MK01_HUMAN
ID MK01_HUMAN Reviewed; 360 AA.
AC P28482; A8CZ64;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 242.
DE RecName: Full=Mitogen-activated protein kinase 1 {ECO:0000305};
DE Short=MAP kinase 1;
DE Short=MAPK 1;
DE EC=2.7.11.24;
DE AltName: Full=ERT1;
DE AltName: Full=Extracellular signal-regulated kinase 2;
DE Short=ERK-2;
DE AltName: Full=MAP kinase isoform p42;
DE Short=p42-MAPK;
DE AltName: Full=Mitogen-activated protein kinase 2;
DE Short=MAP kinase 2;
DE Short=MAPK 2;
GN Name=MAPK1 {ECO:0000312|HGNC:HGNC:6871}; Synonyms=ERK2, PRKM1, PRKM2;
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] (ISOFORM 1).
RX PubMed=1540184; DOI=10.1016/0006-291x(92)91891-s;
RA Owaki H., Makar R., Boulton T.G., Cobb M.H., Geppert T.D.;
RT "Extracellular signal-regulated kinases in T cells: characterization of
RT human ERK1 and ERK2 cDNAs.";
RL Biochem. Biophys. Res. Commun. 182:1416-1422(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=1319925; DOI=10.1016/0014-5793(92)80612-k;
RA Gonzalez F.A., Raden D.L., Rigby M.R., Davis R.J.;
RT "Heterogeneous expression of four MAP kinase isoforms in human tissues.";
RL FEBS Lett. 304:170-178(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND ALTERNATIVE SPLICING.
RA Cheng H., Ren S., Qiu R., Wang M., Feng Y.H.;
RT "Identification of dominant negative Erk1/2 variants in cancer cells.";
RL Submitted (FEB-2006) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M.,
RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C.,
RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E.,
RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C.,
RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G.,
RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V.,
RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M.,
RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E.,
RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F.,
RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M.,
RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A.,
RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D.,
RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y.,
RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S.,
RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E.,
RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A.,
RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L.,
RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P.,
RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P.,
RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q.,
RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J.,
RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J.,
RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D.,
RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T.,
RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P.,
RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K.,
RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L.,
RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J.,
RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E.,
RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P.,
RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y.,
RA Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lung;
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 [6]
RP PROTEIN SEQUENCE OF 2-15, AND ACETYLATION AT ALA-2.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R.,
RA Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass spectrometric
RT identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [7]
RP FUNCTION IN PHOSPHORYLATION OF ERF.
RX PubMed=7588608; DOI=10.1002/j.1460-2075.1995.tb00160.x;
RA Sgouras D.N., Athanasiou M.A., Beal G.J. Jr., Fisher R.J., Blair D.G.,
RA Mavrothalassitis G.J.;
RT "ERF: an ETS domain protein with strong transcriptional repressor activity,
RT can suppress ets-associated tumorigenesis and is regulated by
RT phosphorylation during cell cycle and mitogenic stimulation.";
RL EMBO J. 14:4781-4793(1995).
RN [8]
RP FUNCTION IN PHOSPHORYLATION OF MAPKAPK3.
RX PubMed=8622688; DOI=10.1128/mcb.16.3.868;
RA Sithanandam G., Latif F., Duh F.-M., Bernal R., Smola U., Li H., Kuzmin I.,
RA Wixler V., Geil L., Shrestha S., Lloyd P.A., Bader S., Sekido Y.,
RA Tartof K.D., Kashuba V.I., Zabarovsky E.R., Dean M., Klein G., Lerman M.I.,
RA Minna J.D., Rapp U.R., Allikmets R.;
RT "3pK, a new mitogen-activated protein kinase-activated protein kinase
RT located in the small cell lung cancer tumor suppressor gene region.";
RL Mol. Cell. Biol. 16:868-876(1996).
RN [9]
RP INTERACTION WITH HIV-1 NEF (MICROBIAL INFECTION).
RX PubMed=8794306; DOI=10.1128/jvi.70.10.6701-6708.1996;
RA Greenway A.L., Azad A., Mills J., McPhee D.A.;
RT "Human immunodeficiency virus type 1 Nef binds directly to LCK and mitogen-
RT activated protein kinase, inhibiting kinase activity.";
RL J. Virol. 70:6701-6708(1996).
RN [10]
RP FUNCTION IN PHOSPHORYLATION OF MAPKAPK5.
RX PubMed=9480836; DOI=10.1006/bbrc.1998.8135;
RA Ni H., Wang X.S., Diener K., Yao Z.;
RT "MAPKAPK5, a novel mitogen-activated protein kinase (MAPK)-activated
RT protein kinase, is a substrate of the extracellular-regulated kinase (ERK)
RT and p38 kinase.";
RL Biochem. Biophys. Res. Commun. 243:492-496(1998).
RN [11]
RP FUNCTION IN PHOSPHORYLATION OF RPS6KA5/MSK1.
RX PubMed=9687510; DOI=10.1093/emboj/17.15.4426;
RA Deak M., Clifton A.D., Lucocq J.M., Alessi D.R.;
RT "Mitogen- and stress-activated protein kinase-1 (MSK1) is directly
RT activated by MAPK and SAPK2/p38, and may mediate activation of CREB.";
RL EMBO J. 17:4426-4441(1998).
RN [12]
RP FUNCTION IN PHOSPHORYLATION OF BCL6.
RX PubMed=9649500; DOI=10.1101/gad.12.13.1953;
RA Niu H., Ye B.H., Dalla-Favera R.;
RT "Antigen receptor signaling induces MAP kinase-mediated phosphorylation and
RT degradation of the BCL-6 transcription factor.";
RL Genes Dev. 12:1953-1961(1998).
RN [13]
RP INTERACTION WITH DUSP7.
RX PubMed=9788880; DOI=10.1242/jcs.111.22.3389;
RA Dowd S., Sneddon A.A., Keyse S.M.;
RT "Isolation of the human genes encoding the Pyst1 and Pyst2 phosphatases:
RT characterisation of Pyst2 as a cytosolic dual-specificity MAP kinase
RT phosphatase and its catalytic activation by both MAP and SAP kinases.";
RL J. Cell Sci. 111:3389-3399(1998).
RN [14]
RP INTERACTION WITH DUSP6, AND FUNCTION.
RX PubMed=9596579; DOI=10.1126/science.280.5367.1262;
RA Camps M., Nichols A., Gillieron C., Antonsson B., Muda M., Chabert C.,
RA Boschert U., Arkinstall S.;
RT "Catalytic activation of the phosphatase MKP-3 by ERK2 mitogen-activated
RT protein kinase.";
RL Science 280:1262-1265(1998).
RN [15]
RP DEPHOSPHORYLATION BY DUSP3.
RX PubMed=10224087; DOI=10.1074/jbc.274.19.13271;
RA Todd J.L., Tanner K.G., Denu J.M.;
RT "Extracellular regulated kinases (ERK) 1 and ERK2 are authentic substrates
RT for the dual-specificity protein-tyrosine phosphatase VHR. A novel role in
RT down-regulating the ERK pathway.";
RL J. Biol. Chem. 274:13271-13280(1999).
RN [16]
RP FUNCTION IN PHOSPHORYLATION OF ELK1.
RX PubMed=10637505; DOI=10.1038/sj.onc.1203362;
RA Cruzalegui F.H., Cano E., Treisman R.;
RT "ERK activation induces phosphorylation of Elk-1 at multiple S/T-P motifs
RT to high stoichiometry.";
RL Oncogene 18:7948-7957(1999).
RN [17]
RP FUNCTION IN PHOSPHORYLATION OF DUSP1.
RX PubMed=10617468; DOI=10.1126/science.286.5449.2514;
RA Brondello J.M., Pouyssegur J., McKenzie F.R.;
RT "Reduced MAP kinase phosphatase-1 degradation after p42/p44MAPK-dependent
RT phosphorylation.";
RL Science 286:2514-2517(1999).
RN [18]
RP FUNCTION AS MKNK2 KINASE.
RX PubMed=11154262; DOI=10.1128/mcb.21.3.743-754.2001;
RA Scheper G.C., Morrice N.A., Kleijn M., Proud C.G.;
RT "The mitogen-activated protein kinase signal-integrating kinase Mnk2 is a
RT eukaryotic initiation factor 4E kinase with high levels of basal activity
RT in mammalian cells.";
RL Mol. Cell. Biol. 21:743-754(2001).
RN [19]
RP FUNCTION IN PHOSPHORYLATION OF ATF2.
RX PubMed=12110590; DOI=10.1093/emboj/cdf361;
RA Ouwens D.M., de Ruiter N.D., van der Zon G.C., Carter A.P., Schouten J.,
RA van der Burgt C., Kooistra K., Bos J.L., Maassen J.A., van Dam H.;
RT "Growth factors can activate ATF2 via a two-step mechanism: phosphorylation
RT of Thr71 through the Ras-MEK-ERK pathway and of Thr69 through RalGDS-Src-
RT p38.";
RL EMBO J. 21:3782-3793(2002).
RN [20]
RP FUNCTION IN PHOSPHORYLATION OF IER3, INTERACTION WITH IER3, AND ACTIVITY
RP REGULATION.
RX PubMed=12356731; DOI=10.1093/emboj/cdf488;
RA Garcia J., Ye Y., Arranz V., Letourneux C., Pezeron G., Porteu F.;
RT "IEX-1: a new ERK substrate involved in both ERK survival activity and ERK
RT activation.";
RL EMBO J. 21:5151-5163(2002).
RN [21]
RP INTERACTION WITH NISCH.
RX PubMed=11912194; DOI=10.1074/jbc.m111838200;
RA Sano H., Liu S.C.H., Lane W.S., Piletz J.E., Lienhard G.E.;
RT "Insulin receptor substrate 4 associates with the protein IRAS.";
RL J. Biol. Chem. 277:19439-19447(2002).
RN [22]
RP FUNCTION IN PHOSPHORYLATION OF FRS2.
RX PubMed=12974390; DOI=10.1515/bc.2003.134;
RA Wu Y., Chen Z., Ullrich A.;
RT "EGFR and FGFR signaling through FRS2 is subject to negative feedback
RT control by ERK1/2.";
RL Biol. Chem. 384:1215-1226(2003).
RN [23]
RP FUNCTION IN PHOSPHORYLATION OF DUSP16.
RX PubMed=12794087; DOI=10.1074/jbc.m213254200;
RA Masuda K., Shima H., Katagiri C., Kikuchi K.;
RT "Activation of ERK induces phosphorylation of MAPK phosphatase-7, a JNK
RT specific phosphatase, at Ser-446.";
RL J. Biol. Chem. 278:32448-32456(2003).
RN [24]
RP FUNCTION IN PHOSPHORYLATION OF CASP9.
RX PubMed=12792650; DOI=10.1038/ncb1005;
RA Allan L.A., Morrice N., Brady S., Magee G., Pathak S., Clarke P.R.;
RT "Inhibition of caspase-9 through phosphorylation at Thr 125 by ERK MAPK.";
RL Nat. Cell Biol. 5:647-654(2003).
RN [25]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH NEK2.
