MAPKAPK2 - MAP kinase-activated protein kinase 2 - human protein (Function)
 
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MAPKAPK2 »  MAP kinase-activated protein kinase 2   [ EC 2.7.11.1 ]  (MK2)
 
Gene name:  MAPKAPK2
Entry whose protein(s) existence is based on evidence at protein level
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1 120 2
GENE REF ISO

Function

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Overview 
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.  
16
  • CuratedUniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
  • IEAUniProtKB KW
Protein bindingdefinition[GO:0005515]  
11
  • IPIIntAct
  • IPIUniProtKB
Protein kinase activitydefinition[GO:0004672]  
1
  • TASPINC
Protein serine/threonine kinase activitydefinition[GO:0004674]  
6
  • IDAUniProtKB
  • IDABHF-UCL
Signal transducer activitydefinition[GO:0004871]  
1
  • TASPINC
GO biological process 
3'-UTR-mediated mRNA stabilizationdefinition[GO:0070935]  
3
  • IDAUniProtKB
Cellular response to DNA damage stimulusdefinition[GO:0006974]  
1
  • IMPUniProtKB
Cellular response to vascular endothelial growth factor stimulusdefinition[GO:0035924]  
1
  • IMPBHF-UCL
G2 DNA damage checkpointdefinition[GO:0031572]  
1
  • IMPUniProtKB
Inflammatory responsedefinition[GO:0006954]  
  • ISSOrtholog Curator
Inner ear developmentdefinition[GO:0048839] silver  
  • IEAOrtholog Compara
Macropinocytosisdefinition[GO:0044351]  
  • ISSOrtholog Curator
MAPK cascadedefinition[GO:0000165]  
1
  • TASPINC
Peptidyl-serine phosphorylationdefinition[GO:0018105]  
1
  • IDABHF-UCL
Protein phosphorylationdefinition[GO:0006468]  
1
  • TASPINC
Regulation of interleukin-6 productiondefinition[GO:0032675]  
  • ISSOrtholog Curator
Regulation of tumor necrosis factor productiondefinition[GO:0032680]  
1
  • IDAUniProtKB
Response to cytokinedefinition[GO:0034097]  
1
  • IDAUniProtKB
Response to lipopolysaccharidedefinition[GO:0032496]  
  • ISSOrtholog Curator
Response to stressdefinition[GO:0006950]  
1
  • IDAUniProtKB
Toll-like receptor signaling pathwaydefinition[GO:0002224]  
  • ISSOrtholog Curator
Vascular endothelial growth factor receptor signaling pathwaydefinition[GO:0048010]  
1
  • IMPBHF-UCL
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.  
2
  • CuratedUniProtKB
It is regulated in the following manner
Activated following phosphorylation by p38-alpha/MAPK14 following various stresses. Inhibited following sumoylation. Specifically inhibited by pyrrolopyridine inhibitors.  
  • CuratedUniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
MAPK signaling pathway  hsa04010+9261  
Neurotrophin signaling pathway  hsa04722+9261  
VEGF signaling pathway  hsa04370+9261  
According to Reactome, this protein belongs to the following pathways:
activated TAK1 mediates p38 MAPK activation  REACT_21399  
Butyrate Response Factor 1 (BRF1) destabilizes mRNA  REACT_24915  
CREB phosphorylation  REACT_12524  
Oxidative Stress Induced Senescence  REACT_169436  
p38MAPK events  REACT_12065  
Regulation of HSF1-mediated heat shock response  REACT_200780  
Synthesis of Leukotrienes (LT) and Eoxins (EX)  REACT_150420  
Tristetraprolin (TTP) destabilizes mRNA  REACT_25064  
 
More information is available from:
 

Keywords

Biological process 
DNA damage  definition   [KW-0227]
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: MAPKAPK2
GenomeRNAi: 9261
PRO: PR:P49137
Chemistry
GuidetoPHARMACOLOGY: 2094