MP2K3_HUMAN
ID MP2K3_HUMAN Reviewed; 347 AA.
AC P46734; B3KSK7; Q99441; Q9UE71; Q9UE72;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-2002, sequence version 2.
DT 03-AUG-2022, entry version 216.
DE RecName: Full=Dual specificity mitogen-activated protein kinase kinase 3;
DE Short=MAP kinase kinase 3;
DE Short=MAPKK 3;
DE EC=2.7.12.2 {ECO:0000269|PubMed:8622669};
DE AltName: Full=MAPK/ERK kinase 3;
DE Short=MEK 3;
DE AltName: Full=Stress-activated protein kinase kinase 2;
DE Short=SAPK kinase 2;
DE Short=SAPKK-2;
DE Short=SAPKK2;
GN Name=MAP2K3; Synonyms=MEK3, MKK3, PRKMK3, SKK2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=7839144; DOI=10.1126/science.7839144;
RA Derijard B., Raingeaud J., Barrett T., Wu I.-H., Han J., Ulevitch R.J.,
RA Davis R.J.;
RT "Independent human MAP-kinase signal transduction pathways defined by MEK
RT and MKK isoforms.";
RL Science 267:682-685(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
RX PubMed=8900184; DOI=10.1074/jbc.271.43.26981;
RA Moriguchi T., Toyoshima F., Gotoh Y., Iwamatsu A., Irie K., Mori E.,
RA Kuroyanagi N., Hagiwara M., Matsumoto K., Nishida E.;
RT "Purification and identification of a major activator for p38 from
RT osmotically shocked cells: activation of mitogen-activated protein kinase
RT kinase 6 by osmotic shock, tumor necrosis factor-alpha, and H2O2.";
RL J. Biol. Chem. 271:26981-26988(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE (ISOFORMS 2 AND 3).
RA Han J.;
RL Submitted (AUG-1996) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Trachea;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Leukocyte;
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 [6]
RP PHOSPHORYLATION AT SER-218 AND THR-222, MUTAGENESIS OF SER-218 AND THR-222,
RP CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=8622669; DOI=10.1128/mcb.16.3.1247;
RA Raingeaud J., Whitmarsh A.J., Barrett T., Derijard B., Davis R.J.;
RT "MKK3- and MKK6-regulated gene expression is mediated by the p38 mitogen-
RT activated protein kinase signal transduction pathway.";
RL Mol. Cell. Biol. 16:1247-1255(1996).
RN [7]
RP PHOSPHORYLATION BY TAOK2.
RX PubMed=11279118; DOI=10.1074/jbc.m100681200;
RA Chen Z., Cobb M.H.;
RT "Regulation of stress-responsive mitogen-activated protein (MAP) kinase
RT pathways by TAO2.";
RL J. Biol. Chem. 276:16070-16075(2001).
RN [8]
RP INTERACTION WITH DYRK1B.
RC TISSUE=Muscle;
RX PubMed=11980910; DOI=10.1074/jbc.m203257200;
RA Lim S., Jin K., Friedman E.;
RT "Mirk protein kinase is activated by MKK3 and functions as a
RT transcriptional activator of HNF1alpha.";
RL J. Biol. Chem. 277:25040-25046(2002).
RN [9]
RP INTERACTION WITH ARRB1.
RX PubMed=16709866; DOI=10.4049/jimmunol.176.11.7039;
RA McLaughlin N.J., Banerjee A., Kelher M.R., Gamboni-Robertson F., Hamiel C.,
RA Sheppard F.R., Moore E.E., Silliman C.C.;
RT "Platelet-activating factor-induced clathrin-mediated endocytosis requires
RT beta-arrestin-1 recruitment and activation of the p38 MAPK signalosome at
RT the plasma membrane for actin bundle formation.";
RL J. Immunol. 176:7039-7050(2006).