RX PubMed=15358203; DOI=10.1016/j.bbrc.2004.06.171;
RA Lou Y., Xie W., Zhang D.F., Yao J.H., Luo Z.F., Wang Y.Z., Shi Y.Y.,
RA Yao X.B.;
RT "Nek2A specifies the centrosomal localization of Erk2.";
RL Biochem. Biophys. Res. Commun. 321:495-501(2004).
RN [26]
RP REVIEW ON ROLE IN KIT SIGNALING.
RX PubMed=15526160; DOI=10.1007/s00018-004-4189-6;
RA Ronnstrand L.;
RT "Signal transduction via the stem cell factor receptor/c-Kit.";
RL Cell. Mol. Life Sci. 61:2535-2548(2004).
RN [27]
RP FUNCTION IN PHOSPHORYLATION OF SORBS3.
RX PubMed=15184391; DOI=10.1074/jbc.m402304200;
RA Mitsushima M., Suwa A., Amachi T., Ueda K., Kioka N.;
RT "Extracellular signal-regulated kinase activated by epidermal growth factor
RT and cell adhesion interacts with and phosphorylates vinexin.";
RL J. Biol. Chem. 279:34570-34577(2004).
RN [28]
RP FUNCTION IN PHOSPHORYLATION OF MCL1.
RX PubMed=15241487; DOI=10.1038/sj.onc.1207692;
RA Domina A.M., Vrana J.A., Gregory M.A., Hann S.R., Craig R.W.;
RT "MCL1 is phosphorylated in the PEST region and stabilized upon ERK
RT activation in viable cells, and at additional sites with cytotoxic okadaic
RT acid or taxol.";
RL Oncogene 23:5301-5315(2004).
RN [29]
RP FUNCTION IN PHOSPHORYLATION OF GRB10.
RX PubMed=15952796; DOI=10.1021/bi050413i;
RA Langlais P., Wang C., Dong L.Q., Carroll C.A., Weintraub S.T., Liu F.;
RT "Phosphorylation of Grb10 by mitogen-activated protein kinase:
RT identification of Ser150 and Ser476 of human Grb10zeta as major
RT phosphorylation sites.";
RL Biochemistry 44:8890-8897(2005).
RN [30]
RP FUNCTION IN PHOSPHORYLATION OF DAPK1, SUBCELLULAR LOCATION, AND INTERACTION
RP WITH DAPK1.
RX PubMed=15616583; DOI=10.1038/sj.emboj.7600510;
RA Chen C.H., Wang W.J., Kuo J.C., Tsai H.C., Lin J.R., Chang Z.F., Chen R.H.;
RT "Bidirectional signals transduced by DAPK-ERK interaction promote the
RT apoptotic effect of DAPK.";
RL EMBO J. 24:294-304(2005).
RN [31]
RP DEPHOSPHORYLATION AT THR-185 AND TYR-187 BY DUSP2.
RX PubMed=16288922; DOI=10.1016/j.jmb.2005.10.006;
RA Zhang Q., Muller M., Chen C.H., Zeng L., Farooq A., Zhou M.M.;
RT "New insights into the catalytic activation of the MAPK phosphatase PAC-1
RT induced by its substrate MAPK ERK2 binding.";
RL J. Mol. Biol. 354:777-788(2005).
RN [32]
RP FUNCTION IN PHOSPHORYLATION OF BTG2.
RX PubMed=15788397; DOI=10.1074/jbc.m500318200;
RA Hong J.W., Ryu M.S., Lim I.K.;
RT "Phosphorylation of serine 147 of tis21/BTG2/pc3 by p-Erk1/2 induces Pin-1
RT binding in cytoplasm and cell death.";
RL J. Biol. Chem. 280:21256-21263(2005).
RN [33]
RP FUNCTION IN PHOSPHORYLATION OF RAF1.
RX PubMed=15664191; DOI=10.1016/j.molcel.2004.11.055;
RA Dougherty M.K., Muller J., Ritt D.A., Zhou M., Zhou X.Z., Copeland T.D.,
RA Conrads T.P., Veenstra T.D., Lu K.P., Morrison D.K.;
RT "Regulation of Raf-1 by direct feedback phosphorylation.";
RL Mol. Cell 17:215-224(2005).
RN [34]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [35]
RP INTERACTION WITH ARHGEF2.
RX PubMed=18211802; DOI=10.1016/j.bbrc.2008.01.066;
RA Fujishiro S.H., Tanimura S., Mure S., Kashimoto Y., Watanabe K., Kohno M.;
RT "ERK1/2 phosphorylate GEF-H1 to enhance its guanine nucleotide exchange
RT activity toward RhoA.";
RL Biochem. Biophys. Res. Commun. 368:162-167(2008).
RN [36]
RP FUNCTION, AND INTERACTION WITH HSF4.
RX PubMed=16581800; DOI=10.1128/mcb.26.8.3282-3294.2006;
RA Hu Y., Mivechi N.F.;
RT "Association and regulation of heat shock transcription factor 4b with both
RT extracellular signal-regulated kinase mitogen-activated protein kinase and
RT dual-specificity tyrosine phosphatase DUSP26.";
RL Mol. Cell. Biol. 26:3282-3294(2006).
RN [37]
RP PHOSPHORYLATION.
RX PubMed=17274988; DOI=10.1016/j.febslet.2007.01.039;
RA Degoutin J., Vigny M., Gouzi J.Y.;
RT "ALK activation induces Shc and FRS2 recruitment: Signaling and phenotypic
RT outcomes in PC12 cells differentiation.";
RL FEBS Lett. 581:727-734(2007).
RN [38]
RP INTERACTION WITH ARRB2.
RX PubMed=18435604; DOI=10.1042/bj20080685;
RA Xu T.-R., Baillie G.S., Bhari N., Houslay T.M., Pitt A.M., Adams D.R.,
RA Kolch W., Houslay M.D., Milligan G.;
RT "Mutations of beta-arrestin 2 that limit self-association also interfere
RT with interactions with the beta2-adrenoceptor and the ERK1/2 MAPKs:
RT implications for beta2-adrenoceptor signalling via the ERK1/2 MAPKs.";
RL Biochem. J. 413:51-60(2008).
RN [39]
RP INTERACTION WITH ADAM15.
RX PubMed=18296648; DOI=10.1158/1541-7786.mcr-07-2028;
RA Zhong J.L., Poghosyan Z., Pennington C.J., Scott X., Handsley M.M.,
RA Warn A., Gavrilovic J., Honert K., Kruger A., Span P.N., Sweep F.C.,
RA Edwards D.R.;
RT "Distinct functions of natural ADAM-15 cytoplasmic domain variants in human
RT mammary carcinoma.";
RL Mol. Cancer Res. 6:383-394(2008).
RN [40]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [41]
RP PHOSPHORYLATION AT SER-246 AND SER-248, INTERACTION WITH IPO7, AND
RP SUBCELLULAR LOCATION.
RX PubMed=18760948; DOI=10.1016/j.molcel.2008.08.007;
RA Chuderland D., Konson A., Seger R.;
RT "Identification and characterization of a general nuclear translocation
RT signal in signaling proteins.";
RL Mol. Cell 31:850-861(2008).
RN [42]
RP FUNCTION IN PHOSPHORYLATION OF TPR, INTERACTION WITH TPR, AND MUTAGENESIS
RP OF LYS-54; 176-PRO--ASP-179; THR-185; TYR-187; LEU-234; ASP-318 AND
RP ASP-321.
RX PubMed=18794356; DOI=10.1128/mcb.00925-08;
RA Vomastek T., Iwanicki M.P., Burack W.R., Tiwari D., Kumar D., Parsons J.T.,
RA Weber M.J., Nandicoori V.K.;
RT "Extracellular signal-regulated kinase 2 (ERK2) phosphorylation sites and
RT docking domain on the nuclear pore complex protein Tpr cooperatively
RT regulate ERK2-Tpr interaction.";
RL Mol. Cell. Biol. 28:6954-6966(2008).
RN [43]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-185 AND TYR-187, 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 [44]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [45]
RP FUNCTION AS A TRANSCRIPTIONAL REPRESSOR, AND DNA-BINDING.
RX PubMed=19879846; DOI=10.1016/j.cell.2009.08.037;
RA Hu S., Xie Z., Onishi A., Yu X., Jiang L., Lin J., Rho H.-S., Woodard C.,
RA Wang H., Jeong J.-S., Long S., He X., Wade H., Blackshaw S., Qian J.,
RA Zhu H.;
RT "Profiling the human protein-DNA interactome reveals ERK2 as a
RT transcriptional repressor of interferon signaling.";
RL Cell 139:610-622(2009).
RN [46]
RP FUNCTION IN KIT SIGNALING PATHWAY, AND PHOSPHORYLATION.
RX PubMed=19265199; DOI=10.1074/jbc.m808058200;
RA Sun J., Pedersen M., Ronnstrand L.;
RT "The D816V mutation of c-Kit circumvents a requirement for Src family
RT kinases in c-Kit signal transduction.";
RL J. Biol. Chem. 284:11039-11047(2009).
RN [47]
RP PHOSPHORYLATION AT TYR-187, DEPHOSPHORYLATION AT TYR-187 BY PTPRJ, AND
RP MUTAGENESIS OF ASP-318.
RX PubMed=19494114; DOI=10.1074/jbc.m109.002758;
RA Sacco F., Tinti M., Palma A., Ferrari E., Nardozza A.P.,
RA Hooft van Huijsduijnen R., Takahashi T., Castagnoli L., Cesareni G.;
RT "Tumor suppressor density-enhanced phosphatase-1 (DEP-1) inhibits the RAS
RT pathway by direct dephosphorylation of ERK1/2 kinases.";
RL J. Biol. Chem. 284:22048-22058(2009).
RN [48]
RP PHOSPHORYLATION AT SER-29 BY SGK1, AND INTERACTION WITH SGK1.
RX PubMed=19447520; DOI=10.1016/j.jhep.2009.02.027;
RA Won M., Park K.A., Byun H.S., Kim Y.R., Choi B.L., Hong J.H., Park J.,
RA Seok J.H., Lee Y.H., Cho C.H., Song I.S., Kim Y.K., Shen H.M., Hur G.M.;
RT "Protein kinase SGK1 enhances MEK/ERK complex formation through the
RT phosphorylation of ERK2: implication for the positive regulatory role of
RT SGK1 on the ERK function during liver regeneration.";
RL J. Hepatol. 51:67-76(2009).
RN [49]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-284, 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 [50]
RP PHOSPHORYLATION AT THR-190, ACTIVITY REGULATION, SUBUNIT, AND SUBCELLULAR
RP LOCATION.
RX PubMed=19060905; DOI=10.1038/nm.1893;
RA Lorenz K., Schmitt J.P., Schmitteckert E.M., Lohse M.J.;
RT "A new type of ERK1/2 autophosphorylation causes cardiac hypertrophy.";
RL Nat. Med. 15:75-83(2009).
RN [51]
RP REVIEW ON FUNCTION.
