MGP Database

New search | Record Overview | Ontology/Pathway Information | Domain Information | UniProt Annotations | Related Proteins
MGP003423

UniProt Annotations

Entry Information
Gene Namemitogen-activated protein kinase-activated protein kinase 3
Protein EntryMAPK3_HUMAN
UniProt IDQ16644
SpeciesHuman
Comments
Comment typeDescription
Catalytic ActivityATP + a protein = ADP + a phosphoprotein. {ECO:0000269|PubMed:8774846}.
Enzyme RegulationActivated following phosphorylation by p38- alpha/MAPK14 following various stresses. Inhibited by ligand 5B (2'-[2-(1,3-benzodioxol-5-yl)pyrimidin-4-yl]-5',6'- dihydrospiro[piperidine-4,7'-pyrrolo[3,2-c]pyridin]- 4'(1'h)-one) and ligand P4O (2-[2-(2-fluorophenyl)pyridin-4-yl]-1,5,6,7- tetrahydro- 4h-pyrrolo[3,2-c]pyridin-4-one), 2 ATP-competitive inhibitors.
FunctionStress-activated serine/threonine-protein kinase involved in cytokines production, endocytosis, cell migration, chromatin remodeling 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. MAPKAPK2 and MAPKAPK3, share the same function and substrate specificity, but MAPKAPK3 kinase activity and level in protein expression are lower compared to MAPKAPK2. Phosphorylates HSP27/HSPB1, KRT18, KRT20, 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, such as 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. Involved in toll-like receptor signaling pathway (TLR) in dendritic cells: required for acute TLR-induced macropinocytosis by phosphorylating and activating RPS6KA3. Also acts as a modulator of Polycomb-mediated repression. {ECO:0000269|PubMed:10383393, ECO:0000269|PubMed:15563468, ECO:0000269|PubMed:18021073, ECO:0000269|PubMed:20599781, ECO:0000269|PubMed:8626550, ECO:0000269|PubMed:8774846}.
InteractionP27958:- (xeno); NbExp=5; IntAct=EBI-1384657, EBI-6377335; P04792:HSPB1; NbExp=3; IntAct=EBI-1384657, EBI-352682; Q16539:MAPK14; NbExp=3; IntAct=EBI-1384657, EBI-73946;
PtmPhosphorylated and activated by MAPK1/ERK2 and MAPK3/ERK1. Phosphorylated and activated by MAP kinase p38-alpha/MAPK14 at Thr-201, Ser-251 and Thr-313 (By similarity). {ECO:0000250}.
SimilarityBelongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. {ECO:0000305}.
SimilarityContains 1 protein kinase domain. {ECO:0000255|PROSITE-ProRule:PRU00159}.
Subcellular LocationNucleus {ECO:0000269|PubMed:15302577}. Cytoplasm {ECO:0000269|PubMed:15302577}. Note=Predominantly located in the nucleus, when activated it translocates to the cytoplasm.
SubunitHeterodimer 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 (By similarity). Interacts with TCF3 and with polycomb proteins, such as PCH2 and BMI1/PCGF4. {ECO:0000250, ECO:0000269|PubMed:10781029, ECO:0000269|PubMed:15563468, ECO:0000269|PubMed:19937655, ECO:0000269|PubMed:21565500}.
Tissue SpecificityWidely expressed, with a higher expression level observed in heart and skeletal muscle. No expression in brain. {ECO:0000269|PubMed:8622688, ECO:0000269|PubMed:8626550}.
  logo