MK03_RAT
ID MK03_RAT Reviewed; 380 AA.
AC P21708; Q4PIY8; Q62686; Q9JJ13;
DT 01-MAY-1991, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 5.
DT 03-AUG-2022, entry version 226.
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=MNK1;
DE AltName: Full=Microtubule-associated protein 2 kinase;
DE AltName: Full=p44-ERK1;
GN Name=Mapk3; Synonyms=Erk1, Prkm3;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RX PubMed=1327976; DOI=10.1016/0378-1119(92)90109-3;
RA Marquardt B., Stabel S.;
RT "Sequence of a rat cDNA encoding the ERK1-MAP kinase.";
RL Gene 120:297-299(1992).
RN [2]
RP PROTEIN SEQUENCE OF 2-65; 96-132; 157-209; 213-221; 280-357 AND 361-380
RP (ISOFORM 2), CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2,
RP PHOSPHORYLATION AT THR-203 AND TYR-205, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC TISSUE=Pheochromocytoma;
RA Bienvenut W.V., von Kriegsheim A.F., Kolch W.;
RL Submitted (AUG-2006) to UniProtKB.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 7-380 (ISOFORM 1).
RA Maisonpierre P.C., le Beau M.M., Espinosa R. III, Ip N.Y., Belluscio L.,
RA la Monte S.M., Squinto S., Furth M.E., Yancopoulos G.D.;
RL Submitted (JUL-1991) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP PROTEIN SEQUENCE OF 73-84 AND 183-190, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Brain, and Spinal cord;
RA Lubec G., Afjehi-Sadat L., Kang S.U.;
RL Submitted (JUL-2007) to UniProtKB.
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 14-380 (ISOFORM 1), PARTIAL PROTEIN SEQUENCE,
RP AND TISSUE SPECIFICITY.
RX PubMed=2164259; DOI=10.1126/science.2164259;
RA Boulton T.G., Yancopoulos G.D., Gregory J.S., Slaughter C., Moomaw C.,
RA Hsu J., Cobb M.H.;
RT "An insulin-stimulated protein kinase similar to yeast kinases involved in
RT cell cycle control.";
RL Science 249:64-67(1990).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 14-380 (ISOFORM 1).
RC TISSUE=Brain cortex;
RX PubMed=1716439; DOI=10.1089/dna.1991.10.505;
RA de Miguel C., Kligman D., Patel J., Detera-Wadleigh S.D.;
RT "Molecular analysis of microtubule-associated protein-2 kinase cDNA from
RT mouse and rat brain.";
RL DNA Cell Biol. 10:505-514(1991).
RN [7]
RP PROTEIN SEQUENCE OF 43-64 AND 167-185, AND CHARACTERIZATION.
RX PubMed=1846291; DOI=10.1021/bi00215a038;
RA Boulton T.G., Gregory J.S., Cobb M.H.;
RT "Purification and properties of extracellular signal-regulated kinase 1, an
RT insulin-stimulated microtubule-associated protein 2 kinase.";
RL Biochemistry 30:278-286(1991).
RN [8]
RP RETRACTED PAPER.
RX PubMed=10748187; DOI=10.1074/jbc.m910060199;
RA Yung Y., Yao Z., Hanoch T., Seger R.;
RT "ERK1b, a 46-kDa ERK isoform that is differentially regulated by MEK.";
RL J. Biol. Chem. 275:15799-15808(2000).
RN [9]
RP INTERACTION WITH GIT1.
RX PubMed=15923189; DOI=10.1074/jbc.m502271200;
RA Yin G., Zheng Q., Yan C., Berk B.C.;
RT "GIT1 is a scaffold for ERK1/2 activation in focal adhesions.";
RL J. Biol. Chem. 280:27705-27712(2005).
RN [10]
RP RETRACTION NOTICE OF PUBMED:10748187.
RX PubMed=28550140; DOI=10.1074/jbc.a117.910060;
RA Yung Y., Yao Z., Hanoch T., Seger R.;
RL J. Biol. Chem. 292:8854-8854(2017).
RN [11]
RP AUTOPHOSPHORYLATION.
RX PubMed=1712480; DOI=10.1073/pnas.88.14.6142;
RA Seger R., Ahn N.G., Boulton T.G., Yancopoulos G.D., Panayotatos N.,
RA Radziejewska E., Ericsson L., Bratlien R.L., Cobb M.H., Krebs E.G.;
RT "Microtubule-associated protein 2 kinases, ERK1 and ERK2, undergo
RT autophosphorylation on both tyrosine and threonine residues: implications
RT for their mechanism of activation.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:6142-6146(1991).