RX PubMed=16393692; DOI=10.1080/02699050500284218;
RA Yoon S., Seger R.;
RT "The extracellular signal-regulated kinase: multiple substrates regulate
RT diverse cellular functions.";
RL Growth Factors 24:21-44(2006).
RN [52]
RP REVIEW ON FUNCTION, AND REVIEW ON SUBCELLULAR LOCATION.
RX PubMed=19565474; DOI=10.1002/biof.52;
RA Yao Z., Seger R.;
RT "The ERK signaling cascade--views from different subcellular
RT compartments.";
RL BioFactors 35:407-416(2009).
RN [53]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-185 AND TYR-187, AND
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 [54]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [55]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [56]
RP REVIEW ON ACTIVITY REGULATION, AND REVIEW ON FUNCTION.
RX PubMed=21779493; DOI=10.1177/1947601911407328;
RA Wortzel I., Seger R.;
RT "The ERK cascade: distinct functions within various subcellular
RT organelles.";
RL Genes Cancer 2:195-209(2011).
RN [57]
RP FUNCTION, AND INTERACTION WITH PML.
RX PubMed=22033920; DOI=10.1074/jbc.m111.289512;
RA Lim J.H., Liu Y., Reineke E., Kao H.Y.;
RT "Mitogen-activated protein kinase extracellular signal-regulated kinase 2
RT phosphorylates and promotes Pin1 protein-dependent promyelocytic leukemia
RT protein turnover.";
RL J. Biol. Chem. 286:44403-44411(2011).
RN [58]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-185 AND TYR-187, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [59]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [60]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [61]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-185 AND TYR-187, AND
RP IDENTIFICATION BY MASS 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 [62]
RP INTERACTION WITH STYX.
RX PubMed=23847209; DOI=10.1073/pnas.1301985110;
RA Reiterer V., Fey D., Kolch W., Kholodenko B.N., Farhan H.;
RT "Pseudophosphatase STYX modulates cell-fate decisions and cell migration by
RT spatiotemporal regulation of ERK1/2.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:E2934-2943(2013).
RN [63]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [64]
RP INTERACTION WITH ZNF263.
RX PubMed=32051553; DOI=10.1038/s41388-020-1206-7;
RA Yu Z., Feng J., Wang W., Deng Z., Zhang Y., Xiao L., Wang Z., Liu C.,
RA Liu Q., Chen S., Wu M.;
RT "The EGFR-ZNF263 signaling axis silences SIX3 in glioblastoma
RT epigenetically.";
RL Oncogene 39:3163-3178(2020).
RN [65] {ECO:0007744|PDB:1PME}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) IN COMPLEX WITH INHIBITOR.
RX PubMed=9827991; DOI=10.1002/pro.5560071102;
RA Fox T., Coll J.T., Xie X., Ford P.J., Germann U.A., Porter M.D.,
RA Pazhanisamy S., Fleming M.A., Galullo V., Su M.S., Wilson K.P.;
RT "A single amino acid substitution makes ERK2 susceptible to pyridinyl
RT imidazole inhibitors of p38 MAP kinase.";
RL Protein Sci. 7:2249-2255(1998).
RN [66] {ECO:0007744|PDB:1TVO}
RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) IN COMPLEX WITH INHIBITOR.
RX PubMed=16139248; DOI=10.1016/j.bbrc.2005.08.082;
RA Ohori M., Kinoshita T., Okubo M., Sato K., Yamazaki A., Arakawa H.,
RA Nishimura S., Inamura N., Nakajima H., Neya M., Miyake H., Fujii T.;
RT "Identification of a selective ERK inhibitor and structural determination
RT of the inhibitor-ERK2 complex.";
RL Biochem. Biophys. Res. Commun. 336:357-363(2005).
RN [67] {ECO:0007744|PDB:1WZY}
RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) IN COMPLEX WITH INHIBITOR.
RX PubMed=16242327; DOI=10.1016/j.bmcl.2005.09.055;
RA Kinoshita T., Warizaya M., Ohori M., Sato K., Neya M., Fujii T.;
RT "Crystal structure of human ERK2 complexed with a pyrazolo[3,4-c]pyridazine
RT derivative.";
RL Bioorg. Med. Chem. Lett. 16:55-58(2006).
RN [68] {ECO:0007744|PDB:3W55}
RP X-RAY CRYSTALLOGRAPHY (3.00 ANGSTROMS) IN COMPLEX WITH INHIBITOR.
RX PubMed=17194451; DOI=10.1016/j.bbrc.2006.12.083;
RA Ohori M., Kinoshita T., Yoshimura S., Warizaya M., Nakajima H., Miyake H.;
RT "Role of a cysteine residue in the active site of ERK and the MAPKK
RT family.";
RL Biochem. Biophys. Res. Commun. 353:633-637(2007).
RN [69] {ECO:0007744|PDB:2OJG, ECO:0007744|PDB:2OJI, ECO:0007744|PDB:2OJJ}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 2-359 IN COMPLEX WITH INHIBITOR.
RX PubMed=17300186; DOI=10.1021/jm061381f;
RA Aronov A.M., Baker C., Bemis G.W., Cao J., Chen G., Ford P.J.,
RA Germann U.A., Green J., Hale M.R., Jacobs M., Janetka J.W., Maltais F.,
RA Martinez-Botella G., Namchuk M.N., Straub J., Tang Q., Xie X.;
RT "Flipped out: structure-guided design of selective pyrazolylpyrrole ERK
RT inhibitors.";
RL J. Med. Chem. 50:1280-1287(2007).
RN [70] {ECO:0007744|PDB:3D42, ECO:0007744|PDB:3D44}
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 186-191, AND PHOSPHORYLATION AT
RP TYR-187.
RX PubMed=19053285; DOI=10.1021/bi801724n;
RA Critton D.A., Tortajada A., Stetson G., Peti W., Page R.;
RT "Structural basis of substrate recognition by hematopoietic tyrosine
RT phosphatase.";
RL Biochemistry 47:13336-13345(2008).
RN [71] {ECO:0007744|PDB:3I5Z, ECO:0007744|PDB:3I60}
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) IN COMPLEX WITH INHIBITOR.
RX PubMed=19827834; DOI=10.1021/jm900630q;
RA Aronov A.M., Tang Q., Martinez-Botella G., Bemis G.W., Cao J., Chen G.,
RA Ewing N.P., Ford P.J., Germann U.A., Green J., Hale M.R., Jacobs M.,
RA Janetka J.W., Maltais F., Markland W., Namchuk M.N., Nanthakumar S.,
RA Poondru S., Straub J., ter Haar E., Xie X.;
RT "Structure-guided design of potent and selective pyrimidylpyrrole
RT inhibitors of extracellular signal-regulated kinase (ERK) using
RT conformational control.";
RL J. Med. Chem. 52:6362-6368(2009).
RN [72]
RP VARIANTS NS13 ASN-74; TYR-80; VAL-174; ASN-318; GLY-318; GLN-322 AND
RP ARG-323, INVOLVEMENT IN NS13, CHARACTERIZATION OF VARIANTS NS13 ASN-74;
RP TYR-80; VAL-174; ASN-318; GLY-318 AND ARG-323, SUBCELLULAR LOCATION,
RP FUNCTION, AND INTERACTION WITH MAP2K1 AND DUSP6.
RX PubMed=32721402; DOI=10.1016/j.ajhg.2020.06.018;
RA Motta M., Pannone L., Pantaleoni F., Bocchinfuso G., Radio F.C.,
RA Cecchetti S., Ciolfi A., Di Rocco M., Elting M.W., Brilstra E.H., Boni S.,
RA Mazzanti L., Tamburrino F., Walsh L., Payne K., Fernandez-Jaen A.,
RA Ganapathi M., Chung W.K., Grange D.K., Dave-Wala A., Reshmi S.C.,
RA Bartholomew D.W., Mouhlas D., Carpentieri G., Bruselles A., Pizzi S.,
RA Bellacchio E., Piceci-Sparascio F., Lissewski C., Brinkmann J.,
RA Waclaw R.R., Waisfisz Q., van Gassen K., Wentzensen I.M., Morrow M.M.,
RA Alvarez S., Martinez-Garcia M., De Luca A., Memo L., Zampino G., Rossi C.,
RA Seri M., Gelb B.D., Zenker M., Dallapiccola B., Stella L., Prada C.E.,
RA Martinelli S., Flex E., Tartaglia M.;
RT "Enhanced MAPK1 function causes a neurodevelopmental disorder within the
RT RASopathy clinical spectrum.";
RL Am. J. Hum. Genet. 107:499-513(2020).
CC -!- FUNCTION: Serine/threonine kinase which acts as an essential component
CC of the MAP kinase signal transduction pathway. MAPK1/ERK2 and
CC MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK
CC cascade. They participate also in a signaling cascade initiated by
CC activated KIT and KITLG/SCF. Depending on the cellular context, the
CC MAPK/ERK cascade mediates diverse biological functions such as cell
CC growth, adhesion, survival and differentiation through the regulation
CC of transcription, translation, cytoskeletal rearrangements. The
CC MAPK/ERK cascade also plays a role in initiation and regulation of
CC meiosis, mitosis, and postmitotic functions in differentiated cells by
CC phosphorylating a number of transcription factors. About 160 substrates
CC have already been discovered for ERKs. Many of these substrates are
CC localized in the nucleus, and seem to participate in the regulation of
CC transcription upon stimulation. However, other substrates are found in
CC the cytosol as well as in other cellular organelles, and those are
CC responsible for processes such as translation, mitosis and apoptosis.
CC Moreover, the MAPK/ERK cascade is also involved in the regulation of
CC the endosomal dynamics, including lysosome processing and endosome
CC cycling through the perinuclear recycling compartment (PNRC); as well
CC as in the fragmentation of the Golgi apparatus during mitosis. The
CC substrates include transcription factors (such as ATF2, BCL6, ELK1,
CC ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN,
CC GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such
CC as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of
CC translation (such as EIF4EBP1) and a variety of other signaling-related
CC molecules (like ARHGEF2, DCC, FRS2 or GRB10). Protein kinases (such as
CC RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK,
CC MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or
CC MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are
CC other substrates which enable the propagation the MAPK/ERK signal to
CC additional cytosolic and nuclear targets, thereby extending the
CC specificity of the cascade. Mediates phosphorylation of TPR in response
CC to EGF stimulation. May play a role in the spindle assembly checkpoint.
CC Phosphorylates PML and promotes its interaction with PIN1, leading to
CC PML degradation. Phosphorylates CDK2AP2 (By similarity).
