MK13_HUMAN
ID MK13_HUMAN Reviewed; 365 AA.
AC O15264; O14739; O15124; Q5U4A5; Q6FI46; Q9UNU0;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 207.
DE RecName: Full=Mitogen-activated protein kinase 13;
DE Short=MAP kinase 13;
DE Short=MAPK 13;
DE EC=2.7.11.24;
DE AltName: Full=Mitogen-activated protein kinase p38 delta;
DE Short=MAP kinase p38 delta;
DE AltName: Full=Stress-activated protein kinase 4;
GN Name=MAPK13; Synonyms=PRKM13, SAPK4;
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), AND ACTIVITY REGULATION.
RC TISSUE=Pituitary;
RX PubMed=9218798; DOI=10.1093/emboj/16.12.3563;
RA Goedert M., Cuenda A., Craxton M., Jakes R., Cohen P.;
RT "Activation of the novel stress-activated protein kinase SAPK4 by cytokines
RT and cellular stresses is mediated by SKK3 (MKK6); comparison of its
RT substrate specificity with that of other SAP kinases.";
RL EMBO J. 16:3563-3571(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PHOSPHORYLATION AT THR-180 AND
RP TYR-182, MUTAGENESIS OF THR-180 AND TYR-182, ACTIVITY REGULATION, AND
RP TISSUE SPECIFICITY.
RC TISSUE=Liver;
RX PubMed=9374491; DOI=10.1074/jbc.272.48.30122;
RA Jiang Y., Gram H., Zhao M., New L., Gu J., Feng L., Di Padova F.,
RA Ulevitch R.J., Han J.;
RT "Characterization of the structure and function of the fourth member of p38
RT group mitogen-activated protein kinases, p38delta.";
RL J. Biol. Chem. 272:30122-30128(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=9295308; DOI=10.1074/jbc.272.38.23668;
RA Wang X.S., Diener K., Manthey C.L., Wang S.-W., Rosenzweig B., Bray J.,
RA Delaney J., Cole C., Zukowski M., Yao Z.;
RT "Molecular cloning and characterization of a novel p38 mitogen-activated
RT protein kinase.";
RL J. Biol. Chem. 272:23668-23674(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=9207191; DOI=10.1006/bbrc.1997.6849;
RA Kumar S., McDonnell P.C., Gum R.J., Hand A.T., Lee J.C., Young P.R.;
RT "Novel homologues of CSBP/p38 MAP kinase: activation, substrate specificity
RT and sensitivity to inhibition by pyridinyl imidazoles.";
RL Biochem. Biophys. Res. Commun. 235:533-538(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=10066767; DOI=10.1074/jbc.274.11.7095;
RA Hu M.C.-T., Wang Y.-P., Mikhail A., Qiu W.R., Tan T.-H.;
RT "Murine p38-delta mitogen-activated protein kinase, a developmentally
RT regulated protein kinase that is activated by stress and proinflammatory
RT cytokines.";
RL J. Biol. Chem. 274:7095-7102(1999).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=10727080; DOI=10.3109/10425179909033952;
RA Herbison C.E., Sayer D.C., Bellgard M., Allcock R.J.N., Christiansen F.T.,
RA Price P.;
RT "Structure and polymorphism of two stress-activated protein kinase genes
RT centromeric of the MHC: SAPK2a and SAPK4.";
RL DNA Seq. 10:229-243(1999).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [10]
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 [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Lung, and 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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [12]
RP FUNCTION IN PHOSPHORYLATION OF STMN1.
RX PubMed=9731215; DOI=10.1006/bbrc.1998.9250;
RA Parker C.G., Hunt J., Diener K., McGinley M., Soriano B., Keesler G.A.,
RA Bray J., Yao Z., Wang X.S., Kohno T., Lichenstein H.S.;
RT "Identification of stathmin as a novel substrate for p38 delta.";
RL Biochem. Biophys. Res. Commun. 249:791-796(1998).
RN [13]
RP TISSUE SPECIFICITY.
RX PubMed=10201954;
RA Hale K.K., Trollinger D., Rihanek M., Manthey C.L.;
RT "Differential expression and activation of p38 mitogen-activated protein
RT kinase alpha, beta, gamma, and delta in inflammatory cell lineages.";
RL J. Immunol. 162:4246-4252(1999).
