ID MK12_HUMAN Reviewed; 367 AA.
AC P53778; Q14260; Q6IC53; Q99588; Q99672;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1998, sequence version 3.
DT 02-NOV-2016, entry version 184.
DE RecName: Full=Mitogen-activated protein kinase 12;
DE Short=MAP kinase 12;
DE Short=MAPK 12;
DE EC=2.7.11.24 {ECO:0000269|PubMed:10212242};
DE AltName: Full=Extracellular signal-regulated kinase 6;
DE Short=ERK-6;
DE AltName: Full=Mitogen-activated protein kinase p38 gamma;
DE Short=MAP kinase p38 gamma;
DE AltName: Full=Stress-activated protein kinase 3;
GN Name=MAPK12; Synonyms=ERK6, SAPK3;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY,
RP AND MUTAGENESIS OF TYR-185.
RC TISSUE=Skeletal muscle;
RX PubMed=8633070; DOI=10.1073/pnas.93.9.4355;
RA Lechner C., Zahalka M.A., Giot J.-F., Moeller N.P.H., Ullrich A.;
RT "ERK6, a mitogen-activated protein kinase involved in C2C12 myoblast
RT differentiation.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:4355-4359(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Skeletal muscle;
RX PubMed=9169156; DOI=10.1006/geno.1997.4633;
RA Goedert M., Hasegawa J., Craxton M., Leversha M.A., Clegg S.;
RT "Assignment of the human stress-activated protein kinase-3 gene
RT (SAPK3) to chromosome 22q13.3 by fluorescence in situ hybridization.";
RL Genomics 41:501-502(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=8920915; DOI=10.1006/bbrc.1996.1662;
RA Li Z., Jiang Y., Ulevitch R.J., Han J.;
RT "The primary structure of p38 gamma: a new member of p38 group of MAP
RT kinases.";
RL Biochem. Biophys. Res. Commun. 228:334-340(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT
RP MET-103.
RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA Beare D.M., Dunham I.;
RT "A genome annotation-driven approach to cloning the human ORFeome.";
RL Genome Biol. 5:R84.1-R84.11(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M.,
RA Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K.,
RA Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Buck D., Burgess J.,
RA Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G.,
RA Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R.,
RA Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E.,
RA Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G.,
RA Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S.,
RA Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A.,
RA Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M.,
RA Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T.,
RA Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J.,
RA Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T.,
RA Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T.,
RA Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L.,
RA Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M.,
RA Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J.,
RA Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S.,
RA Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T.,
RA Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I.,
RA Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H.,
RA Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L.,
RA Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z.,
RA Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P.,
RA Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S.,
RA Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J.,
RA Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T.,
RA Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J.,
RA Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S.,
RA Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E.,
RA Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P.,
RA Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E.,
RA O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X.,
RA Khan A.S., Lane L., Tilahun Y., Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Pancreas;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP FUNCTION IN PHOSPHORYLATION OF ATF2; ELK1 AND MBP, AND ENZYME
RP REGULATION.
RX PubMed=9430721; DOI=10.1074/jbc.273.3.1741;
RA Enslen H., Raingeaud J., Davis R.J.;
RT "Selective activation of p38 mitogen-activated protein (MAP) kinase
RT isoforms by the MAP kinase kinases MKK3 and MKK6.";
RL J. Biol. Chem. 273:1741-1748(1998).
RN [8]
RP INTERACTION WITH SNTA1, ENZYME REGULATION, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND CATALYTIC ACTIVITY.
RX PubMed=10212242; DOI=10.1074/jbc.274.18.12626;
RA Hasegawa M., Cuenda A., Spillantini M.G., Thomas G.M.,
RA Buee-Scherrer V., Cohen P., Goedert M.;
RT "Stress-activated protein kinase-3 interacts with the PDZ domain of
RT alpha1-syntrophin. A mechanism for specific substrate recognition.";
RL J. Biol. Chem. 274:12626-12631(1999).
RN [9]
RP PHOSPHORYLATION BY MAP2K6/MKK6.
