MAPK3_HUMAN
ID MAPK3_HUMAN Reviewed; 382 AA.
AC Q16644; B5BU67;
DT 06-DEC-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 187.
DE RecName: Full=MAP kinase-activated protein kinase 3;
DE Short=MAPK-activated protein kinase 3;
DE Short=MAPKAP kinase 3;
DE Short=MAPKAP-K3;
DE Short=MAPKAPK-3;
DE Short=MK-3;
DE EC=2.7.11.1;
DE AltName: Full=Chromosome 3p kinase;
DE Short=3pK;
GN Name=MAPKAPK3;
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], FUNCTION, TISSUE SPECIFICITY, AND
RP PHOSPHORYLATION.
RX PubMed=8626550; DOI=10.1074/jbc.271.14.8488;
RA McLaughlin M.M., Kumar S., McDonnell P.C., Van Horn S., Lee J.C.,
RA Livi G.P., Young P.R.;
RT "Identification of mitogen-activated protein (MAP) kinase-activated protein
RT kinase-3, a novel substrate of CSBP p38 MAP kinase.";
RL J. Biol. Chem. 271:8488-8492(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND PHOSPHORYLATION BY
RP MAPK1/ERK2 AND MAPK3/ERK1.
RC TISSUE=Heart;
RX PubMed=8622688; DOI=10.1128/mcb.16.3.868;
RA Sithanandam G., Latif F., Duh F.-M., Bernal R., Smola U., Li H., Kuzmin I.,
RA Wixler V., Geil L., Shrestha S., Lloyd P.A., Bader S., Sekido Y.,
RA Tartof K.D., Kashuba V.I., Zabarovsky E.R., Dean M., Klein G., Lerman M.I.,
RA Minna J.D., Rapp U.R., Allikmets R.;
RT "3pK, a new mitogen-activated protein kinase-activated protein kinase
RT located in the small cell lung cancer tumor suppressor gene region.";
RL Mol. Cell. Biol. 16:868-876(1996).
RN [3]
RP ERRATUM OF PUBMED:8622688.
RA Sithanandam G., Latif F., Duh F.-M., Bernal R., Smola U., Li H., Kuzmin I.,
RA Wixler V., Geil L., Shrestha S., Lloyd P.A., Bader S., Sekido Y.,
RA Tartof K.D., Kashuba V.I., Zabarovsky E.R., Dean M., Klein G., Lerman M.I.,
RA Minna J.D., Rapp U.R., Allikmets R.;
RL Mol. Cell. Biol. 16:1880-1880(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=19054851; DOI=10.1038/nmeth.1273;
RA Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R.,
RA Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y.,
RA Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B.,
RA Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y.,
RA Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A.,
RA Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y.,
RA Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T.,
RA Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y.,
RA Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S.,
RA Nomura N.;
RT "Human protein factory for converting the transcriptome into an in vitro-
RT expressed proteome.";
RL Nat. Methods 5:1011-1017(2008).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon, and Skin;
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 [7]
RP CATALYTIC ACTIVITY, AND FUNCTION IN PHOSPHORYLATION OF HSPB1.
RX PubMed=8774846; DOI=10.1016/0014-5793(96)00816-2;
RA Clifton A.D., Young P.R., Cohen P.;
RT "A comparison of the substrate specificity of MAPKAP kinase-2 and MAPKAP
RT kinase-3 and their activation by cytokines and cellular stress.";
RL FEBS Lett. 392:209-214(1996).
RN [8]
RP FUNCTION IN PHOSPHORYLATION OF HSPB1.
RX PubMed=10383393; DOI=10.1074/jbc.274.27.18947;
RA Rogalla T., Ehrnsperger M., Preville X., Kotlyarov A., Lutsch G.,
RA Ducasse C., Paul C., Wieske M., Arrigo A.P., Buchner J., Gaestel M.;
RT "Regulation of Hsp27 oligomerization, chaperone function, and protective
RT activity against oxidative stress/tumor necrosis factor alpha by
RT phosphorylation.";
RL J. Biol. Chem. 274:18947-18956(1999).
RN [9]
RP INTERACTION WITH TCF3.
RX PubMed=10781029; DOI=10.1074/jbc.c901040199;
RA Neufeld B., Grosse-Wilde A., Hoffmeyer A., Jordan B.W., Chen P., Dinev D.,
RA Ludwig S., Rapp U.R.;
RT "Serine/Threonine kinases 3pK and MAPK-activated protein kinase 2 interact
RT with the basic helix-loop-helix transcription factor E47 and repress its
RT transcriptional activity.";
RL J. Biol. Chem. 275:20239-20242(2000).
