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: 18 A1|18 2.73 cM
Cellular Component:  cytoplasm; cytosol
Molecular Function:  ATP binding; kinase activity; magnesium ion binding; MAP kinase kinase kinase activity; metal ion binding; nucleotide binding; protein kinase activity; protein serine/threonine kinase activity; transferase activity
Biological Process:  activation of protein kinase activity; cell cycle; immune system process; phosphorylation; protein phosphorylation; signal transduction; signal transduction by protein phosphorylation; stress-activated protein kinase signaling cascade
Reference #:  Q07174 (UniProtKB)
Alt. Names/Synonyms: c-CO; c-COT; Cancer Osaka thyroid oncogene; cancer Osaka thyroid, oncogene; Cot; COT proto-oncogene serine/threonine-protein kinase; Cot/T; Cot/Tpl2; Est; Estf; M3K8; Map3k8; mitogen activated protein kinase kinase kinase 8; Mitogen-activated protein kinase kinase kinase 8; Proto-oncogene c-Cot; Serine/threonine-protein kinase cot; Tpl; Tpl-2; Tpl2; tumor progression locus 2
Gene Symbols: Map3k8
Molecular weight: 52,942 Da
Basal Isoelectric point: 5.76  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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Cross-references to other databases:  STRING  |  Reactome  |  BioGPS  |  KinBase  |  Pfam  |  ENZYME  |  Phospho.ELM  |  NetworKIN  |  UniProtKB  |  Entrez-Gene  |  Ensembl Gene