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 11-NOV-2015, entry version 183. 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; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Hepatoma; RX PubMed=7687743; RA Charest D.L., Jirik F., Harder K., Pelech S.L., Mordret G.; RT "Molecular cloning, expression, and characterization of the human RT mitogen-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 RT 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., RA Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., RA Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., RA Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., RA Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., RA Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., RA Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., RA Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., RA Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., RA Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., RA Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., RA Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., RA 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., RA Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., RA Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., RA Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., RA Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., RA Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., RA Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., RA Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., RA Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., RA 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., RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R., RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., RA 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 RT project: 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; RP 303-318 AND 360-370, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT RP ALA-2, AND 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 RT of 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 RT tissues."; RL FEBS Lett. 304:170-178(1992). RN [11] RP FUNCTION IN PHOSPHORYLATION OF STMN1. RX PubMed=8325880; RA Marklund U., Brattsand G., Shingler V., Gullberg M.; RT "Serine 25 of oncoprotein 18 is a major cytosolic target for the RT mitogen-activated protein kinase."; RL J. Biol. Chem. 268:15039-15047(1993). RN [12] RP INTERACTION WITH HIV-1 NEF. RX PubMed=8794306; RA Greenway A.L., Azad A., Mills J., McPhee D.A.; RT "Human immunodeficiency virus type 1 Nef binds directly to LCK and RT mitogen-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 RT 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 RT (ERK) 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 RT substrates for the dual-specificity protein-tyrosine phosphatase VHR. RT A novel role in 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- RT dependent phosphorylation."; RL Science 286:2514-2517(1999). RN [19] RP FUNCTION IN PHOSPHORYLATION OF IER3, INTERACTION WITH IER3, AND ENZYME 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 RT ERK activation."; RL EMBO J. 21:5151-5163(2002). RN [20] 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 [21] 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 [22] 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 [23] 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., RA 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 [24] 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., RA Schouten J., van der Burgt C., Kooistra K., Bos J.L., Maassen J.A., RA van Dam H.; RT "Growth factors can activate ATF2 via a two-step mechanism: RT phosphorylation of Thr71 through the Ras-MEK-ERK pathway and of Thr69 RT through RalGDS-Src-p38."; RL EMBO J. 21:3782-3793(2002). RN [25] 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 [26] 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 RT Pin-1 binding in cytoplasm and cell death."; RL J. Biol. Chem. 280:21256-21263(2005). RN [27] 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., RA Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in RT signaling networks."; RL Cell 127:635-648(2006). RN [28] 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 RT