RN [10]
RP SUBCELLULAR LOCATION.
RX PubMed=15302577; DOI=10.1016/j.yexcr.2004.05.027;
RA Zakowski V., Keramas G., Kilian K., Rapp U.R., Ludwig S.;
RT "Mitogen-activated 3p kinase is active in the nucleus.";
RL Exp. Cell Res. 299:101-109(2004).
RN [11]
RP FUNCTION, MUTAGENESIS OF LYS-73, AND INTERACTION WITH PHC2 AND BMI1.
RX PubMed=15563468; DOI=10.1074/jbc.m407155200;
RA Voncken J.W., Niessen H., Neufeld B., Rennefahrt U., Dahlmans V.,
RA Kubben N., Holzer B., Ludwig S., Rapp U.R.;
RT "MAPKAP kinase 3pK phosphorylates and regulates chromatin association of
RT the polycomb group protein Bmi1.";
RL J. Biol. Chem. 280:5178-5187(2005).
RN [12]
RP FUNCTION IN PHOSPHORYLATION OF TAB3.
RX PubMed=18021073; DOI=10.1042/bj20071149;
RA Mendoza H., Campbell D.G., Burness K., Hastie J., Ronkina N., Shim J.H.,
RA Arthur J.S., Davis R.J., Gaestel M., Johnson G.L., Ghosh S., Cohen P.;
RT "Roles for TAB1 in regulating the IL-1-dependent phosphorylation of the
RT TAB3 regulatory subunit and activity of the TAK1 complex.";
RL Biochem. J. 409:711-722(2008).
RN [13]
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 [14]
RP FUNCTION.
RX PubMed=20599781; DOI=10.1016/j.bcp.2010.06.021;
RA Ronkina N., Menon M.B., Schwermann J., Tiedje C., Hitti E., Kotlyarov A.,
RA Gaestel M.;
RT "MAPKAP kinases MK2 and MK3 in inflammation: complex regulation of TNF
RT biosynthesis via expression and phosphorylation of tristetraprolin.";
RL Biochem. Pharmacol. 80:1915-1920(2010).
RN [15]
RP REVIEW.
RX PubMed=18508601; DOI=10.2741/3095;
RA Ronkina N., Kotlyarov A., Gaestel M.;
RT "MK2 and MK3--a pair of isoenzymes?";
RL Front. Biosci. 13:5511-5521(2008).
RN [16]
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 [17]
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 [18]
RP TISSUE SPECIFICITY, SUBCELLULAR LOCATION, INVOLVEMENT IN MDPT3, VARIANT
RP MDPT3 PRO-173, AND CHARACTERIZATION OF VARIANT MDPT3 PRO-173.
RX PubMed=26744326; DOI=10.1093/hmg/ddv624;
RA Meunier I., Lenaers G., Bocquet B., Baudoin C., Piro-Megy C., Cubizolle A.,
RA Quiles M., Jean-Charles A., Cohen S.Y., Merle H., Gaudric A., Labesse G.,
RA Manes G., Pequignot M., Cazevieille C., Dhaenens C.M., Fichard A.,
RA Ronkina N., Arthur S.J., Gaestel M., Hamel C.P.;
RT "A dominant mutation in MAPKAPK3, an actor of p38 signaling pathway, causes
RT a new retinal dystrophy involving Bruch's membrane and retinal pigment
RT epithelium.";
RL Hum. Mol. Genet. 25:916-926(2016).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 33-349 IN COMPLEX WITH INHIBITOR
RP P4O.
RX PubMed=19937655; DOI=10.1002/pro.294;
RA Cheng R., Felicetti B., Palan S., Toogood-Johnson I., Scheich C.,
RA Barker J., Whittaker M., Hesterkamp T.;
RT "High-resolution crystal structure of human Mapkap kinase 3 in complex with
RT a high affinity ligand.";
RL Protein Sci. 19:168-173(2010).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (2.09 ANGSTROMS) OF 33-349 IN COMPLEX WITH INHIBITOR
RP 5B.
