ID:M3K8_HUMAN DESCRIPTION: RecName: Full=Mitogen-activated protein kinase kinase kinase 8; EC=2.7.11.25; AltName: Full=Cancer Osaka thyroid oncogene; AltName: Full=Proto-oncogene c-Cot; AltName: Full=Serine/threonine-protein kinase cot; AltName: Full=Tumor progression locus 2; Short=TPL-2; FUNCTION: Required for TLR4 activation of the MEK/ERK pathway. Able to activate NF-kappa-B 1 by stimulating proteasome-mediated proteolysis of NF-kappa-B 1/p105. Plays a role in the cell cycle. The longer form has some transforming activity, although it is much weaker than the activated cot oncoprotein. CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. COFACTOR: Magnesium. SUBUNIT: Forms a ternary complex with NFKB1 and TNIP2. INTERACTION: Q8NFZ5:TNIP2; NbExp=8; IntAct=EBI-354900, EBI-359372; SUBCELLULAR LOCATION: Cytoplasm. TISSUE SPECIFICITY: Expressed in several normal tissues and human tumor-derived cell lines. DEVELOPMENTAL STAGE: Isoform 1 is activated specifically during the S and G2/M phases of the cell cycle. PTM: Autophosphorylated. Isoform 1 undergoes phosphorylation mainly on Ser residues, and isoform 2 on both Ser and Thr residues. SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily. SIMILARITY: Contains 1 protein kinase domain. WEB RESOURCE: Name=SeattleSNPs; URL="http://pga.gs.washington.edu/data/map3k8/";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
Pfam Domains: PF00069 - Protein kinase domain PF07714 - Protein tyrosine and serine/threonine kinase
SCOP Domains: 56112 - Protein kinase-like (PK-like)
ModBase Predicted Comparative 3D Structure on P41279
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0000186 activation of MAPKK activity GO:0002376 immune system process GO:0006468 protein phosphorylation GO:0007049 cell cycle GO:0007165 signal transduction GO:0007346 regulation of mitotic cell cycle GO:0016310 phosphorylation GO:0023014 signal transduction by protein phosphorylation GO:0031098 stress-activated protein kinase signaling cascade GO:0031295 T cell costimulation GO:0032147 activation of protein kinase activity GO:0042981 regulation of apoptotic process GO:0051403 stress-activated MAPK cascade GO:0070498 interleukin-1-mediated signaling pathway
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