RX PubMed=11010976; DOI=10.1074/jbc.M007835200;
RA Alonso G., Ambrosino C., Jones M., Nebreda A.R.;
RT "Differential activation of p38 mitogen-activated protein kinase
RT isoforms depending on signal strength.";
RL J. Biol. Chem. 275:40641-40648(2000).
RN [10]
RP FUNCTION IN REGULATION OF THE G2 CHECKPOINT.
RX PubMed=10848581; DOI=10.1128/MCB.20.13.4543-4552.2000;
RA Wang X., McGowan C.H., Zhao M., He L., Downey J.S., Fearns C.,
RA Wang Y., Huang S., Han J.;
RT "Involvement of the MKK6-p38gamma cascade in gamma-radiation-induced
RT cell cycle arrest.";
RL Mol. Cell. Biol. 20:4543-4552(2000).
RN [11]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Heart;
RX PubMed=11991731; DOI=10.1006/jmcc.2001.1523;
RA Court N.W., dos Remedios C.G., Cordell J., Bogoyevitch M.A.;
RT "Cardiac expression and subcellular localization of the p38 mitogen-
RT activated protein kinase member, stress-activated protein kinase-3
RT (SAPK3).";
RL J. Mol. Cell. Cardiol. 34:413-426(2002).
RN [12]
RP MUTAGENESIS, SUBCELLULAR LOCATION, AND INTERACTION WITH SH3BP5.
RX PubMed=12167088; DOI=10.1042/BJ20020553;
RA Wiltshire C., Matsushita M., Tsukada S., Gillespie D.A., May G.H.;
RT "A new c-Jun N-terminal kinase (JNK)-interacting protein, Sab
RT (SH3BP5), associates with mitochondria.";
RL Biochem. J. 367:577-585(2002).
RN [13]
RP FUNCTION.
RX PubMed=14592936; DOI=10.1152/ajpregu.00563.2003;
RA Ho R.C., Alcazar O., Fujii N., Hirshman M.F., Goodyear L.J.;
RT "p38gamma MAPK regulation of glucose transporter expression and
RT glucose uptake in L6 myotubes and mouse skeletal muscle.";
RL Am. J. Physiol. 286:R342-R349(2004).
RN [14]
RP MUTAGENESIS OF ASP-179 AND PHE-330.
RX PubMed=15284239; DOI=10.1074/jbc.M404595200;
RA Diskin R., Askari N., Capone R., Engelberg D., Livnah O.;
RT "Active mutants of the human p38alpha mitogen-activated protein
RT kinase.";
RL J. Biol. Chem. 279:47040-47049(2004).
RN [15]
RP FUNCTION, INDUCTION, PHOSPHORYLATION, SUBCELLULAR LOCATION, AND
RP UBIQUITINATION.
RX PubMed=17724032; DOI=10.1074/jbc.M703857200;
RA Qi X., Pohl N.M., Loesch M., Hou S., Li R., Qin J.Z., Cuenda A.,
RA Chen G.;
RT "p38alpha antagonizes p38gamma activity through c-Jun-dependent
RT ubiquitin-proteasome pathways in regulating Ras transformation and
RT stress response.";
RL J. Biol. Chem. 282:31398-31408(2007).
RN [16]
RP FUNCTION IN PHOSPHORYLATION OF DLG1.
RX PubMed=20605917; DOI=10.1242/jcs.066514;
RA Sabio G., Cerezo-Guisado M.I., Del Reino P., Inesta-Vaquera F.A.,
RA Rousseau S., Arthur J.S., Campbell D.G., Centeno F., Cuenda A.;
RT "p38gamma regulates interaction of nuclear PSF and RNA with the
RT tumour-suppressor hDlg in response to osmotic shock.";
RL J. Cell Sci. 123:2596-2604(2010).
RN [17]
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.,
RA Buerckstuemmer T., 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 [18]
RP FUNCTION.