RX PubMed=21565500; DOI=10.1016/j.bmcl.2011.04.018;
RA Barf T., Kaptein A., de Wilde S., van der Heijden R., van Someren R.,
RA Demont D., Schultz-Fademrecht C., Versteegh J., van Zeeland M., Seegers N.,
RA Kazemier B., van de Kar B., van Hoek M., de Roos J., Klop H., Smeets R.,
RA Hofstra C., Hornberg J., Oubrie A.;
RT "Structure-based lead identification of ATP-competitive MK2 inhibitors.";
RL Bioorg. Med. Chem. Lett. 21:3818-3822(2011).
RN [21]
RP VARIANTS [LARGE SCALE ANALYSIS] SER-28; ALA-105 AND TYR-276.
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: Stress-activated serine/threonine-protein kinase involved in
CC cytokines production, endocytosis, cell migration, chromatin remodeling
CC and transcriptional regulation. Following stress, it is phosphorylated
CC and activated by MAP kinase p38-alpha/MAPK14, leading to
CC phosphorylation of substrates. Phosphorylates serine in the peptide
CC sequence, Hyd-X-R-X(2)-S, where Hyd is a large hydrophobic residue.
CC MAPKAPK2 and MAPKAPK3, share the same function and substrate
CC specificity, but MAPKAPK3 kinase activity and level in protein
CC expression are lower compared to MAPKAPK2. Phosphorylates HSP27/HSPB1,
CC KRT18, KRT20, RCSD1, RPS6KA3, TAB3 and TTP/ZFP36. Mediates
CC phosphorylation of HSP27/HSPB1 in response to stress, leading to
CC dissociate HSP27/HSPB1 from large small heat-shock protein (sHsps)
CC oligomers and impair their chaperone activities and ability to protect
CC against oxidative stress effectively. Involved in inflammatory response
CC by regulating tumor necrosis factor (TNF) and IL6 production post-
CC transcriptionally: acts by phosphorylating AU-rich elements (AREs)-
CC binding proteins, such as TTP/ZFP36, leading to regulate the stability
CC and translation of TNF and IL6 mRNAs. Phosphorylation of TTP/ZFP36, a
CC major post-transcriptional regulator of TNF, promotes its binding to
CC 14-3-3 proteins and reduces its ARE mRNA affinity leading to inhibition
CC of dependent degradation of ARE-containing transcript. Involved in
CC toll-like receptor signaling pathway (TLR) in dendritic cells: required
CC for acute TLR-induced macropinocytosis by phosphorylating and
CC activating RPS6KA3. Also acts as a modulator of Polycomb-mediated
CC repression. {ECO:0000269|PubMed:10383393, ECO:0000269|PubMed:15563468,
CC ECO:0000269|PubMed:18021073, ECO:0000269|PubMed:20599781,
CC ECO:0000269|PubMed:8626550, ECO:0000269|PubMed:8774846}.
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=2.7.11.1;
CC Evidence={ECO:0000269|PubMed:8774846};
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=2.7.11.1; Evidence={ECO:0000269|PubMed:8774846};
CC -!- ACTIVITY REGULATION: Activated following phosphorylation by p38-
CC alpha/MAPK14 following various stresses. Inhibited by ligand 5B (2'-[2-
CC (1,3-benzodioxol-5-yl)pyrimidin-4-yl]-5',6'-dihydrospiro[piperidine-
CC 4,7'-pyrrolo[3,2-c]pyridin]- 4'(1'h)-one) and ligand P4O (2-[2-(2-
CC fluorophenyl)pyridin-4-yl]-1,5,6,7-tetrahydro- 4h-pyrrolo[3,2-
CC c]pyridin-4-one), 2 ATP-competitive inhibitors.
CC -!- SUBUNIT: Heterodimer with p38-alpha/MAPK14. The heterodimer with p38-
CC alpha/MAPK14 forms a stable complex: molecules are positioned 'face to
CC face' so that the ATP-binding sites of both kinases are at the
CC heterodimer interface (By similarity). Interacts with TCF3 and with
CC polycomb proteins, such as PCH2 and BMI1/PCGF4. {ECO:0000250,
CC ECO:0000269|PubMed:10781029, ECO:0000269|PubMed:15563468,
CC ECO:0000269|PubMed:19937655, ECO:0000269|PubMed:21565500}.
CC -!- INTERACTION:
CC Q16644; P04792: HSPB1; NbExp=3; IntAct=EBI-1384657, EBI-352682;
CC Q16644; Q15759: MAPK11; NbExp=4; IntAct=EBI-1384657, EBI-298304;
CC Q16644; Q16539: MAPK14; NbExp=10; IntAct=EBI-1384657, EBI-73946;
CC Q16644; PRO_0000037566 [P27958]; Xeno; NbExp=5; IntAct=EBI-1384657, EBI-6377335;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:15302577,
CC ECO:0000269|PubMed:26744326}. Cytoplasm {ECO:0000269|PubMed:15302577,
CC ECO:0000269|PubMed:26744326}. Note=Predominantly located in the
CC nucleus, when activated it translocates to the cytoplasm.
