MK03_MOUSE
ID MK03_MOUSE Reviewed; 380 AA.
AC Q63844; Q61531; Q8K0X5; Q91YW5;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 5.
DT 03-AUG-2022, entry version 221.
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 Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Kidney, and Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [2]
RP PROTEIN SEQUENCE OF 2-65; 89-105; 110-132; 157-209; 213-221; 280-288;
RP 304-319 AND 361-371, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT
RP ALA-2, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Embryonic fibroblast;
RA Bienvenut W.V., Serrels B., Brunton V.G., Frame M.C.;
RL Submitted (FEB-2008) to UniProtKB.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 4-380.
RX PubMed=8424957; DOI=10.1016/0167-4781(93)90074-n;
RA Tanner B., Mueckler M.;
RT "Molecular cloning of a mouse extracellular signal regulated kinase (erk-
RT 1).";
RL Biochim. Biophys. Acta 1171:319-320(1993).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 10-19.
RC TISSUE=Pre-B cell;
RX PubMed=1717989; DOI=10.1073/pnas.88.19.8845;
RA Crews C.M., Alessandrini A.A., Erikson R.L.;
RT "Mouse Erk-1 gene product is a serine/threonine protein kinase that has the
RT potential to phosphorylate tyrosine.";
RL Proc. Natl. Acad. Sci. U.S.A. 88:8845-8849(1991).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 77-380.
RC TISSUE=Fetal brain;
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 [6]
RP PROTEIN SEQUENCE OF 136-153 AND 191-209, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC TISSUE=Hippocampus;
RA Lubec G., Klug S.;
RL Submitted (MAR-2007) to UniProtKB.
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 171-209.
RC STRAIN=CBA/J; TISSUE=Bone marrow;
RX PubMed=8444355; DOI=10.1016/0378-1119(93)90411-u;
RA Ershler M.A., Nagorskaya T.V., Visser J.W.M., Belyavsky A.V.;
RT "Novel CDC2-related protein kinases produced in murine hematopoietic stem
RT cells.";
RL Gene 124:305-306(1993).
RN [8]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 171-205.
RX PubMed=1459009;
RA Ershler M.A., Nagorskaya T.V., Visser J.W.M., Belyavsky A.V.;
RT "Identification of new protein kinase genes, similar to kinases of the cdc2
RT family and expressed in murine hematopoietic stem cells.";
RL Dokl. Akad. Nauk SSSR 324:893-897(1992).
RN [9]
RP PHOSPHORYLATION IN RESPONSE TO FLT3 SIGNALING.
RX PubMed=10080542; DOI=10.1002/jlb.65.3.372;
RA Zhang S., Mantel C., Broxmeyer H.E.;
RT "Flt3 signaling involves tyrosyl-phosphorylation of SHP-2 and SHIP and
RT their association with Grb2 and Shc in Baf3/Flt3 cells.";
RL J. Leukoc. Biol. 65:372-380(1999).
RN [10]
RP PHOSPHORYLATION IN RESPONSE TO FLT3 SIGNALING.
RX PubMed=11090077;
RA Mizuki M., Fenski R., Halfter H., Matsumura I., Schmidt R., Muller C.,
RA Gruning W., Kratz-Albers K., Serve S., Steur C., Buchner T., Kienast J.,
RA Kanakura Y., Berdel W.E., Serve H.;
RT "Flt3 mutations from patients with acute myeloid leukemia induce
RT transformation of 32D cells mediated by the Ras and STAT5 pathways.";
RL Blood 96:3907-3914(2000).
RN [11]
RP INTERACTION WITH PEA15, SUBCELLULAR LOCATION, AND FUNCTION OF THE MAPK ERK
RP CASCADE.
RX PubMed=11702783; DOI=10.1016/s1534-5807(01)00035-1;
RA Formstecher E., Ramos J.W., Fauquet M., Calderwood D.A., Hsieh J.C.,
RA Canton B., Nguyen X.T., Barnier J.V., Camonis J., Ginsberg M.H.,
RA Chneiweiss H.;
RT "PEA-15 mediates cytoplasmic sequestration of ERK MAP kinase.";
RL Dev. Cell 1:239-250(2001).
