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MGP003844

UniProt Annotations

Entry Information

Gene Name	mitogen-activated protein kinase-activated protein kinase 2
Protein Entry	MAPK2_HUMAN
UniProt ID	P49137
Species	Human

Comments

Comment type	Description
Alternative Products	Event=Alternative splicing; Named isoforms=2; Name=1; IsoId=P49137-1; Sequence=Displayed; Note=Has a nuclear localization signal.; Name=2; IsoId=P49137-2; Sequence=VSP_004910;
Catalytic Activity	ATP + a protein = ADP + a phosphoprotein. {ECO:0000269\|PubMed:12171911, ECO:0000269\|PubMed:8774846}.
Enzyme Regulation	Activated following phosphorylation by p38- alpha/MAPK14 following various stresses. Inhibited following sumoylation. Specifically inhibited by pyrrolopyridine inhibitors.
Function	Stress-activated serine/threonine-protein kinase involved in cytokines production, endocytosis, reorganization of the cytoskeleton, cell migration, cell cycle control, chromatin remodeling, DNA damage response and transcriptional regulation. Following stress, it is phosphorylated and activated by MAP kinase p38-alpha/MAPK14, leading to phosphorylation of substrates. Phosphorylates serine in the peptide sequence, Hyd-X-R-X(2)-S, where Hyd is a large hydrophobic residue. Phosphorylates ALOX5, CDC25B, CDC25C, ELAVL1, HNRNPA0, HSF1, HSP27/HSPB1, KRT18, KRT20, LIMK1, LSP1, PABPC1, PARN, PDE4A, RCSD1, RPS6KA3, TAB3 and TTP/ZFP36. Mediates phosphorylation of HSP27/HSPB1 in response to stress, leading to dissociate HSP27/HSPB1 from large small heat- shock protein (sHsps) oligomers and impair their chaperone activities and ability to protect against oxidative stress effectively. Involved in inflammatory response by regulating tumor necrosis factor (TNF) and IL6 production post-transcriptionally: acts by phosphorylating AU-rich elements (AREs)-binding proteins ELAVL1, HNRNPA0, PABPC1 and TTP/ZFP36, leading to regulate the stability and translation of TNF and IL6 mRNAs. Phosphorylation of TTP/ZFP36, a major post-transcriptional regulator of TNF, promotes its binding to 14-3-3 proteins and reduces its ARE mRNA affinity leading to inhibition of dependent degradation of ARE-containing transcript. Also involved in late G2/M checkpoint following DNA damage through a process of post-transcriptional mRNA stabilization: following DNA damage, relocalizes from nucleus to cytoplasm and phosphorylates HNRNPA0 and PARN, leading to stabilize GADD45A mRNA. Involved in toll-like receptor signaling pathway (TLR) in dendritic cells: required for acute TLR-induced macropinocytosis by phosphorylating and activating RPS6KA3. {ECO:0000269\|PubMed:10383393, ECO:0000269\|PubMed:11844797, ECO:0000269\|PubMed:12456657, ECO:0000269\|PubMed:12565831, ECO:0000269\|PubMed:14499342, ECO:0000269\|PubMed:14517288, ECO:0000269\|PubMed:15014438, ECO:0000269\|PubMed:15629715, ECO:0000269\|PubMed:16278218, ECO:0000269\|PubMed:16456544, ECO:0000269\|PubMed:17481585, ECO:0000269\|PubMed:18021073, ECO:0000269\|PubMed:20932473, ECO:0000269\|PubMed:8093612, ECO:0000269\|PubMed:8280084, ECO:0000269\|PubMed:8774846}.
Interaction	Q00613:HSF1; NbExp=5; IntAct=EBI-993299, EBI-719620; P04792:HSPB1; NbExp=3; IntAct=EBI-993299, EBI-352682; Q16539:MAPK14; NbExp=5; IntAct=EBI-993299, EBI-73946; Q9QWH1:Phc2 (xeno); NbExp=2; IntAct=EBI-993299, EBI-642357;
Ptm	Phosphorylated and activated by MAP kinase p38-alpha/MAPK14 at Thr-222, Ser-272 and Thr-334. {ECO:0000269\|PubMed:8846784}.
Ptm	Sumoylation inhibits the protein kinase activity. {ECO:0000269\|PubMed:21131586}.
Similarity	Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. {ECO:0000305}.
Similarity	Contains 1 protein kinase domain. {ECO:0000255\|PROSITE-ProRule:PRU00159}.
Subcellular Location	Cytoplasm {ECO:0000269\|PubMed:20932473}. Nucleus {ECO:0000269\|PubMed:20932473}. Note=Phosphorylation and subsequent activation releases the autoinhibitory helix, resulting in the export from the nucleus into the cytoplasm.
Subunit	Heterodimer with p38-alpha/MAPK14. The heterodimer with p38-alpha/MAPK14 forms a stable complex: molecules are positioned 'face to face' so that the ATP-binding sites of both kinases are at the heterodimer interface. Interacts with PHC2. {ECO:0000269\|PubMed:12171911, ECO:0000269\|PubMed:15094067, ECO:0000269\|PubMed:17255097, ECO:0000269\|PubMed:17395714, ECO:0000269\|PubMed:17449059, ECO:0000269\|PubMed:17480064, ECO:0000269\|PubMed:17576063}.
Tissue Specificity	Expressed in all tissues examined.
Web Resource	Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/MAPKAPK2ID41295ch1q32.html";