CC -!- TISSUE SPECIFICITY: Widely expressed, with a higher expression level
CC observed in heart and skeletal muscle. No expression in brain.
CC Expressed in the retinal pigment epithelium (PubMed:26744326).
CC {ECO:0000269|PubMed:26744326, ECO:0000269|PubMed:8622688,
CC ECO:0000269|PubMed:8626550}.
CC -!- PTM: Phosphorylated and activated by MAPK1/ERK2 and MAPK3/ERK1.
CC Phosphorylated and activated by MAP kinase p38-alpha/MAPK14 at Thr-201,
CC Ser-251 and Thr-313 (By similarity). {ECO:0000250}.
CC -!- DISEASE: Macular dystrophy, patterned, 3 (MDPT3) [MIM:617111]: A form
CC of retinal patterned dystrophy, characterized by retinal pigment
CC epithelium and Bruch's membrane changes resembling a 'dry desert land'.
CC It begins around the age of 30 and progresses to retinitis pigmentosa.
CC MDPT3 inheritance is autosomal dominant. {ECO:0000269|PubMed:26744326}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; U43784; AAC50428.1; -; mRNA.
DR EMBL; U09578; AAD09136.1; -; mRNA.
DR EMBL; AB451303; BAG70117.1; -; mRNA.
DR EMBL; CH471055; EAW65131.1; -; Genomic_DNA.
DR EMBL; BC001662; AAH01662.1; -; mRNA.
DR EMBL; BC007591; AAH07591.1; -; mRNA.
DR EMBL; BC010407; AAH10407.1; -; mRNA.
DR CCDS; CCDS2832.1; -.
DR PIR; JC6094; JC6094.
DR RefSeq; NP_001230854.1; NM_001243925.1.
DR RefSeq; NP_001230855.1; NM_001243926.1.
DR RefSeq; NP_004626.1; NM_004635.4.
DR PDB; 3FHR; X-ray; 1.90 A; A=33-349.
DR PDB; 3FXW; X-ray; 2.00 A; A=33-349.
DR PDB; 3R1N; X-ray; 2.09 A; A=33-349.
DR PDB; 3SHE; X-ray; 2.25 A; A=33-349.
DR PDB; 7NRB; X-ray; 1.90 A; A=33-349.
DR PDBsum; 3FHR; -.
DR PDBsum; 3FXW; -.
DR PDBsum; 3R1N; -.
DR PDBsum; 3SHE; -.
DR PDBsum; 7NRB; -.
DR AlphaFoldDB; Q16644; -.
DR SMR; Q16644; -.
DR BioGRID; 113617; 32.
DR ELM; Q16644; -.
DR IntAct; Q16644; 31.
DR MINT; Q16644; -.
DR STRING; 9606.ENSP00000396467; -.
DR BindingDB; Q16644; -.
DR ChEMBL; CHEMBL4670; -.
DR DrugBank; DB08358; 2-(2-QUINOLIN-3-YLPYRIDIN-4-YL)-1,5,6,7-TETRAHYDRO-4H-PYRROLO[3,2-C]PYRIDIN-4-ONE.
DR DrugBank; DB07728; 2-[2-(2-FLUOROPHENYL)PYRIDIN-4-YL]-1,5,6,7-TETRAHYDRO-4H-PYRROLO[3,2-C]PYRIDIN-4-ONE.
DR GuidetoPHARMACOLOGY; 2095; -.
DR iPTMnet; Q16644; -.
DR PhosphoSitePlus; Q16644; -.
DR BioMuta; MAPKAPK3; -.
DR DMDM; 74762148; -.
DR EPD; Q16644; -.
DR jPOST; Q16644; -.
DR MassIVE; Q16644; -.
DR MaxQB; Q16644; -.
DR PaxDb; Q16644; -.
DR PeptideAtlas; Q16644; -.
DR PRIDE; Q16644; -.
DR ProteomicsDB; 60998; -.
DR Antibodypedia; 30996; 337 antibodies from 33 providers.
DR DNASU; 7867; -.
DR Ensembl; ENST00000357955.6; ENSP00000350639.2; ENSG00000114738.11.
