MK03_HUMAN
ID MK03_HUMAN Reviewed; 379 AA.
AC P27361; A8CZ58; B0LPG3; Q8NHX1;
DT 01-AUG-1992, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 03-AUG-2022, entry version 239.
DE RecName: Full=Mitogen-activated protein kinase 3;
DE Short=MAP kinase 3;
DE Short=MAPK 3;
DE EC=2.7.11.24;
DE AltName: Full=ERT2;
DE AltName: Full=Extracellular signal-regulated kinase 1;
DE Short=ERK-1;
DE AltName: Full=Insulin-stimulated MAP2 kinase;
DE AltName: Full=MAP kinase isoform p44;
DE Short=p44-MAPK;
DE AltName: Full=Microtubule-associated protein 2 kinase;
DE AltName: Full=p44-ERK1;
GN Name=MAPK3; Synonyms=ERK1, PRKM3;
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).
RC TISSUE=Hepatoma;
RX PubMed=7687743; DOI=10.1128/mcb.13.8.4679-4690.1993;
RA Charest D.L., Jirik F., Harder K., Pelech S.L., Mordret G.;
RT "Molecular cloning, expression, and characterization of the human mitogen-
RT activated protein kinase p44erk1.";
RL Mol. Cell. Biol. 13:4679-4690(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RA Aebersold D.M., Yung Y., Seger R.;
RT "Properties of human ERK1b.";
RL Submitted (APR-2001) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
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 [GENOMIC DNA].
RG SeattleSNPs variation discovery resource;
RL Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G.,
RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E.,
RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M.,
RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C.,
RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M.,
RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M.,
RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D.,
RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L.,
RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E.,
RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H.,
RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y.,
RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S.,
RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A.,
RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M.,
RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H.,
RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A.,
RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J.,
RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J.,
RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M.,
RA Myers R.M., Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lymph;
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 PROTEIN SEQUENCE OF 2-15; 33-41; 88-94; 117-131; 212-220; 279-287; 303-318
RP AND 360-370, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Hepatoma;
RA Bienvenut W.V., Dhillon A.S., Kolch W.;
RL Submitted (FEB-2008) to UniProtKB.
RN [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 14-379 (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 [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 25-379 (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 [11]
RP FUNCTION IN PHOSPHORYLATION OF STMN1.
RX PubMed=8325880; DOI=10.1016/s0021-9258(18)82435-8;
RA Marklund U., Brattsand G., Shingler V., Gullberg M.;
RT "Serine 25 of oncoprotein 18 is a major cytosolic target for the mitogen-
RT activated protein kinase.";
RL J. Biol. Chem. 268:15039-15047(1993).
RN [12]
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 [13]
RP FUNCTION IN PHOSPHORYLATION OF MKNK1/MNK1.
RX PubMed=9155018; DOI=10.1093/emboj/16.8.1921;
RA Fukunaga R., Hunter T.;
RT "MNK1, a new MAP kinase-activated protein kinase, isolated by a novel
RT expression screening method for identifying protein kinase substrates.";
RL EMBO J. 16:1921-1933(1997).
RN [14]
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 [15]
RP FUNCTION IN PHOSPHORYLATION OF CANX, AND INTERACTION WITH CANX.
RX PubMed=10393181; DOI=10.1093/emboj/18.13.3655;
RA Chevet E., Wong H.N., Gerber D., Cochet C., Fazel A., Cameron P.H.,
RA Gushue J.N., Thomas D.Y., Bergeron J.J.;
RT "Phosphorylation by CK2 and MAPK enhances calnexin association with
RT ribosomes.";
RL EMBO J. 18:3655-3666(1999).
RN [16]
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 [17]
RP SUBCELLULAR LOCATION, INTERACTION WITH MAP2K1/MEK1, AND DOMAIN.
RX PubMed=10521408; DOI=10.1074/jbc.274.43.30349;
RA Rubinfeld H., Hanoch T., Seger R.;
RT "Identification of a cytoplasmic-retention sequence in ERK2.";
RL J. Biol. Chem. 274:30349-30352(1999).