CC {ECO:0000250|UniProtKB:P63086, ECO:0000269|PubMed:10617468,
CC ECO:0000269|PubMed:10637505, ECO:0000269|PubMed:11154262,
CC ECO:0000269|PubMed:12110590, ECO:0000269|PubMed:12356731,
CC ECO:0000269|PubMed:12792650, ECO:0000269|PubMed:12794087,
CC ECO:0000269|PubMed:12974390, ECO:0000269|PubMed:15184391,
CC ECO:0000269|PubMed:15241487, ECO:0000269|PubMed:15616583,
CC ECO:0000269|PubMed:15664191, ECO:0000269|PubMed:15788397,
CC ECO:0000269|PubMed:15952796, ECO:0000269|PubMed:16581800,
CC ECO:0000269|PubMed:18794356, ECO:0000269|PubMed:19265199,
CC ECO:0000269|PubMed:19879846, ECO:0000269|PubMed:22033920,
CC ECO:0000269|PubMed:32721402, ECO:0000269|PubMed:7588608,
CC ECO:0000269|PubMed:8622688, ECO:0000269|PubMed:9480836,
CC ECO:0000269|PubMed:9596579, ECO:0000269|PubMed:9649500,
CC ECO:0000269|PubMed:9687510, ECO:0000303|PubMed:15526160,
CC ECO:0000303|PubMed:16393692, ECO:0000303|PubMed:19565474,
CC ECO:0000303|PubMed:21779493}.
CC -!- FUNCTION: Acts as a transcriptional repressor. Binds to a [GC]AAA[GC]
CC consensus sequence. Repress the expression of interferon gamma-induced
CC genes. Seems to bind to the promoter of CCL5, DMP1, IFIH1, IFITM1,
CC IRF7, IRF9, LAMP3, OAS1, OAS2, OAS3 and STAT1. Transcriptional activity
CC is independent of kinase activity. {ECO:0000269|PubMed:19879846}.
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: Phosphorylated by MAP2K1/MEK1 and MAP2K2/MEK2 on
CC Thr-185 and Tyr-187 in response to external stimuli like insulin or
CC NGF. Both phosphorylations are required for activity. This
CC phosphorylation causes dramatic conformational changes, which enable
CC full activation and interaction of MAPK1/ERK2 with its substrates.
CC Phosphorylation on Ser-29 by SGK1 results in its activation by
CC enhancing its interaction with MAP2K1/MEK1 and MAP2K2/MEK2.
CC Dephosphorylated and inactivated by DUSP1, DUSP3, DUSP6 and DUSP9.
CC Inactivated by pyrimidylpyrrole inhibitors.
CC {ECO:0000269|PubMed:12356731, ECO:0000269|PubMed:19060905}.
CC -!- SUBUNIT: Binds both upstream activators and downstream substrates in
CC multimolecular complexes. This interaction inhibits its tyrosine-kinase
CC activity. Interacts with ADAM15, ARHGEF2, ARRB2, DAPK1 (via death
CC domain), HSF4, IER3, IPO7, NISCH, SGK1, and isoform 1 of NEK2.
CC Interacts (via phosphorylated form) with TPR (via C-terminal region and
CC phosphorylated form); the interaction requires dimerization of
CC MAPK1/ERK2 and increases following EGF stimulation (PubMed:18794356).
CC Interacts with MAP2K1 (PubMed:32721402). Interacts with DUSP6
CC (PubMed:9596579, PubMed:32721402). Interacts (phosphorylated form) with
CC CAV2 ('Tyr-19'-phosphorylated form); the interaction, promoted by
CC insulin, leads to nuclear location and MAPK1 activation. Interacts with
CC MORG1, PEA15 and MKNK2 (By similarity). MKNK2 isoform 1 binding
CC prevents from dephosphorylation and inactivation (By similarity).
CC Interacts with DCC (By similarity). The phosphorylated form interacts
CC with PML (isoform PML-4). Interacts with STYX. Interacts with CDK2AP2.
CC Interacts with CAVIN4 (By similarity). Interacts with DUSP7; the
CC interaction enhances DUSP7 phosphatase activity (PubMed:9788880).
CC Interacts with GIT1; this interaction is necessary for MAPK1
CC localization to focal adhesions (By similarity). Interacts with ZNF263
CC (PubMed:32051553). {ECO:0000250|UniProtKB:P63085,
CC ECO:0000250|UniProtKB:P63086, ECO:0000269|PubMed:11912194,
CC ECO:0000269|PubMed:12356731, ECO:0000269|PubMed:15358203,
CC ECO:0000269|PubMed:15616583, ECO:0000269|PubMed:16139248,
CC ECO:0000269|PubMed:16242327, ECO:0000269|PubMed:16581800,
CC ECO:0000269|PubMed:17194451, ECO:0000269|PubMed:17300186,
CC ECO:0000269|PubMed:18211802, ECO:0000269|PubMed:18296648,
CC ECO:0000269|PubMed:18435604, ECO:0000269|PubMed:18760948,
CC ECO:0000269|PubMed:18794356, ECO:0000269|PubMed:19060905,
CC ECO:0000269|PubMed:19447520, ECO:0000269|PubMed:19827834,
CC ECO:0000269|PubMed:22033920, ECO:0000269|PubMed:23847209,
CC ECO:0000269|PubMed:32051553, ECO:0000269|PubMed:32721402,
CC ECO:0000269|PubMed:9596579, ECO:0000269|PubMed:9788880,
CC ECO:0000269|PubMed:9827991}.
CC -!- SUBUNIT: (Microbial infection) Interacts with HIV-1 Nef through its SH3
CC domain. {ECO:0000269|PubMed:8794306}.
CC -!- INTERACTION:
CC P28482; P05067: APP; NbExp=3; IntAct=EBI-959949, EBI-77613;
CC P28482; P53004: BLVRA; NbExp=2; IntAct=EBI-959949, EBI-7410441;
CC P28482; P15882: CHN1; NbExp=3; IntAct=EBI-959949, EBI-718947;
CC P28482; Q7L5N1: COPS6; NbExp=2; IntAct=EBI-959949, EBI-486838;
CC P28482; P28562: DUSP1; NbExp=3; IntAct=EBI-959949, EBI-975493;
CC P28482; Q13115: DUSP4; NbExp=6; IntAct=EBI-959949, EBI-6591081;
CC P28482; Q16690: DUSP5; NbExp=3; IntAct=EBI-959949, EBI-7487376;
CC P28482; Q16828: DUSP6; NbExp=5; IntAct=EBI-959949, EBI-746870;
CC P28482; Q99956: DUSP9; NbExp=4; IntAct=EBI-959949, EBI-3906678;
CC P28482; Q9BRK4: LZTS2; NbExp=4; IntAct=EBI-959949, EBI-741037;
CC P28482; Q02750: MAP2K1; NbExp=2; IntAct=EBI-959949, EBI-492564;
CC P28482; P28482: MAPK1; NbExp=3; IntAct=EBI-959949, EBI-959949;
CC P28482; Q16539-3: MAPK14; NbExp=5; IntAct=EBI-959949, EBI-6932370;
CC P28482; Q99750: MDFI; NbExp=3; IntAct=EBI-959949, EBI-724076;
CC P28482; Q9BUB5: MKNK1; NbExp=10; IntAct=EBI-959949, EBI-73837;
CC P28482; P35548: MSX2; NbExp=3; IntAct=EBI-959949, EBI-6447480;
CC P28482; Q15121: PEA15; NbExp=4; IntAct=EBI-959949, EBI-714410;
CC P28482; Q9UPG8: PLAGL2; NbExp=3; IntAct=EBI-959949, EBI-2876622;
CC P28482; P62487: POLR2G; NbExp=3; IntAct=EBI-959949, EBI-347928;
CC P28482; P35813: PPM1A; NbExp=19; IntAct=EBI-959949, EBI-989143;
CC P28482; Q6NYC8: PPP1R18; NbExp=3; IntAct=EBI-959949, EBI-2557469;
CC P28482; P25786: PSMA1; NbExp=3; IntAct=EBI-959949, EBI-359352;
CC P28482; A2A3K4: PTPDC1; NbExp=3; IntAct=EBI-959949, EBI-11603375;
CC P28482; P35236: PTPN7; NbExp=6; IntAct=EBI-959949, EBI-2265723;
CC P28482; Q12913: PTPRJ; NbExp=7; IntAct=EBI-959949, EBI-2264500;
CC P28482; Q15256: PTPRR; NbExp=3; IntAct=EBI-959949, EBI-2265659;
CC P28482; Q15256-5: PTPRR; NbExp=3; IntAct=EBI-959949, EBI-18347359;
CC P28482; O76064: RNF8; NbExp=3; IntAct=EBI-959949, EBI-373337;
CC P28482; Q15418: RPS6KA1; NbExp=7; IntAct=EBI-959949, EBI-963034;
CC P28482; Q15349: RPS6KA2; NbExp=9; IntAct=EBI-959949, EBI-1384149;
CC P28482; P51812: RPS6KA3; NbExp=7; IntAct=EBI-959949, EBI-1046616;
CC P28482; P29353-2: SHC1; NbExp=4; IntAct=EBI-959949, EBI-1000553;
CC P28482; P61764: STXBP1; NbExp=3; IntAct=EBI-959949, EBI-960169;
CC P28482; Q08117-2: TLE5; NbExp=3; IntAct=EBI-959949, EBI-11741437;
CC P28482; Q9Y296: TRAPPC4; NbExp=3; IntAct=EBI-959949, EBI-722888;
CC P28482; B2RXF5: ZBTB42; NbExp=3; IntAct=EBI-959949, EBI-12287587;
CC P28482; A0A384NQ31; NbExp=3; IntAct=EBI-959949, EBI-12903728;
CC P28482; Q9U1H0: cic; Xeno; NbExp=2; IntAct=EBI-959949, EBI-98330;
CC P28482; Q05922: Dusp2; Xeno; NbExp=2; IntAct=EBI-959949, EBI-7898692;
CC P28482; P02687: MBP; Xeno; NbExp=2; IntAct=EBI-959949, EBI-908215;
CC P28482; Q8VSP9: ospF; Xeno; NbExp=5; IntAct=EBI-959949, EBI-6506625;
CC P28482; P0A2M9: spvC; Xeno; NbExp=3; IntAct=EBI-959949, EBI-15676035;
CC P28482; Q69559: U24; Xeno; NbExp=2; IntAct=EBI-959949, EBI-8015758;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton, spindle {ECO:0000250}.
CC Nucleus {ECO:0000269|PubMed:32721402}. Cytoplasm, cytoskeleton,
CC microtubule organizing center, centrosome. Cytoplasm
CC {ECO:0000269|PubMed:32721402}. Membrane, caveola
CC {ECO:0000250|UniProtKB:P63086}. Cell junction, focal adhesion
CC {ECO:0000250|UniProtKB:P63085}. Note=Associated with the spindle during
CC prometaphase and metaphase (By similarity). PEA15-binding and
CC phosphorylated DAPK1 promote its cytoplasmic retention. Phosphorylation
CC at Ser- 246 and Ser-248 as well as autophosphorylation at Thr-190
CC promote nuclear localization. {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P28482-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P28482-2; Sequence=VSP_047815;
CC -!- DOMAIN: The TXY motif contains the threonine and tyrosine residues
CC whose phosphorylation activates the MAP kinases.
CC -!- PTM: Phosphorylated upon KIT and FLT3 signaling (By similarity). Dually
CC phosphorylated on Thr-185 and Tyr-187, which activates the enzyme.
CC Undergoes regulatory phosphorylation on additional residues such as
CC Ser-246 and Ser-248 in the kinase insert domain (KID) These
CC phosphorylations, which are probably mediated by more than one kinase,
CC are important for binding of MAPK1/ERK2 to importin-7 (IPO7) and its
CC nuclear translocation. In addition, autophosphorylation of Thr-190 was
CC shown to affect the subcellular localization of MAPK1/ERK2 as well.