DR Ensembl; ENST00000446044.5; ENSP00000396467.1; ENSG00000114738.11.
DR Ensembl; ENST00000621469.5; ENSP00000478922.1; ENSG00000114738.11.
DR GeneID; 7867; -.
DR KEGG; hsa:7867; -.
DR MANE-Select; ENST00000621469.5; ENSP00000478922.1; NM_001243925.2; NP_001230854.1.
DR UCSC; uc003day.3; human.
DR CTD; 7867; -.
DR DisGeNET; 7867; -.
DR GeneCards; MAPKAPK3; -.
DR HGNC; HGNC:6888; MAPKAPK3.
DR HPA; ENSG00000114738; Tissue enhanced (heart muscle, skeletal muscle, tongue).
DR MalaCards; MAPKAPK3; -.
DR MIM; 602130; gene.
DR MIM; 617111; phenotype.
DR neXtProt; NX_Q16644; -.
DR OpenTargets; ENSG00000114738; -.
DR Orphanet; 466718; Martinique crinkled retinal pigment epitheliopathy.
DR PharmGKB; PA30632; -.
DR VEuPathDB; HostDB:ENSG00000114738; -.
DR eggNOG; KOG0604; Eukaryota.
DR GeneTree; ENSGT00940000154089; -.
DR InParanoid; Q16644; -.
DR OMA; DRAMWED; -.
DR OrthoDB; 843707at2759; -.
DR PhylomeDB; Q16644; -.
DR TreeFam; TF312891; -.
DR PathwayCommons; Q16644; -.
DR Reactome; R-HSA-171007; p38MAPK events.
DR Reactome; R-HSA-2559580; Oxidative Stress Induced Senescence.
DR Reactome; R-HSA-4420097; VEGFA-VEGFR2 Pathway.
DR Reactome; R-HSA-450302; activated TAK1 mediates p38 MAPK activation.
DR SignaLink; Q16644; -.
DR SIGNOR; Q16644; -.
DR BioGRID-ORCS; 7867; 14 hits in 1112 CRISPR screens.
DR ChiTaRS; MAPKAPK3; human.
DR EvolutionaryTrace; Q16644; -.
DR GeneWiki; MAPKAPK3; -.
DR GenomeRNAi; 7867; -.
DR Pharos; Q16644; Tchem.
DR PRO; PR:Q16644; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q16644; protein.
DR Bgee; ENSG00000114738; Expressed in apex of heart and 199 other tissues.
DR ExpressionAtlas; Q16644; baseline and differential.
DR Genevisible; Q16644; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0009931; F:calcium-dependent protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0005516; F:calmodulin binding; IBA:GO_Central.
DR GO; GO:0004683; F:calmodulin-dependent protein kinase activity; IBA:GO_Central.
DR GO; GO:0004708; F:MAP kinase kinase activity; TAS:ProtInc.
DR GO; GO:0051019; F:mitogen-activated protein kinase binding; IBA:GO_Central.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0044351; P:macropinocytosis; ISS:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:BHF-UCL.
DR GO; GO:0046777; P:protein autophosphorylation; IBA:GO_Central.
DR GO; GO:0034097; P:response to cytokine; IDA:UniProtKB.
DR GO; GO:0032496; P:response to lipopolysaccharide; ISS:UniProtKB.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0002224; P:toll-like receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0048010; P:vascular endothelial growth factor receptor signaling pathway; TAS:Reactome.
DR Gene3D; 4.10.1170.10; -; 1.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR027442; MAPKAPK_C.