RN [12]
RP FUNCTION IN PHOSPHORYLATION OF FOS, AND SUBCELLULAR LOCATION.
RX PubMed=12134156; DOI=10.1038/ncb822;
RA Murphy L.O., Smith S., Chen R.H., Fingar D.C., Blenis J.;
RT "Molecular interpretation of ERK signal duration by immediate early gene
RT products.";
RL Nat. Cell Biol. 4:556-564(2002).
RN [13]
RP INTERACTION WITH MORG1.
RX PubMed=15118098; DOI=10.1073/pnas.0305894101;
RA Vomastek T., Schaeffer H.-J., Tarcsafalvi A., Smolkin M.E.,
RA Bissonette E.A., Weber M.J.;
RT "Modular construction of a signaling scaffold: MORG1 interacts with
RT components of the ERK cascade and links ERK signaling to specific
RT agonists.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:6981-6986(2004).
RN [14]
RP PHOSPHORYLATION OF SPZ1.
RX PubMed=15899793; DOI=10.1158/0008-5472.can-04-3658;
RA Hsu S.-H., Hsieh-Li H.-M., Huang H.-Y., Huang P.-H., Li H.;
RT "bHLH-zip transcription factor Spz1 mediates mitogen-activated protein
RT kinase cell proliferation, transformation, and tumorigenesis.";
RL Cancer Res. 65:4041-4050(2005).
RN [15]
RP INTERACTION WITH GIT1, AND SUBCELLULAR LOCATION.
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 [16]
RP INTERACTION WITH MKNK2.
RX PubMed=16162500; DOI=10.1074/jbc.m508356200;
RA Parra J.L., Buxade M., Proud C.G.;
RT "Features of the catalytic domains and C termini of the MAPK signal-
RT integrating kinases Mnk1 and Mnk2 determine their differing activities and
RT regulatory properties.";
RL J. Biol. Chem. 280:37623-37633(2005).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-203 AND TYR-205, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Mast cell;
RX PubMed=17947660; DOI=10.4049/jimmunol.179.9.5864;
RA Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y.,
RA Kawakami T., Salomon A.R.;
RT "Quantitative time-resolved phosphoproteomic analysis of mast cell
RT signaling.";
RL J. Immunol. 179:5864-5876(2007).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-203 AND TYR-205, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=18034455; DOI=10.1021/pr0701254;
RA Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P.;
RT "Large-scale identification and evolution indexing of tyrosine
RT phosphorylation sites from murine brain.";
RL J. Proteome Res. 7:311-318(2008).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-203 AND TYR-205, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic fibroblast;
RX PubMed=19131326; DOI=10.1074/mcp.m800451-mcp200;
RA Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.;
RT "Large scale localization of protein phosphorylation by use of electron
RT capture dissociation mass spectrometry.";
RL Mol. Cell. Proteomics 8:904-912(2009).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-203 AND TYR-205, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Lung, Pancreas, Spleen,
RC and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [22]
RP PHOSPHORYLATION IN RESPONSE TO FLT3 SIGNALING.
RX PubMed=21262971; DOI=10.1074/jbc.m110.205021;
RA Arora D., Stopp S., Bohmer S.A., Schons J., Godfrey R., Masson K.,
RA Razumovskaya E., Ronnstrand L., Tanzer S., Bauer R., Bohmer F.D.,
RA Muller J.P.;
RT "Protein-tyrosine phosphatase DEP-1 controls receptor tyrosine kinase FLT3
RT signaling.";
RL J. Biol. Chem. 286:10918-10929(2011).
RN [23]
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 [24]
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 [25]
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).