RX PubMed=21172807; DOI=10.1242/jcs.068254;
RA Kukkonen-Macchi A., Sicora O., Kaczynska K., Oetken-Lindholm C.,
RA Pouwels J., Laine L., Kallio M.J.;
RT "Loss of p38gamma MAPK induces pleiotropic mitotic defects and massive
RT cell death.";
RL J. Cell Sci. 124:216-227(2011).
RN [19]
RP INVOLVEMENT IN CANCER.
RX PubMed=21532888; DOI=10.1593/neo.101748;
RA Meng F., Zhang H., Liu G., Kreike B., Chen W., Sethi S., Miller F.R.,
RA Wu G.;
RT "p38gamma mitogen-activated protein kinase contributes to oncogenic
RT properties maintenance and resistance to poly (ADP-ribose)-polymerase-
RT 1 inhibition in breast cancer.";
RL Neoplasia 13:472-482(2011).
RN [20]
RP REVIEW ON ENZYME REGULATION, AND REVIEW ON FUNCTION.
RX PubMed=20626350; DOI=10.1042/BJ20100323;
RA Cuadrado A., Nebreda A.R.;
RT "Mechanisms and functions of p38 MAPK signalling.";
RL Biochem. J. 429:403-417(2010).
RN [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-185, AND IDENTIFICATION
RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS), COFACTOR, AND SUBUNIT.
RX PubMed=10508788; DOI=10.1016/S0969-2126(99)80173-7;
RA Bellon S., Fitzgibbon M.J., Fox T., Hsiao H.M., Wilson K.P.;
RT "The structure of phosphorylated p38gamma is monomeric and reveals a
RT conserved activation-loop conformation.";
RL Structure 7:1057-1065(1999).
RN [23]
RP VARIANTS [LARGE SCALE ANALYSIS] MET-103 AND ASN-230.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C.,
RA Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S.,
RA O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S.,
RA Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E.,
RA Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J.,
RA Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K.,
RA Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T.,
RA West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P.,
RA Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E.,
RA DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E.,
RA Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T.,
RA Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Serine/threonine kinase which acts as an essential
CC component of the MAP kinase signal transduction pathway. MAPK12 is
CC one of the four p38 MAPKs which play an important role in the
CC cascades of cellular responses evoked by extracellular stimuli
CC such as proinflammatory cytokines or physical stress leading to
CC direct activation of transcription factors such as ELK1 and ATF2.
CC Accordingly, p38 MAPKs phosphorylate a broad range of proteins and
CC it has been estimated that they may have approximately 200 to 300
CC substrates each. Some of the targets are downstream kinases such
CC as MAPKAPK2, which are activated through phosphorylation and
CC further phosphorylate additional targets. Plays a role in myoblast
CC differentiation and also in the down-regulation of cyclin D1 in
CC response to hypoxia in adrenal cells suggesting MAPK12 may inhibit
CC cell proliferation while promoting differentiation. Phosphorylates
CC DLG1. Following osmotic shock, MAPK12 in the cell nucleus
CC increases its association with nuclear DLG1, thereby causing
CC dissociation of DLG1-SFPQ complexes. This function is independent
CC of its catalytic activity and could affect mRNA processing and/or
CC gene transcription to aid cell adaptation to osmolarity changes in
CC the environment. Regulates UV-induced checkpoint signaling and
CC repair of UV-induced DNA damage and G2 arrest after gamma-
CC radiation exposure. MAPK12 is involved in the regulation of SLC2A1
CC expression and basal glucose uptake in L6 myotubes; and negatively
CC regulates SLC2A4 expression and contraction-mediated glucose
CC uptake in adult skeletal muscle. C-Jun (JUN) phosphorylation is
CC stimulated by MAPK14 and inhibited by MAPK12, leading to a
CC distinct AP-1 regulation. MAPK12 is required for the normal
CC kinetochore localization of PLK1, prevents chromosomal instability
CC and supports mitotic cell viability. MAPK12-signaling is also
CC positively regulating the expansion of transient amplifying
CC myogenic precursor cells during muscle growth and regeneration.