both extracellular signal-regulated kinase mitogen-activated protein RT kinase and dual-specificity tyrosine phosphatase DUSP26."; RL Mol. Cell. Biol. 26:3282-3294(2006). RN [29] 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 RT phenotypic outcomes in PC12 cells differentiation."; RL FEBS Lett. 581:727-734(2007). RN [30] 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 RT interfere with interactions with the beta2-adrenoceptor and the ERK1/2 RT MAPKs: implications for beta2-adrenoceptor signalling via the ERK1/2 RT MAPKs."; RL Biochem. J. 413:51-60(2008). RN [31] 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 RT human mammary carcinoma."; RL Mol. Cancer Res. 6:383-394(2008). RN [32] 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 RT the kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [33] 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., RA Parsons J.T., Weber M.J., Nandicoori V.K.; RT "Extracellular signal-regulated kinase 2 (ERK2) phosphorylation sites RT and docking domain on the nuclear pore complex protein Tpr RT cooperatively regulate ERK2-Tpr interaction."; RL Mol. Cell. Biol. 28:6954-6966(2008). RN [34] 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 [35] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., RA Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in RT a refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [36] 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 [37] 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 RT RAS pathway by direct dephosphorylation of ERK1/2 kinases."; RL J. Biol. Chem. 284:22048-22058(2009). RN [38] 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., RA Hur G.M.; RT "Protein kinase SGK1 enhances MEK/ERK complex formation through the RT phosphorylation of ERK2: implication for the positive regulatory role RT of SGK1 on the ERK function during liver regeneration."; RL J. Hepatol. 51:67-76(2009). RN [39] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-198, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200; RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., RA Mann M., Daub H.; RT "Large-scale proteomics analysis of the human kinome."; RL Mol. Cell. Proteomics 8:1751-1764(2009). RN [40] RP PHOSPHORYLATION AT THR-207, ENZYME REGULATION, SUBUNIT, AND RP SUBCELLULAR 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 RT hypertrophy."; RL Nat. Med. 15:75-83(2009). RN [41] RP REVIEW ON FUNCTION. RX PubMed=16393692; DOI=10.1080/02699050500284218; RA Yoon S., Seger R.; RT "The extracellular signal-regulated kinase: multiple substrates RT regulate diverse cellular functions."; RL Growth Factors 24:21-44(2006). RN [42] 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 [43] 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 [44] 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., RA Mann M.; RT "Quantitative phosphoproteomics reveals widespread full RT phosphorylation site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [45] 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., RA Buerckstuemmer T., 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 [46] RP REVIEW ON ENZYME 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 [47] 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., RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., RA Blagoev B.; RT "System-wide temporal characterization of the proteome and RT phosphoproteome of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [48] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.M111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., RA Meinnel T., 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 [49] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS RP SPECTROMETRY [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., RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., RA Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N- RT terminal acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [50] 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 RT cells by dose-dependent regulation of DNA damage signaling."; RL J. Biol. Chem. 289:18258-18269(2014). RN [51] RP X-RAY CRYSTALLOGRAPHY (2.39 ANGSTROMS), AND PHOSPHORYLATION AT RP 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 [52] 