MAP4K2 - Mitogen-activated protein kinase kinase kinase kinase 2 - human protein (Function)
 
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MAP4K2 »  Mitogen-activated protein kinase kinase kinase kinase 2   [ EC 2.7.11.1 ]
 
Protein also known as:  B lymphocyte serine/threonine-protein kinase.
Gene name:  MAP4K2
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 
Serine/threonine-protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Acts as a MAPK kinase kinase kinase (MAP4K) and is an upstream activator of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway and to a lesser extend of the p38 MAPKs signaling pathway. Required for the efficient activation of JNKs by TRAF6-dependent stimuli, including pathogen-associated molecular patterns (PAMPs) such as polyinosine-polycytidine (poly(IC)), lipopolysaccharides (LPS), lipid A, peptidoglycan (PGN), or bacterial flagellin. To a lesser degree, IL-1 and engagement of CD40 also stimulate MAP4K2-mediated JNKs activation. The requirement for MAP4K2/GCK is most pronounced for LPS signaling, and extends to LPS stimulation of c-Jun phosphorylation and induction of IL-8. Enhances MAP3K1 oligomerization, which may relieve N-terminal mediated MAP3K1 autoinhibition and lead to activation following autophosphorylation. Mediates also the SAP/JNK signaling pathway and the p38 MAPKs signaling pathway through activation of the MAP3Ks MAP3K10/MLK2 and MAP3K11/MLK3. May play a role in the regulation of vesicle targeting or fusion. Regulation of vesicle targeting or fusion.  
6
  • CuratedUniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
1
  • IDAUniProtKB
MAP kinase kinase kinase kinase activitydefinition[GO:0008349] silver  
  • IBARefGenome
Mitogen-activated protein kinase kinase kinase bindingdefinition[GO:0031435]  
1
  • IPIUniProtKB
Protein bindingdefinition[GO:0005515]  
1
  • IPIIntAct
Protein serine/threonine kinase activitydefinition[GO:0004674]  
1
  • IDAUniProtKB
Small GTPase regulator activitydefinition[GO:0005083] silver  
  • IEAInterPro 2 GO
GO biological process 
Activation of JUN kinase activitydefinition[GO:0007257]  
1
  • IDAUniProtKB
Activation of MAPKKK activitydefinition[GO:0000185] silver  
  • IBARefGenome
Immune responsedefinition[GO:0006955]  
1
  • TASPINC
Innate immune responsedefinition[GO:0045087]  
  • IEAUniProtKB KW
Intracellular signal transductiondefinition[GO:0035556]  
1
  • IDAUniProtKB
JNK cascadedefinition[GO:0007254]  
1
  • TASPINC
Positive regulation of JNK cascadedefinition[GO:0046330]  
1
  • IDAUniProtKB
Protein phosphorylationdefinition[GO:0006468]  
1
  • IDAUniProtKB
Vesicle targetingdefinition[GO:0006903] silver  
  • IEAOrtholog Compara
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 requires the following cofactor
Magnesium.  
1
  • CuratedUniProtKB
It is regulated in the following manner
The tumor necrosis factor (TNF), as well as endotoxins and proinflammatory stimuli such as polyinosine-polycytidine (poly(IC)), lipopolysaccharides (LPS), peptidoglycan (PGN), flagellin, or lipid A activate MAP4K2 by promoting its autophosphorylation.  
2
  • CuratedUniProtKB
Pathways 
According to KEGG, this protein belongs to the following pathway:
MAPK signaling pathway  hsa04010+5871  
 

Keywords

Biological process 
Immunity  definition   [KW-0391]
Innate immunity  definition   [KW-0399]
Stress response  definition   [KW-0346]
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: MAP4K2
GenomeRNAi: 5871
PRO: PR:Q12851
Chemistry
GuidetoPHARMACOLOGY: 2086