CC {ECO:0000269|PubMed:10848581, ECO:0000269|PubMed:14592936,
CC ECO:0000269|PubMed:17724032, ECO:0000269|PubMed:20605917,
CC ECO:0000269|PubMed:21172807, ECO:0000269|PubMed:8633070,
CC ECO:0000269|PubMed:9430721}.
CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
CC {ECO:0000269|PubMed:10212242}.
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:10508788};
CC Note=Binds 2 magnesium ions. {ECO:0000269|PubMed:10508788};
CC -!- ENZYME REGULATION: Activated by phosphorylation on threonine and
CC tyrosine. MAP2K3/MKK3 and MAP2K6/MKK6 are both essential for the
CC activation of MAPK12 induced by environmental stress, whereas
CC MAP2K6/MKK6 is the major MAPK12 activator in response to TNF-
CC alpha. {ECO:0000269|PubMed:10212242, ECO:0000269|PubMed:9430721}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=37 uM for ATP {ECO:0000269|PubMed:10212242};
CC KM=313 uM for EGFR substrate peptide
CC {ECO:0000269|PubMed:10212242};
CC KM=254 uM for GST-ATF2 {ECO:0000269|PubMed:10212242};
CC -!- SUBUNIT: Monomer. Interacts with the PDZ domain of the syntrophin
CC SNTA1. Interacts with SH3BP5. Interacts with LIN7C, SCRIB and
CC SYNJ2BP (By similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC Q16512:PKN1; NbExp=2; IntAct=EBI-602406, EBI-602382;
CC P29074:PTPN4; NbExp=2; IntAct=EBI-602406, EBI-710431;
CC Q8IUQ4:SIAH1; NbExp=3; IntAct=EBI-602406, EBI-747107;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Mitochondrion.
CC Note=Mitochondrial when associated with SH3BP5. In skeletal muscle
CC colocalizes with SNTA1 at the neuromuscular junction and
CC throughout the sarcolemma (By similarity). {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P53778-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P53778-2; Sequence=VSP_055224;
CC Note=No experimental confirmation available.;
CC -!- TISSUE SPECIFICITY: Highly expressed in skeletal muscle and heart.
CC {ECO:0000269|PubMed:11991731, ECO:0000269|PubMed:8633070}.
CC -!- INDUCTION: Expression of MAPK12 is down-regulation by MAPK14
CC activation. {ECO:0000269|PubMed:17724032}.
CC -!- DOMAIN: The TXY motif contains the threonine and tyrosine residues
CC whose phosphorylation activates the MAP kinases.
CC -!- PTM: Dually phosphorylated on Thr-183 and Tyr-185 by MAP2K3/MKK3
CC and MAP2K6/MKK6, which activates the enzyme.
CC {ECO:0000269|PubMed:11010976, ECO:0000269|PubMed:17724032}.
CC -!- PTM: Ubiquitinated. Ubiquitination leads to degradation by the
CC proteasome pathway. {ECO:0000269|PubMed:17724032}.
CC -!- DISEASE: Note=MAPK is overexpressed in highly metastatic breast
CC cancer cell lines and its expression is preferentially associated
CC with basal-like and metastatic phenotypes of breast tumor samples.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC
CC Ser/Thr protein kinase family. MAP kinase subfamily.
CC {ECO:0000305}.
CC -!- SIMILARITY: Contains 1 protein kinase domain.
CC {ECO:0000255|PROSITE-ProRule:PRU00159}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/MAPK12ID41290ch22q13.html";
DR EMBL; X79483; CAA55984.1; -; mRNA.
DR EMBL; Y10487; CAA71511.1; -; mRNA.
DR EMBL; U66243; AAB40118.1; -; mRNA.
DR EMBL; CR456515; CAG30401.1; -; mRNA.
DR EMBL; AL022328; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC015741; AAH15741.1; -; mRNA.
DR CCDS; CCDS14089.1; -. [P53778-1]
DR CCDS; CCDS77688.1; -. [P53778-2]
DR PIR; JC5252; JC5252.
DR PIR; JC6138; JC6138.