RN [12]
RP PHOSPHORYLATION OF EIF4EBP1.
RX PubMed=7939721; DOI=10.1126/science.7939721;
RA Lin T.-A., Kong X., Haystead T.A.J., Pause A., Belsham G.J., Sonenberg N.,
RA Lawrence J.C. Jr.;
RT "PHAS-I as a link between mitogen-activated protein kinase and translation
RT initiation.";
RL Science 266:653-656(1994).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-203 AND TYR-205, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=16641100; DOI=10.1073/pnas.0600895103;
RA Hoffert J.D., Pisitkun T., Wang G., Shen R.-F., Knepper M.A.;
RT "Quantitative phosphoproteomics of vasopressin-sensitive renal cells:
RT regulation of aquaporin-2 phosphorylation at two sites.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:7159-7164(2006).
RN [14]
RP IDENTIFICATION IN A COMPLEX WITH BRAF; HRAS; MAP2K1 AND RGS14.
RX PubMed=19319189; DOI=10.1371/journal.pone.0004884;
RA Willard F.S., Willard M.D., Kimple A.J., Soundararajan M., Oestreich E.A.,
RA Li X., Sowa N.A., Kimple R.J., Doyle D.A., Der C.J., Zylka M.J.,
RA Snider W.D., Siderovski D.P.;
RT "Regulator of G-protein signaling 14 (RGS14) is a selective H-Ras
RT effector.";
RL PLoS ONE 4:E4884-E4884(2009).
RN [15]
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 [16]
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 [17]
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 [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-203 AND TYR-205, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [19]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH CAVIN4.
RX PubMed=24567387; DOI=10.1073/pnas.1315359111;
RA Ogata T., Naito D., Nakanishi N., Hayashi Y.K., Taniguchi T., Miyagawa K.,
RA Hamaoka T., Maruyama N., Matoba S., Ikeda K., Yamada H., Oh H., Ueyama T.;
RT "MURC/Cavin-4 facilitates recruitment of ERK to caveolae and concentric
RT cardiac hypertrophy induced by alpha1-adrenergic receptors.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:3811-3816(2014).
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.
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-203 and Tyr-205 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 -!- 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. Interacts with ADAM15, ARRB2, CANX, DAPK1
CC (via death domain), HSF4, IER3, MAP2K1/MEK1, MORG1, NISCH, PEA15, SGK1
CC and MKNK2. MKNK2 isoform 1 binding prevents from dephosphorylation and
CC inactivation. Interacts with TPR. Interacts with HSF1 (via D domain and
CC preferentially with hyperphosphorylated form); this interaction occurs
CC upon heat shock. Interacts with CDKN2AIP (By similarity). Interacts
CC with CAVIN4 (PubMed:24567387). Interacts with GIT1; this interaction is
CC necessary for MAPK3 localization to focal adhesions (PubMed:15923189).
CC Interacts with ZNF263 (By similarity). {ECO:0000250|UniProtKB:P27361,
CC ECO:0000250|UniProtKB:Q63844, ECO:0000269|PubMed:15923189,
CC ECO:0000269|PubMed:24567387}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:24567387}. Nucleus.
CC Membrane, caveola {ECO:0000269|PubMed:24567387}. Cell junction, focal
CC adhesion {ECO:0000250|UniProtKB:Q63844}. Note=Autophosphorylation at
CC Thr-207 promotes nuclear localization (By similarity). PEA15-binding
CC redirects the biological outcome of MAPK3 kinase-signaling by
CC sequestering MAPK3 into the cytoplasm (By similarity).
CC {ECO:0000250|UniProtKB:P27361, ECO:0000250|UniProtKB:Q63844}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=A;
CC IsoId=P21708-1; Sequence=Displayed;
CC Name=2; Synonyms=B;
CC IsoId=P21708-2; Sequence=VSP_004830;
CC -!- TISSUE SPECIFICITY: Highest levels within the nervous system, expressed
CC in different tissues, mostly in intestine, placenta and lung.
CC {ECO:0000269|PubMed:2164259}.
CC -!- DEVELOPMENTAL STAGE: Increased expression during development.
CC -!- DOMAIN: The TXY motif contains the threonine and tyrosine residues
CC whose phosphorylation activates the MAP kinases.