RN [18]
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 [19]
RP INTERACTION WITH HSF1.
RX PubMed=10747973; DOI=10.1074/jbc.m000958200;
RA Dai R., Frejtag W., He B., Zhang Y., Mivechi N.F.;
RT "c-Jun NH2-terminal kinase targeting and phosphorylation of heat shock
RT factor-1 suppress its transcriptional activity.";
RL J. Biol. Chem. 275:18210-18218(2000).
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 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 [23]
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 [24]
RP INTERACTION 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 [25]
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 [26]
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 [27]
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 [28]
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 [29]
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 [30]
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 [31]
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 [32]
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 [33]
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 [34]
RP INTERACTION WITH TPR.
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 [35]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-202 AND TYR-204, 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 [36]
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 [37]
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 [38]
RP PHOSPHORYLATION AT TYR-204, AND DEPHOSPHORYLATION AT TYR-204 BY PTPRJ.
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 [39]
RP 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 [40]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-198, 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 [41]
RP PHOSPHORYLATION AT THR-207, 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 [42]
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 [43]
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 [44]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-202 AND TYR-204, 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 [45]
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 [46]
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 [47]
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 [48]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-202 AND TYR-204, 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 [49]
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 [50]
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 [51]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-202 AND TYR-204, 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 [52]
RP INTERACTION WITH CDKN2AIP.
RX PubMed=24825908; DOI=10.1074/jbc.m114.547208;
RA Cheung C.T., Singh R., Kalra R.S., Kaul S.C., Wadhwa R.;
RT "Collaborator of ARF (CARF) regulates proliferative fate of human cells by
RT dose-dependent regulation of DNA damage signaling.";
RL J. Biol. Chem. 289:18258-18269(2014).
RN [53]
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 [54]
RP X-RAY CRYSTALLOGRAPHY (2.39 ANGSTROMS), AND PHOSPHORYLATION AT TYR-204.
RX PubMed=18983981; DOI=10.1016/j.bbrc.2008.10.127;
RA Kinoshita T., Yoshida I., Nakae S., Okita K., Gouda M., Matsubara M.,
RA Yokota K., Ishiguro H., Tada T.;
RT "Crystal structure of human mono-phosphorylated ERK1 at Tyr204.";
RL Biochem. Biophys. Res. Commun. 377:1123-1127(2008).
RN [55]
RP VARIANT [LARGE SCALE ANALYSIS] LYS-323.
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: 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, FRS2 or GRB10). Protein kinases (such as RAF1,
CC 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. {ECO:0000269|PubMed:10393181,
CC ECO:0000269|PubMed:10617468, ECO:0000269|PubMed:12110590,
CC ECO:0000269|PubMed:12356731, ECO:0000269|PubMed:12974390,
CC ECO:0000269|PubMed:15788397, ECO:0000269|PubMed:15952796,
CC ECO:0000269|PubMed:16581800, ECO:0000269|PubMed:19265199,
CC ECO:0000269|PubMed:8325880, ECO:0000269|PubMed:9155018,
CC ECO:0000269|PubMed:9480836}.
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-202 and Tyr-204 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 Dephosphorylated and inactivated by DUSP3, DUSP6 and DUSP9.
CC {ECO:0000269|PubMed:12356731, ECO:0000269|PubMed:19060905}.
CC -!- SUBUNIT: Binds both upstream activators and downstream substrates in
CC multimolecular complexes. Found in a complex with at least BRAF, HRAS,
CC MAP2K1/MEK1, MAPK3 and RGS14 (By similarity). Interacts with ADAM15,
CC ARRB2, CANX, DAPK1 (via death domain), HSF4, IER3, MAP2K1/MEK1, MORG1,
CC NISCH, and SGK1. Interacts with PEA15 and MKNK2 (By similarity). MKNK2
CC isoform 1 binding prevents from dephosphorylation and inactivation (By
CC similarity). Interacts with TPR. Interacts with CDKN2AIP. Interacts
CC with HSF1 (via D domain and preferentially with hyperphosphorylated
CC form); this interaction occurs upon heat shock (PubMed:10747973).
