Tchem MAP3K8 Mitogen-activated protein kinase kinase kinase 8

Protein Summary

Description

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. This gene is an oncogene that encodes a member of the serine/threonine protein kinase family. The encoded protein localizes to the cytoplasm and can activate both the MAP kinase and JNK kinase pathways. This protein was shown to activate IkappaB kinases, and thus induce the nuclear production of NF-kappaB. This protein was also found to promote the production of TNF-alpha and IL-2 during T lymphocyte activation. This gene may also utilize a downstream in-frame translation start codon, and thus produce an isoform containing a shorter N-terminus. The shorter isoform has been shown to display weaker transforming activity. Alternate splicing results in multiple transcript variants that encode the same protein. [provided by RefSeq, Sep 2011]

Uniprot Accession IDs

• P41279
• A8K2Q5
• D3DRX1
• Q14275
• Q5T855
• Q9HC81

Gene Name

• MAP3K8

Ensembl ID

• ENST00000263056
• ENSP00000263056
• ENSG00000107968
• ENST00000375321
• ENSP00000364470
• ENST00000542547
• ENSP00000443610

Symbol

• COT
• ESTF
• COT
• EST
• ESTF
• TPL2
• AURA2
• MEKK8
• Tpl-2
• c-COT

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
hub protein	1
molecular function	0.98
virus perturbation	0.97
PubMedID	0.94
transcription factor binding site profile	0.88

Protein Classes

DTO Classes

Protein / Kinase / Protein Kinase / Ste Group / Ste-unique Family / Mitogen-activated Protein Kinase Kinase Kinase 8

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 251.59   (req: < 5)

Gene RIFs: 93   (req: <= 3)

Antibodies: 552   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 251.59   (req: >= 5)

Gene RIFs: 93   (req: > 3)

Antibodies: 552   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 12

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 54

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0