CC -!- PTM: Phosphorylated upon FLT3 and KIT signaling. Ligand-activated ALK
CC induces tyrosine phosphorylation (By similarity). Dephosphorylated by
CC PTPRJ at Tyr-205 (By similarity). Dually phosphorylated on Thr-203 and
CC Tyr-205, which activates the enzyme. {ECO:0000250,
CC ECO:0000269|PubMed:7939721, ECO:0000269|Ref.2}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC protein kinase family. MAP kinase subfamily. {ECO:0000305}.
CC -!- CAUTION: The publication has been retracted as they falsified western
CC blot data. {ECO:0000305|PubMed:10748187, ECO:0000305|PubMed:28550140}.
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DR EMBL; S46779; AAA11604.1; -; mRNA.
DR EMBL; X65198; CAA46318.1; -; mRNA.
DR EMBL; AF155236; AAF71666.1; -; mRNA.
DR EMBL; M61177; AAA63486.1; -; mRNA.
DR EMBL; M38194; AAA41123.1; -; mRNA.
DR EMBL; U12008; AAA20009.1; -; mRNA.
DR PIR; JC1451; JC1451.
DR RefSeq; NP_059043.1; NM_017347.2. [P21708-1]
DR AlphaFoldDB; P21708; -.
DR SMR; P21708; -.
DR BioGRID; 248427; 5.
DR CORUM; P21708; -.
DR DIP; DIP-487N; -.
DR IntAct; P21708; 271.
DR MINT; P21708; -.
DR STRING; 10116.ENSRNOP00000026627; -.
DR ChEMBL; CHEMBL5809; -.
DR iPTMnet; P21708; -.
DR PhosphoSitePlus; P21708; -.
DR SwissPalm; P21708; -.
DR jPOST; P21708; -.
DR PaxDb; P21708; -.
DR PRIDE; P21708; -.
DR GeneID; 50689; -.
DR KEGG; rno:50689; -.
DR UCSC; RGD:3046; rat. [P21708-1]
DR CTD; 5595; -.
DR RGD; 3046; Mapk3.
DR VEuPathDB; HostDB:ENSRNOG00000053583; -.
DR eggNOG; KOG0660; Eukaryota.
DR HOGENOM; CLU_000288_181_1_1; -.
DR InParanoid; P21708; -.
DR OMA; EIMTFRP; -.
DR OrthoDB; 741207at2759; -.
DR PhylomeDB; P21708; -.
DR TreeFam; TF105097; -.
DR BRENDA; 2.7.11.24; 5301.
DR Reactome; R-RNO-110056; MAPK3 (ERK1) activation.
DR Reactome; R-RNO-112409; RAF-independent MAPK1/3 activation.
DR Reactome; R-RNO-1169408; ISG15 antiviral mechanism.
DR Reactome; R-RNO-1181150; Signaling by NODAL.
DR Reactome; R-RNO-1295596; Spry regulation of FGF signaling.
DR Reactome; R-RNO-1502540; Signaling by Activin.
DR Reactome; R-RNO-162658; Golgi Cisternae Pericentriolar Stack Reorganization.
DR Reactome; R-RNO-170968; Frs2-mediated activation.
DR Reactome; R-RNO-198753; ERK/MAPK targets.
DR Reactome; R-RNO-202670; ERKs are inactivated.
DR Reactome; R-RNO-2029482; Regulation of actin dynamics for phagocytic cup formation.
DR Reactome; R-RNO-2173796; SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.
DR Reactome; R-RNO-2559580; Oxidative Stress Induced Senescence.
DR Reactome; R-RNO-2559582; Senescence-Associated Secretory Phenotype (SASP).
DR Reactome; R-RNO-2559585; Oncogene Induced Senescence.
DR Reactome; R-RNO-2871796; FCERI mediated MAPK activation.
DR Reactome; R-RNO-3371453; Regulation of HSF1-mediated heat shock response.
DR Reactome; R-RNO-375165; NCAM signaling for neurite out-growth.
DR Reactome; R-RNO-445144; Signal transduction by L1.
DR Reactome; R-RNO-450341; Activation of the AP-1 family of transcription factors.
DR Reactome; R-RNO-456926; Thrombin signalling through proteinase activated receptors (PARs).
DR Reactome; R-RNO-5654726; Negative regulation of FGFR1 signaling.
DR Reactome; R-RNO-5654727; Negative regulation of FGFR2 signaling.
DR Reactome; R-RNO-5654732; Negative regulation of FGFR3 signaling.