CC -!- FUNCTION: Serine/threonine kinase which acts as an essential component
CC of the MAP kinase signal transduction pathway. MAPK1/ERK2 and
CC MAPK3/ERK1 are the 2 MAPKs which play an important role in the MAPK/ERK
CC cascade. They participate also in a signaling cascade initiated by
CC activated KIT and KITLG/SCF. Depending on the cellular context, the
CC MAPK/ERK cascade mediates diverse biological functions such as cell
CC growth, adhesion, survival and differentiation through the regulation
CC of transcription, translation, cytoskeletal rearrangements. The
CC MAPK/ERK cascade also plays a role in initiation and regulation of
CC meiosis, mitosis, and postmitotic functions in differentiated cells by
CC phosphorylating a number of transcription factors. About 160 substrates
CC have already been discovered for ERKs. Many of these substrates are
CC localized in the nucleus, and seem to participate in the regulation of
CC transcription upon stimulation. However, other substrates are found in
CC the cytosol as well as in other cellular organelles, and those are
CC responsible for processes such as translation, mitosis and apoptosis.
CC Moreover, the MAPK/ERK cascade is also involved in the regulation of
CC the endosomal dynamics, including lysosome processing and endosome
CC cycling through the perinuclear recycling compartment (PNRC); as well
CC as in the fragmentation of the Golgi apparatus during mitosis. The
CC substrates include transcription factors (such as ATF2, BCL6, ELK1,
CC ERF, FOS, HSF4 or SPZ1), cytoskeletal elements (such as CANX, CTTN,
CC GJA1, MAP2, MAPT, PXN, SORBS3 or STMN1), regulators of apoptosis (such
CC as BAD, BTG2, CASP9, DAPK1, IER3, MCL1 or PPARG), regulators of
CC translation (such as EIF4EBP1) and a variety of other signaling-related
CC molecules (like ARHGEF2, FRS2 or GRB10). Protein kinases (such as RAF1,
CC RPS6KA1/RSK1, RPS6KA3/RSK2, RPS6KA2/RSK3, RPS6KA6/RSK4, SYK,
CC MKNK1/MNK1, MKNK2/MNK2, RPS6KA5/MSK1, RPS6KA4/MSK2, MAPKAPK3 or
CC MAPKAPK5) and phosphatases (such as DUSP1, DUSP4, DUSP6 or DUSP16) are
CC other substrates which enable the propagation the MAPK/ERK signal to
CC additional cytosolic and nuclear targets, thereby extending the
CC specificity of the cascade. {ECO:0000269|PubMed:11702783,
CC ECO:0000269|PubMed:12134156}.
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 TPR. Interacts with
CC ADAM15, ARRB2, CANX, DAPK1 (via death domain), HSF4, IER3, MAP2K1/MEK1,
CC NISCH, and SGK1 (By similarity). Interacts with MORG1
CC (PubMed:15118098). Interacts with PEA15 (PubMed:11702783). Interacts
CC with isoform 1 of MKNK2 and this binding prevents from
CC dephosphorylation and inactivation (PubMed:16162500). Interacts with
CC CDKN2AIP. Interacts with HSF1 (via D domain and preferentially with
CC hyperphosphorylated form); this interaction occurs upon heat shock.
CC Interacts with CAVIN4 (By similarity). Interacts with GIT1; this
CC interaction is necessary for MAPK3 localization to focal adhesions
CC (PubMed:15923189). Interacts with ZNF263 (By similarity).
CC {ECO:0000250|UniProtKB:P21708, ECO:0000250|UniProtKB:P27361,
CC ECO:0000269|PubMed:11702783, ECO:0000269|PubMed:15118098,
CC ECO:0000269|PubMed:15923189, ECO:0000269|PubMed:16162500}.
CC -!- INTERACTION:
CC Q63844; Q60793: Klf4; NbExp=3; IntAct=EBI-397682, EBI-3043905;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P21708}.
CC Nucleus. Membrane, caveola {ECO:0000250|UniProtKB:P21708}. Cell
CC junction, focal adhesion {ECO:0000269|PubMed:15923189}.
CC Note=Autophosphorylation at Thr-207 promotes nuclear localization (By
CC similarity). PEA15-binding redirects the biological outcome of MAPK3
CC kinase-signaling by sequestering MAPK3 into the cytoplasm
CC (PubMed:11702783). {ECO:0000250|UniProtKB:P27361,
CC ECO:0000269|PubMed:11702783}.
