MAP3K8 - Mitogen-activated protein kinase kinase kinase 8 - human protein (Function)
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MAP3K8 »  Mitogen-activated protein kinase kinase kinase 8   [ EC ]
Protein also known as:  Serine/threonine-protein kinase cot.
Gene name:  MAP3K8
Entry whose protein(s) existence is based on evidence at protein level
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Required for lipopolysaccharide (LPS)-induced, TLR4-mediated activation of the MAPK/ERK pathway in macrophages, thus being critical for production of the proinflammatory cytokine TNF-alpha (TNF) during immune responses. Involved in the regulation of T-helper cell differentiation and IFNG expression in T-cells. Involved in mediating host resistance to bacterial infection through negative regulation of type I interferon (IFN) production. In vitro, activates MAPK/ERK pathway in response to IL1 in an IRAK1-independent manner, leading to up-regulation of IL8 and CCL4. Transduces CD40 and TNFRSF1A signals that activate ERK in B-cells and macrophages, and thus may play a role in the regulation of immunoglobulin production. May also play a role in the transduction of TNF signals that activate JNK and NF-kappa-B in some cell types. In adipocytes, activates MAPK/ERK pathway in an IKBKB-dependent manner in response to IL1B and TNF, but not insulin, leading to induction of lipolysis. Plays a role in the cell cycle.  
  • CuratedUniProtKB
Isoform  Iso 1   Shows some transforming activity, although it is much weaker than that of the activated oncogenic variant.  
  • CuratedUniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
  • IEAUniProtKB KW
Magnesium ion bindingdefinition[GO:0000287] silver  
  • IEAInterPro 2 GO
MAP kinase kinase kinase activitydefinition[GO:0004709]  
  • IEAEC 2 GO
Protein bindingdefinition[GO:0005515]  
  • IPIIntAct
Protein serine/threonine kinase activitydefinition[GO:0004674]  
GO biological process 
Activation of MAPKK activitydefinition[GO:0000186]  
  • IBARefGenome
  • IEAInterPro 2 GO
  • IEAEC 2 GO
Cell cycledefinition[GO:0007049]  
  • IEAUniProtKB KW
MAPK cascadedefinition[GO:0000165]  
  • IEAEC 2 GO
  • IBARefGenome
  • IEAInterPro 2 GO
Protein phosphorylationdefinition[GO:0006468] silver  
  • IEAInterPro 2 GO
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reaction
EC ATP + a protein ADP + a phosphoprotein.  
  • CuratedUniProtKB
It requires the following cofactor
  • CuratedUniProtKB
According to KEGG, this protein belongs to the following pathways:
MAPK signaling pathway  hsa04010+1326  
T cell receptor signaling pathway  hsa04660+1326  
Toll-like receptor signaling pathway  hsa04620+1326  
According to Reactome, this protein belongs to the following pathways:
CD28 dependent PI3K/Akt signaling  REACT_19358  
Interleukin-1 signaling  REACT_22442  
Can be converted to an oncogenic protein by proviral activation, leading to a C-terminally truncated protein with transforming activity.  
  • CuratedUniProtKB


Biological process 
Cell cycle  definition   [KW-0131]
Immunity  definition   [KW-0391]
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

GeneWiki: MAP3K8
GenomeRNAi: 1326
PRO: PR:P41279