CC Interacts with CAVIN4 (By similarity). Interacts with GIT1; this
CC interaction is necessary for MAPK3 localization to focal adhesions (By
CC similarity). Interacts with ZNF263 (PubMed:32051553).
CC {ECO:0000250|UniProtKB:P21708, ECO:0000250|UniProtKB:Q63844,
CC ECO:0000269|PubMed:10393181, ECO:0000269|PubMed:10521408,
CC ECO:0000269|PubMed:10747973, ECO:0000269|PubMed:11912194,
CC ECO:0000269|PubMed:12356731, ECO:0000269|PubMed:15616583,
CC ECO:0000269|PubMed:16581800, ECO:0000269|PubMed:18296648,
CC ECO:0000269|PubMed:18435604, ECO:0000269|PubMed:18794356,
CC ECO:0000269|PubMed:19060905, ECO:0000269|PubMed:19447520,
CC ECO:0000269|PubMed:24825908, ECO:0000269|PubMed:32051553}.
CC -!- SUBUNIT: (Microbial infection) Binds to HIV-1 Nef through its SH3
CC domain. This interaction inhibits its tyrosine-kinase activity.
CC {ECO:0000269|PubMed:8794306}.
CC -!- INTERACTION:
CC P27361; Q9HCU0: CD248; NbExp=3; IntAct=EBI-73995, EBI-9680942;
CC P27361; P53355: DAPK1; NbExp=5; IntAct=EBI-73995, EBI-358616;
CC P27361; P49366: DHPS; NbExp=10; IntAct=EBI-73995, EBI-741925;
CC P27361; P28562: DUSP1; NbExp=3; IntAct=EBI-73995, EBI-975493;
CC P27361; Q16828: DUSP6; NbExp=5; IntAct=EBI-73995, EBI-746870;
CC P27361; P19419: ELK1; NbExp=2; IntAct=EBI-73995, EBI-726632;
CC P27361; Q49AJ0-4: FAM135B; NbExp=3; IntAct=EBI-73995, EBI-25835236;
CC P27361; Q96NJ5: KLHL32; NbExp=3; IntAct=EBI-73995, EBI-6426390;
CC P27361; Q02750: MAP2K1; NbExp=2; IntAct=EBI-73995, EBI-492564;
CC P27361; Q16539: MAPK14; NbExp=5; IntAct=EBI-73995, EBI-73946;
CC P27361; P27361: MAPK3; NbExp=2; IntAct=EBI-73995, EBI-73995;
CC P27361; Q96HT8: MRFAP1L1; NbExp=3; IntAct=EBI-73995, EBI-748896;
CC P27361; Q6GQQ9-2: OTUD7B; NbExp=3; IntAct=EBI-73995, EBI-25830200;
CC P27361; Q9ULW8: PADI3; NbExp=3; IntAct=EBI-73995, EBI-10488185;
CC P27361; Q15121: PEA15; NbExp=4; IntAct=EBI-73995, EBI-714410;
CC P27361; P14618-1: PKM; NbExp=3; IntAct=EBI-73995, EBI-4304679;
CC P27361; Q8N490: PNKD; NbExp=4; IntAct=EBI-73995, EBI-746368;
CC P27361; P23467: PTPRB; NbExp=2; IntAct=EBI-73995, EBI-1265766;
CC P27361; Q12913: PTPRJ; NbExp=5; IntAct=EBI-73995, EBI-2264500;
CC P27361; Q14160: SCRIB; NbExp=2; IntAct=EBI-73995, EBI-357345;
CC P27361; P13051-2: UNG; NbExp=3; IntAct=EBI-73995, EBI-25834258;
CC P27361; Q08509: Eps8; Xeno; NbExp=2; IntAct=EBI-73995, EBI-375596;
CC P27361; Q60793: Klf4; Xeno; NbExp=2; IntAct=EBI-73995, EBI-3043905;
CC P27361; Q9EPI6: Nsmf; Xeno; NbExp=2; IntAct=EBI-73995, EBI-6899705;
CC P27361; Q62132: Ptprr; Xeno; NbExp=3; IntAct=EBI-73995, EBI-6954051;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P21708}.
