(data stored in ACNUC8465 zone)

SWISSPROT: 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   11-DEC-2019, entry version 203.
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, AND ACETYLATION.
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). Interacts
CC       with Yersinia yopJ (PubMed:16728640). {ECO:0000250|UniProtKB:O09110,
CC       ECO:0000269|PubMed:11980910, ECO:0000269|PubMed:16709866,
CC       ECO:0000269|PubMed:16728640, ECO:0000269|PubMed:21224381}.
CC   -!- INTERACTION:
CC       Q9Y463:DYRK1B; NbExp=2; IntAct=EBI-602462, EBI-634187;
CC       Q5S007:LRRK2; NbExp=5; IntAct=EBI-602462, EBI-5323863;
CC       Q99683:MAP3K5; NbExp=4; IntAct=EBI-602462, EBI-476263;
CC       Q16539:MAPK14; NbExp=2; IntAct=EBI-602462, EBI-73946;
CC       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: Yersinia yopJ may acetylate Ser/Thr residues, preventing
CC       phosphorylation and activation, thus blocking the MAPK signaling
CC       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}.
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   SMR; P46734; -.
DR   BioGrid; 111592; 123.
DR   CORUM; P46734; -.
DR   DIP; DIP-34242N; -.
DR   IntAct; P46734; 22.
DR   MINT; P46734; -.
DR   STRING; 9606.ENSP00000345083; -.
DR   BindingDB; P46734; -.
DR   ChEMBL; CHEMBL2109; -.
DR   DrugBank; DB12010; Fostamatinib.
DR   DrugCentral; P46734; -.
DR   GuidetoPHARMACOLOGY; 2064; -.
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   PaxDb; P46734; -.
DR   PeptideAtlas; P46734; -.
DR   PRIDE; P46734; -.
DR   ProteomicsDB; 55750; -. [P46734-1]
DR   ProteomicsDB; 55751; -. [P46734-2]
DR   ProteomicsDB; 55752; -. [P46734-3]
DR   DNASU; 5606; -.
DR   Ensembl; ENST00000316920; ENSP00000319139; ENSG00000034152. [P46734-2]
DR   Ensembl; ENST00000342679; ENSP00000345083; ENSG00000034152. [P46734-1]
DR   Ensembl; ENST00000361818; ENSP00000355081; ENSG00000034152. [P46734-2]
DR   Ensembl; ENST00000613338; ENSP00000478619; ENSG00000034152. [P46734-2]
DR   GeneID; 5606; -.
DR   KEGG; hsa:5606; -.
DR   UCSC; uc021tsq.2; human. [P46734-1]
DR   CTD; 5606; -.
DR   DisGeNET; 5606; -.
DR   EuPathDB; HostDB:ENSG00000034152.18; -.
DR   GeneCards; MAP2K3; -.
DR   HGNC; HGNC:6843; MAP2K3.
DR   HPA; CAB018548; -.
DR   MIM; 602315; gene.
DR   neXtProt; NX_P46734; -.
DR   OpenTargets; ENSG00000034152; -.
DR   PharmGKB; PA30588; -.
DR   eggNOG; KOG0984; Eukaryota.
DR   eggNOG; ENOG410XT3F; LUCA.
DR   GeneTree; ENSGT00940000160875; -.
DR   HOGENOM; HOG000234206; -.
DR   InParanoid; P46734; -.
DR   KO; K04432; -.
DR   OMA; ETDMASF; -.
DR   OrthoDB; 81952at2759; -.
DR   PhylomeDB; P46734; -.
DR   TreeFam; TF350701; -.
DR   BRENDA; 2.7.12.2; 2681.
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   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 241 organ(s), highest expression level in buccal mucosa cell.
DR   ExpressionAtlas; P46734; baseline and differential.
DR   Genevisible; P46734; HS.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
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:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
DR   GO; GO:0004713; F:protein tyrosine kinase activity; IEA:UniProtKB-KW.
DR   GO; GO:0000187; P:activation of MAPK activity; IBA:GO_Central.
DR   GO; GO:0032147; P:activation of protein kinase activity; IBA:GO_Central.
DR   GO; GO:0060048; P:cardiac muscle contraction; IEA:Ensembl.
DR   GO; GO:0035924; P:cellular response to vascular endothelial growth factor stimulus; IMP:BHF-UCL.
DR   GO; GO:0006954; P:inflammatory response; IEA:Ensembl.
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: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:0042035; P:regulation of cytokine biosynthetic process; IEA:Ensembl.
DR   GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR   GO; GO:0023014; P:signal transduction by protein phosphorylation; IBA:GO_Central.
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;
DR   PRODOM; P46734.
DR   SWISS-2DPAGE; P46734.
KW   Acetylation; Alternative splicing; ATP-binding; Disease mutation; Kinase;
KW   Nucleotide-binding; Phosphoprotein; Polymorphism; 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   NP_BIND         70..78
FT                   /note="ATP"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   ACT_SITE        190
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT                   ECO:0000255|PROSITE-ProRule:PRU10027"
FT   BINDING         93
FT                   /note="ATP"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   MOD_RES         1
FT                   /note="N-acetylmethionine"
FT                   /evidence="ECO:0000244|PubMed:19413330,
FT                   ECO:0000244|PubMed:20068231, ECO:0000244|PubMed:22814378"
FT   MOD_RES         3
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000244|PubMed:20068231"
FT   MOD_RES         15
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000244|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
//

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