CC -!- DOMAIN: The TXY motif contains the threonine and tyrosine residues
CC whose phosphorylation activates the MAP kinases.
CC -!- PTM: Dually phosphorylated on Thr-203 and Tyr-205, which activates the
CC enzyme. Ligand-activated ALK induces tyrosine phosphorylation (By
CC similarity). Dephosphorylated by PTPRJ at Tyr-205 (By similarity).
CC Autophosphorylated on threonine and tyrosine residues in vitro.
CC Phosphorylated upon FLT3 and KIT signaling (By similarity).
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC protein kinase family. MAP kinase subfamily. {ECO:0000305}.
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DR EMBL; BC013754; AAH13754.1; -; mRNA.
DR EMBL; BC029712; AAH29712.1; -; mRNA.
DR EMBL; S58470; AAB19973.1; -; mRNA.
DR EMBL; X64605; CAA45889.1; -; mRNA.
DR CCDS; CCDS21841.1; -.
DR PIR; S28184; S28184.
DR RefSeq; NP_036082.1; NM_011952.2.
DR AlphaFoldDB; Q63844; -.
DR SMR; Q63844; -.
DR BioGRID; 204970; 27.
DR CORUM; Q63844; -.
DR DIP; DIP-31078N; -.
DR ELM; Q63844; -.
DR IntAct; Q63844; 10.
DR MINT; Q63844; -.
DR STRING; 10090.ENSMUSP00000051619; -.
DR BindingDB; Q63844; -.
DR ChEMBL; CHEMBL5510; -.
DR iPTMnet; Q63844; -.
DR PhosphoSitePlus; Q63844; -.
DR SwissPalm; Q63844; -.
DR EPD; Q63844; -.
DR jPOST; Q63844; -.
DR MaxQB; Q63844; -.
DR PaxDb; Q63844; -.
DR PeptideAtlas; Q63844; -.
DR PRIDE; Q63844; -.
DR ProteomicsDB; 295945; -.
DR Antibodypedia; 1203; 2396 antibodies from 58 providers.
DR DNASU; 26417; -.
DR Ensembl; ENSMUST00000057669; ENSMUSP00000051619; ENSMUSG00000063065.
DR GeneID; 26417; -.
DR KEGG; mmu:26417; -.
DR UCSC; uc009jsm.1; mouse.
DR CTD; 5595; -.
DR MGI; MGI:1346859; Mapk3.
DR VEuPathDB; HostDB:ENSMUSG00000063065; -.
DR eggNOG; KOG0660; Eukaryota.
DR GeneTree; ENSGT00940000160691; -.
DR InParanoid; Q63844; -.
DR OMA; EIMTFRP; -.
DR OrthoDB; 741207at2759; -.
DR PhylomeDB; Q63844; -.
DR TreeFam; TF105097; -.
DR Reactome; R-MMU-110056; MAPK3 (ERK1) activation.
DR Reactome; R-MMU-112409; RAF-independent MAPK1/3 activation.
DR Reactome; R-MMU-1169408; ISG15 antiviral mechanism.
DR Reactome; R-MMU-1181150; Signaling by NODAL.
DR Reactome; R-MMU-1295596; Spry regulation of FGF signaling.
DR Reactome; R-MMU-1502540; Signaling by Activin.
DR Reactome; R-MMU-162658; Golgi Cisternae Pericentriolar Stack Reorganization.
DR Reactome; R-MMU-170968; Frs2-mediated activation.
DR Reactome; R-MMU-198753; ERK/MAPK targets.
DR Reactome; R-MMU-202670; ERKs are inactivated.
DR Reactome; R-MMU-2029482; Regulation of actin dynamics for phagocytic cup formation.
DR Reactome; R-MMU-2173796; SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.
DR Reactome; R-MMU-2559580; Oxidative Stress Induced Senescence.
DR Reactome; R-MMU-2559582; Senescence-Associated Secretory Phenotype (SASP).
DR Reactome; R-MMU-2559585; Oncogene Induced Senescence.