CC Ligand-activated ALK induces tyrosine phosphorylation. Dephosphorylated
CC by PTPRJ at Tyr-187. Phosphorylation on Ser-29 by SGK1 results in its
CC activation by enhancing its interaction with MAP2K1/MEK1 and
CC MAP2K2/MEK2. DUSP3 and DUSP6 dephosphorylate specifically MAPK1/ERK2
CC and MAPK3/ERK1 whereas DUSP9 dephosphorylates a broader range of MAPKs.
CC Dephosphorylated by DUSP1 and DUSP2 at Thr-185 and Tyr-187 (By
CC similarity) (PubMed:16288922). {ECO:0000250,
CC ECO:0000250|UniProtKB:P63085, ECO:0000269|PubMed:16288922,
CC ECO:0000269|PubMed:17274988, ECO:0000269|PubMed:18760948,
CC ECO:0000269|PubMed:19053285, ECO:0000269|PubMed:19060905,
CC ECO:0000269|PubMed:19265199, ECO:0000269|PubMed:19447520,
CC ECO:0000269|PubMed:19494114}.
CC -!- PTM: ISGylated. {ECO:0000250}.
CC -!- DISEASE: Noonan syndrome 13 (NS13) [MIM:619087]: A form of Noonan
CC syndrome, a disease characterized by short stature, facial dysmorphic
CC features such as hypertelorism, a downward eyeslant and low-set
CC posteriorly rotated ears, and a high incidence of congenital heart
CC defects and hypertrophic cardiomyopathy. Other features can include a
CC short neck with webbing or redundancy of skin, deafness, motor delay,
CC variable intellectual deficits, multiple skeletal defects,
CC cryptorchidism, and bleeding diathesis. Individuals with Noonan
CC syndrome are at risk of juvenile myelomonocytic leukemia, a
CC myeloproliferative disorder characterized by excessive production of
CC myelomonocytic cells. NS13 inheritance is autosomal dominant. There is
CC considerable variability in severity. {ECO:0000269|PubMed:32721402}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
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=CAA77753.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Extracellular signal-regulated
CC kinase entry;
CC URL="https://en.wikipedia.org/wiki/Extracellular_signal-regulated_kinase";
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/MAPK1ID41288ch22q11.html";
CC ---------------------------------------------------------------------------
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DR EMBL; M84489; AAA58459.1; -; mRNA.
DR EMBL; Z11694; CAA77752.1; -; mRNA.
DR EMBL; Z11695; CAA77753.1; ALT_INIT; mRNA.
DR EMBL; DQ399292; ABD60303.1; -; mRNA.
DR EMBL; AP000553; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP000554; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP000555; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC017832; AAH17832.1; -; mRNA.
DR CCDS; CCDS13795.1; -. [P28482-1]
DR PIR; JQ1400; JQ1400.
DR RefSeq; NP_002736.3; NM_002745.4. [P28482-1]
DR RefSeq; NP_620407.1; NM_138957.3. [P28482-1]
DR PDB; 1PME; X-ray; 2.00 A; A=1-360.
DR PDB; 1TVO; X-ray; 2.50 A; A=1-360.
DR PDB; 1WZY; X-ray; 2.50 A; A=1-360.
DR PDB; 2OJG; X-ray; 2.00 A; A=2-360.
DR PDB; 2OJI; X-ray; 2.60 A; A=2-360.
DR PDB; 2OJJ; X-ray; 2.40 A; A=2-360.
DR PDB; 2Y9Q; X-ray; 1.55 A; A=1-360.
DR PDB; 3D42; X-ray; 2.46 A; B=184-191.
DR PDB; 3D44; X-ray; 1.90 A; B=184-191.
DR PDB; 3I5Z; X-ray; 2.20 A; A=1-360.
DR PDB; 3I60; X-ray; 2.50 A; A=1-360.
DR PDB; 3SA0; X-ray; 1.59 A; A=1-360.
DR PDB; 3TEI; X-ray; 2.40 A; A=1-360.
DR PDB; 3W55; X-ray; 3.00 A; A=1-360.
DR PDB; 4FMQ; X-ray; 2.10 A; A=1-360.
DR PDB; 4FUX; X-ray; 2.20 A; A=1-360.
DR PDB; 4FUY; X-ray; 2.00 A; A=1-360.
DR PDB; 4FV0; X-ray; 2.10 A; A=1-360.
DR PDB; 4FV1; X-ray; 1.99 A; A=1-360.
DR PDB; 4FV2; X-ray; 2.00 A; A=1-360.
DR PDB; 4FV3; X-ray; 2.20 A; A=1-360.
DR PDB; 4FV4; X-ray; 2.50 A; A=1-360.
DR PDB; 4FV5; X-ray; 2.40 A; A=1-360.
DR PDB; 4FV6; X-ray; 2.50 A; A=1-360.
DR PDB; 4FV7; X-ray; 1.90 A; A=1-360.
DR PDB; 4FV8; X-ray; 2.00 A; A=1-360.
DR PDB; 4FV9; X-ray; 2.11 A; A=1-360.
DR PDB; 4G6N; X-ray; 2.00 A; A=1-360.
DR PDB; 4G6O; X-ray; 2.20 A; A=1-360.
DR PDB; 4H3P; X-ray; 2.30 A; A/D=1-360.
DR PDB; 4H3Q; X-ray; 2.20 A; A=1-360.
DR PDB; 4IZ5; X-ray; 3.19 A; A/B/C/D=8-360.
DR PDB; 4IZ7; X-ray; 1.80 A; A/C=8-360.
DR PDB; 4IZA; X-ray; 1.93 A; A/C=8-360.
DR PDB; 4N0S; X-ray; 1.80 A; A=1-360.
DR PDB; 4NIF; X-ray; 2.15 A; B/E=1-360.
DR PDB; 4O6E; X-ray; 1.95 A; A=13-360.
DR PDB; 4QP1; X-ray; 2.70 A; A/B=1-360.
DR PDB; 4QP2; X-ray; 2.23 A; A/B=1-360.
DR PDB; 4QP3; X-ray; 2.60 A; A/B=1-360.
DR PDB; 4QP4; X-ray; 2.20 A; A/B=1-360.
DR PDB; 4QP6; X-ray; 3.10 A; A/B=1-360.
DR PDB; 4QP7; X-ray; 2.25 A; A/B=1-360.
DR PDB; 4QP8; X-ray; 2.45 A; A/B=1-360.
DR PDB; 4QP9; X-ray; 2.00 A; A=1-360.
DR PDB; 4QPA; X-ray; 2.85 A; A/B=1-360.
DR PDB; 4QTA; X-ray; 1.45 A; A=1-360.
DR PDB; 4QTE; X-ray; 1.50 A; A=1-360.
DR PDB; 4XJ0; X-ray; 2.58 A; A/B=12-360.
DR PDB; 4ZXT; X-ray; 2.00 A; A=1-360.
DR PDB; 4ZZM; X-ray; 1.89 A; A=11-360.
DR PDB; 4ZZN; X-ray; 1.33 A; A=11-360.
DR PDB; 4ZZO; X-ray; 1.63 A; A=11-360.
DR PDB; 5AX3; X-ray; 2.98 A; A=1-360.
DR PDB; 5BUE; X-ray; 2.40 A; A=2-360.
DR PDB; 5BUI; X-ray; 2.12 A; A=2-360.
DR PDB; 5BUJ; X-ray; 1.85 A; A=2-360.
DR PDB; 5BVD; X-ray; 1.90 A; A=2-360.
DR PDB; 5BVE; X-ray; 2.00 A; A=2-360.
DR PDB; 5BVF; X-ray; 1.90 A; A=2-360.
DR PDB; 5K4I; X-ray; 1.76 A; A=9-360.
DR PDB; 5LCJ; X-ray; 1.78 A; A=1-360.
DR PDB; 5LCK; X-ray; 1.89 A; A=1-360.
DR PDB; 5NGU; X-ray; 2.74 A; A=1-360.
DR PDB; 5NHF; X-ray; 2.14 A; A=1-360.
DR PDB; 5NHH; X-ray; 1.94 A; A=1-360.
DR PDB; 5NHJ; X-ray; 2.12 A; A=1-360.
DR PDB; 5NHL; X-ray; 2.07 A; A=1-360.
DR PDB; 5NHO; X-ray; 2.24 A; A=1-360.
DR PDB; 5NHP; X-ray; 1.99 A; A=1-360.
DR PDB; 5NHV; X-ray; 2.00 A; A=1-360.
DR PDB; 5V60; X-ray; 2.18 A; A=8-360.
DR PDB; 5V61; X-ray; 2.20 A; A=8-360.
DR PDB; 5V62; X-ray; 1.90 A; A=10-360.
DR PDB; 5WP1; X-ray; 1.40 A; A=4-360.
DR PDB; 6D5Y; X-ray; 2.86 A; A=13-360.
DR PDB; 6DMG; X-ray; 2.20 A; A=11-357.
DR PDB; 6G54; X-ray; 2.05 A; A=1-360.
DR PDB; 6G8X; X-ray; 1.76 A; A=1-360.
DR PDB; 6G91; X-ray; 1.80 A; A=1-360.
DR PDB; 6G92; X-ray; 1.99 A; A=1-360.
DR PDB; 6G93; X-ray; 1.67 A; A=1-360.
DR PDB; 6G97; X-ray; 1.90 A; A=1-360.
DR PDB; 6G9A; X-ray; 1.91 A; A=1-360.
DR PDB; 6G9D; X-ray; 1.80 A; A=1-360.
DR PDB; 6G9H; X-ray; 1.73 A; A=1-360.
DR PDB; 6G9J; X-ray; 1.98 A; A=1-360.
DR PDB; 6G9K; X-ray; 1.94 A; A=1-360.
DR PDB; 6G9M; X-ray; 1.86 A; A=1-360.
DR PDB; 6G9N; X-ray; 1.76 A; A=1-360.
DR PDB; 6GDM; X-ray; 1.91 A; A=1-360.
DR PDB; 6GDQ; X-ray; 1.86 A; A=1-360.
DR PDB; 6GE0; X-ray; 1.82 A; A=1-360.
DR PDB; 6GJB; X-ray; 1.82 A; A=1-360.
DR PDB; 6GJD; X-ray; 1.58 A; A=1-360.
DR PDB; 6NBS; X-ray; 1.90 A; A=9-360.
DR PDB; 6OPG; X-ray; 2.90 A; A=8-360.
DR PDB; 6OPH; X-ray; 2.40 A; A=8-360.
DR PDB; 6OPI; X-ray; 3.00 A; A=8-360.
DR PDB; 6Q7K; X-ray; 1.84 A; A=1-360.
DR PDB; 6Q7S; X-ray; 1.73 A; A=1-360.
DR PDB; 6Q7T; X-ray; 1.60 A; A=1-360.
DR PDB; 6QA1; X-ray; 1.58 A; A=1-360.
DR PDB; 6QA3; X-ray; 1.57 A; A=1-360.
