P45985

Background

Protein Name
Dual specificity mitogen-activated protein kinase kinase 4
Gene Name
MAP2K4
Organism
Homo sapiens

Annotations

Function
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 MAP2K7/MKK7, 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 shows preference for phosphorylation of the Tyr residue and MAP2K7/MKK7 for the Thr residue. The phosphorylation of the Thr residue by MAP2K7/MKK7 seems to be the prerequisite for JNK activation at least in response to proinflammatory cytokines, while other stimuli activate both MAP2K4/MKK4 and MAP2K7/MKK7 which synergistically phosphorylate JNKs. MAP2K4 is required for maintaining peripheral lymphoid homeostasis. The MKK/JNK signaling pathway is also involved in mitochondrial death signaling pathway, including the release cytochrome c, leading to apoptosis. Whereas MAP2K7/MKK7 exclusively activates JNKs, MAP2K4/MKK4 additionally activates the p38 MAPKs MAPK11, MAPK12, MAPK13 and MAPK14.

Mapping Statistics

Site Maximum Consensus Site Population Minimum Consensus Site Population Median Consensus Site Population
MPP 31 3 15.5
AAS 23 2 15.0
MT3 16 9 12.5
ATP 25 15 20.0
CMP 22 3 10.0
DRS 19 3 12.0
PDIG 2 2 2.0

Mapping Results

PDB ID Maximum Consensus Site Population
MPP site AAS site MT3 site LBP site ATP site DEF site DFG site CMP site PMP site EDI site DRS site PDIG site PIF site
Total Druggable Structures per Site 2 3 1 0 1 0 0 2 0 0 1 0 0
3ALO 31 23 16 0 0 0 0 0 0 0 8 0 0
3ALN 25 18 9 0 25 0 0 22 0 0 19 2 0
3VUT 0 17 0 0 0 0 0 19 0 0 13 0 0