RN [14]
RP INTERACTION WITH MAPK8IP2.
RX PubMed=11378392; DOI=10.1016/s0960-9822(01)00232-9;
RA Schoorlemmer J., Goldfarb M.;
RT "Fibroblast growth factor homologous factors are intracellular signaling
RT proteins.";
RL Curr. Biol. 11:793-797(2001).
RN [15]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=11500363; DOI=10.1093/emboj/20.16.4360;
RA Knebel A., Morrice N., Cohen P.;
RT "A novel method to identify protein kinase substrates: eEF2 kinase is
RT phosphorylated and inhibited by SAPK4/p38delta.";
RL EMBO J. 20:4360-4369(2001).
RN [16]
RP FUNCTION IN PHOSPHORYLATION OF MAPT.
RX PubMed=11943212; DOI=10.1016/s0014-5793(02)02460-2;
RA Buee-Scherrer V., Goedert M.;
RT "Phosphorylation of microtubule-associated protein tau by stress-activated
RT protein kinases in intact cells.";
RL FEBS Lett. 515:151-154(2002).
RN [17]
RP FUNCTION IN PHOSPHORYLATION OF MAPT.
RX PubMed=15632108; DOI=10.1242/jcs.01655;
RA Feijoo C., Campbell D.G., Jakes R., Goedert M., Cuenda A.;
RT "Evidence that phosphorylation of the microtubule-associated protein Tau by
RT SAPK4/p38delta at Thr50 promotes microtubule assembly.";
RL J. Cell Sci. 118:397-408(2005).
RN [18]
RP FUNCTION IN KERATINOCYTE APOPTOSIS.
RX PubMed=17256148; DOI=10.1007/s00403-006-0727-4;
RA Kraft C.A., Efimova T., Eckert R.L.;
RT "Activation of PKCdelta and p38delta MAPK during okadaic acid dependent
RT keratinocyte apoptosis.";
RL Arch. Dermatol. Res. 299:71-83(2007).
RN [19]
RP FUNCTION IN PHOSPHORYLATION OF MYB.
RX PubMed=18006338; DOI=10.1016/j.bcmd.2007.09.010;
RA Pani E., Ferrari S.;
RT "p38MAPK delta controls c-Myb degradation in response to stress.";
RL Blood Cells Mol. Dis. 40:388-394(2008).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-47, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Platelet;
RX PubMed=18088087; DOI=10.1021/pr0704130;
RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT "Phosphoproteome of resting human platelets.";
RL J. Proteome Res. 7:526-534(2008).
RN [21]
RP DEPHOSPHORYLATION BY DUSP1, AND FUNCTION.
RX PubMed=18367666; DOI=10.1073/pnas.0801453105;
RA Zhou X., Ferraris J.D., Dmitrieva N.I., Liu Y., Burg M.B.;
RT "MKP-1 inhibits high NaCl-induced activation of p38 but does not inhibit
RT the activation of TonEBP/OREBP: opposite roles of p38alpha and p38delta.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:5620-5625(2008).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-350, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [23]
RP FUNCTION.
RX PubMed=20478268; DOI=10.1016/j.bbrc.2010.05.072;
RA Ozawa S., Ito S., Kato Y., Kubota E., Hata R.;
RT "Human p38 delta MAP kinase mediates UV irradiation induced up-regulation
RT of the gene expression of chemokine BRAK/CXCL14.";
RL Biochem. Biophys. Res. Commun. 396:1060-1064(2010).
RN [24]
RP REVIEW ON FUNCTION.
RX PubMed=20090411; DOI=10.4161/cc.9.3.10541;
RA Efimova T.;
RT "p38delta mitogen-activated protein kinase regulates skin homeostasis and
RT tumorigenesis.";
RL Cell Cycle 9:498-505(2010).
RN [25]
RP REVIEW ON ACTIVITY 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 [26]
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 [27]
RP X-RAY CRYSTALLOGRAPHY (2.09 ANGSTROMS) OF 2-352.
RG New York structural genomix research consortium (NYSGXRC);
RT "Crystal structure of p38delta kinase.";
RL Submitted (JUN-2009) to the PDB data bank.
RN [28]
RP VARIANTS [LARGE SCALE ANALYSIS] LEU-41; VAL-282 AND THR-300.