CC Nucleus. Membrane, caveola {ECO:0000250|UniProtKB:P21708}. Cell
CC junction, focal adhesion {ECO:0000250|UniProtKB:Q63844}.
CC Note=Autophosphorylation at Thr-207 promotes nuclear localization
CC (PubMed:19060905). PEA15-binding redirects the biological outcome of
CC MAPK3 kinase-signaling by sequestering MAPK3 into the cytoplasm (By
CC similarity). {ECO:0000250|UniProtKB:Q63844,
CC ECO:0000269|PubMed:19060905}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P27361-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P27361-2; Sequence=VSP_041906;
CC Name=3; Synonyms=ERK1b;
CC IsoId=P27361-3; Sequence=VSP_041907;
CC -!- DOMAIN: The TXY motif contains the threonine and tyrosine residues
CC whose phosphorylation activates the MAP kinases.
CC {ECO:0000269|PubMed:10521408}.
CC -!- PTM: Phosphorylated upon KIT and FLT3 signaling (By similarity). Dually
CC phosphorylated on Thr-202 and Tyr-204, which activates the enzyme.
CC Ligand-activated ALK induces tyrosine phosphorylation. Dephosphorylated
CC by PTPRJ at Tyr-204. {ECO:0000250, ECO:0000269|PubMed:17274988,
CC ECO:0000269|PubMed:18983981, ECO:0000269|PubMed:19060905,
CC ECO:0000269|PubMed:19265199, ECO:0000269|PubMed:19494114}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC protein kinase family. MAP kinase subfamily. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/MAPK3ID425ch16p11.html";
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; X60188; CAA42744.1; -; mRNA.
DR EMBL; AY033607; AAK52329.1; -; mRNA.
DR EMBL; DQ399291; ABD60302.1; -; mRNA.
DR EMBL; EU332853; ABY87542.1; -; Genomic_DNA.
DR EMBL; AC012645; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471238; EAW79912.1; -; Genomic_DNA.
DR EMBL; CH471238; EAW79915.1; -; Genomic_DNA.
DR EMBL; BC013992; AAH13992.1; -; mRNA.
DR EMBL; M84490; AAA36142.1; -; mRNA.
DR EMBL; Z11696; CAA77754.1; -; mRNA.
DR CCDS; CCDS10672.1; -. [P27361-1]
DR CCDS; CCDS42148.1; -. [P27361-2]
DR CCDS; CCDS42149.1; -. [P27361-3]
DR PIR; A48082; A48082.
DR RefSeq; NP_001035145.1; NM_001040056.2. [P27361-3]
DR RefSeq; NP_001103361.1; NM_001109891.1. [P27361-2]
DR RefSeq; NP_002737.2; NM_002746.2. [P27361-1]
DR PDB; 2ZOQ; X-ray; 2.39 A; A/B=1-379.
DR PDB; 4QTB; X-ray; 1.40 A; A/B=1-379.
DR PDB; 6GES; X-ray; 2.07 A; A/B=1-379.
DR PDBsum; 2ZOQ; -.
DR PDBsum; 4QTB; -.
DR PDBsum; 6GES; -.
DR AlphaFoldDB; P27361; -.
DR SMR; P27361; -.
DR BioGRID; 111581; 300.
DR CORUM; P27361; -.
DR DIP; DIP-30985N; -.
DR ELM; P27361; -.
DR IntAct; P27361; 177.
DR MINT; P27361; -.
DR STRING; 9606.ENSP00000263025; -.
DR BindingDB; P27361; -.
DR ChEMBL; CHEMBL3385; -.
DR DrugBank; DB04604; 5-iodotubercidin.
DR DrugBank; DB00945; Acetylsalicylic acid.
DR DrugBank; DB01169; Arsenic trioxide.
DR DrugBank; DB08862; Cholecystokinin.
DR DrugBank; DB01017; Minocycline.
DR DrugBank; DB02733; Purvalanol.
DR DrugBank; DB06195; Seliciclib.
