembl.
DR GO; GO:0032156; C:septin cytoskeleton; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004707; F:MAP kinase activity; ISS:UniProtKB.
DR GO; GO:0046982; F:protein heterodimerization activity; IEA:Ensembl.
DR GO; GO:0019901; F:protein kinase binding; IEA:Ensembl.
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:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0060999; P:positive regulation of dendritic spine development; IEA:Ensembl.
DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR008350; MAPK_ERK3/4.
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 PRINTS; PR01771; ERK3ERK4MAPK.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 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; ATP-binding; Cell cycle; Cytoplasm; Kinase;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Ubl conjugation.
FT CHAIN 1..721
FT /note="Mitogen-activated protein kinase 6"
FT /id="PRO_0000186257"
FT DOMAIN 20..316
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 701..721
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 189..191
FT /note="SEG motif"
FT MOTIF 332..337
FT /note="FRIEDE motif"
FT ACT_SITE 152
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 26..34
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 49
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 189
FT /note="Phosphoserine; by PAK1, PAK2 and PAK3"
FT /evidence="ECO:0000269|PubMed:21177870,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 386
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 452
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 556
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 558
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 665
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 684
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT CROSSLNK 1
FT /note="Peptide (Met-Gly) (interchain with G-Cter in
FT ubiquitin)"
FT /evidence="ECO:0000269|PubMed:15226418"
FT VARIANT 290
FT /note="L -> V (in dbSNP:rs35697691)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:17344846"
FT /id="VAR_042256"
FT CONFLICT 229
FT /note="K -> R (in Ref. 4; BAG36392)"
FT /evidence="ECO:0000305"
FT CONFLICT 527
FT /note="F -> L (in Ref. 4; BAG70115)"
FT /evidence="ECO:0000305"
FT STRAND 14..16
FT /evidence="ECO:0007829|PDB:7AQB"
FT TURN 17..19
FT /evidence="ECO:0007829|PDB:7AQB"
FT STRAND 20..25
FT /evidence="ECO:0007829|PDB:7AQB"
FT STRAND 34..39
FT /evidence="ECO:0007829|PDB:7AQB"
FT TURN 40..42
FT /evidence="ECO:0007829|PDB:7AQB"
FT STRAND 45..52
FT /evidence="ECO:0007829|PDB:7AQB"
FT HELIX 56..70
FT /evidence="ECO:0007829|PDB:7AQB"
FT STRAND 80..84
FT /evidence="ECO:0007829|PDB:7AQB"
FT STRAND 86..88
FT /evidence="ECO:0007829|PDB:6YLC"
FT STRAND 102..109
FT /evidence="ECO:0007829|PDB:7AQB"
FT STRAND 112..114
FT /evidence="ECO:0007829|PDB:7AQB"
FT HELIX 115..120
FT /evidence="ECO:0007829|PDB:7AQB"
FT HELIX 126..145
FT /evidence="ECO:0007829|PDB:7AQB"
FT STRAND 148..150
FT /evidence="ECO:0007829|PDB:6YLC"
FT HELIX 155..157
FT /evidence="ECO:0007829|PDB:7AQB"
FT STRAND 158..161
FT /evidence="ECO:0007829|PDB:7AQB"
FT TURN 162..165
FT /evidence="ECO:0007829|PDB:7AQB"
FT STRAND 166..169
FT /evidence="ECO:0007829|PDB:7AQB"
FT STRAND 174..176
FT /evidence="ECO:0007829|PDB:6YLC"
FT HELIX 180..182
FT /evidence="ECO:0007829|PDB:6YLC"
FT TURN 183..186
FT /evidence="ECO:0007829|PDB:6YKY"
FT HELIX 190..192
FT /evidence="ECO:0007829|PDB:7AQB"
FT HELIX 200..204
FT /evidence="ECO:0007829|PDB:7AQB"
FT HELIX 211..227
FT /evidence="ECO:0007829|PDB:7AQB"
FT HELIX 237..247
FT /evidence="ECO:0007829|PDB:7AQB"
FT HELIX 253..260
FT /evidence="ECO:0007829|PDB:7AQB"
FT HELIX 265..270
FT /evidence="ECO:0007829|PDB:7AQB"
FT STRAND 271..273
FT /evidence="ECO:0007829|PDB:6YLL"
FT HELIX 278..281
FT /evidence="ECO:0007829|PDB:7AQB"
FT STRAND 282..285
FT /evidence="ECO:0007829|PDB:6YLC"
FT HELIX 287..294
FT /evidence="ECO:0007829|PDB:7AQB"
FT HELIX 301..303
FT /evidence="ECO:0007829|PDB:7AQB"
FT HELIX 307..312
FT /evidence="ECO:0007829|PDB:7AQB"
FT HELIX 314..317
FT /evidence="ECO:0007829|PDB:7AQB"
SQ SEQUENCE 721 AA; 82681 MW; DAA3AAA9B98BB31F CRC64;
MAEKFESLMN IHGFDLGSRY MDLKPLGCGG NGLVFSAVDN DCDKRVAIKK IVLTDPQSVK
HALREIKIIR RLDHDNIVKV FEILGPSGSQ LTDDVGSLTE LNSVYIVQEY METDLANVLE
QGPLLEEHAR LFMYQLLRGL KYIHSANVLH RDLKPANLFI NTEDLVLKIG DFGLARIMDP
HYSHKGHLSE GLVTKWYRSP RLLLSPNNYT KAIDMWAAGC IFAEMLTGKT LFAGAHELEQ
MQLILESIPV VHEEDRQELL SVIPVYIRND MTEPHKPLTQ LLPGISREAL DFLEQILTFS
PMDRLTAEEA LSHPYMSIYS FPMDEPISSH PFHIEDEVDD ILLMDETHSH IYNWERYHDC
QFSEHDWPVH NNFDIDEVQL DPRALSDVTD EEEVQVDPRK YLDGDREKYL EDPAFDTNYS
TEPCWQYSDH HENKYCDLEC SHTCNYKTRS SSYLDNLVWR ESEVNHYYEP KLIIDLSNWK
EQSKEKSDKK GKSKCERNGL VKAQIALEEA SQQLAGKERE KNQGFDFDSF IAGTIQLSSQ
HEPTDVVDKL NDLNSSVSQL ELKSLISKSV SQEKQEKGMA NLAQLEALYQ SSWDSQFVSG
GEDCFFINQF CEVRKDEQVE KENTYTSYLD KFFSRKEDTE MLETEPVEDG KLGERGHEEG
FLNNSGEFLF NKQLESIGIP QFHSPVGSPL KSIQATLTPS AMKSSPQIPH QTYSSILKHL
N