DR Reactome; R-MMU-2871796; FCERI mediated MAPK activation.
DR Reactome; R-MMU-3371453; Regulation of HSF1-mediated heat shock response.
DR Reactome; R-MMU-375165; NCAM signaling for neurite out-growth.
DR Reactome; R-MMU-445144; Signal transduction by L1.
DR Reactome; R-MMU-450341; Activation of the AP-1 family of transcription factors.
DR Reactome; R-MMU-456926; Thrombin signalling through proteinase activated receptors (PARs).
DR Reactome; R-MMU-5654726; Negative regulation of FGFR1 signaling.
DR Reactome; R-MMU-5654727; Negative regulation of FGFR2 signaling.
DR Reactome; R-MMU-5654732; Negative regulation of FGFR3 signaling.
DR Reactome; R-MMU-5654733; Negative regulation of FGFR4 signaling.
DR Reactome; R-MMU-5663213; RHO GTPases Activate WASPs and WAVEs.
DR Reactome; R-MMU-5668599; RHO GTPases Activate NADPH Oxidases.
DR Reactome; R-MMU-5673001; RAF/MAP kinase cascade.
DR Reactome; R-MMU-5674135; MAP2K and MAPK activation.
DR Reactome; R-MMU-5674499; Negative feedback regulation of MAPK pathway.
DR Reactome; R-MMU-5675221; Negative regulation of MAPK pathway.
DR Reactome; R-MMU-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling.
DR Reactome; R-MMU-73728; RNA Polymerase I Promoter Opening.
DR Reactome; R-MMU-74749; Signal attenuation.
DR Reactome; R-MMU-8939211; ESR-mediated signaling.
DR Reactome; R-MMU-9627069; Regulation of the apoptosome activity.
DR Reactome; R-MMU-982772; Growth hormone receptor signaling.
DR BioGRID-ORCS; 26417; 3 hits in 76 CRISPR screens.
DR ChiTaRS; Mapk3; mouse.
DR PRO; PR:Q63844; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q63844; protein.
DR Bgee; ENSMUSG00000063065; Expressed in granulocyte and 261 other tissues.
DR ExpressionAtlas; Q63844; baseline and differential.
DR Genevisible; Q63844; MM.
DR GO; GO:0005901; C:caveola; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005856; C:cytoskeleton; TAS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
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:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0031143; C:pseudopodium; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0004707; F:MAP kinase activity; IDA:MGI.
DR GO; GO:0004708; F:MAP kinase kinase activity; IMP:MGI.
DR GO; GO:0019902; F:phosphatase binding; ISO:MGI.
DR GO; GO:0001784; F:phosphotyrosine residue binding; IMP:MGI.
DR GO; GO:0004672; F:protein kinase activity; IDA:MGI.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISO:MGI.
DR GO; GO:0097110; F:scaffold protein binding; ISO:MGI.
DR GO; GO:0007568; P:aging; ISO:MGI.
DR GO; GO:0009887; P:animal organ morphogenesis; IDA:MGI.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0060020; P:Bergmann glial cell differentiation; IGI:MGI.
DR GO; GO:0030509; P:BMP signaling pathway; ISO:MGI.
DR GO; GO:0061308; P:cardiac neural crest cell development involved in heart development; IGI:MGI.
DR GO; GO:0051216; P:cartilage development; IDA:MGI.
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:MGI.
DR GO; GO:0071276; P:cellular response to cadmium ion; ISO:MGI.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:MGI.
DR GO; GO:1903351; P:cellular response to dopamine; ISO:MGI.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEA:Ensembl.
DR GO; GO:0034614; P:cellular response to reactive oxygen species; ISO:MGI.
DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IGI:MGI.
DR GO; GO:0046697; P:decidualization; ISO:MGI.
DR GO; GO:0006975; P:DNA damage induced protein phosphorylation; ISO:MGI.
DR GO; GO:0070371; P:ERK1 and ERK2 cascade; IGI:MGI.
DR GO; GO:0060324; P:face development; IGI:MGI.