RN [10]
RP INTERACTION WITH YOPJ (MICROBIAL INFECTION), AND ACETYLATION (MICROBIAL
RP INFECTION).
RX PubMed=16728640; DOI=10.1126/science.1126867;
RA Mukherjee S., Keitany G., Li Y., Wang Y., Ball H.L., Goldsmith E.J.,
RA Orth K.;
RT "Yersinia YopJ acetylates and inhibits kinase activation by blocking
RT phosphorylation.";
RL Science 312:1211-1214(2006).
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, 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., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGE SCALE
RP ANALYSIS] AT SER-3 AND SER-15, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [14]
RP FUNCTION, AND IDENTIFICATION IN A COMPLEX WITH AKAP13; PKN1; MAPK14; ZAK
RP AND MAP2K3.
RX PubMed=21224381; DOI=10.1074/jbc.m110.185645;
RA Cariolato L., Cavin S., Diviani D.;
RT "A-kinase anchoring protein (AKAP)-Lbc anchors a PKN-based signaling
RT complex involved in alpha1-adrenergic receptor-induced p38 activation.";
RL J. Biol. Chem. 286:7925-7937(2011).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, 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., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [16]
RP VARIANTS COLON CANCER TRP-175 AND VAL-215.
RX PubMed=11414763; DOI=10.1006/geno.2001.6551;
RA Teng D.-H., Chen Y., Lian L., Ha P.C., Tavtigian S.V., Wong A.K.C.;
RT "Mutation analyses of 268 candidate genes in human tumor cell lines.";
RL Genomics 74:352-364(2001).
RN [17]
RP VARIANTS [LARGE SCALE ANALYSIS] THR-26; PRO-68; THR-84; ILE-90; LEU-94;
RP TRP-96; HIS-293 AND MET-339.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Dual specificity kinase. Is activated by cytokines and
CC environmental stress in vivo. Catalyzes the concomitant phosphorylation
CC of a threonine and a tyrosine residue in the MAP kinase p38. Part of a
CC signaling cascade that begins with the activation of the adrenergic
CC receptor ADRA1B and leads to the activation of MAPK14.
CC {ECO:0000269|PubMed:21224381, ECO:0000269|PubMed:8622669}.
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=2.7.12.2;
CC Evidence={ECO:0000269|PubMed:8622669};
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=2.7.12.2; Evidence={ECO:0000269|PubMed:8622669};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.12.2;
CC Evidence={ECO:0000269|PubMed:8622669};
CC -!- ACTIVITY REGULATION: Activated by dual phosphorylation on Ser-218 and
CC Thr-222. {ECO:0000269|PubMed:8622669}.
CC -!- SUBUNIT: Component of a signaling complex containing at least AKAP13,
CC PKN1, MAPK14, ZAK and MAP2K3. Within this complex, AKAP13 interacts
CC directly with PKN1, which in turn recruits MAPK14, MAP2K3 and ZAK
CC (PubMed:21224381). Binds to DYRK1B/MIRK and increases its kinase
CC activity (PubMed:11980910). Part of a complex with MAP3K3, RAC1 and
CC CCM2 (By similarity). Interacts with ARRB1 (PubMed:16709866).
CC {ECO:0000250|UniProtKB:O09110, ECO:0000269|PubMed:11980910,
CC ECO:0000269|PubMed:16709866, ECO:0000269|PubMed:21224381}.
CC -!- SUBUNIT: (Microbial infection) Interacts with Yersinia YopJ.
CC {ECO:0000269|PubMed:16728640}.
