Tchem MAP3K5 Mitogen-activated protein kinase kinase kinase 5

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 signaling for determination of cell fate such as differentiation and survival. Plays a crucial role in the apoptosis signal transduction pathway through mitochondria-dependent caspase activation. MAP3K5/ASK1 is required for the innate immune response, which is essential for host defense against a wide range of pathogens. Mediates signal transduction of various stressors like oxidative stress as well as by receptor-mediated inflammatory signals, such as the tumor necrosis factor (TNF) or lipopolysaccharide (LPS). 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 MAP2K4/SEK1, MAP2K3/MKK3, MAP2K6/MKK6 and MAP2K7/MKK7. These MAP2Ks in turn activate p38 MAPKs and c-jun N-terminal kinases (JNKs). Both p38 MAPK and JNKs control the transcription factors activator protein-1 (AP-1). Mitogen-activated protein kinase (MAPK) signaling cascades include MAPK or extracellular signal-regulated kinase (ERK), MAPK kinase (MKK or MEK), and MAPK kinase kinase (MAPKKK or MEKK). MAPKK kinase/MEKK phosphorylates and activates its downstream protein kinase, MAPK kinase/MEK, which in turn activates MAPK. The kinases of these signaling cascades are highly conserved, and homologs exist in yeast, Drosophila, and mammalian cells. MAPKKK5 contains 1,374 amino acids with all 11 kinase subdomains. Northern blot analysis shows that MAPKKK5 transcript is abundantly expressed in human heart and pancreas. The MAPKKK5 protein phosphorylates and activates MKK4 (aliases SERK1, MAPKK4) in vitro, and activates c-Jun N-terminal kinase (JNK)/stress-activated protein kinase (SAPK) during transient expression in COS and 293 cells; MAPKKK5 does not activate MAPK/ERK. [provided by RefSeq, Jul 2008]

Uniprot Accession IDs

• Q99683
• A6NIA0
• B4DGB2
• Q5THN3
• Q99461

Gene Name

• MAP3K5

Ensembl ID

• ENST00000359015
• ENSP00000351908
• ENSG00000197442

Symbol

• ASK1
• MAPKKK5
• MEKK5
• ASK1
• MEKK5
• MAPKKK5

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
hub protein	1
kinase	1
molecular function	1
PubMedID	0.96
biological term	0.94

Protein Classes

DTO Classes

Protein / Kinase / Protein Kinase / Ste Group / Ste11 Family / Mitogen-activated Protein Kinase Kinase Kinase 5

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: 881.44   (req: < 5)

Gene RIFs: 192   (req: <= 3)

Antibodies: 1449   (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: 881.44   (req: >= 5)

Gene RIFs: 192   (req: > 3)

Antibodies: 1449   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 41

Tchem

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

Active Ligands: 127

Tclin

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

Active Drug: 0