DR RefSeq; NP_001290181.1; NM_001303252.1. [P53778-2]
DR RefSeq; NP_002960.2; NM_002969.4. [P53778-1]
DR UniGene; Hs.432642; -.
DR PDB; 1CM8; X-ray; 2.40 A; A/B=1-367.
DR PDB; 4QUM; X-ray; 2.52 A; B=182-190.
DR PDBsum; 1CM8; -.
DR PDBsum; 4QUM; -.
DR ProteinModelPortal; P53778; -.
DR SMR; P53778; -.
DR BioGrid; 112207; 24.
DR DIP; DIP-34241N; -.
DR IntAct; P53778; 13.
DR MINT; MINT-90266; -.
DR STRING; 9606.ENSP00000215659; -.
DR BindingDB; P53778; -.
DR ChEMBL; CHEMBL4674; -.
DR GuidetoPHARMACOLOGY; 1501; -.
DR iPTMnet; P53778; -.
DR PhosphoSitePlus; P53778; -.
DR BioMuta; MAPK12; -.
DR DMDM; 2851522; -.
DR EPD; P53778; -.
DR MaxQB; P53778; -.
DR PaxDb; P53778; -.
DR PeptideAtlas; P53778; -.
DR PRIDE; P53778; -.
DR DNASU; 6300; -.
DR Ensembl; ENST00000215659; ENSP00000215659; ENSG00000188130. [P53778-1]
DR Ensembl; ENST00000622558; ENSP00000479972; ENSG00000188130. [P53778-2]
DR GeneID; 6300; -.
DR KEGG; hsa:6300; -.
DR UCSC; uc003bkl.2; human. [P53778-1]
DR CTD; 6300; -.
DR DisGeNET; 6300; -.
DR GeneCards; MAPK12; -.
DR HGNC; HGNC:6874; MAPK12.
DR HPA; CAB025483; -.
DR HPA; HPA054562; -.
DR MIM; 602399; gene.
DR neXtProt; NX_P53778; -.
DR OpenTargets; ENSG00000188130; -.
DR PharmGKB; PA30619; -.
DR eggNOG; KOG0660; Eukaryota.
DR eggNOG; ENOG410XNY0; LUCA.
DR GeneTree; ENSGT00550000074271; -.
DR HOGENOM; HOG000233024; -.
DR HOVERGEN; HBG014652; -.
DR InParanoid; P53778; -.
DR KO; K04441; -.
DR OMA; MKHEKLG; -.
DR OrthoDB; EOG091G08QL; -.
DR PhylomeDB; P53778; -.
DR TreeFam; TF105100; -.
DR BioCyc; ZFISH:HS01100-MONOMER; -.
DR BRENDA; 2.7.11.24; 2681.
DR Reactome; R-HSA-168638; NOD1/2 Signaling Pathway.
DR Reactome; R-HSA-171007; p38MAPK events.
DR Reactome; R-HSA-2151209; Activation of PPARGC1A (PGC-1alpha) by phosphorylation.
DR Reactome; R-HSA-375170; CDO in myogenesis.
DR Reactome; R-HSA-376172; DSCAM interactions.
DR Reactome; R-HSA-4420097; VEGFA-VEGFR2 Pathway.
DR SignaLink; P53778; -.
DR SIGNOR; P53778; -.
DR EvolutionaryTrace; P53778; -.
DR GeneWiki; MAPK12; -.
DR GenomeRNAi; 6300; -.
DR PRO; PR:P53778; -.
DR Proteomes; UP000005640; Chromosome 22.
DR Bgee; ENSG00000188130; -.
DR CleanEx; HS_MAPK12; -.
DR ExpressionAtlas; P53778; baseline and differential.
DR Genevisible; P53778; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:HPA.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
DR GO; GO:0004707; F:MAP kinase activity; TAS:ProtInc.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0007050; P:cell cycle arrest; TAS:ProtInc.
DR GO; GO:0006975; P:DNA damage induced protein phosphorylation; TAS:ProtInc.
DR GO; GO:0007517; P:muscle organ development; TAS:ProtInc.
