Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

MAP4K2 (Q12851) - Overview - Molecular Target Synopsis

Protein


MAP4K2, Mitogen-activated protein kinase kinase kinase kinase 2
Enzyme Classification 2.7.11.1
UniProt Q12851

Also Known as M4K2_HUMAN, MAP4K2, GCK, RAB8IP

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. Interacts with TRAF2, TRAF6, MAP3K1/MEKK1 and MAP3K11/MLK3. Interacts with RAB8A.

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: MAP4K2 is active in the following subcellular-locations: basolateral cell membrane, cytoplasm, golgi apparatus membrane.
GO terms: MAP4K2 is active in the following subcellular-locations: basolateral plasma membrane, cytoplasm, Golgi membrane.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project MAP4K2 has gain in 3 cell-lines, loss in 0 cell-lines and no signal in 1002 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: T47D, HCT_116, SK_MEL_5

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: UKE-1, HEL, KG-1

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: SK-N-SH, HUVEC, HeLa-S3

(see details)

RNA Interference


MAP4K2 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: MDAMB453, MDAMB436. (see details)

3D Structures


At greater than 50% identity similarity to MAP4K2 there are:
4 structures (6 chains) solved
3 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


MAP4K2 has been screened with 698 compounds (1253 bioactivities), 20 compounds have bioactivities that show binding affinity of <= 500nM (22 bioactivities). (see details)