MK13_MOUSE
ID MK13_MOUSE Reviewed; 366 AA.
AC Q9Z1B7; Q99M57;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 12-FEB-2003, sequence version 2.
DT 03-AUG-2022, entry version 177.
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=Serk4;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Jiang Y., Han J.;
RL Submitted (DEC-1996) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Mammary gland;
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 [3]
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 [4]
RP FUNCTION IN PHOSPHORYLATION OF PRKD1.
RX PubMed=19135240; DOI=10.1016/j.cell.2008.11.018;
RA Sumara G., Formentini I., Collins S., Sumara I., Windak R., Bodenmiller B.,
RA Ramracheya R., Caille D., Jiang H., Platt K.A., Meda P., Aebersold R.,
RA Rorsman P., Ricci R.;
RT "Regulation of PKD by the MAPK p38delta in insulin secretion and glucose
RT homeostasis.";
RL Cell 136:235-248(2009).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-182, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Lung;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP FUNCTION.
RX PubMed=21558321; DOI=10.1093/carcin/bgr079;
RA Cerezo-Guisado M.I., del Reino P., Remy G., Kuma Y., Arthur J.S.,
RA Gallego-Ortega D., Cuenda A.;
RT "Evidence of p38gamma and p38delta involvement in cell transformation
RT processes.";
RL Carcinogenesis 32:1093-1099(2011).
RN [7]
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 [8]
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).
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:19135240, ECO:0000269|PubMed:21558321}.
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 -!- SUBUNIT: Interacts with MAPK8IP2. {ECO:0000269|PubMed:11378392}.
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 (By similarity).
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC protein kinase family. MAP kinase subfamily. {ECO:0000305}.
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DR EMBL; U81823; AAD09229.1; -; mRNA.
DR EMBL; BC001992; AAH01992.1; -; mRNA.
DR CCDS; CCDS28584.1; -.
DR RefSeq; NP_036080.2; NM_011950.2.
DR AlphaFoldDB; Q9Z1B7; -.
DR SMR; Q9Z1B7; -.
DR BioGRID; 204968; 84.
DR STRING; 10090.ENSMUSP00000004986; -.
DR BindingDB; Q9Z1B7; -.
DR ChEMBL; CHEMBL2111473; -.
DR iPTMnet; Q9Z1B7; -.
DR PhosphoSitePlus; Q9Z1B7; -.
DR MaxQB; Q9Z1B7; -.
DR PaxDb; Q9Z1B7; -.
DR PRIDE; Q9Z1B7; -.
DR ProteomicsDB; 295675; -.
DR Antibodypedia; 2088; 910 antibodies from 39 providers.
DR DNASU; 26415; -.
DR Ensembl; ENSMUST00000233984; ENSMUSP00000156387; ENSMUSG00000004864.
DR GeneID; 26415; -.
DR KEGG; mmu:26415; -.
DR UCSC; uc008bro.2; mouse.
DR CTD; 5603; -.
DR MGI; MGI:1346864; Mapk13.
DR VEuPathDB; HostDB:ENSMUSG00000004864; -.
DR eggNOG; KOG0660; Eukaryota.
DR GeneTree; ENSGT00940000159584; -.
DR HOGENOM; CLU_000288_181_1_1; -.
DR InParanoid; Q9Z1B7; -.
DR OMA; PFEHTLF; -.
DR OrthoDB; 683132at2759; -.
DR PhylomeDB; Q9Z1B7; -.
DR TreeFam; TF105100; -.
DR Reactome; R-MMU-168638; NOD1/2 Signaling Pathway.
DR Reactome; R-MMU-376172; DSCAM interactions.
DR Reactome; R-MMU-4420097; VEGFA-VEGFR2 Pathway.
DR BioGRID-ORCS; 26415; 4 hits in 73 CRISPR screens.
DR ChiTaRS; Mapk13; mouse.
DR PRO; PR:Q9Z1B7; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; Q9Z1B7; protein.
DR Bgee; ENSMUSG00000004864; Expressed in granulocyte and 180 other tissues.
DR ExpressionAtlas; Q9Z1B7; baseline and differential.
DR Genevisible; Q9Z1B7; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; ISO:MGI.
DR GO; GO:0004707; F:MAP kinase activity; ISS:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISO:MGI.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0072740; P:cellular response to anisomycin; ISO:MGI.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; ISO:MGI.
DR GO; GO:0071347; P:cellular response to interleukin-1; ISO:MGI.
DR GO; GO:1903936; P:cellular response to sodium arsenite; ISO:MGI.
DR GO; GO:0072709; P:cellular response to sorbitol; ISO:MGI.
DR GO; GO:0034644; P:cellular response to UV; ISO:MGI.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; ISO:MGI.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; ISO:MGI.
DR GO; GO:0006468; P:protein phosphorylation; ISO:MGI.
DR GO; GO:0006970; P:response to osmotic stress; ISO:MGI.
DR GO; GO:0051403; P:stress-activated MAPK cascade; ISS: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 ATP-binding; Cell cycle; Kinase; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Stress response;
KW Transcription; Transcription regulation; Transferase.
FT CHAIN 1..366
FT /note="Mitogen-activated protein kinase 13"
FT /id="PRO_0000186287"
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 180
FT /note="Phosphothreonine; by MAP2K3, MAP2K4, MAP2K6 and
FT MAP2K7"
FT /evidence="ECO:0000250|UniProtKB:O15264"
FT MOD_RES 182
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 350
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O15264"
FT CONFLICT 45
FT /note="K -> R (in Ref. 1; AAD09229)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 366 AA; 42072 MW; 45D23D7BD404B3FE CRC64;
MSLTRKRGFY KQDINKTAWE LPKTYLAPAH VGSGAYGAVC SAIDKRTGEK VAIKKLSRPF
QSEIFAKRAY RELLLLKHMH HENVIGLLDV FTPASSLRSF HDFYLVMPFM QTDLQKIMGM
EFSEDKVQYL VYQMLKGLKY IHSAGIVHRD LKPGNLAVNE DCELKILDFG LARHTDTEMT
GYVVTRWYRA PEVILSWMHY NQTVDIWSVG CIMAEMLTGK TLFKGKDYLD QLTQILKVTG
VPGAEFVQKL KDKAAKSYIQ SLPQSPKKDF TQLFPRASPQ AADLLDKMLE LDVDKRLTAA
QALAHPFFEP FRDPEEETEA QQPFDDALEH EKLSVDEWKQ HIYKEISNFS PIARKDSRRR
SGMKLQ