DR Reactome; R-RNO-5654733; Negative regulation of FGFR4 signaling.
DR Reactome; R-RNO-5663213; RHO GTPases Activate WASPs and WAVEs.
DR Reactome; R-RNO-5668599; RHO GTPases Activate NADPH Oxidases.
DR Reactome; R-RNO-5673001; RAF/MAP kinase cascade.
DR Reactome; R-RNO-5674135; MAP2K and MAPK activation.
DR Reactome; R-RNO-5674499; Negative feedback regulation of MAPK pathway.
DR Reactome; R-RNO-5675221; Negative regulation of MAPK pathway.
DR Reactome; R-RNO-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR Reactome; R-RNO-73728; RNA Polymerase I Promoter Opening.
DR Reactome; R-RNO-74749; Signal attenuation.
DR Reactome; R-RNO-8939211; ESR-mediated signaling.
DR Reactome; R-RNO-9627069; Regulation of the apoptosome activity.
DR Reactome; R-RNO-982772; Growth hormone receptor signaling.
DR PRO; PR:P21708; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000053583; Expressed in jejunum and 19 other tissues.
DR Genevisible; P21708; RN.
DR GO; GO:0005901; C:caveola; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; TAS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0005769; C:early endosome; TAS: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:0005739; C:mitochondrion; TAS:UniProtKB.
DR GO; GO:0005635; C:nuclear envelope; ISO:RGD.
DR GO; GO:0005654; C:nucleoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR GO; GO:0031143; C:pseudopodium; ISO:RGD.
DR GO; GO:0005524; F:ATP binding; IDA:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0004707; F:MAP kinase activity; IDA:UniProtKB.
DR GO; GO:0004708; F:MAP kinase kinase activity; ISO:RGD.
DR GO; GO:0019902; F:phosphatase binding; ISO:RGD.
DR GO; GO:0001784; F:phosphotyrosine residue binding; ISO:RGD.
DR GO; GO:0004672; F:protein kinase activity; ISO:RGD.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISO:RGD.
DR GO; GO:0097110; F:scaffold protein binding; IPI:BHF-UCL.
DR GO; GO:0007568; P:aging; IDA:RGD.
DR GO; GO:0009887; P:animal organ morphogenesis; ISO:RGD.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0019369; P:arachidonic acid metabolic process; IEP:RGD.
DR GO; GO:0060020; P:Bergmann glial cell differentiation; ISO:RGD.
DR GO; GO:0030509; P:BMP signaling pathway; ISO:RGD.
DR GO; GO:0061308; P:cardiac neural crest cell development involved in heart development; ISO:RGD.
DR GO; GO:0051216; P:cartilage development; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0071276; P:cellular response to cadmium ion; ISO:RGD.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISO:RGD.
DR GO; GO:1903351; P:cellular response to dopamine; ISO:RGD.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; ISO:RGD.
DR GO; GO:0034614; P:cellular response to reactive oxygen species; ISO:RGD.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; ISO:RGD.
DR GO; GO:0046697; P:decidualization; IDA:RGD.
DR GO; GO:0006975; P:DNA damage induced protein phosphorylation; ISO:RGD.
DR GO; GO:0070371; P:ERK1 and ERK2 cascade; ISO:RGD.
DR GO; GO:0060324; P:face development; ISO:RGD.
DR GO; GO:0070498; P:interleukin-1-mediated signaling pathway; ISO:RGD.
DR GO; GO:0035556; P:intracellular signal transduction; IDA:RGD.
DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; ISO:RGD.
DR GO; GO:0060425; P:lung morphogenesis; ISO:RGD.
DR GO; GO:0000165; P:MAPK cascade; IMP:RGD.
DR GO; GO:2000657; P:negative regulation of apolipoprotein binding; ISO:RGD.
DR GO; GO:0014032; P:neural crest cell development; ISO:RGD.
DR GO; GO:0042473; P:outer ear morphogenesis; ISO:RGD.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IMP:RGD.
DR GO; GO:0038083; P:peptidyl-tyrosine autophosphorylation; ISO:RGD.
DR GO; GO:0016310; P:phosphorylation; ISO:RGD.
DR GO; GO:0031281; P:positive regulation of cyclase activity; ISO:RGD.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISO:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
DR GO; GO:0035066; P:positive regulation of histone acetylation; ISO:RGD.
DR GO; GO:0033129; P:positive regulation of histone phosphorylation; ISO:RGD.