DR DrugBank; DB00605; Sulindac.
DR DrugBank; DB13930; Ulixertinib.
DR DrugCentral; P27361; -.
DR GuidetoPHARMACOLOGY; 1494; -.
DR MoonDB; P27361; Predicted.
DR iPTMnet; P27361; -.
DR MetOSite; P27361; -.
DR PhosphoSitePlus; P27361; -.
DR BioMuta; MAPK3; -.
DR DMDM; 232066; -.
DR CPTAC; CPTAC-1050; -.
DR CPTAC; CPTAC-1051; -.
DR CPTAC; CPTAC-1357; -.
DR CPTAC; CPTAC-1358; -.
DR CPTAC; CPTAC-1359; -.
DR CPTAC; CPTAC-1542; -.
DR CPTAC; CPTAC-880; -.
DR EPD; P27361; -.
DR jPOST; P27361; -.
DR MassIVE; P27361; -.
DR MaxQB; P27361; -.
DR PaxDb; P27361; -.
DR PeptideAtlas; P27361; -.
DR PRIDE; P27361; -.
DR ProteomicsDB; 54383; -. [P27361-1]
DR ProteomicsDB; 54384; -. [P27361-2]
DR ProteomicsDB; 54385; -. [P27361-3]
DR Antibodypedia; 1203; 2396 antibodies from 58 providers.
DR CPTC; P27361; 6 antibodies.
DR DNASU; 5595; -.
DR Ensembl; ENST00000263025.9; ENSP00000263025.4; ENSG00000102882.12. [P27361-1]
DR Ensembl; ENST00000322266.9; ENSP00000327293.5; ENSG00000102882.12. [P27361-2]
DR Ensembl; ENST00000395199.7; ENSP00000378625.3; ENSG00000102882.12. [P27361-3]
DR Ensembl; ENST00000395202.5; ENSP00000378628.1; ENSG00000102882.12. [P27361-2]
DR GeneID; 5595; -.
DR KEGG; hsa:5595; -.
DR MANE-Select; ENST00000263025.9; ENSP00000263025.4; NM_002746.3; NP_002737.2.
DR UCSC; uc002dws.4; human. [P27361-1]
DR CTD; 5595; -.
DR DisGeNET; 5595; -.
DR GeneCards; MAPK3; -.
DR HGNC; HGNC:6877; MAPK3.
DR HPA; ENSG00000102882; Low tissue specificity.
DR MIM; 601795; gene.
DR neXtProt; NX_P27361; -.
DR OpenTargets; ENSG00000102882; -.
DR PharmGKB; PA30622; -.
DR VEuPathDB; HostDB:ENSG00000102882; -.
DR eggNOG; KOG0660; Eukaryota.
DR GeneTree; ENSGT00940000160691; -.
DR HOGENOM; CLU_000288_181_1_1; -.
DR InParanoid; P27361; -.
DR OMA; EIMTFRP; -.
DR PhylomeDB; P27361; -.
DR TreeFam; TF105097; -.
DR BRENDA; 2.7.11.24; 2681.
DR PathwayCommons; P27361; -.
DR Reactome; R-HSA-110056; MAPK3 (ERK1) activation.
DR Reactome; R-HSA-112409; RAF-independent MAPK1/3 activation.
DR Reactome; R-HSA-1169408; ISG15 antiviral mechanism.
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. [P27361-3]
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-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-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-73728; RNA Polymerase I Promoter Opening.
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-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-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 SignaLink; P27361; -.
DR SIGNOR; P27361; -.
DR BioGRID-ORCS; 5595; 30 hits in 1119 CRISPR screens.
DR ChiTaRS; MAPK3; human.
DR EvolutionaryTrace; P27361; -.
DR GeneWiki; MAPK3; -.
DR GenomeRNAi; 5595; -.
DR Pharos; P27361; Tchem.
DR PRO; PR:P27361; -.
DR Proteomes; UP000005640; Chromosome 16.
DR RNAct; P27361; protein.
DR Bgee; ENSG00000102882; Expressed in right frontal lobe and 196 other tissues.