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: Serine/threonine kinase which acts as an essential component
CC of the MAP kinase signal transduction pathway. MAPK13 is one of the
CC four p38 MAPKs which play an important role in the cascades of cellular
CC responses evoked by extracellular stimuli such as pro-inflammatory
CC cytokines or physical stress leading to direct activation of
CC transcription factors such as ELK1 and ATF2. Accordingly, p38 MAPKs
CC phosphorylate a broad range of proteins and it has been estimated that
CC they may have approximately 200 to 300 substrates each. MAPK13 is one
CC of the less studied p38 MAPK isoforms. Some of the targets are
CC downstream kinases such as MAPKAPK2, which are activated through
CC phosphorylation and further phosphorylate additional targets. Plays a
CC role in the regulation of protein translation by phosphorylating and
CC inactivating EEF2K. Involved in cytoskeletal remodeling through
CC phosphorylation of MAPT and STMN1. Mediates UV irradiation induced up-
CC regulation of the gene expression of CXCL14. Plays an important role in
CC the regulation of epidermal keratinocyte differentiation, apoptosis and
CC skin tumor development. Phosphorylates the transcriptional activator
CC MYB in response to stress which leads to rapid MYB degradation via a
CC proteasome-dependent pathway. MAPK13 also phosphorylates and down-
CC regulates PRKD1 during regulation of insulin secretion in pancreatic
CC beta cells. {ECO:0000269|PubMed:11500363, ECO:0000269|PubMed:11943212,
CC ECO:0000269|PubMed:15632108, ECO:0000269|PubMed:17256148,
CC ECO:0000269|PubMed:18006338, ECO:0000269|PubMed:18367666,
CC ECO:0000269|PubMed:20478268, ECO:0000269|PubMed:9731215}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.24;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.24;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC -!- ACTIVITY REGULATION: Activated by phosphorylation on threonine and
CC tyrosine by dual specificity kinases, MAP2K3/MKK3, MAP2K6/MKK6,
CC MAP2K4/MKK4 and MAP2K7/MKK7. Activation by ultraviolet radiation,
CC hyperosmotic shock, anisomycin or by TNF-alpha is mediated by
CC MAP2K3/MKK3. Inhibited by dual specificity phosphatase DUSP1.
CC {ECO:0000269|PubMed:11500363, ECO:0000269|PubMed:9218798,
CC ECO:0000269|PubMed:9374491}.
CC -!- SUBUNIT: Interacts with MAPK8IP2. {ECO:0000269|PubMed:11378392}.
CC -!- INTERACTION:
CC O15264; P21462: FPR1; NbExp=3; IntAct=EBI-2116951, EBI-2869495;
CC O15264; Q15139: PRKD1; NbExp=6; IntAct=EBI-2116951, EBI-1181072;
CC O15264; P40763: STAT3; NbExp=2; IntAct=EBI-2116951, EBI-518675;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O15264-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O15264-2; Sequence=VSP_056558, VSP_056559;
CC -!- TISSUE SPECIFICITY: Expressed in testes, pancreas, small intestine,
CC lung and kidney. Abundant in macrophages, also present in neutrophils,
CC CD4+ T-cells, and endothelial cells. {ECO:0000269|PubMed:10201954,
CC ECO:0000269|PubMed:9374491}.
CC -!- DOMAIN: The TXY motif contains the threonine and tyrosine residues
CC whose phosphorylation activates the MAP kinases.
CC -!- PTM: Dually phosphorylated on Thr-180 and Tyr-182 by MAP2K3/MKK3,
CC MAP2K4/MKK4, MAP2K6/MKK6 and MAP2K7/MKK7, which activates the enzyme.
CC Dephosphorylated by dual specificity phosphatase DUSP1.
CC {ECO:0000269|PubMed:9374491}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC protein kinase family. MAP kinase subfamily. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/MAPK13ID41291ch6p21.html";
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DR EMBL; Y10488; CAA71512.1; -; mRNA.
DR EMBL; U93232; AAB87639.1; -; mRNA.
DR EMBL; AF015256; AAC51758.1; -; mRNA.
DR EMBL; AF004709; AAC51374.1; -; mRNA.
DR EMBL; AF092535; AAD23377.1; -; mRNA.
DR EMBL; AF100546; AAF36772.1; -; mRNA.
DR EMBL; BT007221; AAP35885.1; -; mRNA.
