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

MAP3K4 (Q9Y6R4) - Overview - Molecular Target Synopsis

Protein


MAP3K4, Mitogen-activated protein kinase kinase kinase 4
Enzyme Classification 2.7.11.25
UniProt Q9Y6R4

Also Known as M3K4_HUMAN, MAP3K4, KIAA0213, MAPKKK4, MEKK4, MTK1

Component of a protein kinase signal transduction cascade. Activates the CSBP2, P38 and JNK MAPK pathways, but not the ERK pathway. Specifically phosphorylates and activates MAP2K4 and MAP2K6. Monomer and homodimer. Homodimerization enhances kinase activity. Interacts with TRAF4; this promotes homodimerization (PubMed:16157600). Binds both upstream activators and downstream substrates in multimolecular complexes. Interacts with AXIN1 and DIXDC1; interaction with DIXDC1 prevents interaction with AXIN1 (PubMed:15262978). Interacts with GADD45 and MAP2K6 (PubMed:12052864). Interacts with ZFP36; this interaction enhances the association with SH3KBP1/CIN85 (PubMed:20221403). Interacts with SH3KBP1; this interaction enhances the association with ZFP36 (PubMed:20221403). Interacts with CDC42.

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: MAP3K4 is active in the following subcellular-locations: cytoplasm, perinuclear region.
GO terms: MAP3K4 is active in the following subcellular-locations: cytoplasm, perinuclear region of cytoplasm.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project MAP3K4 has gain in 1 cell-lines, loss in 6 cell-lines and no signal in 998 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: SNB_19, U251, K_562

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: RC-K8, VMRC-LCD, JHH-7

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: K562, SK-N-SH, HSMM

(see details)

RNA Interference


MAP3K4 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: CROE33, OAW42. (see details)

3D Structures


At greater than 35% identity similarity to MAP3K4 there are:
46 structures (94 chains) solved
43 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


MAP3K4 has been screened with 129 compounds (187 bioactivities), 5 compounds have bioactivities that show binding affinity of <= 500nM (7 bioactivities). (see details)