DR ExpressionAtlas; P27361; baseline and differential.
DR Genevisible; P27361; HS.
DR GO; GO:0005901; C:caveola; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS: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: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:0005739; C:mitochondrion; TAS:UniProtKB.
DR GO; GO:0005635; C:nuclear envelope; IDA:BHF-UCL.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0031143; C:pseudopodium; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0004707; F:MAP kinase activity; IDA:UniProtKB.
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:GO_Central.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0060020; P:Bergmann glial cell differentiation; IEA:Ensembl.
DR GO; GO:0030509; P:BMP signaling pathway; IMP:BHF-UCL.
DR GO; GO:0061308; P:cardiac neural crest cell development involved in heart development; IEA:Ensembl.
DR GO; GO:0051216; P:cartilage 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:1903351; P:cellular response to dopamine; IMP:CAFA.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEP:UniProtKB.
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:0006975; P:DNA damage induced protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0070371; P:ERK1 and ERK2 cascade; IEA:Ensembl.
DR GO; GO:0060324; P:face development; IEA:Ensembl.
DR GO; GO:0070498; P:interleukin-1-mediated signaling pathway; IMP:BHF-UCL.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IEA:Ensembl.
DR GO; GO:0060425; P:lung morphogenesis; IEA:Ensembl.
DR GO; GO:0000165; P:MAPK cascade; NAS:BHF-UCL.
DR GO; GO:2000657; P:negative regulation of apolipoprotein binding; IEA:Ensembl.
DR GO; GO:0042473; P:outer ear morphogenesis; IEA:Ensembl.
DR GO; GO:0038083; P:peptidyl-tyrosine autophosphorylation; IDA:UniProtKB.
DR GO; GO:0016310; P:phosphorylation; IDA:UniProtKB.
DR GO; GO:0031281; P:positive regulation of cyclase activity; IMP:CACAO.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IMP:BHF-UCL.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:CAFA.
DR GO; GO:0035066; P:positive regulation of histone acetylation; IMP:BHF-UCL.
DR GO; GO:0033129; P:positive regulation of histone phosphorylation; IMP:BHF-UCL.
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:0001934; P:positive regulation of protein phosphorylation; IMP:BHF-UCL.
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:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:BHF-UCL.
DR GO; GO:1904417; P:positive regulation of xenophagy; IEA:Ensembl.
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:0051090; P:regulation of DNA-binding transcription factor activity; IEA:Ensembl.
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: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:0019233; P:sensory perception of pain; IEA:Ensembl.
DR GO; GO:0051403; P:stress-activated MAPK cascade; IDA:CAFA.
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 GO; GO:0006351; P:transcription, DNA-templated; IEA:Ensembl.
DR GO; GO:0098792; P:xenophagy; 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; Direct protein sequencing;
KW Host-virus interaction; Kinase; Membrane; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.8, ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378"
FT CHAIN 2..379
FT /note="Mitogen-activated protein kinase 3"
FT /id="PRO_0000186251"
FT DOMAIN 42..330
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..26
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 202..204