DR EMBL; CR536490; CAG38729.1; -; mRNA.
DR EMBL; Z95152; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471081; EAX03874.1; -; Genomic_DNA.
DR EMBL; CH471081; EAX03875.1; -; Genomic_DNA.
DR EMBL; BC000433; AAH00433.1; -; mRNA.
DR EMBL; BC001641; AAH01641.1; -; mRNA.
DR EMBL; BC004428; AAH04428.1; -; mRNA.
DR EMBL; BC085196; AAH85196.1; -; mRNA.
DR CCDS; CCDS4818.1; -. [O15264-1]
DR PIR; JC5528; JC5528.
DR RefSeq; NP_002745.1; NM_002754.4. [O15264-1]
DR PDB; 3COI; X-ray; 2.09 A; A=2-352.
DR PDB; 4EYJ; X-ray; 2.10 A; A=1-352.
DR PDB; 4EYM; X-ray; 2.35 A; A=1-352.
DR PDB; 4MYG; X-ray; 2.59 A; A/B=1-352.
DR PDB; 4YNO; X-ray; 1.70 A; A=1-352.
DR PDB; 5EKN; X-ray; 2.59 A; A=1-352.
DR PDB; 5EKO; X-ray; 2.00 A; A=1-352.
DR PDBsum; 3COI; -.
DR PDBsum; 4EYJ; -.
DR PDBsum; 4EYM; -.
DR PDBsum; 4MYG; -.
DR PDBsum; 4YNO; -.
DR PDBsum; 5EKN; -.
DR PDBsum; 5EKO; -.
DR AlphaFoldDB; O15264; -.
DR SMR; O15264; -.
DR BioGRID; 111589; 45.
DR IntAct; O15264; 112.
DR MINT; O15264; -.
DR STRING; 9606.ENSP00000211287; -.
DR BindingDB; O15264; -.
DR ChEMBL; CHEMBL2939; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugBank; DB05157; KC706.
DR DrugBank; DB01017; Minocycline.
DR DrugCentral; O15264; -.
DR GuidetoPHARMACOLOGY; 1502; -.
DR iPTMnet; O15264; -.
DR PhosphoSitePlus; O15264; -.
DR BioMuta; MAPK13; -.
DR CPTAC; CPTAC-876; -.
DR CPTAC; CPTAC-877; -.
DR EPD; O15264; -.
DR jPOST; O15264; -.
DR MassIVE; O15264; -.
DR MaxQB; O15264; -.
DR PaxDb; O15264; -.
DR PeptideAtlas; O15264; -.
DR PRIDE; O15264; -.
DR ProteomicsDB; 48552; -. [O15264-1]
DR ProteomicsDB; 65225; -.
DR ABCD; O15264; 8 sequenced antibodies.
DR Antibodypedia; 2088; 910 antibodies from 39 providers.
DR DNASU; 5603; -.
DR Ensembl; ENST00000211287.9; ENSP00000211287.4; ENSG00000156711.17. [O15264-1]
DR Ensembl; ENST00000373766.9; ENSP00000362871.5; ENSG00000156711.17. [O15264-2]
DR GeneID; 5603; -.
DR KEGG; hsa:5603; -.
DR MANE-Select; ENST00000211287.9; ENSP00000211287.4; NM_002754.5; NP_002745.1.
DR UCSC; uc003ols.5; human. [O15264-1]
DR CTD; 5603; -.
DR DisGeNET; 5603; -.
DR GeneCards; MAPK13; -.
DR HGNC; HGNC:6875; MAPK13.
DR HPA; ENSG00000156711; Tissue enhanced (esophagus).
DR MIM; 602899; gene.
DR neXtProt; NX_O15264; -.
DR OpenTargets; ENSG00000156711; -.
DR PharmGKB; PA30620; -.
DR VEuPathDB; HostDB:ENSG00000156711; -.
DR eggNOG; KOG0660; Eukaryota.
DR GeneTree; ENSGT00940000159584; -.
DR HOGENOM; CLU_000288_181_1_1; -.
DR InParanoid; O15264; -.
DR OMA; PFEHTLF; -.
DR PhylomeDB; O15264; -.
DR TreeFam; TF105100; -.
DR BRENDA; 2.7.11.24; 2681.
