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

MAP2K7 (O14733) - Overview - Molecular Target Synopsis


MAP2K7, Dual specificity mitogen-activated protein kinase kinase 7
Enzyme Classification
UniProt O14733

Also Known as MP2K7_HUMAN, MAP2K7, JNKK2, MEK7, MKK7, PRKMK7, SKK4

Dual specificity protein kinase which acts as an essential component of the MAP kinase signal transduction pathway. Essential component of the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. With MAP2K4/MKK4, is the one of the only known kinase to directly activate the stress-activated protein kinase/c-Jun N-terminal kinases MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3. MAP2K4/MKK4 and MAP2K7/MKK7 both activate the JNKs by phosphorylation, but they differ in their preference for the phosphorylation site in the Thr-Pro-Tyr motif. MAP2K4/MKK4 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The monophosphorylation of JNKs on the Thr residue is sufficient to increase JNK activity indicating that MAP2K7/MKK7 is important to trigger JNK activity, while the additional phosphorylation of the Tyr residue by MAP2K4/MKK4 ensures optimal JNK activation. Has a specific role in JNK signal transduction pathway activated by proinflammatory cytokines. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis. Part of a non-canonical MAPK signaling pathway, composed of the upstream MAP3K12 kinase and downstream MAP kinases MAPK1/ERK2 and MAPK3/ERK1, that enhances the AP-1-mediated transcription of APP in response to APOE (PubMed:28111074). Interacts with isoform 1 of VRK2. Interacts (via its D domain) with its substrates MAPK8/JNK1, MAPK9/JNK2 and MAPK10/JNK3 (By similarity). Interacts (via its DVD domain) with MAP3Ks activators like MAP3K5/ASK1 and MAP3K1/MEKK1 (By similarity). Interacts with MAPK8IP1/JIP1, MAPK8IP2/JIP2 and MAPK8IP3/JIP3 scaffold proteins. Interacts with RASSF7, the interaction promotes phosphorylation. Found in a complex with SH3RF1, RAC1, MAP3K11/MLK3, MAPK8IP1/JIP1 and MAPK8/JNK1. Found in a complex with SH3RF1, RAC2, MAP3K7/TAK1, MAPK8IP1/JIP1, MAPK8/JNK1 and MAPK9/JNK2.

Inspect Structure
See all 3D Structures for MAP2K7

Isoforms / Transcripts (Protein Coding)

Sub-cellular localization

UniProt: MAP2K7 is active in the following subcellular-locations: cytoplasm, nucleus.
GO terms: MAP2K7 is active in the following subcellular-locations: cytoplasm, cytosol, nucleus.

GO terms

Gene Copy Number Variation

In COSMIC - Cell Lines Project MAP2K7 has gain in 0 cell-lines, loss in 1 cell-lines and no signal in 1004 cell-lines. (see details)

Gene Expression

In NCI60, the highest expressing cell lines are: OVCAR_5, HL_60, SK_OV_3

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: HN, MG-63, NCI-H1155

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, K562, HeLa-S3

(see details)

RNA Interference

MAP2K7 was reported in the following RNAI studies:

Cell - Large Scale Profiling of Kinase Dependencies in Cancer Cell Lines, the highest RNAi cell lines are: MHM, SF188. (see details)

3D Structures

For MAP2K7 there are:
19 structures (22 chains) solved
11 are solved in complex with at least one small molecule ligand

(see details)
Molecular Target 3D Synopsis

Screening and Chemistry

MAP2K7 has been screened with 442 compounds (615 bioactivities), 5 compounds have bioactivities that show binding affinity of <= 500nM (5 bioactivities). (see details)