MAPKAPK3 - MAP kinase-activated protein kinase 3 - human protein (Function)
 
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MAPKAPK3 »  MAP kinase-activated protein kinase 3   [ EC 2.7.11.1 ]  (MK-3)
 
Protein also known as:  Chromosome 3p kinase (3pK).
Gene name:  MAPKAPK3
Entry whose protein(s) existence is based on evidence at protein level
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GENE REF ISO

Function

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Overview 
Stress-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.  
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  • CuratedUniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
  • IEAUniProtKB KW
MAP kinase kinase activitydefinition[GO:0004708]  
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  • TASPINC
Protein bindingdefinition[GO:0005515]  
3
  • IPIIntAct
  • IPIUniProtKB
Protein serine/threonine kinase activitydefinition[GO:0004674]  
2
  • IDABHF-UCL
  • IDAUniProtKB
GO biological process 
Macropinocytosisdefinition[GO:0044351]  
  • ISSOrtholog Curator
Peptidyl-serine phosphorylationdefinition[GO:0018105]  
1
  • IDABHF-UCL
Response to cytokinedefinition[GO:0034097]  
1
  • IDAUniProtKB
Response to lipopolysaccharidedefinition[GO:0032496]  
  • ISSOrtholog Curator
Response to stressdefinition[GO:0006950]  
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  • TASPINC
Signal transductiondefinition[GO:0007165]  
1
  • TASPINC
Toll-like receptor signaling pathwaydefinition[GO:0002224]  
  • ISSOrtholog Curator
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC 2.7.11.1: ATP + a protein ADP + a phosphoprotein.  
1
  • CuratedUniProtKB
It is regulated in the following manner
Activated 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.  
  • CuratedUniProtKB
Pathways 
According to KEGG, this protein belongs to the following pathways:
MAPK signaling pathway  hsa04010+7867  
VEGF signaling pathway  hsa04370+7867  
According to Reactome, this protein belongs to the following pathways:
activated TAK1 mediates p38 MAPK activation  REACT_21399  
Oxidative Stress Induced Senescence  REACT_169436  
p38MAPK events  REACT_12065  
 

Keywords

Molecular function 
Kinase  definition   [KW-0418]
Serine/threonine-protein kinase  definition   [KW-0723]
Transferase  definition   [KW-0808]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: MAPKAPK3
GenomeRNAi: 7867
PRO: PR:Q16644
Chemistry
GuidetoPHARMACOLOGY: 2095