MAP3K8 | Mitogen-activated protein kinase kinase kinase 8
 
image/svg+xmlExtracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion None Substrate Localization legend

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Sequence Viewer
Gene
Synonyms
COT ESTF
Protein Name
Mitogen-activated protein kinase kinase kinase 8
UniProt ID
P41279 [go to UniProt ] [go to PDBe-KB ]
Ensembl Gene ID
NCBI Gene ID
Molecular Weight
52925
Protein Length
467
Protein Domain
3D Structure
(PDB ID : 5iu2)
Target by Small Molecules
Protein-protein Interaction Database
Gene Expression
Drugs and Diseases
Enzyme Class
2.7.11.25; (BRENDA)
Catalytic Site
Catalytic Activity
ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein]ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein]
Localization
Cytoplasm;
Function
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. Isoform 1 shows some transforming activity, although it is much weaker than that of the activated oncogenic variant.
Gene Ontology
GO:0005737; GO:0005829; GO:0005524; GO:0000287; GO:0004709; GO:0004674; GO:0032147; GO:0007049; GO:0070498; GO:0006468; GO:0023014; GO:0051403; GO:0031098; GO:0031295