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   27-MAR-2024, entry version 234.
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, DEPTOR, FRS2 or GRB10). Protein kinases (such
CC       as RAF1, RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK,
CC       MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or
CC       MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are
CC       other substrates which enable the propagation the MAPK/ERK signal to
CC       additional cytosolic and nuclear targets, thereby extending the
CC       specificity of the cascade.
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). Interacts with EBF4.
CC       {ECO:0000250|UniProtKB:P27361, ECO:0000250|UniProtKB:Q63844,
CC       ECO:0000269|PubMed:15923189, 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   -!- PTM: Ubiquitinated by TRIM15 via 'Lys-63'-linked ubiquitination;
CC       leading to activation. Deubiquitinated by CYLD.
CC       {ECO:0000250|UniProtKB:P27361}.
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; 273.
DR   MINT; P21708; -.
DR   STRING; 10116.ENSRNOP00000070784; -.
DR   ChEMBL; CHEMBL5809; -.
DR   GlyGen; P21708; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; P21708; -.
DR   PhosphoSitePlus; P21708; -.
DR   SwissPalm; P21708; -.
DR   jPOST; P21708; -.
DR   PaxDb; 10116-ENSRNOP00000026627; -.
DR   Ensembl; ENSRNOT00055045334; ENSRNOP00055037155; ENSRNOG00055026224. [P21708-1]
DR   Ensembl; ENSRNOT00060053835; ENSRNOP00060044673; ENSRNOG00060030957. [P21708-1]
DR   Ensembl; ENSRNOT00065027942; ENSRNOP00065022060; ENSRNOG00065016730. [P21708-1]
DR   GeneID; 50689; -.
DR   KEGG; rno:50689; -.
DR   UCSC; RGD:3046; rat. [P21708-1]
DR   AGR; RGD:3046; -.
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   OrthoDB; 158564at2759; -.
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-2173795; Downregulation of SMAD2/3:SMAD4 transcriptional activity.
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-877300; Interferon gamma signaling.
DR   Reactome; R-RNO-881907; Gastrin-CREB signalling pathway via PKC and MAPK.
DR   Reactome; R-RNO-8939211; ESR-mediated signaling.
DR   Reactome; R-RNO-9627069; Regulation of the apoptosome activity.
DR   Reactome; R-RNO-9732724; IFNG signaling activates MAPKs.
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 cell types or tissues.
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; ISO:RGD.
DR   GO; GO:0005769; C:early endosome; TAS:UniProtKB.
DR   GO; GO:0005925; C:focal adhesion; TAS:UniProtKB.
DR   GO; GO:0098978; C:glutamatergic synapse; ISO:RGD.
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; ISO: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:0140297; F:DNA-binding transcription factor binding; ISO:RGD.
DR   GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR   GO; GO:0004707; F:MAP kinase activity; IDA:UniProtKB.
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: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: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: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:0006974; P:DNA damage response; ISO:RGD.
DR   GO; GO:0006351; P:DNA-templated transcription; ISO:RGD.
DR   GO; GO:0038133; P:ERBB2-ERBB3 signaling pathway; 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:0008286; P:insulin receptor signaling pathway; ISO:RGD.
DR   GO; GO:0048009; P:insulin-like growth factor receptor signaling pathway; 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:0050804; P:modulation of chemical synaptic transmission; ISO:RGD.
DR   GO; GO:0042552; P:myelination; ISO:RGD.
DR   GO; GO:1904262; P:negative regulation of TORC1 signaling; 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:0016310; P:phosphorylation; ISO:RGD.
DR   GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; 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: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: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: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:0014044; P:Schwann cell development; ISO:RGD.
DR   GO; GO:0019233; P:sensory perception of pain; ISO:RGD.
DR   GO; GO:0042770; P:signal transduction in response to DNA damage; 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:0098792; P:xenophagy; ISO:RGD.
DR   CDD; cd07849; STKc_ERK1_2_like; 1.
DR   Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
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   PANTHER; PTHR24055; MITOGEN-ACTIVATED PROTEIN KINASE; 1.
DR   PANTHER; PTHR24055:SF393; MITOGEN-ACTIVATED PROTEIN KINASE 3; 1.
DR   Pfam; PF00069; Pkinase; 1.
DR   PRINTS; PR01770; ERK1ERK2MAPK.
DR   SMART; SM00220; S_TKc; 1.
DR   SUPFAM; SSF56112; Protein kinase-like (PK-like); 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.
DR   Genevisible; P21708; RN.
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; Ubl conjugation.
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
//