Gene content    
MAP3K8 ( by HUGO)
Mitogen-Activated Protein Kinase Kinase Kinase 8
Oncogene
Mitogen-Activated Protein Kinase Kinase Kinase 8
COT
ESTF
Proto-Oncogene C-Cot
Tumor Progression Locus 2
EST
TPL2
MEKK8
Tpl-2
c-COT
Cot (Cancer Osaka Thyroid) Oncogene
Ewing Sarcoma Transformant
Proto-Oncogene Serine/Threoine Protein Kinase
EC 2.7.11.25
TPL-2
Cancer Osaka Thyroid Oncogene
Serine/Threonine-Protein Kinase Cot
NCBI: 10p11.23    Ensembl: 10p11.23
M3K8_HUMANSize: 467 amino acidsMass: 52925 Da

  • Subunit: Forms a ternary complex with NFKB1/p105 and TNIP2. Interacts with NFKB1; the interaction increases the stability of MAP3K8 but inhibits its MEK phosphorylation activity, whereas loss of interaction following LPS stimulation leads to its degradation. Interacts with CD40 and TRAF6; the interaction is required for ERK activation. Interacts with KSR2; the interaction inhibits ERK and NF-kappa-B activation Developmental stage: Isoform 1 is activated specifically during the S and G2/M phases of the cell cycle Miscellaneous: Can be converted to an oncogenic protein by proviral activation, leading to a C-terminally truncated protein with transforming activity
  • Tissue specificity: Expressed in several normal tissues and human tumor-derived cell lines [IMAGE] Custom PCR Arrays for MAP3K8 Primer Products: [IMAGE] OriGene qPCR primer pairs and template standards for MAP3K8 OriGene qSTAR qPCR primer pairs in human, mouse for MAP3K8 [IM
  • 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
                          
    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 Catalytic activity: ATP + a protein = ADP + a phosphoprotein
  • Catalytic activity:
    ATP + a protein = ADP + a phosphoprotein
  • Similarity:
    Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily
                          
    Contains 1 protein kinase domain [IMAGE]
  • Protein Domain/Family    
    Source ID Domain Name Type
    InterProIPR000719Prot_kinase_domProtein kinaseDomain
    IPR008271Ser/Thr_kinase_ASSerine/threonine protein kinase, active siteActive Sites
    IPR011009Kinase-like_domProtein kinase-likeDomain

    Gene Ontology    
    Type Term Evidence Source Pub
    Molecular Function protein binding IPI GOA 14743216
    protein serine/threonine kinase activity TAS GOA 8226782

    MAP3K8 cross reference    
    PubMed OMIM Entrez Gene NCKU SNP Nucleotide UniProt Genome Data Viewer HomoloGene