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., RA Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., RA O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., RA Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E., RA Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., RA Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., RA Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., RA West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., RA Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., RA DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., RA Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., RA Yuen S.T., Leung S.Y., Wooster R., 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 CC component of the MAP kinase signal transduction pathway. CC MAPK1/ERK2 and MAPK3/ERK1 are the 2 MAPKs which play an important CC role in the MAPK/ERK cascade. They participate also in a signaling CC cascade initiated by activated KIT and KITLG/SCF. Depending on the CC cellular context, the MAPK/ERK cascade mediates diverse biological CC functions such as cell growth, adhesion, survival and CC differentiation through the regulation of transcription, CC translation, cytoskeletal rearrangements. The MAPK/ERK cascade CC plays also a role in initiation and regulation of meiosis, CC mitosis, and postmitotic functions in differentiated cells by CC phosphorylating a number of transcription factors. About 160 CC substrates have already been discovered for ERKs. Many of these CC substrates are localized in the nucleus, and seem to participate CC in the regulation of transcription upon stimulation. However, CC other substrates are found in the cytosol as well as in other CC cellular organelles, and those are responsible for processes such CC as translation, mitosis and apoptosis. Moreover, the MAPK/ERK CC cascade is also involved in the regulation of the endosomal CC dynamics, including lysosome processing and endosome cycling CC through the perinuclear recycling compartment (PNRC); as well as CC in the fragmentation of the Golgi apparatus during mitosis. The CC substrates include transcription factors (such as ATF2, BCL6, CC ELK1, ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CC CANX, CTTN, GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of CC apoptosis (such as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), CC regulators of translation (such as EIF4EBP1) and a variety of CC other signaling-related molecules (like ARHGEF2, FRS2 or GRB10). CC Protein kinases (such as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, CC RPS6KA2/RSK3, RPS6KA6/RSK4, SYK, MKNK1/MNK1, MKNK2/MNK2, CC RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or MAPKAPK5) and phosphatases CC (such as DUSP1, DUSP4, DUSP6 or DUSP16) are other substrates which CC enable the propagation the MAPK/ERK signal to additional cytosolic CC and nuclear targets, thereby extending the specificity of the CC 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: ATP + a protein = ADP + a phosphoprotein. CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; CC -!- ENZYME REGULATION: Phosphorylated by MAP2K1/MEK1 and MAP2K2/MEK2 CC on Thr-202 and Tyr-204 in response to external stimuli like CC insulin or NGF. Both phosphorylations are required for activity. CC This phosphorylation causes dramatic conformational changes, which CC enable full activation and interaction of MAPK1/ERK2 with its CC substrates. Dephosphorylated and inactivated by DUSP3, DUSP6 and CC DUSP9. {ECO:0000269|PubMed:12356731, ECO:0000269|PubMed:19060905}. CC -!- SUBUNIT: Binds both upstream activators and downstream substrates CC in multimolecular complexes. Found in a complex with at least CC BRAF, HRAS, MAP2K1/MEK1, MAPK3 and RGS14 (By similarity). Binds to CC HIV-1 Nef through its SH3 domain. This interaction inhibits its CC tyrosine-kinase activity. Interacts with ADAM15, ARRB2, CANX, CC DAPK1 (via death domain), HSF4, IER3, MAP2K1/MEK1, MORG1, NISCH, CC and SGK1. Interacts with PEA15 and MKNK2 (By similarity). MKNK2 CC isoform 1 binding prevents from dephosphorylation and inactivation CC (By similarity). Interacts with TPR. Interacts with CDKN2AIP. CC {ECO:0000250, ECO:0000269|PubMed:10393181, CC ECO:0000269|PubMed:10521408, 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:8794306}. CC -!