Cot an oncogenic Ser/Thr kinase of the STE group. Activates I kappa-B kinases, thus inducing the nuclear translocation of NF-kappaB. Involved in the regulation of T-helper cell differentiation and IFNG expression in T-cells. 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 mediating host resistance to bacterial infection through negative regulation of type I interferon (IFN) production. 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. Two alternative initiation human isoforms have been reported. Isoform 1 shows some transforming activity, although it is much weaker than that of the activated oncogenic variant. Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily. Expressed in several normal tissues and human tumor-derived cell lines. Note: This description may include information from UniProtKB.
Protein type: EC; Kinase, protein; Oncoprotein; Protein kinase, STE; Protein kinase, Ser/Thr (non-receptor); STE group; STE-Unique family
Chromosomal Location of Human Ortholog: 10p11.23
Cellular Component:  cytosol
Molecular Function:  ATP binding; magnesium ion binding; MAP kinase kinase kinase activity; protein binding
Biological Process:  activation of MAPKK activity; cell cycle; interleukin-1-mediated signaling pathway; protein phosphorylation; stress-activated MAPK cascade; T cell costimulation
Disease: Lung Cancer
Reference #:  P41279 (UniProtKB)
Alt. Names/Synonyms: augmented in rheumatoid arthritis 2; AURA2; c-COT; Cancer Osaka thyroid oncogene; COT; cot (cancer Osaka thyroid) oncogene; EST; ESTF; Ewing sarcoma transformant; FLJ10486; M3K8; MAP3K8; MEKK8; Mitogen-activated protein kinase kinase kinase 8; Proto-oncogene c-Cot; proto-oncogene serine/threoine protein kinase; Serine/threonine-protein kinase cot; TPL-2; TPL2; Tumor progression locus 2; tumor progression locus-2
Gene Symbols: MAP3K8
Molecular weight: 52,925 Da
Basal Isoelectric point: 5.54  Predict pI for various phosphorylation states
CST Pathways:  Actin Dynamics  |  B Cell Receptor Signaling  |  Growth And Differentiation Control by MAPKs  |  NF-kB Signaling  |  PI3K/Akt Signaling  |  SAPK/JNK Signaling Cascades
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