Molecular Target Synopsis
Domains and Structures
Drugs and Clinical Candidates
Ligand Efficiency Plot
Family Cladogram
Interaction Network
Gene Expression
Gene Copy Number Variation
Germline Genetics

MAP4K2 (Q12851) - Overview - Molecular Target Synopsis


MAP4K2, Mitogen-activated protein kinase kinase kinase kinase 2
Enzyme Classification
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 (By similarity).

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.

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:
7 structures (12 chains) solved
6 are solved in complex with at least one small molecule ligand
3 are solved with an approved drug

MAP4K2 is solved in complex with the approved drug(s):


(see details)
Molecular Target 3D Synopsis

Screening and Chemistry

MAP4K2 has been screened with 1119 compounds (1935 bioactivities), 41 compounds have bioactivities that show binding affinity of <= 500nM (48 bioactivities). (see details)