ID:MP2K7_HUMAN DESCRIPTION: RecName: Full=Dual specificity mitogen-activated protein kinase kinase 7; Short=MAP kinase kinase 7; Short=MAPKK 7; EC=2.7.12.2; AltName: Full=JNK-activating kinase 2; AltName: Full=MAPK/ERK kinase 7; Short=MEK 7; AltName: Full=Stress-activated protein kinase kinase 4; Short=SAPK kinase 4; Short=SAPKK-4; Short=SAPKK4; AltName: Full=c-Jun N-terminal kinase kinase 2; Short=JNK kinase 2; Short=JNKK 2; 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 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. CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. COFACTOR: Magnesium. ENZYME REGULATION: Activated by phosphorylation by specific MAP kinase kinase kinases such as MAP3K1/MEKK1, MAP3K3/MEKK3, MAP3K11/MLK3 and MAP3K12/DLK. SUBUNIT: 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 scafforld proteins. INTERACTION: P45983:MAPK8; NbExp=3; IntAct=EBI-492627, EBI-286483; SUBCELLULAR LOCATION: Nucleus. Cytoplasm (By similarity). TISSUE SPECIFICITY: Ubiquitous; with highest level of expression in skeletal muscle. Isoform 3 is found at low levels in placenta, fetal liver, and skeletal muscle. DOMAIN: The DVD domain (redidues 377-400) contains a conserved docking site and is found in the mammalian MAP kinase kinases (MAP2Ks). The DVD sites bind to their specific upstream MAP kinase kinase kinases (MAP3Ks) and are essential for activation. DOMAIN: The D domain (redidues 37-57) contains a conserved docking site and is required for the binding to MAPK substrates. PTM: Activated by phosphorylation on Ser-271 and Thr-275 by MAP kinase kinase kinases (MAP3Ks) (By similarity). SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily. SIMILARITY: Contains 1 protein kinase domain. SEQUENCE CAUTION: Sequence=AAB97813.1; Type=Erroneous termination; Positions=420; Note=Translated as stop; Sequence=AAB97813.1; Type=Frameshift; Positions=402, 410;
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on O14733
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0006468 protein phosphorylation GO:0006915 apoptotic process GO:0006970 response to osmotic stress GO:0007165 signal transduction GO:0007257 activation of JUN kinase activity GO:0007346 regulation of mitotic cell cycle GO:0009408 response to heat GO:0009411 response to UV GO:0016310 phosphorylation GO:0018108 peptidyl-tyrosine phosphorylation GO:0032212 positive regulation of telomere maintenance via telomerase GO:0034612 response to tumor necrosis factor GO:0042981 regulation of apoptotic process GO:0051403 stress-activated MAPK cascade GO:0051973 positive regulation of telomerase activity GO:1904355 positive regulation of telomere capping
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Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
