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

MAP2K6 (P52564) - Overview - Molecular Target Synopsis

Protein


MAP2K6, Dual specificity mitogen-activated protein kinase kinase 6
Enzyme Classification 2.7.12.2
UniProt P52564

Also Known as MP2K6_HUMAN, MAP2K6, MEK6, MKK6, PRKMK6, SKK3

Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. With MAP3K3/MKK3, catalyzes the concomitant phosphorylation of a threonine and a tyrosine residue in the MAP kinases p38 MAPK11, MAPK12, MAPK13 and MAPK14 and plays an important role in the regulation of cellular responses to cytokines and all kinds of stresses. Especially, MAP2K3/MKK3 and MAP2K6/MKK6 are both essential for the activation of MAPK11 and MAPK13 induced by environmental stress, whereas MAP2K6/MKK6 is the major MAPK11 activator in response to TNF. MAP2K6/MKK6 also phosphorylates and activates PAK6. The p38 MAP kinase signal transduction pathway leads to direct activation of transcription factors. Nuclear targets of p38 MAP kinase include the transcription factors ATF2 and ELK1. Within the p38 MAPK signal transduction pathway, MAP3K6/MKK6 mediates phosphorylation of STAT4 through MAPK14 activation, and is therefore required for STAT4 activation and STAT4-regulated gene expression in response to IL-12 stimulation. The pathway is also crucial for IL-6-induced SOCS3 expression and down-regulation of IL-6-mediated gene induction; and for IFNG-dependent gene transcription. Has a role in osteoclast differentiation through NF-kappa-B transactivation by TNFSF11, and in endochondral ossification and since SOX9 is another likely downstream target of the p38 MAPK pathway. MAP2K6/MKK6 mediates apoptotic cell death in thymocytes. Acts also as a regulator for melanocytes dendricity, through the modulation of Rho family GTPases. Dimer. Interacts with Yersinia yopJ. Interacts (via its D domain) with its substrates MAPK11, MAPK12, MAPK13 and MAPK14 (By similarity). Interacts (via its DVD domain) with MAP3Ks activators like MAP3K5/ASK1, MAP3K1/MEKK1, MAP3K2/MEKK2, MAP3K3/MEKK3, MAP3K4/MEKK4, MAP3K7/TAK1, MAP3K11/MLK3 and MAP3K17/TAOK2 (By similarity). Interacts with DCTN1. Interacts with EIF2AK2/PKR.

5ETF
8 RESIDUE FRAGMENT OF
DUAL SPECIFICITY MITOGEN-ACTIVATED PROTEIN KINASE KINASE 6
IN THE STRUCTURE OF
STRUCTURE OF DEAD KINASE MAPK14 WITH BOUND THE KIM DOMAIN OF MKK6
RCSB/PDB
Inspect Structure
See all 3D Structures for MAP2K6

Isoforms / Transcripts (Protein Coding)


Sub-cellular localization


UniProt: MAP2K6 is active in the following subcellular-locations: cytoplasm, cytoskeleton, nucleus.
GO terms: MAP2K6 is active in the following subcellular-locations: cytoplasm, cytoskeleton, cytosol, nucleoplasm, nucleus.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project MAP2K6 has gain in 4 cell-lines, loss in 1 cell-lines and no signal in 1000 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: SW_620, MOLT_4, A549

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: HM7, MKN-45, NCI-H727

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, NHLF, HSMM

(see details)

RNA Interference


MAP2K6 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: CAL51, OVISE. (see details)

3D Structures


For MAP2K6 there are:
5 structures (8 chains) solved
2 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis

Screening and Chemistry


MAP2K6 has been screened with 455 compounds (746 bioactivities), 4 compounds have bioactivities that show binding affinity of <= 500nM (7 bioactivities). (see details)