DR GO; GO:0010759; P:positive regulation of macrophage chemotaxis; ISO:RGD.
DR GO; GO:0120041; P:positive regulation of macrophage proliferation; ISO:RGD.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:RGD.
DR GO; GO:0051973; P:positive regulation of telomerase activity; ISO:RGD.
DR GO; GO:1904355; P:positive regulation of telomere capping; ISO:RGD.
DR GO; GO:0032212; P:positive regulation of telomere maintenance via telomerase; ISO:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0045727; P:positive regulation of translation; IMP:RGD.
DR GO; GO:1904417; P:positive regulation of xenophagy; ISO:RGD.
DR GO; GO:0006468; P:protein phosphorylation; IDA:RGD.
DR GO; GO:0065003; P:protein-containing complex assembly; IMP:UniProtKB.
DR GO; GO:0030641; P:regulation of cellular pH; ISO:RGD.
DR GO; GO:0051493; P:regulation of cytoskeleton organization; TAS:UniProtKB.
DR GO; GO:0051090; P:regulation of DNA-binding transcription factor activity; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0032872; P:regulation of stress-activated MAPK cascade; TAS:UniProtKB.
DR GO; GO:0070849; P:response to epidermal growth factor; ISS:UniProtKB.
DR GO; GO:0043330; P:response to exogenous dsRNA; ISO:RGD.
DR GO; GO:0032496; P:response to lipopolysaccharide; ISO:RGD.
DR GO; GO:0009636; P:response to toxic substance; IDA:RGD.
DR GO; GO:0019233; P:sensory perception of pain; ISO:RGD.
DR GO; GO:0051403; P:stress-activated MAPK cascade; ISO:RGD.
DR GO; GO:0048538; P:thymus development; ISO:RGD.
DR GO; GO:0030878; P:thyroid gland development; ISO:RGD.
DR GO; GO:0060440; P:trachea formation; ISO:RGD.
DR GO; GO:0006351; P:transcription, DNA-templated; ISO:RGD.
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 Acetylation; Alternative splicing; Apoptosis; ATP-binding; Cell cycle;
KW Cell junction; Cytoplasm; Direct protein sequencing; Kinase; Membrane;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.2"
FT CHAIN 2..380
FT /note="Mitogen-activated protein kinase 3"
FT /id="PRO_0000186253"
FT DOMAIN 43..331
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOTIF 203..205
FT /note="TXY"
FT ACT_SITE 167
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 49..57
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 72
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.2"
FT MOD_RES 199
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P27361"
FT MOD_RES 203
FT /note="Phosphothreonine; by MAP2K1 and MAP2K2"
FT /evidence="ECO:0000269|Ref.2, ECO:0007744|PubMed:16641100,
FT ECO:0007744|PubMed:22673903"
FT MOD_RES 205
FT /note="Phosphotyrosine; by MAP2K1 and MAP2K2"
FT /evidence="ECO:0000269|Ref.2, ECO:0007744|PubMed:16641100,
FT ECO:0007744|PubMed:22673903"
FT MOD_RES 208
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P27361"
FT VAR_SEQ 340
FT /note="E -> EVSRPPAAGRGISVPSVRPVPYCLCPQ (in isoform 2)"
FT /evidence="ECO:0000269|Ref.2"
FT /id="VSP_004830"
FT CONFLICT 95
FT /note="R -> G (in Ref. 1; AAA11604/CAA46318, 3; AAA63486
FT and 6; AAA20009)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 380 AA; 43081 MW; 49C4EA95B627237F CRC64;
MAAAAAAPGG GGGEPRGTAG VVPVVPGEVE VVKGQPFDVG PRYTQLQYIG EGAYGMVSSA
YDHVRKTRVA IKKISPFEHQ TYCQRTLREI QILLRFRHEN VIGIRDILRA PTLEAMRDVY
IVQDLMETDL YKLLKSQQLS NDHICYFLYQ ILRGLKYIHS ANVLHRDLKP SNLLINTTCD
LKICDFGLAR IADPEHDHTG FLTEYVATRW YRAPEIMLNS KGYTKSIDIW SVGCILAEML
SNRPIFPGKH YLDQLNHILG ILGSPSQEDL NCIINMKARN YLQSLPSKTK VAWAKLFPKS
DSKALDLLDR MLTFNPNKRI TVEEALAHPY LEQYYDPTDE PVAEEPFTFD MELDDLPKER
LKELIFQETA RFQPGAPEAP