CC -!- INTERACTION:
CC P46734; Q9Y463: DYRK1B; NbExp=2; IntAct=EBI-602462, EBI-634187;
CC P46734; Q5S007: LRRK2; NbExp=5; IntAct=EBI-602462, EBI-5323863;
CC P46734; Q99683: MAP3K5; NbExp=6; IntAct=EBI-602462, EBI-476263;
CC P46734; Q16539: MAPK14; NbExp=5; IntAct=EBI-602462, EBI-73946;
CC P46734; Q9BSI4: TINF2; NbExp=2; IntAct=EBI-602462, EBI-717399;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=3; Synonyms=3b;
CC IsoId=P46734-1; Sequence=Displayed;
CC Name=1;
CC IsoId=P46734-2; Sequence=VSP_004878;
CC Name=2; Synonyms=3c;
CC IsoId=P46734-3; Sequence=VSP_004877;
CC -!- TISSUE SPECIFICITY: Abundant expression is seen in the skeletal muscle.
CC It is also widely expressed in other tissues.
CC -!- PTM: Autophosphorylated. Phosphorylation on Ser-218 and Thr-222 by MAP
CC kinase kinase kinases regulates positively the kinase activity
CC (PubMed:8622669). Phosphorylated by TAOK2 (PubMed:11279118).
CC {ECO:0000269|PubMed:11279118, ECO:0000269|PubMed:8622669}.
CC -!- PTM: (Microbial infection) Yersinia YopJ may acetylate Ser/Thr
CC residues, preventing phosphorylation and activation, thus blocking the
CC MAPK signaling pathway. {ECO:0000269|PubMed:16728640}.
CC -!- DISEASE: Note=Defects in MAP2K3 may be involved in colon cancer.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
CC protein kinase family. MAP kinase kinase subfamily. {ECO:0000305}.
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DR EMBL; L36719; AAC41718.1; -; mRNA.
DR EMBL; D87116; BAA13248.1; -; mRNA.
DR EMBL; U66839; AAB40652.1; -; mRNA.
DR EMBL; U66840; AAB40653.1; -; Genomic_DNA.
DR EMBL; AK093838; BAG52769.1; -; mRNA.
DR EMBL; BC032478; AAH32478.1; -; mRNA.
DR CCDS; CCDS11217.1; -. [P46734-1]
DR CCDS; CCDS11218.1; -. [P46734-2]
DR RefSeq; NP_001303261.1; NM_001316332.1. [P46734-2]
DR RefSeq; NP_002747.2; NM_002756.4. [P46734-2]
DR RefSeq; NP_659731.1; NM_145109.2. [P46734-1]
DR RefSeq; XP_005256780.1; XM_005256723.2. [P46734-2]
DR RefSeq; XP_011522261.1; XM_011523959.1. [P46734-2]
DR RefSeq; XP_016880347.1; XM_017024858.1. [P46734-2]
DR RefSeq; XP_016880348.1; XM_017024859.1. [P46734-2]
DR AlphaFoldDB; P46734; -.
DR SMR; P46734; -.
DR BioGRID; 111592; 235.
DR CORUM; P46734; -.
DR DIP; DIP-34242N; -.
DR IntAct; P46734; 97.
DR MINT; P46734; -.
DR STRING; 9606.ENSP00000345083; -.
DR BindingDB; P46734; -.
DR ChEMBL; CHEMBL2109; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; P46734; -.
DR GuidetoPHARMACOLOGY; 2064; -.
DR GlyGen; P46734; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P46734; -.
DR PhosphoSitePlus; P46734; -.
DR BioMuta; MAP2K3; -.
DR DMDM; 24638466; -.
DR CPTAC; CPTAC-814; -.
DR CPTAC; CPTAC-815; -.
DR EPD; P46734; -.
DR jPOST; P46734; -.
DR MassIVE; P46734; -.
DR MaxQB; P46734; -.
DR PaxDb; P46734; -.
DR PeptideAtlas; P46734; -.
DR PRIDE; P46734; -.
DR ProteomicsDB; 55750; -. [P46734-1]
DR ProteomicsDB; 55751; -. [P46734-2]
DR ProteomicsDB; 55752; -. [P46734-3]
DR Antibodypedia; 4342; 1466 antibodies from 43 providers.
DR DNASU; 5606; -.