DR PDB; 6QA4; X-ray; 1.60 A; A=1-360.
DR PDB; 6QAG; X-ray; 2.07 A; A=1-360.
DR PDB; 6QAH; X-ray; 1.58 A; A=1-360.
DR PDB; 6QAL; X-ray; 1.57 A; A=1-360.
DR PDB; 6QAQ; X-ray; 1.58 A; A=1-360.
DR PDB; 6QAW; X-ray; 1.84 A; A=1-360.
DR PDB; 6RQ4; X-ray; 1.96 A; A=1-360.
DR PDB; 6SLG; X-ray; 1.33 A; A=1-360.
DR PDB; 7AUV; X-ray; 1.76 A; A=1-360.
DR PDB; 7E73; X-ray; 2.28 A; A=1-360.
DR PDB; 7E75; X-ray; 2.48 A; A=1-360.
DR PDB; 7NQQ; X-ray; 1.94 A; A=1-360.
DR PDB; 7NQW; X-ray; 1.77 A; A=1-360.
DR PDB; 7NR3; X-ray; 1.90 A; A=1-360.
DR PDB; 7NR5; X-ray; 1.77 A; A=1-360.
DR PDB; 7NR8; X-ray; 1.63 A; A=1-360.
DR PDB; 7NR9; X-ray; 1.91 A; A=1-360.
DR PDB; 7OPM; X-ray; 2.45 A; A=1-360.
DR PDB; 7W5O; X-ray; 2.35 A; A/B=1-360.
DR PDBsum; 1PME; -.
DR PDBsum; 1TVO; -.
DR PDBsum; 1WZY; -.
DR PDBsum; 2OJG; -.
DR PDBsum; 2OJI; -.
DR PDBsum; 2OJJ; -.
DR PDBsum; 2Y9Q; -.
DR PDBsum; 3D42; -.
DR PDBsum; 3D44; -.
DR PDBsum; 3I5Z; -.
DR PDBsum; 3I60; -.
DR PDBsum; 3SA0; -.
DR PDBsum; 3TEI; -.
DR PDBsum; 3W55; -.
DR PDBsum; 4FMQ; -.
DR PDBsum; 4FUX; -.
DR PDBsum; 4FUY; -.
DR PDBsum; 4FV0; -.
DR PDBsum; 4FV1; -.
DR PDBsum; 4FV2; -.
DR PDBsum; 4FV3; -.
DR PDBsum; 4FV4; -.
DR PDBsum; 4FV5; -.
DR PDBsum; 4FV6; -.
DR PDBsum; 4FV7; -.
DR PDBsum; 4FV8; -.
DR PDBsum; 4FV9; -.
DR PDBsum; 4G6N; -.
DR PDBsum; 4G6O; -.
DR PDBsum; 4H3P; -.
DR PDBsum; 4H3Q; -.
DR PDBsum; 4IZ5; -.
DR PDBsum; 4IZ7; -.
DR PDBsum; 4IZA; -.
DR PDBsum; 4N0S; -.
DR PDBsum; 4NIF; -.
DR PDBsum; 4O6E; -.
DR PDBsum; 4QP1; -.
DR PDBsum; 4QP2; -.
DR PDBsum; 4QP3; -.
DR PDBsum; 4QP4; -.
DR PDBsum; 4QP6; -.
DR PDBsum; 4QP7; -.
DR PDBsum; 4QP8; -.
DR PDBsum; 4QP9; -.
DR PDBsum; 4QPA; -.
DR PDBsum; 4QTA; -.
DR PDBsum; 4QTE; -.
DR PDBsum; 4XJ0; -.
DR PDBsum; 4ZXT; -.
DR PDBsum; 4ZZM; -.
DR PDBsum; 4ZZN; -.
DR PDBsum; 4ZZO; -.
DR PDBsum; 5AX3; -.
DR PDBsum; 5BUE; -.
DR PDBsum; 5BUI; -.
DR PDBsum; 5BUJ; -.
DR PDBsum; 5BVD; -.
DR PDBsum; 5BVE; -.
DR PDBsum; 5BVF; -.
DR PDBsum; 5K4I; -.
DR PDBsum; 5LCJ; -.
DR PDBsum; 5LCK; -.
DR PDBsum; 5NGU; -.
DR PDBsum; 5NHF; -.
DR PDBsum; 5NHH; -.
DR PDBsum; 5NHJ; -.
DR PDBsum; 5NHL; -.
DR PDBsum; 5NHO; -.
DR PDBsum; 5NHP; -.
DR PDBsum; 5NHV; -.
DR PDBsum; 5V60; -.
DR PDBsum; 5V61; -.
DR PDBsum; 5V62; -.
DR PDBsum; 5WP1; -.
DR PDBsum; 6D5Y; -.
DR PDBsum; 6DMG; -.
DR PDBsum; 6G54; -.
DR PDBsum; 6G8X; -.
DR PDBsum; 6G91; -.
DR PDBsum; 6G92; -.
DR PDBsum; 6G93; -.
DR PDBsum; 6G97; -.
DR PDBsum; 6G9A; -.
DR PDBsum; 6G9D; -.
DR PDBsum; 6G9H; -.
DR PDBsum; 6G9J; -.
DR PDBsum; 6G9K; -.
DR PDBsum; 6G9M; -.
DR PDBsum; 6G9N; -.
DR PDBsum; 6GDM; -.
DR PDBsum; 6GDQ; -.
DR PDBsum; 6GE0; -.
DR PDBsum; 6GJB; -.
DR PDBsum; 6GJD; -.
DR PDBsum; 6NBS; -.
DR PDBsum; 6OPG; -.
DR PDBsum; 6OPH; -.
DR PDBsum; 6OPI; -.
DR PDBsum; 6Q7K; -.
DR PDBsum; 6Q7S; -.
DR PDBsum; 6Q7T; -.
DR PDBsum; 6QA1; -.
DR PDBsum; 6QA3; -.
DR PDBsum; 6QA4; -.
DR PDBsum; 6QAG; -.
DR PDBsum; 6QAH; -.
DR PDBsum; 6QAL; -.
DR PDBsum; 6QAQ; -.
DR PDBsum; 6QAW; -.
DR PDBsum; 6RQ4; -.
DR PDBsum; 6SLG; -.
DR PDBsum; 7AUV; -.
DR PDBsum; 7E73; -.
DR PDBsum; 7E75; -.
DR PDBsum; 7NQQ; -.
DR PDBsum; 7NQW; -.
DR PDBsum; 7NR3; -.
DR PDBsum; 7NR5; -.
DR PDBsum; 7NR8; -.
DR PDBsum; 7NR9; -.
DR PDBsum; 7OPM; -.
DR PDBsum; 7W5O; -.
DR AlphaFoldDB; P28482; -.
DR BMRB; P28482; -.
DR SMR; P28482; -.
DR BioGRID; 111580; 397.
DR CORUM; P28482; -.
DR DIP; DIP-519N; -.
DR ELM; P28482; -.
DR IntAct; P28482; 158.
DR MINT; P28482; -.
DR STRING; 9606.ENSP00000215832; -.
DR BindingDB; P28482; -.
DR ChEMBL; CHEMBL4040; -.
DR DrugBank; DB07788; (3R,5Z,8S,9S,11E)-8,9,16-TRIHYDROXY-14-METHOXY-3-METHYL-3,4,9,10-TETRAHYDRO-1H-2-BENZOXACYCLOTETRADECINE-1,7(8H)-DIONE.
DR DrugBank; DB07264; (S)-N-(1-(3-CHLORO-4-FLUOROPHENYL)-2-HYDROXYETHYL)-4-(4-(3-CHLOROPHENYL)-1H-PYRAZOL-3-YL)-1H-PYRROLE-2-CARBOXAMIDE.
DR DrugBank; DB08521; 4-[4-(4-Fluorophenyl)-2-[4-[(R)-methylsulfinyl]phenyl]-1H-imidazol-5-yl]pyridine.
DR DrugBank; DB07794; 5-(2-PHENYLPYRAZOLO[1,5-A]PYRIDIN-3-YL)-1H-PYRAZOLO[3,4-C]PYRIDAZIN-3-AMINE.
DR DrugBank; DB08513; [4-({5-(AMINOCARBONYL)-4-[(3-METHYLPHENYL)AMINO]PYRIMIDIN-2-YL}AMINO)PHENYL]ACETIC ACID.
DR DrugBank; DB00945; Acetylsalicylic acid.
DR DrugBank; DB01169; Arsenic trioxide.
DR DrugBank; DB07905; Hypothemycin.
DR DrugBank; DB01017; Minocycline.
DR DrugBank; DB06877; N,N-DIMETHYL-4-(4-PHENYL-1H-PYRAZOL-3-YL)-1H-PYRROLE-2-CARBOXAMIDE.
DR DrugBank; DB07010; N-BENZYL-4-[4-(3-CHLOROPHENYL)-1H-PYRAZOL-3-YL]-1H-PYRROLE-2-CARBOXAMIDE.
DR DrugBank; DB02116; Olomoucine.
DR DrugBank; DB06641; Perifosine.
DR DrugBank; DB02482; Phosphonothreonine.
DR DrugBank; DB02733; Purvalanol.
DR DrugBank; DB04338; SB220025.
DR DrugBank; DB06195; Seliciclib.
DR DrugBank; DB11120; Turpentine.
DR DrugBank; DB13930; Ulixertinib.
DR DrugCentral; P28482; -.
DR GuidetoPHARMACOLOGY; 1495; -.
DR MoonDB; P28482; Predicted.
DR MoonProt; P28482; -.
DR iPTMnet; P28482; -.
DR MetOSite; P28482; -.
DR PhosphoSitePlus; P28482; -.
DR SwissPalm; P28482; -.
DR BioMuta; MAPK1; -.
DR DMDM; 119554; -.
DR OGP; P28482; -.
DR CPTAC; CPTAC-1352; -.
DR CPTAC; CPTAC-1353; -.
DR CPTAC; CPTAC-1354; -.
DR CPTAC; CPTAC-1541; -.
DR CPTAC; CPTAC-870; -.
DR CPTAC; CPTAC-871; -.
DR EPD; P28482; -.
DR jPOST; P28482; -.
DR MassIVE; P28482; -.
DR MaxQB; P28482; -.
DR PaxDb; P28482; -.
DR PeptideAtlas; P28482; -.
DR PRIDE; P28482; -.
DR ProteomicsDB; 1826; -.
DR ProteomicsDB; 54488; -. [P28482-1]
DR Antibodypedia; 3785; 1901 antibodies from 55 providers.
DR CPTC; P28482; 4 antibodies.
DR DNASU; 5594; -.
DR Ensembl; ENST00000215832.11; ENSP00000215832.7; ENSG00000100030.15. [P28482-1]
DR Ensembl; ENST00000398822.7; ENSP00000381803.3; ENSG00000100030.15. [P28482-1]
DR Ensembl; ENST00000544786.1; ENSP00000440842.1; ENSG00000100030.15. [P28482-2]
DR GeneID; 5594; -.
DR KEGG; hsa:5594; -.
