Tchem MAP3K7 Mitogen-activated protein kinase kinase kinase 7

Protein Summary

Description

Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. Plays an important role in the cascades of cellular responses evoked by changes in the environment. Mediates signal transduction of TRAF6, various cytokines including interleukin-1 (IL-1), transforming growth factor-beta (TGFB), TGFB-related factors like BMP2 and BMP4, toll-like receptors (TLR), tumor necrosis factor receptor CD40 and B-cell receptor (BCR). Ceramides are also able to activate MAP3K7/TAK1. Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade and the p38 MAPK signal transduction cascade through the phosphorylation and activation of several MAP kinase kinases like MAP2K1/MEK1, MAP2K3/MKK3, MAP2K6/MKK6 and MAP2K7/MKK7. These MAP2Ks in turn activate p38 MAPKs, c-jun N-terminal kinases (JNKs) and I-kappa-B kinase complex (IKK). Both p38 MAPK and JNK pathways control the transcription factors activator protein-1 (AP-1), while nuclear factor-kappa B is activated by IKK. MAP3K7 activates also IKBKB and MAPK8/JNK1 in response to TRAF6 signaling and mediates BMP2-induced apoptosis. In osmotic stress signaling, plays a major role in the activation of MAPK8/JNK1, but not that of NF-kappa-B. Promotes TRIM5 capsid-specific restriction activity. The protein encoded by this gene is a member of the serine/threonine protein kinase family. This kinase mediates the signaling transduction induced by TGF beta and morphogenetic protein (BMP), and controls a variety of cell functions including transcription regulation and apoptosis. In response to IL-1, this protein forms a kinase complex including TRAF6, MAP3K7P1/TAB1 and MAP3K7P2/TAB2; this complex is required for the activation of nuclear factor kappa B. This kinase can also activate MAPK8/JNK, MAP2K4/MKK4, and thus plays a role in the cell response to environmental stresses. Four alternatively spliced transcript variants encoding distinct isoforms have been reported. [provided by RefSeq, Jul 2008]

Uniprot Accession IDs

• O43318
• B2RE27
• E1P523
• O43317
• O43319
• Q5TDN2
• Q5TDN3
• Q5TDT7
• Q9NTR3
• Q9NZ70

Gene Name

• MAP3K7

Ensembl ID

• ENST00000369325
• ENSP00000358331
• ENSG00000135341
• ENST00000369327
• ENSP00000358333
• ENST00000369329
• ENSP00000358335
• ENST00000369332
• ENSP00000358338

Symbol

• TAK1
• CSCF
• FMD2
• TAK1
• MEKK7
• TGF1a

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	1
hub protein	1
kinase perturbation	0.99
molecular function	0.99
transcription factor perturbation	0.94

Protein Classes

DTO Classes

Protein / Kinase / Protein Kinase / Tkl Group / Mlk Family / Tak1 Subfamily / Mitogen-activated Protein Kinase Kinase Kinase 7

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: 244.18   (req: < 5)

Gene RIFs: 187   (req: <= 3)

Antibodies: 1045   (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: 244.18   (req: >= 5)

Gene RIFs: 187   (req: > 3)

Antibodies: 1045   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 33

Tchem

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

Active Ligands: 42

Tclin

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

Active Drug: 1