DR GO; GO:0045445; P:myoblast differentiation; IDA:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:BHF-UCL.
DR GO; GO:0051149; P:positive regulation of muscle cell differentiation; TAS:Reactome.
DR GO; GO:0010952; P:positive regulation of peptidase activity; NAS:ParkinsonsUK-UCL.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IEA:UniProtKB-KW.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW.
DR GO; GO:0048010; P:vascular endothelial growth factor receptor signaling pathway; TAS:Reactome.
DR InterPro; IPR011009; Kinase-like_dom.
DR InterPro; IPR003527; MAP_kinase_CS.
DR InterPro; IPR008352; MAPK_p38.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR Pfam; PF00069; Pkinase; 1.
DR PRINTS; PR01773; P38MAPKINASE.
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.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ATP-binding; Cell cycle;
KW Complete proteome; Cytoplasm; Kinase; Magnesium; Metal-binding;
KW Mitochondrion; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Polymorphism; Reference proteome; Serine/threonine-protein kinase;
KW Stress response; Transcription; Transcription regulation; Transferase;
KW Ubl conjugation.
FT CHAIN 1 367 Mitogen-activated protein kinase 12.
FT /FTId=PRO_0000186282.
FT DOMAIN 27 311 Protein kinase. {ECO:0000255|PROSITE-
FT ProRule:PRU00159}.
FT NP_BIND 33 41 ATP. {ECO:0000255|PROSITE-
FT ProRule:PRU00159}.
FT MOTIF 183 185 TXY.
FT ACT_SITE 153 153 Proton acceptor. {ECO:0000255|PROSITE-
FT ProRule:PRU00159}.
FT BINDING 56 56 ATP. {ECO:0000255|PROSITE-
FT ProRule:PRU00159}.
FT MOD_RES 183 183 Phosphothreonine; by MAP2K3 and MAP2K6.
FT {ECO:0000250}.
FT MOD_RES 185 185 Phosphotyrosine.
FT {ECO:0000244|PubMed:23186163}.
FT VAR_SEQ 142 151 Missing (in isoform 2).
FT {ECO:0000303|PubMed:15461802}.
FT /FTId=VSP_055224.
FT VARIANT 103 103 T -> M (in dbSNP:rs34422484).
FT {ECO:0000269|PubMed:15461802,
FT ECO:0000269|PubMed:17344846}.
FT /FTId=VAR_042265.
FT VARIANT 230 230 D -> N (in dbSNP:rs35396905).
FT {ECO:0000269|PubMed:17344846}.
FT /FTId=VAR_042266.
FT VARIANT 244 244 T -> M (in dbSNP:rs2066776).
FT /FTId=VAR_012002.
FT MUTAGEN 179 179 D->A: Emulation of the active state.
FT {ECO:0000269|PubMed:15284239}.
FT MUTAGEN 185 185 Y->F: Loss of activity.
FT {ECO:0000269|PubMed:8633070}.
FT MUTAGEN 330 330 F->S: No effect.
FT {ECO:0000269|PubMed:15284239}.
FT CONFLICT 7 7 A -> T (in Ref. 1; CAA55984).
FT {ECO:0000305}.
FT CONFLICT 70 70 R -> L (in Ref. 1; CAA55984).
FT {ECO:0000305}.
FT CONFLICT 138 138 L -> M (in Ref. 1; CAA55984).
FT {ECO:0000305}.
FT CONFLICT 201 202 MR -> IA (in Ref. 1; CAA55984).
FT {ECO:0000305}.
FT CONFLICT 261 261 Y -> N (in Ref. 3; AAB40118).
FT {ECO:0000305}.
FT CONFLICT 297 298 EQ -> DI (in Ref. 1; CAA55984).
FT {ECO:0000305}.
FT CONFLICT 300 300 V -> L (in Ref. 1; CAA55984).
FT {ECO:0000305}.
FT CONFLICT 305 305 A -> F (in Ref. 1; CAA55984).
FT {ECO:0000305}.