- INTERACTION: CC P53355:DAPK1; NbExp=5; IntAct=EBI-73995, EBI-358616; CC P49366:DHPS; NbExp=2; IntAct=EBI-73995, EBI-741925; CC P28562:DUSP1; NbExp=5; IntAct=EBI-73995, EBI-975493; CC P19419:ELK1; NbExp=2; IntAct=EBI-73995, EBI-726632; CC Q02750:MAP2K1; NbExp=2; IntAct=EBI-73995, EBI-492564; CC P28482:MAPK1; NbExp=3; IntAct=EBI-73995, EBI-959949; CC Q16539:MAPK14; NbExp=5; IntAct=EBI-73995, EBI-73946; CC Q9EPI6:Nsmf (xeno); NbExp=2; IntAct=EBI-73995, EBI-6899705; CC P14618-1:PKM; NbExp=3; IntAct=EBI-73995, EBI-4304679; CC Q8N490:PNKD; NbExp=4; IntAct=EBI-73995, EBI-746368; CC P23467:PTPRB; NbExp=2; IntAct=EBI-73995, EBI-1265766; CC Q12913:PTPRJ; NbExp=5; IntAct=EBI-73995, EBI-2264500; CC Q62132:Ptprr (xeno); NbExp=3; IntAct=EBI-73995, EBI-6954051; CC Q15349:RPS6KA2; NbExp=2; IntAct=EBI-73995, EBI-1384149; CC Q14160:SCRIB; NbExp=2; IntAct=EBI-73995, EBI-357345; CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Autophosphorylation CC at Thr-207 promotes nuclear localization. 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). CC Dually phosphorylated on Thr-202 and Tyr-204, which activates the CC enzyme. Ligand-activated ALK induces tyrosine phosphorylation. CC Dephosphorylated by PTPRJ at Tyr-204. {ECO:0000250, CC ECO:0000269|PubMed:17274988, ECO:0000269|PubMed:18983981, CC ECO:0000269|PubMed:19060905, ECO:0000269|PubMed:19265199, CC ECO:0000269|PubMed:19494114}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC CC Ser/Thr protein kinase family. MAP kinase subfamily. CC {ECO:0000305}. CC -!- SIMILARITY: Contains 1 protein kinase domain. CC {ECO:0000255|PROSITE-ProRule:PRU00159}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and 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 UniGene; Hs.861; -. 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 PDBsum; 2ZOQ; -. DR PDBsum; 4QTB; -. DR ProteinModelPortal; P27361; -. DR SMR; P27361; 24-374. DR BioGrid; 111581; 138. DR DIP; DIP-30985N; -. DR IntAct; P27361; 60. DR MINT; MINT-99599; -. DR STRING; 9606.ENSP00000263025; -. DR BindingDB; P27361; -. DR ChEMBL; CHEMBL1907606; -. DR DrugBank; DB01169; Arsenic trioxide. DR DrugBank; DB00605; Sulindac. DR GuidetoPHARMACOLOGY; 1494; -. DR PhosphoSite; P27361; -. DR BioMuta; MAPK3; -. DR DMDM; 232066; -. DR MaxQB; P27361; -. DR PaxDb; P27361; -. DR PRIDE; P27361; -. DR DNASU; 5595; -. DR Ensembl; ENST00000263025; ENSP00000263025; ENSG00000102882. [P27361-1] DR Ensembl; ENST00000322266; ENSP00000327293; ENSG00000102882. [P27361-2] DR Ensembl; ENST00000395199; ENSP00000378625; ENSG00000102882. [P27361-3] DR Ensembl; ENST00000395202; ENSP00000378628; ENSG00000102882. [P27361-2] DR GeneID; 5595; -. DR KEGG; hsa:5595; -. DR UCSC; uc002dwr.3; human. [P27361-1] DR UCSC; uc002dwt.3; human. [P27361-3] DR UCSC; uc002dwv.4; human. [P27361-2] DR CTD; 5595; -. DR GeneCards; MAPK3; -. DR HGNC; HGNC:6877; MAPK3. DR HPA; CAB002683; -. DR HPA; HPA003995; -. DR HPA; HPA005700; -. DR HPA; HPA030069; -. DR MIM; 601795; gene. DR neXtProt; NX_P27361; -. DR PharmGKB; PA30622; -. DR eggNOG; KOG0660; Eukaryota. DR eggNOG; ENOG410XNY0; LUCA. DR GeneTree; ENSGT00550000074298; -. DR HOGENOM; HOG000233024; -. DR HOVERGEN; HBG014652; -. DR InParanoid; P27361; -. DR KO; K04371; -. DR OMA; RAPCADS; -. DR OrthoDB; EOG7M3J0K; -. DR PhylomeDB; P27361; -. DR TreeFam; TF105097; -. DR BRENDA; 2.7.11.24; 2681. 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-162658; Golgi Cisternae Pericentriolar Stack Reorganization. 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-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-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-5654736; Signaling by FGFR1. DR Reactome; R-HSA-5654738; Signaling by FGFR2. DR Reactome; R-HSA-5654741; Signaling by FGFR3. DR Reactome; R-HSA-5654743; Signaling by FGFR4. DR Reactome; R-HSA-5663213; RHO GTPases Activate WASPs and WAVEs. 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-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-982772; Growth hormone receptor signaling. DR SignaLink; P27361; -. DR EvolutionaryTrace; P27361; -. DR GeneWiki; MAPK3; -. DR GenomeRNAi; 5595; -. DR NextBio; 21714; -. DR PRO; PR:P27361; -. DR Proteomes; UP000005640; Chromosome 16. DR Bgee; P27361; -. DR CleanEx; HS_MAPK3; -. DR ExpressionAtlas; P27361; baseline and differential. DR Genevisible; P27361; HS. DR GO; GO:0005901; C:caveola; TAS: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:0070062; C:extracellular exosome; IDA:UniProtKB. 