DR MANE-Select; ENST00000215832.11; ENSP00000215832.7; NM_002745.5; NP_002736.3.
DR UCSC; uc010gtk.2; human. [P28482-1]
DR CTD; 5594; -.
DR DisGeNET; 5594; -.
DR GeneCards; MAPK1; -.
DR GeneReviews; MAPK1; -.
DR HGNC; HGNC:6871; MAPK1.
DR HPA; ENSG00000100030; Low tissue specificity.
DR MalaCards; MAPK1; -.
DR MIM; 176948; gene.
DR MIM; 619087; phenotype.
DR neXtProt; NX_P28482; -.
DR OpenTargets; ENSG00000100030; -.
DR Orphanet; 261330; Distal 22q11.2 microdeletion syndrome.
DR PharmGKB; PA30616; -.
DR VEuPathDB; HostDB:ENSG00000100030; -.
DR eggNOG; KOG0660; Eukaryota.
DR GeneTree; ENSGT00940000156771; -.
DR HOGENOM; CLU_000288_181_1_1; -.
DR InParanoid; P28482; -.
DR OMA; SFFDFDY; -.
DR PhylomeDB; P28482; -.
DR TreeFam; TF105097; -.
DR BRENDA; 2.7.11.24; 2681.
DR PathwayCommons; P28482; -.
DR Reactome; R-HSA-111995; phospho-PLA2 pathway.
DR Reactome; R-HSA-112409; RAF-independent MAPK1/3 activation.
DR Reactome; R-HSA-112411; MAPK1 (ERK2) activation.
DR Reactome; R-HSA-1181150; Signaling by NODAL.
DR Reactome; R-HSA-1295596; Spry regulation of FGF signaling.
DR Reactome; R-HSA-1502540; Signaling by Activin.
DR Reactome; R-HSA-162658; Golgi Cisternae Pericentriolar Stack Reorganization.
DR Reactome; R-HSA-170968; Frs2-mediated activation.
DR Reactome; R-HSA-198753; ERK/MAPK targets.
DR Reactome; R-HSA-202670; ERKs are inactivated.
DR Reactome; R-HSA-2029482; Regulation of actin dynamics for phagocytic cup formation.
DR Reactome; R-HSA-2173796; SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.
DR Reactome; R-HSA-2559580; Oxidative Stress Induced Senescence.
DR Reactome; R-HSA-2559582; Senescence-Associated Secretory Phenotype (SASP).
DR Reactome; R-HSA-2559585; Oncogene Induced Senescence.
DR Reactome; R-HSA-2871796; FCERI mediated MAPK activation.
DR Reactome; R-HSA-3371453; Regulation of HSF1-mediated heat shock response.
DR Reactome; R-HSA-375165; NCAM signaling for neurite out-growth.
DR Reactome; R-HSA-437239; Recycling pathway of L1.
DR Reactome; R-HSA-444257; RSK activation.
DR Reactome; R-HSA-445144; Signal transduction by L1.
DR Reactome; R-HSA-450341; Activation of the AP-1 family of transcription factors.
DR Reactome; R-HSA-456926; Thrombin signalling through proteinase activated receptors (PARs).
DR Reactome; R-HSA-5654726; Negative regulation of FGFR1 signaling.
DR Reactome; R-HSA-5654727; Negative regulation of FGFR2 signaling.
DR Reactome; R-HSA-5654732; Negative regulation of FGFR3 signaling.
DR Reactome; R-HSA-5654733; Negative regulation of FGFR4 signaling.
DR Reactome; R-HSA-5663213; RHO GTPases Activate WASPs and WAVEs.
DR Reactome; R-HSA-5668599; RHO GTPases Activate NADPH Oxidases.
DR Reactome; R-HSA-5673001; RAF/MAP kinase cascade.
DR Reactome; R-HSA-5674135; MAP2K and MAPK activation.
DR Reactome; R-HSA-5674499; Negative feedback regulation of MAPK pathway.
DR Reactome; R-HSA-5675221; Negative regulation of MAPK pathway.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR Reactome; R-HSA-6802946; Signaling by moderate kinase activity BRAF mutants.
DR Reactome; R-HSA-6802948; Signaling by high-kinase activity BRAF mutants.
DR Reactome; R-HSA-6802952; Signaling by BRAF and RAF1 fusions.
DR Reactome; R-HSA-6802955; Paradoxical activation of RAF signaling by kinase inactive BRAF.
DR Reactome; R-HSA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR Reactome; R-HSA-74749; Signal attenuation.
DR Reactome; R-HSA-879415; Advanced glycosylation endproduct receptor signaling.
DR Reactome; R-HSA-881907; Gastrin-CREB signalling pathway via PKC and MAPK.
DR Reactome; R-HSA-8939211; ESR-mediated signaling.
DR Reactome; R-HSA-8940973; RUNX2 regulates osteoblast differentiation.
DR Reactome; R-HSA-8943724; Regulation of PTEN gene transcription.
DR Reactome; R-HSA-9627069; Regulation of the apoptosome activity.
DR Reactome; R-HSA-9634635; Estrogen-stimulated signaling through PRKCZ.
DR Reactome; R-HSA-9634638; Estrogen-dependent nuclear events downstream of ESR-membrane signaling.
DR Reactome; R-HSA-9635465; Suppression of apoptosis.
DR Reactome; R-HSA-9649948; Signaling downstream of RAS mutants.
DR Reactome; R-HSA-9652169; Signaling by MAP2K mutants.
DR Reactome; R-HSA-9652817; Signaling by MAPK mutants.
DR Reactome; R-HSA-9656223; Signaling by RAF1 mutants.
DR Reactome; R-HSA-9664422; FCGR3A-mediated phagocytosis.
DR Reactome; R-HSA-9725371; Nuclear events stimulated by ALK signaling in cancer.
DR Reactome; R-HSA-982772; Growth hormone receptor signaling.
DR SABIO-RK; P28482; -.
DR SignaLink; P28482; -.
DR SIGNOR; P28482; -.
DR BioGRID-ORCS; 5594; 147 hits in 1126 CRISPR screens.
DR ChiTaRS; MAPK1; human.
DR EvolutionaryTrace; P28482; -.
DR GeneWiki; MAPK1; -.
DR GenomeRNAi; 5594; -.
DR Pharos; P28482; Tchem.
DR PRO; PR:P28482; -.
DR Proteomes; UP000005640; Chromosome 22.
DR RNAct; P28482; protein.
DR Bgee; ENSG00000100030; Expressed in middle temporal gyrus and 209 other tissues.
DR ExpressionAtlas; P28482; baseline and differential.
DR Genevisible; P28482; HS.
DR GO; GO:0035578; C:azurophil granule lumen; TAS:Reactome.
DR GO; GO:0005901; C:caveola; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; TAS:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:UniProtKB.
DR GO; GO:0005769; C:early endosome; TAS:UniProtKB.
DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:1904813; C:ficolin-1-rich granule lumen; TAS:Reactome.
DR GO; GO:0005925; C:focal adhesion; TAS:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; TAS:UniProtKB.
DR GO; GO:0005770; C:late endosome; TAS:UniProtKB.
DR GO; GO:0005815; C:microtubule organizing center; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; TAS:UniProtKB.
DR GO; GO:0072686; C:mitotic spindle; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0031143; C:pseudopodium; IEA:Ensembl.
DR GO; GO:0045202; C:synapse; IEA:GOC.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0004707; F:MAP kinase activity; IBA:GO_Central.
DR GO; GO:0004708; F:MAP kinase kinase activity; IEA:Ensembl.
DR GO; GO:0019902; F:phosphatase binding; IPI:UniProtKB.
DR GO; GO:0001784; F:phosphotyrosine residue binding; IEA:Ensembl.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0008353; F:RNA polymerase II CTD heptapeptide repeat kinase activity; ISS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; TAS:ProtInc.
DR GO; GO:0050853; P:B cell receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0060020; P:Bergmann glial cell differentiation; IEA:Ensembl.
DR GO; GO:0061308; P:cardiac neural crest cell development involved in heart development; IEA:Ensembl.
DR GO; GO:0072584; P:caveolin-mediated endocytosis; TAS:UniProtKB.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0007166; P:cell surface receptor signaling pathway; IBA:GO_Central.
DR GO; GO:0034198; P:cellular response to amino acid starvation; IDA:CAFA.
DR GO; GO:0071276; P:cellular response to cadmium ion; IMP:CAFA.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IEA:Ensembl.
DR GO; GO:1903351; P:cellular response to dopamine; IMP:CAFA.
DR GO; GO:0034614; P:cellular response to reactive oxygen species; IMP:CAFA.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IEA:Ensembl.
DR GO; GO:0007268; P:chemical synaptic transmission; TAS:ProtInc.
DR GO; GO:0006935; P:chemotaxis; TAS:ProtInc.
DR GO; GO:0019858; P:cytosine metabolic process; IEA:Ensembl.
DR GO; GO:0038127; P:ERBB signaling pathway; IDA:UniProtKB.
DR GO; GO:0070371; P:ERK1 and ERK2 cascade; IDA:UniProtKB.
DR GO; GO:0060324; P:face development; IEA:Ensembl.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0060716; P:labyrinthine layer blood vessel development; IEA:Ensembl.
DR GO; GO:0007611; P:learning or memory; NAS:ARUK-UCL.
DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IEA:Ensembl.
DR GO; GO:0060291; P:long-term synaptic potentiation; IEA:Ensembl.
DR GO; GO:0060425; P:lung morphogenesis; IEA:Ensembl.
DR GO; GO:0033598; P:mammary gland epithelial cell proliferation; IEA:Ensembl.
DR GO; GO:0045596; P:negative regulation of cell differentiation; IEA:Ensembl.
DR GO; GO:0042473; P:outer ear morphogenesis; IEA:Ensembl.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:BHF-UCL.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; ISS:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:CAFA.
DR GO; GO:0010759; P:positive regulation of macrophage chemotaxis; IGI:ARUK-UCL.
DR GO; GO:0120041; P:positive regulation of macrophage proliferation; IGI:ARUK-UCL.
DR GO; GO:0010800; P:positive regulation of peptidyl-threonine phosphorylation; IDA:UniProtKB.
DR GO; GO:0051973; P:positive regulation of telomerase activity; IMP:BHF-UCL.
DR GO; GO:1904355; P:positive regulation of telomere capping; IMP:BHF-UCL.
DR GO; GO:0032212; P:positive regulation of telomere maintenance via telomerase; IMP:BHF-UCL.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0030641; P:regulation of cellular pH; IEA:Ensembl.
DR GO; GO:0051493; P:regulation of cytoskeleton organization; TAS:UniProtKB.
DR GO; GO:2000641; P:regulation of early endosome to late endosome transport; TAS:UniProtKB.
DR GO; GO:0090170; P:regulation of Golgi inheritance; TAS:UniProtKB.
DR GO; GO:0030278; P:regulation of ossification; IEA:Ensembl.
DR GO; GO:0031647; P:regulation of protein stability; ISS:UniProtKB.
DR GO; GO:0032872; P:regulation of stress-activated MAPK cascade; TAS:UniProtKB.