DR Ensembl; ENST00000316920.10; ENSP00000319139.6; ENSG00000034152.19. [P46734-2]
DR Ensembl; ENST00000342679.9; ENSP00000345083.4; ENSG00000034152.19. [P46734-1]
DR Ensembl; ENST00000361818.9; ENSP00000355081.5; ENSG00000034152.19. [P46734-2]
DR Ensembl; ENST00000613338.4; ENSP00000478619.1; ENSG00000034152.19. [P46734-2]
DR GeneID; 5606; -.
DR KEGG; hsa:5606; -.
DR MANE-Select; ENST00000342679.9; ENSP00000345083.4; NM_145109.3; NP_659731.1.
DR UCSC; uc021tsq.2; human. [P46734-1]
DR CTD; 5606; -.
DR DisGeNET; 5606; -.
DR GeneCards; MAP2K3; -.
DR HGNC; HGNC:6843; MAP2K3.
DR HPA; ENSG00000034152; Tissue enhanced (bone).
DR MIM; 602315; gene.
DR neXtProt; NX_P46734; -.
DR OpenTargets; ENSG00000034152; -.
DR PharmGKB; PA30588; -.
DR VEuPathDB; HostDB:ENSG00000034152; -.
DR eggNOG; KOG0984; Eukaryota.
DR GeneTree; ENSGT00940000160875; -.
DR HOGENOM; CLU_000288_63_23_1; -.
DR InParanoid; P46734; -.
DR OMA; RITCVSK; -.
DR OrthoDB; 81952at2759; -.
DR PhylomeDB; P46734; -.
DR TreeFam; TF350701; -.
DR BRENDA; 2.7.12.2; 2681.
DR PathwayCommons; P46734; -.
DR Reactome; R-HSA-2559580; Oxidative Stress Induced Senescence.
DR Reactome; R-HSA-450302; activated TAK1 mediates p38 MAPK activation.
DR Reactome; R-HSA-5210891; Uptake and function of anthrax toxins. [P46734-3]
DR SignaLink; P46734; -.
DR SIGNOR; P46734; -.
DR BioGRID-ORCS; 5606; 60 hits in 1126 CRISPR screens.
DR ChiTaRS; MAP2K3; human.
DR GeneWiki; MAP2K3; -.
DR GenomeRNAi; 5606; -.
DR Pharos; P46734; Tchem.
DR PRO; PR:P46734; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; P46734; protein.
DR Bgee; ENSG00000034152; Expressed in buccal mucosa cell and 208 other tissues.
DR ExpressionAtlas; P46734; baseline and differential.
DR Genevisible; P46734; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004708; F:MAP kinase kinase activity; IBA:GO_Central.
DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IEA:UniProtKB-KW.
DR GO; GO:0060048; P:cardiac muscle contraction; IEA:Ensembl.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEA:Ensembl.
DR GO; GO:0072709; P:cellular response to sorbitol; IEA:Ensembl.
DR GO; GO:0035924; P:cellular response to vascular endothelial growth factor stimulus; IMP:BHF-UCL.
DR GO; GO:0090398; P:cellular senescence; TAS:Reactome.
DR GO; GO:0007507; P:heart development; IEA:Ensembl.
DR GO; GO:0006954; P:inflammatory response; IEA:Ensembl.
DR GO; GO:0000165; P:MAPK cascade; IBA:GO_Central.
DR GO; GO:0035331; P:negative regulation of hippo signaling; IMP:FlyBase.
DR GO; GO:0038066; P:p38MAPK cascade; IMP:BHF-UCL.
DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; IMP:BHF-UCL.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IEA:Ensembl.
DR GO; GO:0051770; P:positive regulation of nitric-oxide synthase biosynthetic process; IEA:Ensembl.
DR GO; GO:0045860; P:positive regulation of protein kinase activity; IDA:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0001817; P:regulation of cytokine production; IEA:Ensembl.
