MAPKAPK5 - MAP kinase-activated protein kinase 5 - human protein (Function)
 
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MAPKAPK5 »  MAP kinase-activated protein kinase 5   [ EC 2.7.11.1 ]  (MK5)
 
Protein also known as:  p38-regulated/activated protein kinase (PRAK).
Gene name:  MAPKAPK5
Entry whose protein(s) existence is based on evidence at protein level
extend overview
1 35 2
GENE REF ISO

Function

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Overview 
Tumor suppressor serine/threonine-protein kinase involved in mTORC1 signaling and post-transcriptional regulation. Phosphorylates FOXO3, ERK3/MAPK6, ERK4/MAPK4, HSP27/HSPB1, p53/TP53 and RHEB. Acts as a tumor suppressor by mediating Ras-induced senescence and phosphorylating p53/TP53. Involved in post-transcriptional regulation of MYC by mediating phosphorylation of FOXO3: phosphorylation of FOXO3 leads to promote nuclear localization of FOXO3, enabling expression of miR-34b and miR-34c, 2 post-transcriptional regulators of MYC that bind to the 3'UTR of MYC transcript and prevent MYC translation. Acts as a negative regulator of mTORC1 signaling by mediating phosphorylation and inhibition of RHEB. Part of the atypical MAPK signaling via its interaction with ERK3/MAPK6 or ERK4/MAPK4: the precise role of the complex formed with ERK3/MAPK6 or ERK4/MAPK4 is still unclear, but the complex follows a complex set of phosphorylation events: upon interaction with atypical MAPK (ERK3/MAPK6 or ERK4/MAPK4), ERK3/MAPK6 (or ERK4/MAPK4) is phosphorylated and then mediates phosphorylation and activation of MAPKAPK5, which in turn phosphorylates ERK3/MAPK6 (or ERK4/MAPK4). Mediates phosphorylation of HSP27/HSPB1 in response to PKA/PRKACA stimulation, inducing F-actin rearrangement.  
5
  • CuratedUniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
  • IEAUniProtKB KW
MAP kinase kinase activitydefinition[GO:0004708]  
1
  • TASPINC
Mitogen-activated protein kinase bindingdefinition[GO:0051019] silver  
  • IEAOrtholog Compara
P53 bindingdefinition[GO:0002039]  
1
  • IDAUniProtKB
Protein bindingdefinition[GO:0005515]  
6
  • IPIIntAct
  • IPIUniProtKB
Protein serine/threonine kinase activitydefinition[GO:0004674]  
2
  • IDAUniProtKB
GO biological process 
Activation of MAPK activitydefinition[GO:0000187]  
1
  • TASGOC
MAPK cascadedefinition[GO:0000165]  
1
  • TASGOC
Negative regulation of TOR signalingdefinition[GO:0032007]  
  • ISSOrtholog Curator
Protein autophosphorylationdefinition[GO:0046777]  
1
  • IDAUniProtKB
Ras protein signal transductiondefinition[GO:0007265]  
1
  • IDAUniProtKB
Regulation of translationdefinition[GO:0006417]  
1
  • IDAUniProtKB
Signal transductiondefinition[GO:0007165]  
1
  • TASPINC
Stress-induced premature senescencedefinition[GO:0090400]  
1
  • IDAUniProtKB
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.  
  • CuratedUniProtKB
It is regulated in the following manner
Activated following phosphorylation at Thr-182 by p38-alpha/MAPK14, p38-beta/MAPK11, ERK2/MAPK1, ERK3/MAPK6, and ERK4/MAPK4. Activated by stress-related extracellular stimuli; such as H(2)O(2), arsenite, anisomycin TNF alpha and also PMA and the calcium ionophore A23187; but to a lesser extent. In vitro, activated by SQSTM1. Inhibited by diterpenoid alkaloid noroxoaconitine.  
2
  • CuratedUniProtKB
Pathways 
According to KEGG, this protein belongs to the following pathway:
MAPK signaling pathway  hsa04010+8550  
According to Reactome, this protein belongs to the following pathway:
Cellular responses to stress  REACT_120956  
Caution 
The role of p38 MAPK kinases is unclear in phosphorylation and activation of MAPKAPK5. According to some reports, it interacts and is phosphorylated by p38-alpha/MAPK14 and p38-beta/MAPK11 (PubMed9628874 and PubMed12808055). According to other reports, it is not activated by p38-alpha/MAPK14 and p38-beta/MAPK11. An explanation for these discrepancies, might be that the interaction with p38 MAPK kinases is weak and occurs only under specific conditions.  
2
  • CuratedUniProtKB
 

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: MAPKAPK5
GenomeRNAi: 8550
PRO: PR:Q8IW41
Chemistry
GuidetoPHARMACOLOGY: 2096