DR GO; GO:0070498; P:interleukin-1-mediated signaling pathway; ISO:MGI.
DR GO; GO:0035556; P:intracellular signal transduction; ISO:MGI.
DR GO; GO:0031663; P:lipopolysaccharide-mediated signaling pathway; IDA:MGI.
DR GO; GO:0060425; P:lung morphogenesis; IGI:MGI.
DR GO; GO:0000165; P:MAPK cascade; ISO:MGI.
DR GO; GO:2000657; P:negative regulation of apolipoprotein binding; IMP:BHF-UCL.
DR GO; GO:0014032; P:neural crest cell development; IGI:MGI.
DR GO; GO:0042473; P:outer ear morphogenesis; IGI:MGI.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; ISO:MGI.
DR GO; GO:0038083; P:peptidyl-tyrosine autophosphorylation; ISO:MGI.
DR GO; GO:0016310; P:phosphorylation; ISO:MGI.
DR GO; GO:0031281; P:positive regulation of cyclase activity; ISO:MGI.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISO:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI.
DR GO; GO:0035066; P:positive regulation of histone acetylation; ISO:MGI.
DR GO; GO:0033129; P:positive regulation of histone phosphorylation; ISO:MGI.
DR GO; GO:0010759; P:positive regulation of macrophage chemotaxis; ISO:MGI.
DR GO; GO:0120041; P:positive regulation of macrophage proliferation; ISO:MGI.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:MGI.
DR GO; GO:0051973; P:positive regulation of telomerase activity; ISO:MGI.
DR GO; GO:1904355; P:positive regulation of telomere capping; ISO:MGI.
DR GO; GO:0032212; P:positive regulation of telomere maintenance via telomerase; ISO:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0045727; P:positive regulation of translation; ISO:MGI.
DR GO; GO:1904417; P:positive regulation of xenophagy; IGI:MGI.
DR GO; GO:0006468; P:protein phosphorylation; IDA:MGI.
DR GO; GO:0065003; P:protein-containing complex assembly; ISO:MGI.
DR GO; GO:0030641; P:regulation of cellular pH; IMP:MGI.
DR GO; GO:0051493; P:regulation of cytoskeleton organization; TAS:UniProtKB.
DR GO; GO:0051090; P:regulation of DNA-binding transcription factor activity; IMP: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; IGI:MGI.
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; IDA:MGI.
DR GO; GO:0032496; P:response to lipopolysaccharide; IDA:MGI.
DR GO; GO:0009636; P:response to toxic substance; ISO:MGI.
DR GO; GO:0019233; P:sensory perception of pain; IMP:UniProtKB.
DR GO; GO:0007165; P:signal transduction; TAS:MGI.
DR GO; GO:0051403; P:stress-activated MAPK cascade; ISO:MGI.
DR GO; GO:0048538; P:thymus development; IGI:MGI.
DR GO; GO:0030878; P:thyroid gland development; IGI:MGI.
DR GO; GO:0060440; P:trachea formation; IGI:MGI.
DR GO; GO:0006351; P:transcription, DNA-templated; IMP:UniProtKB.
DR GO; GO:0098792; P:xenophagy; IGI:MGI.
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; Apoptosis; ATP-binding; Cell cycle; Cell junction; Cytoplasm;
KW Direct protein sequencing; Kinase; Membrane; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|Ref.2"
FT CHAIN 2..380
FT /note="Mitogen-activated protein kinase 3"
FT /id="PRO_0000186252"
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:0007744|PubMed:17947660,
FT ECO:0007744|PubMed:18034455, ECO:0007744|PubMed:19131326,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 205
FT /note="Phosphotyrosine; by MAP2K1 and MAP2K2"
FT /evidence="ECO:0007744|PubMed:17947660,
FT ECO:0007744|PubMed:18034455, ECO:0007744|PubMed:19131326,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 208
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P27361"
FT CONFLICT 178
FT /note="T -> P (in Ref. 7; CAA45889 and 8; no nucleotide
FT entry)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 380 AA; 43066 MW; 49C14A95B627237F 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 RFQPGAPEGP