FT /note="TXY"
FT ACT_SITE 166
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 48..56
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 71
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000269|Ref.8, ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378"
FT MOD_RES 198
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT MOD_RES 202
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 204
FT /note="Phosphotyrosine; by MAP2K1 and MAP2K2"
FT /evidence="ECO:0000269|PubMed:18983981,
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 207
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:19060905"
FT VAR_SEQ 259..302
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.3"
FT /id="VSP_041906"
FT VAR_SEQ 340..379
FT /note="PVAEEPFTFAMELDDLPKERLKELIFQETARFQPGVLEAP -> VGQSPAAV
FT GLGAGEQGGT (in isoform 3)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_041907"
FT VARIANT 323
FT /note="E -> K (in dbSNP:rs55859133)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042253"
FT CONFLICT 174
FT /note="I -> S (in Ref. 1; CAA42744 and 2; AAK52329)"
FT /evidence="ECO:0000305"
FT STRAND 29..31
FT /evidence="ECO:0007829|PDB:4QTB"
FT STRAND 34..36
FT /evidence="ECO:0007829|PDB:4QTB"
FT TURN 39..41
FT /evidence="ECO:0007829|PDB:4QTB"
FT STRAND 42..51
FT /evidence="ECO:0007829|PDB:4QTB"
FT STRAND 54..61
FT /evidence="ECO:0007829|PDB:4QTB"
FT TURN 62..65
FT /evidence="ECO:0007829|PDB:4QTB"
FT STRAND 66..73
FT /evidence="ECO:0007829|PDB:4QTB"
FT HELIX 79..94
FT /evidence="ECO:0007829|PDB:4QTB"
FT STRAND 105..107
FT /evidence="ECO:0007829|PDB:4QTB"
FT TURN 112..114
FT /evidence="ECO:0007829|PDB:4QTB"
FT STRAND 118..122
FT /evidence="ECO:0007829|PDB:4QTB"
FT STRAND 126..128
FT /evidence="ECO:0007829|PDB:4QTB"
FT HELIX 129..135
FT /evidence="ECO:0007829|PDB:4QTB"
FT HELIX 140..159
FT /evidence="ECO:0007829|PDB:4QTB"
FT HELIX 169..171
FT /evidence="ECO:0007829|PDB:4QTB"
FT STRAND 172..174
FT /evidence="ECO:0007829|PDB:4QTB"
FT STRAND 180..182
FT /evidence="ECO:0007829|PDB:4QTB"
FT HELIX 193..195
FT /evidence="ECO:0007829|PDB:4QTB"
FT HELIX 208..210
FT /evidence="ECO:0007829|PDB:4QTB"
FT HELIX 213..215
FT /evidence="ECO:0007829|PDB:4QTB"
FT TURN 216..218
FT /evidence="ECO:0007829|PDB:4QTB"
FT HELIX 225..240
FT /evidence="ECO:0007829|PDB:4QTB"
FT HELIX 250..261
FT /evidence="ECO:0007829|PDB:4QTB"
FT HELIX 266..269
FT /evidence="ECO:0007829|PDB:4QTB"
FT HELIX 275..282
FT /evidence="ECO:0007829|PDB:4QTB"
FT HELIX 292..295
FT /evidence="ECO:0007829|PDB:4QTB"
FT HELIX 301..310
FT /evidence="ECO:0007829|PDB:4QTB"
FT HELIX 315..317
FT /evidence="ECO:0007829|PDB:4QTB"
FT HELIX 321..325
FT /evidence="ECO:0007829|PDB:4QTB"
FT HELIX 328..330
FT /evidence="ECO:0007829|PDB:4QTB"
FT TURN 331..333
FT /evidence="ECO:0007829|PDB:4QTB"
FT HELIX 336..338
FT /evidence="ECO:0007829|PDB:4QTB"
FT HELIX 350..354
FT /evidence="ECO:0007829|PDB:4QTB"
FT HELIX 357..368
FT /evidence="ECO:0007829|PDB:4QTB"
FT HELIX 369..371
FT /evidence="ECO:0007829|PDB:4QTB"
SQ SEQUENCE 379 AA; 43136 MW; E6020CE413EC41F7 CRC64;
MAAAAAQGGG GGEPRRTEGV GPGVPGEVEM VKGQPFDVGP RYTQLQYIGE GAYGMVSSAY
DHVRKTRVAI KKISPFEHQT YCQRTLREIQ ILLRFRHENV IGIRDILRAS TLEAMRDVYI
VQDLMETDLY KLLKSQQLSN DHICYFLYQI LRGLKYIHSA NVLHRDLKPS NLLINTTCDL
KICDFGLARI ADPEHDHTGF LTEYVATRWY RAPEIMLNSK GYTKSIDIWS VGCILAEMLS
NRPIFPGKHY LDQLNHILGI LGSPSQEDLN CIINMKARNY LQSLPSKTKV AWAKLFPKSD
SKALDLLDRM LTFNPNKRIT VEEALAHPYL EQYYDPTDEP VAEEPFTFAM ELDDLPKERL
KELIFQETAR FQPGVLEAP