FT CONFLICT 307 307 A -> S (in Ref. 1; CAA55984).
FT {ECO:0000305}.
FT CONFLICT 332 333 DV -> YF (in Ref. 1; CAA55984).
FT {ECO:0000305}.
FT STRAND 17 21 {ECO:0000244|PDB:1CM8}.
FT STRAND 24 32 {ECO:0000244|PDB:1CM8}.
FT STRAND 41 46 {ECO:0000244|PDB:1CM8}.
FT TURN 47 49 {ECO:0000244|PDB:1CM8}.
FT STRAND 52 57 {ECO:0000244|PDB:1CM8}.
FT HELIX 65 80 {ECO:0000244|PDB:1CM8}.
FT STRAND 90 93 {ECO:0000244|PDB:1CM8}.
FT TURN 99 101 {ECO:0000244|PDB:1CM8}.
FT STRAND 106 110 {ECO:0000244|PDB:1CM8}.
FT STRAND 113 115 {ECO:0000244|PDB:1CM8}.
FT HELIX 116 122 {ECO:0000244|PDB:1CM8}.
FT HELIX 127 146 {ECO:0000244|PDB:1CM8}.
FT HELIX 156 158 {ECO:0000244|PDB:1CM8}.
FT STRAND 159 161 {ECO:0000244|PDB:1CM8}.
FT STRAND 167 169 {ECO:0000244|PDB:1CM8}.
FT HELIX 189 191 {ECO:0000244|PDB:1CM8}.
FT HELIX 195 198 {ECO:0000244|PDB:1CM8}.
FT TURN 199 201 {ECO:0000244|PDB:1CM8}.
FT HELIX 207 221 {ECO:0000244|PDB:1CM8}.
FT HELIX 231 242 {ECO:0000244|PDB:1CM8}.
FT HELIX 247 251 {ECO:0000244|PDB:1CM8}.
FT HELIX 256 264 {ECO:0000244|PDB:1CM8}.
FT HELIX 273 275 {ECO:0000244|PDB:1CM8}.
FT HELIX 282 291 {ECO:0000244|PDB:1CM8}.
FT TURN 296 298 {ECO:0000244|PDB:1CM8}.
FT HELIX 302 307 {ECO:0000244|PDB:1CM8}.
FT HELIX 309 311 {ECO:0000244|PDB:1CM8}.
FT TURN 312 314 {ECO:0000244|PDB:1CM8}.
FT HELIX 337 349 {ECO:0000244|PDB:1CM8}.
CC --------------------------------------------------------------------------
CC The following FT lines are automated annotations from the MyHits database.
CC --------------------------------------------------------------------------
FT MYHIT 62 165 ipat:MAPK [T]
FT MYHIT 27 311 ipfam:Pkinase [T]
FT MYHIT 27 311 ismart:S_TKc [T]
FT MYHIT 33 57 ipat:PROTEIN_KINASE_ATP [T]
FT MYHIT 27 311 iprf:PROTEIN_KINASE_DOM [T]
SQ SEQUENCE 367 AA; 41940 MW; EF680401D8E40610 CRC64;
MSSPPPARSG FYRQEVTKTA WEVRAVYRDL QPVGSGAYGA VCSAVDGRTG AKVAIKKLYR
PFQSELFAKR AYRELRLLKH MRHENVIGLL DVFTPDETLD DFTDFYLVMP FMGTDLGKLM
KHEKLGEDRI QFLVYQMLKG LRYIHAAGII HRDLKPGNLA VNEDCELKIL DFGLARQADS
EMTGYVVTRW YRAPEVILNW MRYTQTVDIW SVGCIMAEMI TGKTLFKGSD HLDQLKEIMK
VTGTPPAEFV QRLQSDEAKN YMKGLPELEK KDFASILTNA SPLAVNLLEK MLVLDAEQRV
TAGEALAHPY FESLHDTEDE PQVQKYDDSF DDVDRTLDEW KRVTYKEVLS FKPPRQLGAR
VSKETPL
//
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