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:0015630; C:microtubule cytoskeleton; IDA:HPA. DR GO; GO:0005739; C:mitochondrion; TAS:UniProtKB. DR GO; GO:0005635; C:nuclear envelope; IDA:BHF-UCL. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; TAS:UniProtKB. DR GO; GO:0043234; C:protein complex; IEA:Ensembl. DR GO; GO:0031143; C:pseudopodium; IEA:Ensembl. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0004707; F:MAP kinase activity; IDA:UniProtKB. DR GO; GO:0019902; F:phosphatase binding; IPI:UniProtKB. DR GO; GO:0000187; P:activation of MAPK activity; TAS:Reactome. DR GO; GO:0000186; P:activation of MAPKK activity; TAS:Reactome. DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW. DR GO; GO:0019369; P:arachidonic acid metabolic process; IEA:Ensembl. DR GO; GO:0007411; P:axon guidance; TAS:Reactome. DR GO; GO:0007596; P:blood coagulation; TAS:Reactome. DR GO; GO:0030509; P:BMP signaling pathway; IMP:BHF-UCL. 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:0034605; P:cellular response to heat; TAS:Reactome. DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEP:UniProtKB. DR GO; GO:0019221; P:cytokine-mediated signaling pathway; TAS:Reactome. DR GO; GO:0006975; P:DNA damage induced protein phosphorylation; IDA:UniProtKB. DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome. DR GO; GO:0070371; P:ERK1 and ERK2 cascade; IEA:Ensembl. DR GO; GO:0038095; P:Fc-epsilon receptor signaling pathway; TAS:Reactome. DR GO; GO:0038096; P:Fc-gamma receptor signaling pathway involved in phagocytosis; TAS:Reactome. DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; TAS:Reactome. DR GO; GO:0010467; P:gene expression; TAS:Reactome. DR GO; GO:0045087; P:innate immune response; TAS:Reactome. DR GO; GO:0008286; P:insulin receptor signaling pathway; TAS:Reactome. DR GO; GO:0070498; P:interleukin-1-mediated signaling pathway; IMP:BHF-UCL. DR GO; GO:0060397; P:JAK-STAT cascade involved in growth hormone signaling pathway; TAS:Reactome. 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:0000189; P:MAPK import into nucleus; IEA:Ensembl. DR GO; GO:0002755; P:MyD88-dependent toll-like receptor signaling pathway; TAS:Reactome. DR GO; GO:0002756; P:MyD88-independent toll-like receptor signaling pathway; TAS:Reactome. DR GO; GO:2000657; P:negative regulation of apolipoprotein binding; IEA:Ensembl. DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; TAS:Reactome. DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IEA:Ensembl. DR GO; GO:0038083; P:peptidyl-tyrosine autophosphorylation; IDA:UniProtKB. DR GO; GO:0016310; P:phosphorylation; IDA:UniProtKB. DR GO; GO:0030168; P:platelet activation; TAS:Reactome. 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: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:0001934; P:positive regulation of protein phosphorylation; IMP:BHF-UCL. DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IMP:BHF-UCL. DR GO; GO:0045727; P:positive regulation of translation; IEA:Ensembl. DR GO; GO:0006461; P:protein complex assembly; IEA:Ensembl. DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB. DR GO; GO:0007265; P:Ras protein signal transduction; TAS:Reactome. DR GO; GO:1900034; P:regulation of cellular response to heat; TAS:Reactome. 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:0051090; P:regulation of sequence-specific DNA binding transcription factor activity; TAS:Reactome. 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:0009636; P:response to toxic substance; IEA:Ensembl. DR GO; GO:0019233; P:sensory perception of pain; IEA:Ensembl. DR GO; GO:0007264; P:small GTPase mediated signal transduction; TAS:Reactome. DR GO; GO:0051403; P:stress-activated MAPK cascade; TAS:Reactome. DR GO; GO:0034166; P:toll-like receptor 10 signaling pathway; TAS:Reactome. DR GO; GO:0034134; P:toll-like receptor 2 signaling pathway; TAS:Reactome. DR GO; GO:0034138; P:toll-like receptor 3 signaling pathway; TAS:Reactome. DR GO; GO:0034142; P:toll-like receptor 4 signaling pathway; TAS:Reactome. DR GO; GO:0034146; P:toll-like receptor 5 signaling pathway; TAS:Reactome. DR GO; GO:0034162; P:toll-like receptor 9 signaling pathway; TAS:Reactome. DR