DR GO; GO:0070849; P:response to epidermal growth factor; IDA:UniProtKB.
DR GO; GO:0043330; P:response to exogenous dsRNA; IEA:Ensembl.
DR GO; GO:0035094; P:response to nicotine; ISS:ARUK-UCL.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0051403; P:stress-activated MAPK cascade; IDA:CAFA.
DR GO; GO:0050852; P:T cell receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0048538; P:thymus development; IEA:Ensembl.
DR GO; GO:0030878; P:thyroid gland development; IEA:Ensembl.
DR GO; GO:0060440; P:trachea formation; IEA:Ensembl.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR003527; MAP_kinase_CS.
DR InterPro; IPR008349; MAPK_ERK1/2.
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; PR01770; ERK1ERK2MAPK.
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; Apoptosis; ATP-binding;
KW Cell cycle; Cell junction; Cytoplasm; Cytoskeleton;
KW Direct protein sequencing; Disease variant; DNA-binding;
KW Host-virus interaction; Kinase; Membrane; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Repressor;
KW Serine/threonine-protein kinase; Transcription; Transcription regulation;
KW Transferase; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:12665801,
FT ECO:0007744|PubMed:19413330, ECO:0007744|PubMed:22223895,
FT ECO:0007744|PubMed:22814378"
FT CHAIN 2..360
FT /note="Mitogen-activated protein kinase 1"
FT /id="PRO_0000186247"
FT DOMAIN 25..313
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DNA_BIND 259..277
FT MOTIF 185..187
FT /note="TXY"
FT /evidence="ECO:0000269|PubMed:18760948"
FT MOTIF 318..322
FT /note="Cytoplasmic retention motif"
FT /evidence="ECO:0000269|PubMed:18760948"
FT MOTIF 327..333
FT /note="Nuclear translocation motif"
FT /evidence="ECO:0000269|PubMed:18760948"
FT ACT_SITE 149
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 31..39
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 54
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|PubMed:12665801,
FT ECO:0007744|PubMed:19413330, ECO:0007744|PubMed:22223895,
FT ECO:0007744|PubMed:22814378"
FT MOD_RES 29
FT /note="Phosphoserine; by SGK1"
FT /evidence="ECO:0000269|PubMed:19447520"
FT MOD_RES 185
FT /note="Phosphothreonine; by MAP2K1 and MAP2K2"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 187
FT /note="Phosphotyrosine; by MAP2K1 and MAP2K2"
FT /evidence="ECO:0000269|PubMed:19053285,
FT ECO:0000269|PubMed:19494114, ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 190
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:19060905"
FT MOD_RES 246
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18760948"
FT MOD_RES 248
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18760948"
FT MOD_RES 284
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT VAR_SEQ 242..285
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_047815"
FT VARIANT 74
FT /note="I -> N (in NS13; results in increased MAPK
FT signaling; reduced interaction wth DUSP6; no effect on
FT interaction with MAP2K1)"
FT /evidence="ECO:0000269|PubMed:32721402"
FT /id="VAR_085093"
FT VARIANT 80
FT /note="H -> Y (in NS13; results in increased MAPK
FT signaling; reduced interaction wth DUSP6; no effect on
FT interaction with MAP2K1)"
FT /evidence="ECO:0000269|PubMed:32721402"
FT /id="VAR_085094"
FT VARIANT 174
FT /note="A -> V (in NS13; results in increased MAPK
FT signaling; increased translocation to the nucleus; reduced
FT interaction wth DUSP6; no effect on interaction with
FT MAP2K1)"
FT /evidence="ECO:0000269|PubMed:32721402"
FT /id="VAR_085095"
FT VARIANT 318
FT /note="D -> G (in NS13; results in increased MAPK
FT signaling; increased translocation to the nucleus; reduced
FT interaction wth DUSP6; no effect on interaction with
FT MAP2K1)"
FT /evidence="ECO:0000269|PubMed:32721402"
FT /id="VAR_085096"
FT VARIANT 318
FT /note="D -> N (in NS13; results in increased MAPK
FT signaling; increased translocation to the nucleus; reduced
FT interaction wth DUSP6; no effect on interaction with
FT MAP2K1)"
FT /evidence="ECO:0000269|PubMed:32721402"
FT /id="VAR_085097"
FT VARIANT 322
FT /note="E -> Q (in NS13)"
FT /evidence="ECO:0000269|PubMed:32721402"
FT /id="VAR_085098"
FT VARIANT 323
FT /note="P -> R (in NS13; results in increased MAPK
FT signaling; increased translocation to the nucleus; reduced
FT interaction wth DUSP6; no effect on interaction with
FT MAP2K1)"
FT /evidence="ECO:0000269|PubMed:32721402"
FT /id="VAR_085099"
FT MUTAGEN 54
FT /note="K->R: Does not inhibit interaction with MAP2K1."
FT /evidence="ECO:0000269|PubMed:18794356"
FT MUTAGEN 176..179
FT /note="Missing: Inhibits homodimerization and interaction
FT with TPR."
FT /evidence="ECO:0000269|PubMed:18794356"
FT MUTAGEN 185
FT /note="T->A: Inhibits interaction with TPR; when associated
FT with A-187."
FT /evidence="ECO:0000269|PubMed:18794356"
FT MUTAGEN 187
FT /note="Y->A: Inhibits interaction with TPR; when associated
FT with A-185."
FT /evidence="ECO:0000269|PubMed:18794356"
FT MUTAGEN 234
FT /note="L->A: Inhibits interaction with TPR."
FT /evidence="ECO:0000269|PubMed:18794356"
FT MUTAGEN 318
FT /note="D->A: Loss of dephosphorylation by PTPRJ."
FT /evidence="ECO:0000269|PubMed:18794356,
FT ECO:0000269|PubMed:19494114"
FT MUTAGEN 318
FT /note="D->N: Inhibits interaction with MAP2K1 but not with
FT TPR; when associated with N-321."
FT /evidence="ECO:0000269|PubMed:18794356,
FT ECO:0000269|PubMed:19494114"
FT MUTAGEN 321
FT /note="D->N: Inhibits interaction with MAP2K1 but not with
FT TPR; when associated with N-318."
FT /evidence="ECO:0000269|PubMed:18794356"
FT CONFLICT 91
FT /note="R -> Q (in Ref. 2; CAA77752)"
FT /evidence="ECO:0000305"
FT STRAND 12..14
FT /evidence="ECO:0007829|PDB:4QTA"
FT STRAND 17..19
FT /evidence="ECO:0007829|PDB:4QTA"
FT TURN 22..24
FT /evidence="ECO:0007829|PDB:4ZZN"
FT STRAND 25..34
FT /evidence="ECO:0007829|PDB:4ZZN"
FT STRAND 37..44
FT /evidence="ECO:0007829|PDB:4ZZN"
FT TURN 45..48
FT /evidence="ECO:0007829|PDB:4ZZN"
FT STRAND 49..56
FT /evidence="ECO:0007829|PDB:4ZZN"
FT STRAND 59..61
FT /evidence="ECO:0007829|PDB:6G92"
FT HELIX 62..77
FT /evidence="ECO:0007829|PDB:4ZZN"
FT STRAND 81..83
FT /evidence="ECO:0007829|PDB:5AX3"
FT STRAND 88..90
FT /evidence="ECO:0007829|PDB:4ZZN"
FT TURN 95..97
FT /evidence="ECO:0007829|PDB:4ZZN"
FT STRAND 101..106
FT /evidence="ECO:0007829|PDB:4ZZN"
FT STRAND 109..111
FT /evidence="ECO:0007829|PDB:4ZZN"
FT HELIX 112..118
FT /evidence="ECO:0007829|PDB:4ZZN"
FT HELIX 123..142
FT /evidence="ECO:0007829|PDB:4ZZN"
FT HELIX 152..154
FT /evidence="ECO:0007829|PDB:4ZZN"
FT STRAND 155..157
FT /evidence="ECO:0007829|PDB:4ZZN"
FT TURN 159..161
FT /evidence="ECO:0007829|PDB:4IZ5"
FT STRAND 163..165
FT /evidence="ECO:0007829|PDB:4ZZN"
FT HELIX 168..170
FT /evidence="ECO:0007829|PDB:3I5Z"
FT HELIX 176..178
FT /evidence="ECO:0007829|PDB:4ZZN"
FT TURN 181..185
FT /evidence="ECO:0007829|PDB:2Y9Q"
FT HELIX 191..193
FT /evidence="ECO:0007829|PDB:4ZZN"
FT HELIX 196..200
FT /evidence="ECO:0007829|PDB:4ZZN"
FT STRAND 201..203
FT /evidence="ECO:0007829|PDB:5K4I"
FT HELIX 208..223
FT /evidence="ECO:0007829|PDB:4ZZN"
FT HELIX 235..244
FT /evidence="ECO:0007829|PDB:4ZZN"
FT HELIX 249..253
FT /evidence="ECO:0007829|PDB:4ZZN"
FT HELIX 258..265
FT /evidence="ECO:0007829|PDB:4ZZN"
FT HELIX 275..278
FT /evidence="ECO:0007829|PDB:4ZZN"
FT STRAND 280..282
FT /evidence="ECO:0007829|PDB:5NHO"
FT HELIX 284..293
FT /evidence="ECO:0007829|PDB:4ZZN"
FT TURN 298..300
FT /evidence="ECO:0007829|PDB:4ZZN"
FT HELIX 304..308
FT /evidence="ECO:0007829|PDB:4ZZN"
FT HELIX 311..313
FT /evidence="ECO:0007829|PDB:4ZZN"
FT TURN 314..316
FT /evidence="ECO:0007829|PDB:4ZZN"
FT HELIX 319..321
FT /evidence="ECO:0007829|PDB:4ZZN"
FT HELIX 331..334
FT /evidence="ECO:0007829|PDB:5V62"
FT HELIX 335..337
FT /evidence="ECO:0007829|PDB:5K4I"
FT HELIX 340..351
FT /evidence="ECO:0007829|PDB:4ZZN"
FT HELIX 352..354
FT /evidence="ECO:0007829|PDB:4ZZN"
FT TURN 356..358
FT /evidence="ECO:0007829|PDB:1PME"
SQ SEQUENCE 360 AA; 41390 MW; E85D0B2A5D2D724E CRC64;
MAAAAAAGAG PEMVRGQVFD VGPRYTNLSY IGEGAYGMVC SAYDNVNKVR VAIKKISPFE
HQTYCQRTLR EIKILLRFRH ENIIGINDII RAPTIEQMKD VYIVQDLMET DLYKLLKTQH
LSNDHICYFL YQILRGLKYI HSANVLHRDL KPSNLLLNTT CDLKICDFGL ARVADPDHDH
TGFLTEYVAT RWYRAPEIML NSKGYTKSID IWSVGCILAE MLSNRPIFPG KHYLDQLNHI
LGILGSPSQE DLNCIINLKA RNYLLSLPHK NKVPWNRLFP NADSKALDLL DKMLTFNPHK
RIEVEQALAH PYLEQYYDPS DEPIAEAPFK FDMELDDLPK EKLKELIFEE TARFQPGYRS
