Tchem MAP4K2 Mitogen-activated protein kinase kinase kinase kinase 2

Protein Summary

Description

Serine/threonine-protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Acts as a MAPK kinase kinase kinase (MAP4K) and is an upstream activator of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway and to a lesser extent of the p38 MAPKs signaling pathway. Required for the efficient activation of JNKs by TRAF6-dependent stimuli, including pathogen-associated molecular patterns (PAMPs) such as polyinosine-polycytidine (poly(IC)), lipopolysaccharides (LPS), lipid A, peptidoglycan (PGN), or bacterial flagellin. To a lesser degree, IL-1 and engagement of CD40 also stimulate MAP4K2-mediated JNKs activation. The requirement for MAP4K2/GCK is most pronounced for LPS signaling, and extends to LPS stimulation of c-Jun phosphorylation and induction of IL-8. Enhances MAP3K1 oligomerization, which may relieve N-terminal mediated MAP3K1 autoinhibition and lead to activation following autophosphorylation. Mediates also the SAP/JNK signaling pathway and the p38 MAPKs signaling pathway through activation of the MAP3Ks MAP3K10/MLK2 and MAP3K11/MLK3. May play a role in the regulation of vesicle targeting or fusion. regulation of vesicle targeting or fusion. The protein encoded by this gene is a member of the serine/threonine protein kinase family. Although this kinase is found in many tissues, its expression in lymphoid follicles is restricted to the cells of germinal centre, where it may participate in B-cell differentiation. This kinase can be activated by TNF-alpha, and has been shown to specifically activate MAP kinases. This kinase is also found to interact with TNF receptor-associated factor 2 (TRAF2), which is involved in the activation of MAP3K1/MEKK1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

Uniprot Accession IDs

• Q12851
• Q86VU3

Gene Name

• MAP4K2

Ensembl ID

• ENST00000294066
• ENSP00000294066
• ENSG00000168067
• ENST00000377350
• ENSP00000366567

Symbol

• GCK
• RAB8IP
• GCK
• BL44
• RAB8IP

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
molecular function	0.98
small molecule	0.89
protein domain	0.85
biological process	0.73
histone modification site profile	0.73

Protein Classes

DTO Classes

Protein / Kinase / Protein Kinase / Ste Group / Ste20 Family / Khs Subfamily / Mitogen-activated Protein Kinase Kinase Kinase Kinase 2

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: 44.26   (req: < 5)

Gene RIFs: 8   (req: <= 3)

Antibodies: 229   (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: 44.26   (req: >= 5)

Gene RIFs: 8   (req: > 3)

Antibodies: 229   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 15

Tchem

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

Active Ligands: 53

Tclin

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

Active Drug: 1