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MGP002442

UniProt Annotations

Entry Information

Gene Name	mitogen-activated protein kinase 13
Protein Entry	MK13_HUMAN
UniProt ID	O15264
Species	Human

Comments

Comment type	Description
Alternative Products	Event=Alternative splicing; Named isoforms=2; Name=1; IsoId=O15264-1; Sequence=Displayed; Name=2; IsoId=O15264-2; Sequence=VSP_056558, VSP_056559; Note=No experimental confirmation available.;
Catalytic Activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
Domain	The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.
Enzyme Regulation	Activated by phosphorylation on threonine and tyrosine by dual specificity kinases, MAP2K3/MKK3, MAP2K6/MKK6, MAP2K4/MKK4 and MAP2K7/MKK7. Activation by ultraviolet radiation, hyperosmotic shock, anisomycin or by TNF-alpha is mediated by MAP2K3/MKK3. Inhibited by dual specificity phosphatase DUSP1. {ECO:0000269\|PubMed:11500363, ECO:0000269\|PubMed:9218798, ECO:0000269\|PubMed:9374491}.
Function	Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. MAPK13 is one of the four p38 MAPKs which play an important role in the cascades of cellular responses evoked by extracellular stimuli such as proinflammatory cytokines or physical stress leading to direct activation of transcription factors such as ELK1 and ATF2. Accordingly, p38 MAPKs phosphorylate a broad range of proteins and it has been estimated that they may have approximately 200 to 300 substrates each. MAPK13 is one of the less studied p38 MAPK isoforms. Some of the targets are downstream kinases such as MAPKAPK2, which are activated through phosphorylation and further phosphorylate additional targets. Plays a role in the regulation of protein translation by phosphorylating and inactivating EEF2K. Involved in cytoskeletal remodeling through phosphorylation of MAPT and STMN1. Mediates UV irradiation induced up-regulation of the gene expression of CXCL14. Plays an important role in the regulation of epidermal keratinocyte differentiation, apoptosis and skin tumor development. Phosphorylates the transcriptional activator MYB in response to stress which leads to rapid MYB degradation via a proteasome-dependent pathway. MAPK13 also phosphorylates and down-regulates PRKD1 during regulation of insulin secretion in pancreatic beta cells. {ECO:0000269\|PubMed:11500363, ECO:0000269\|PubMed:11943212, ECO:0000269\|PubMed:15632108, ECO:0000269\|PubMed:17256148, ECO:0000269\|PubMed:18006338, ECO:0000269\|PubMed:18367666, ECO:0000269\|PubMed:20478268, ECO:0000269\|PubMed:9731215}.
Interaction	P21462:FPR1; NbExp=3; IntAct=EBI-2116951, EBI-2869495; Q15139:PRKD1; NbExp=6; IntAct=EBI-2116951, EBI-1181072;
Ptm	Dually phosphorylated on Thr-180 and Tyr-182 by MAP2K3/MKK3, MAP2K4/MKK4, MAP2K6/MKK6 and MAP2K7/MKK7, which activates the enzyme. Dephosphorylated by dual specificity phosphatase DUSP1. {ECO:0000269\|PubMed:18088087, ECO:0000269\|PubMed:19369195, ECO:0000269\|PubMed:9374491}.
Similarity	Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily. {ECO:0000305}.
Similarity	Contains 1 protein kinase domain. {ECO:0000255\|PROSITE-ProRule:PRU00159}.
Subunit	Interacts with MAPK8IP2. {ECO:0000269\|PubMed:11378392}.
Tissue Specificity	Expressed in testes, pancreas, small intestine, lung and kidney. Abundant in macrophages, also present in neutrophils, CD4+ T-cells, and endothelial cells. {ECO:0000269\|PubMed:10201954, ECO:0000269\|PubMed:9374491}.
Web Resource	Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/MAPK13ID41291ch6p21.html";