DR PathwayCommons; O15264; -.
DR Reactome; R-HSA-168638; NOD1/2 Signaling Pathway.
DR Reactome; R-HSA-171007; p38MAPK events.
DR Reactome; R-HSA-376172; DSCAM interactions.
DR Reactome; R-HSA-4420097; VEGFA-VEGFR2 Pathway.
DR SignaLink; O15264; -.
DR SIGNOR; O15264; -.
DR BioGRID-ORCS; 5603; 17 hits in 1107 CRISPR screens.
DR ChiTaRS; MAPK13; human.
DR EvolutionaryTrace; O15264; -.
DR GeneWiki; MAPK13; -.
DR GenomeRNAi; 5603; -.
DR Pharos; O15264; Tchem.
DR PRO; PR:O15264; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; O15264; protein.
DR Bgee; ENSG00000156711; Expressed in tongue squamous epithelium and 169 other tissues.
DR ExpressionAtlas; O15264; baseline and differential.
DR Genevisible; O15264; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004707; F:MAP kinase activity; IDA:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:BHF-UCL.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0072740; P:cellular response to anisomycin; IDA:UniProtKB.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IDA:UniProtKB.
DR GO; GO:0071347; P:cellular response to interleukin-1; IDA:UniProtKB.
DR GO; GO:1903936; P:cellular response to sodium arsenite; IDA:UniProtKB.
DR GO; GO:0072709; P:cellular response to sorbitol; IDA:UniProtKB.
DR GO; GO:0034644; P:cellular response to UV; IDA:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:BHF-UCL.
DR GO; GO:0050729; P:positive regulation of inflammatory response; IC:BHF-UCL.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IMP:BHF-UCL.
DR GO; GO:0006970; P:response to osmotic stress; IDA:UniProtKB.
DR GO; GO:0051403; P:stress-activated MAPK cascade; IDA:UniProtKB.
DR CDD; cd07879; STKc_p38delta; 1.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR003527; MAP_kinase_CS.
DR InterPro; IPR008352; MAPK_p38-like.
DR InterPro; IPR038785; p38delta.
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; Kinase;
KW Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Stress response; Transcription;
KW Transcription regulation; Transferase.
FT CHAIN 1..365
FT /note="Mitogen-activated protein kinase 13"
FT /id="PRO_0000186286"
FT DOMAIN 25..308
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOTIF 180..182
FT /note="TXY"
FT ACT_SITE 150
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 31..39
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 54
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 47
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18088087"
FT MOD_RES 180
FT /note="Phosphothreonine; by MAP2K3, MAP2K4, MAP2K6 and
FT MAP2K7"
FT /evidence="ECO:0000269|PubMed:9374491"
FT MOD_RES 182
FT /note="Phosphotyrosine; by MAP2K3, MAP2K4, MAP2K6 and
FT MAP2K7"
FT /evidence="ECO:0000269|PubMed:9374491"
FT MOD_RES 350
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19369195"
FT VAR_SEQ 204..256
FT /note="VDIWSVGCIMAEMLTGKTLFKGKDYLDQLTQILKVTGVPGTEFVQKLNDKAA
FT K -> GQILHPVPATDPQEGFHSAVPTGQPPGCGPAGEDAGARRGQAPDGRAGPHPSL
FT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_056558"
FT VAR_SEQ 257..364
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_056559"
FT VARIANT 41
FT /note="S -> L (in dbSNP:rs55776345)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042267"
FT VARIANT 282
FT /note="A -> V (in dbSNP:rs55990045)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042268"
FT VARIANT 300
FT /note="A -> T (in dbSNP:rs41270090)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_042269"
FT MUTAGEN 180
FT /note="T->A: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:9374491"
FT MUTAGEN 182
FT /note="Y->A: Loss of kinase activity."