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 3D-structure; Acetylation; ATP-binding; Cytoplasm; Disease variant; Kinase;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..382
FT /note="MAP kinase-activated protein kinase 3"
FT /id="PRO_0000086293"
FT DOMAIN 44..304
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..34
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 307..343
FT /note="Autoinhibitory helix"
FT /evidence="ECO:0000250"
FT REGION 345..369
FT /note="p38 MAPK-binding site"
FT /evidence="ECO:0000250"
FT REGION 357..382
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 335..344
FT /note="Nuclear export signal (NES)"
FT /evidence="ECO:0000250"
FT MOTIF 350..353
FT /note="Bipartite nuclear localization signal 1"
FT /evidence="ECO:0000250"
FT MOTIF 364..368
FT /note="Bipartite nuclear localization signal 2"
FT /evidence="ECO:0000250"
FT COMPBIAS 368..382
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 166
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 50..58
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 73
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:22814378"
FT MOD_RES 201
FT /note="Phosphothreonine; by MAPK14"
FT /evidence="ECO:0000250|UniProtKB:Q3UMW7"
FT MOD_RES 251
FT /note="Phosphoserine; by MAPK14"
FT /evidence="ECO:0000250"
FT MOD_RES 307
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 313
FT /note="Phosphothreonine; by MAPK14"
FT /evidence="ECO:0000250"
FT VARIANT 28
FT /note="P -> S (in a glioblastoma multiforme sample; somatic
FT mutation; dbSNP:rs375412266)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040755"
FT VARIANT 105
FT /note="E -> A (in an ovarian endometrioid sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040756"
FT VARIANT 173
FT /note="L -> P (in MDPT3; decreased localization to the
FT nucleus; dbSNP:rs886037913)"
FT /evidence="ECO:0000269|PubMed:26744326"
FT /id="VAR_077085"
FT VARIANT 276
FT /note="D -> Y (in dbSNP:rs56107897)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040757"
FT MUTAGEN 73
FT /note="K->M: Higher affinity toward PCH2."
FT /evidence="ECO:0000269|PubMed:15563468"
FT HELIX 39..41
FT /evidence="ECO:0007829|PDB:3FHR"
FT STRAND 43..53
FT /evidence="ECO:0007829|PDB:3FHR"
FT STRAND 56..63
FT /evidence="ECO:0007829|PDB:3FHR"
FT TURN 64..66
FT /evidence="ECO:0007829|PDB:3FHR"
FT STRAND 69..78
FT /evidence="ECO:0007829|PDB:3FHR"
FT HELIX 79..91
FT /evidence="ECO:0007829|PDB:3FHR"
FT STRAND 100..108
FT /evidence="ECO:0007829|PDB:3FHR"
FT STRAND 111..119
FT /evidence="ECO:0007829|PDB:3FHR"
FT HELIX 126..131
FT /evidence="ECO:0007829|PDB:3FHR"
FT HELIX 140..159
FT /evidence="ECO:0007829|PDB:3FHR"
FT HELIX 169..171
FT /evidence="ECO:0007829|PDB:3FHR"
FT STRAND 172..175
FT /evidence="ECO:0007829|PDB:3FHR"
FT STRAND 183..185
FT /evidence="ECO:0007829|PDB:3FHR"
FT HELIX 218..237
FT /evidence="ECO:0007829|PDB:3FHR"
FT TURN 267..269
FT /evidence="ECO:0007829|PDB:3FHR"
FT STRAND 271..273
FT /evidence="ECO:0007829|PDB:3R1N"
FT HELIX 275..284
FT /evidence="ECO:0007829|PDB:3FHR"
FT HELIX 289..291
FT /evidence="ECO:0007829|PDB:3FHR"
FT HELIX 295..300
FT /evidence="ECO:0007829|PDB:3FHR"
FT HELIX 302..305
FT /evidence="ECO:0007829|PDB:3FHR"
FT HELIX 307..309
FT /evidence="ECO:0007829|PDB:3FHR"
FT HELIX 317..323
FT /evidence="ECO:0007829|PDB:3FHR"
FT HELIX 325..327
FT /evidence="ECO:0007829|PDB:3FHR"
FT HELIX 328..343
FT /evidence="ECO:0007829|PDB:3FHR"
FT STRAND 344..346
FT /evidence="ECO:0007829|PDB:7NRB"
SQ SEQUENCE 382 AA; 42987 MW; 405F958B7F54E6F3 CRC64;
MDGETAEEQG GPVPPPVAPG GPGLGGAPGG RREPKKYAVT DDYQLSKQVL GLGVNGKVLE
CFHRRTGQKC ALKLLYDSPK ARQEVDHHWQ ASGGPHIVCI LDVYENMHHG KRCLLIIMEC
MEGGELFSRI QERGDQAFTE REAAEIMRDI GTAIQFLHSH NIAHRDVKPE NLLYTSKEKD
AVLKLTDFGF AKETTQNALQ TPCYTPYYVA PEVLGPEKYD KSCDMWSLGV IMYILLCGFP
PFYSNTGQAI SPGMKRRIRL GQYGFPNPEW SEVSEDAKQL IRLLLKTDPT ERLTITQFMN
HPWINQSMVV PQTPLHTARV LQEDKDHWDE VKEEMTSALA TMRVDYDQVK IKDLKTSNNR
LLNKRRKKQA GSSSASQGCN NQ
