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 27-MAR-2024, entry version 205. 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="https://atlasgeneticsoncology.org/gene/43349/MAPK6"; 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; 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; 463. DR CORUM; Q16659; -. DR IntAct; Q16659; 404. DR MINT; Q16659; -. DR STRING; 9606.ENSP00000261845; -. DR BindingDB; Q16659; -. DR ChEMBL; CHEMBL5121; -. DR DrugBank; DB00945; Acetylsalicylic acid. DR DrugBank; DB02587; Colforsin. 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; 9606-ENSP00000261845; -. DR PeptideAtlas; Q16659; -. DR ProteomicsDB; 61018; -. DR Pumba; Q16659; -. DR Antibodypedia; 3920; 645 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 AGR; HGNC:6879; -. 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; 5344491at2759; -. 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 1152 CRISPR screens. DR ChiTaRS; MAPK6; human. DR EvolutionaryTrace; Q16659; -. DR GeneWiki; MAPK6; -. DR GenomeRNAi; 5597; -. DR Pharos; Q16659; Tchem. DR PRO; PR:Q16659; -. DR Proteomes; UP000005640; Chromosome 15. DR RNAct; Q16659; Protein. DR Bgee; ENSG00000069956; Expressed in cartilage tissue and 215 other cell types or tissues. 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 CDD; cd07854; STKc_MAPK4_6; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. 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 PANTHER; PTHR24055; MITOGEN-ACTIVATED PROTEIN KINASE; 1. DR PANTHER; PTHR24055:SF171; MITOGEN-ACTIVATED PROTEIN KINASE 6; 1. DR Pfam; PF00069; Pkinase; 1. DR PRINTS; PR01771; ERK3ERK4MAPK. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. DR Genevisible; Q16659; HS. 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 //