GO; GO:0002224; P:toll-like receptor signaling pathway; TAS:Reactome. DR GO; GO:0038123; P:toll-like receptor TLR1:TLR2 signaling pathway; TAS:Reactome. DR GO; GO:0038124; P:toll-like receptor TLR6:TLR2 signaling pathway; TAS:Reactome. DR GO; GO:0060440; P:trachea formation; IEA:Ensembl. DR GO; GO:0006360; P:transcription from RNA polymerase I promoter; TAS:Reactome. DR GO; GO:0006361; P:transcription initiation from RNA polymerase I promoter; TAS:Reactome. DR GO; GO:0035666; P:TRIF-dependent toll-like receptor signaling pathway; TAS:Reactome. DR GO; GO:0048010; P:vascular endothelial growth factor receptor signaling pathway; TAS:Reactome. DR GO; GO:0016032; P:viral process; IEA:UniProtKB-KW. DR InterPro; IPR011009; Kinase-like_dom. 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; IPR002290; Ser/Thr_dual-sp_kinase. 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; KW ATP-binding; Cell cycle; Complete proteome; Cytoplasm; KW Direct protein sequencing; Host-virus interaction; Kinase; KW Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; KW Reference proteome; Serine/threonine-protein kinase; Transferase. FT INIT_MET 1 1 Removed. {ECO:0000244|PubMed:19413330, FT ECO:0000244|PubMed:22223895, FT ECO:0000244|PubMed:22814378, FT ECO:0000269|Ref.8}. FT CHAIN 2 379 Mitogen-activated protein kinase 3. FT /FTId=PRO_0000186251. FT DOMAIN 42 330 Protein kinase. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT NP_BIND 48 56 ATP. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT MOTIF 202 204 TXY. FT ACT_SITE 166 166 Proton acceptor. {ECO:0000255|PROSITE- FT ProRule:PRU00159, ECO:0000255|PROSITE- FT ProRule:PRU10027}. FT BINDING 71 71 ATP. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT MOD_RES 2 2 N-acetylalanine. FT {ECO:0000244|PubMed:19413330, FT ECO:0000244|PubMed:22223895, FT ECO:0000244|PubMed:22814378, FT ECO:0000269|Ref.8}. FT MOD_RES 198 198 Phosphothreonine. FT {ECO:0000244|PubMed:19369195}. FT MOD_RES 202 202 Phosphothreonine; by MAP2K1 and MAP2K2. FT {ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:19690332, FT ECO:0000244|PubMed:21406692}. FT MOD_RES 204 204 Phosphotyrosine; by MAP2K1 and MAP2K2. FT {ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:19690332, FT ECO:0000244|PubMed:21406692, FT ECO:0000269|PubMed:18983981, FT ECO:0000269|PubMed:19494114}. FT MOD_RES 207 207 Phosphothreonine; by autocatalysis. FT {ECO:0000269|PubMed:19060905}. FT VAR_SEQ 259 302 Missing (in isoform 2). FT {ECO:0000303|Ref.3}. FT /FTId=VSP_041906. FT VAR_SEQ 340 379 PVAEEPFTFAMELDDLPKERLKELIFQETARFQPGVLEAP FT -> VGQSPAAVGLGAGEQGGT (in isoform 3). FT {ECO:0000303|Ref.2}. FT /FTId=VSP_041907. FT VARIANT 323 323 E -> K (in dbSNP:rs55859133). FT {ECO:0000269|PubMed:17344846}. FT /FTId=VAR_042253. FT CONFLICT 174 174 I -> S (in Ref. 1; CAA42744 and 2; FT AAK52329). {ECO:0000305}. FT STRAND 29 31 {ECO:0000244|PDB:4QTB}. FT STRAND 34 36 {ECO:0000244|PDB:4QTB}. FT TURN 39 41 {ECO:0000244|PDB:4QTB}. FT STRAND 42 51 {ECO:0000244|PDB:4QTB}. FT STRAND 54 61 {ECO:0000244|PDB:4QTB}. FT TURN 62 65 {ECO:0000244|PDB:4QTB}. FT STRAND 66 73 {ECO:0000244|PDB:4QTB}. FT HELIX 79 94 {ECO:0000244|PDB:4QTB}. FT STRAND 105 107 {ECO:0000244|PDB:4QTB}. FT TURN 112 114 {ECO:0000244|PDB:4QTB}. FT STRAND 118 122 {ECO:0000244|PDB:4QTB}. FT STRAND 126 128 {ECO:0000244|PDB:4QTB}. FT HELIX 129 135 {ECO:0000244|PDB:4QTB}. FT HELIX 140 159 {ECO:0000244|PDB:4QTB}. FT HELIX 169 171 {ECO:0000244|PDB:4QTB}. FT STRAND 172 174 {ECO:0000244|PDB:4QTB}. FT STRAND 180 182 {ECO:0000244|PDB:4QTB}. FT HELIX 193 195 {ECO:0000244|PDB:4QTB}. FT HELIX 208 210 {ECO:0000244|PDB:4QTB}. FT HELIX 213 215 {ECO:0000244|PDB:4QTB}. FT TURN 216 218 {ECO:0000244|PDB:4QTB}. FT HELIX 225 240 {ECO:0000244|PDB:4QTB}. FT HELIX 250 261 {ECO:0000244|PDB:4QTB}. FT HELIX 266 269 {ECO:0000244|PDB:4QTB}. FT HELIX 275 282 {ECO:0000244|PDB:4QTB}. FT HELIX 292 295 {ECO:0000244|PDB:4QTB}. FT HELIX 301 310 {ECO:0000244|PDB:4QTB}. FT HELIX 315 317 {ECO:0000244|PDB:4QTB}. FT HELIX 321 325 {ECO:0000244|PDB:4QTB}. FT HELIX 328 330 {ECO:0000244|PDB:4QTB}. FT TURN 331 333 {ECO:0000244|PDB:4QTB}. FT HELIX 336 338 {ECO:0000244|PDB:4QTB}. FT HELIX 350 354 {ECO:0000244|PDB:4QTB}. FT HELIX 357 368 {ECO:0000244|PDB:4QTB}. FT HELIX 369 371 {ECO:0000244|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 //