DR GO; GO:0002931; P:response to ischemia; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR InterPro; IPR011009; Kinase-like_dom_sf.
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 SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 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; ATP-binding; Disease variant; Kinase;
KW Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Tyrosine-protein kinase.
FT CHAIN 1..347
FT /note="Dual specificity mitogen-activated protein kinase
FT kinase 3"
FT /id="PRO_0000086378"
FT DOMAIN 64..325
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..46
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..15
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 190
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 70..78
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 93
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:22814378"
FT MOD_RES 3
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 15
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 218
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:8622669"
FT MOD_RES 222
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:8622669"
FT VAR_SEQ 1..29
FT /note="Missing (in isoform 1)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:7839144"
FT /id="VSP_004878"
FT VAR_SEQ 1..16
FT /note="MESPASSQPASMPQSK -> MGVQGTLMSRDSQTPHLLSIL (in
FT isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_004877"
FT VARIANT 26
FT /note="R -> T"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040817"
FT VARIANT 40
FT /note="P -> T (in dbSNP:rs33911218)"
FT /id="VAR_046062"
FT VARIANT 55
FT /note="R -> T (in dbSNP:rs36047035)"
FT /id="VAR_061742"
FT VARIANT 68
FT /note="S -> P (in dbSNP:rs34105301)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_046063"
FT VARIANT 84
FT /note="A -> T (in dbSNP:rs2305873)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_046064"
FT VARIANT 90
FT /note="M -> I (in dbSNP:rs36076766)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_046065"
FT VARIANT 94
FT /note="R -> L (in dbSNP:rs56067280)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_046066"
FT VARIANT 96
FT /note="R -> W (in dbSNP:rs56216806)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_046067"
FT VARIANT 175
FT /note="R -> W (in colon cancer; dbSNP:rs1339756947)"
FT /evidence="ECO:0000269|PubMed:11414763"
FT /id="VAR_014208"
FT VARIANT 215
FT /note="L -> V (in colon cancer; dbSNP:rs989026404)"
FT /evidence="ECO:0000269|PubMed:11414763"
FT /id="VAR_014209"
FT VARIANT 293
FT /note="R -> H (in dbSNP:rs35206134)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_046068"
FT VARIANT 339
FT /note="V -> M (in dbSNP:rs2363198)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_046069"
FT MUTAGEN 218
FT /note="S->A: Inactivation."
FT /evidence="ECO:0000269|PubMed:8622669"
FT MUTAGEN 218
FT /note="S->E: Constitutive activation."
FT /evidence="ECO:0000269|PubMed:8622669"
FT MUTAGEN 222
FT /note="T->A: Inactivation."
FT /evidence="ECO:0000269|PubMed:8622669"
FT MUTAGEN 222
FT /note="T->E: Constitutive activation."
FT /evidence="ECO:0000269|PubMed:8622669"
FT CONFLICT 341
FT /note="E -> K (in Ref. 1 and 3)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 347 AA; 39318 MW; A80BA4FDFF8F75A2 CRC64;
MESPASSQPA SMPQSKGKSK RKKDLRISCM SKPPAPNPTP PRNLDSRTFI TIGDRNFEVE
ADDLVTISEL GRGAYGVVEK VRHAQSGTIM AVKRIRATVN SQEQKRLLMD LDINMRTVDC
FYTVTFYGAL FREGDVWICM ELMDTSLDKF YRKVLDKNMT IPEDILGEIA VSIVRALEHL
HSKLSVIHRD VKPSNVLINK EGHVKMCDFG ISGYLVDSVA KTMDAGCKPY MAPERINPEL
NQKGYNVKSD VWSLGITMIE MAILRFPYES WGTPFQQLKQ VVEEPSPQLP ADRFSPEFVD
FTAQCLRKNP AERMSYLELM EHPFFTLHKT KKTDIAAFVK EILGEDS