FT /evidence="ECO:0000269|PubMed:9374491"
FT CONFLICT 13..14
FT /note="DV -> EL (in Ref. 4; AAC51374)"
FT /evidence="ECO:0000305"
FT CONFLICT 39
FT /note="V -> W (in Ref. 4; AAC51374)"
FT /evidence="ECO:0000305"
FT CONFLICT 56
FT /note="L -> P (in Ref. 3; AAC51758)"
FT /evidence="ECO:0000305"
FT CONFLICT 166
FT /note="I -> V (in Ref. 3; AAC51758)"
FT /evidence="ECO:0000305"
FT CONFLICT 224
FT /note="K -> R (in Ref. 3; AAC51758 and 5; AAD23377)"
FT /evidence="ECO:0000305"
FT HELIX 4..8
FT /evidence="ECO:0007829|PDB:3COI"
FT STRAND 9..14
FT /evidence="ECO:0007829|PDB:4YNO"
FT STRAND 17..22
FT /evidence="ECO:0007829|PDB:4YNO"
FT STRAND 25..33
FT /evidence="ECO:0007829|PDB:4YNO"
FT STRAND 35..44
FT /evidence="ECO:0007829|PDB:4YNO"
FT TURN 45..47
FT /evidence="ECO:0007829|PDB:4YNO"
FT STRAND 50..56
FT /evidence="ECO:0007829|PDB:4YNO"
FT HELIX 63..78
FT /evidence="ECO:0007829|PDB:4YNO"
FT STRAND 88..91
FT /evidence="ECO:0007829|PDB:4YNO"
FT STRAND 95..97
FT /evidence="ECO:0007829|PDB:4YNO"
FT STRAND 104..108
FT /evidence="ECO:0007829|PDB:4YNO"
FT STRAND 111..113
FT /evidence="ECO:0007829|PDB:3COI"
FT HELIX 114..117
FT /evidence="ECO:0007829|PDB:4YNO"
FT HELIX 124..143
FT /evidence="ECO:0007829|PDB:4YNO"
FT HELIX 153..155
FT /evidence="ECO:0007829|PDB:4YNO"
FT STRAND 156..158
FT /evidence="ECO:0007829|PDB:4YNO"
FT STRAND 164..166
FT /evidence="ECO:0007829|PDB:4YNO"
FT HELIX 186..188
FT /evidence="ECO:0007829|PDB:4MYG"
FT HELIX 191..195
FT /evidence="ECO:0007829|PDB:4YNO"
FT TURN 196..198
FT /evidence="ECO:0007829|PDB:4MYG"
FT HELIX 204..218
FT /evidence="ECO:0007829|PDB:4YNO"
FT STRAND 222..226
FT /evidence="ECO:0007829|PDB:3COI"
FT HELIX 228..239
FT /evidence="ECO:0007829|PDB:4YNO"
FT HELIX 244..247
FT /evidence="ECO:0007829|PDB:4YNO"
FT HELIX 253..261
FT /evidence="ECO:0007829|PDB:4YNO"
FT HELIX 270..273
FT /evidence="ECO:0007829|PDB:4YNO"
FT HELIX 279..288
FT /evidence="ECO:0007829|PDB:4YNO"
FT TURN 293..295
FT /evidence="ECO:0007829|PDB:4YNO"
FT HELIX 299..303
FT /evidence="ECO:0007829|PDB:4YNO"
FT HELIX 306..308
FT /evidence="ECO:0007829|PDB:4YNO"
FT TURN 309..311
FT /evidence="ECO:0007829|PDB:4YNO"
FT HELIX 314..316
FT /evidence="ECO:0007829|PDB:4YNO"
FT HELIX 327..329
FT /evidence="ECO:0007829|PDB:4YNO"
FT HELIX 335..347
FT /evidence="ECO:0007829|PDB:4YNO"
SQ SEQUENCE 365 AA; 42090 MW; 52E749EDB2973DDF CRC64;
MSLIRKKGFY KQDVNKTAWE LPKTYVSPTH VGSGAYGSVC SAIDKRSGEK VAIKKLSRPF
QSEIFAKRAY RELLLLKHMQ HENVIGLLDV FTPASSLRNF YDFYLVMPFM QTDLQKIMGM
EFSEEKIQYL VYQMLKGLKY IHSAGVVHRD LKPGNLAVNE DCELKILDFG LARHADAEMT
GYVVTRWYRA PEVILSWMHY NQTVDIWSVG CIMAEMLTGK TLFKGKDYLD QLTQILKVTG
VPGTEFVQKL NDKAAKSYIQ SLPQTPRKDF TQLFPRASPQ AADLLEKMLE LDVDKRLTAA
QALTHPFFEP FRDPEEETEA QQPFDDSLEH EKLTVDEWKQ HIYKEIVNFS PIARKDSRRR
SGMKL
