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MGP002448

UniProt Annotations

Entry Information
Gene Namemitogen-activated protein kinase kinase 7
Protein EntryMP2K7_HUMAN
UniProt IDO14733
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=4; Name=1; Synonyms=A; IsoId=O14733-1; Sequence=Displayed; Name=2; Synonyms=B; IsoId=O14733-2; Sequence=VSP_004883; Note=May be due to intron retention.; Name=3; Synonyms=gamma1; IsoId=O14733-3; Sequence=VSP_022309; Name=4; IsoId=O14733-4; Sequence=VSP_022310; Note=No experimental confirmation available.;
Catalytic ActivityATP + a protein = ADP + a phosphoprotein.
CofactorName=Mg(2+); Xref=ChEBI:CHEBI:18420;
DomainThe D domain (residues 37-57) contains a conserved docking site and is required for the binding to MAPK substrates. {ECO:0000269|PubMed:15866172}.
DomainThe DVD domain (residues 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. {ECO:0000269|PubMed:15866172}.
Enzyme RegulationActivated by phosphorylation by specific MAP kinase kinase kinases such as MAP3K1/MEKK1, MAP3K3/MEKK3, MAP3K11/MLK3 and MAP3K12/DLK. {ECO:0000269|PubMed:16442502, ECO:0000269|PubMed:9312068}.
FunctionDual 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. {ECO:0000269|PubMed:9312068, ECO:0000269|PubMed:9372971, ECO:0000269|PubMed:9535930, ECO:0000269|Ref.5}.
InteractionO15519-1:CFLAR; NbExp=2; IntAct=EBI-492605, EBI-4567563; Q5S007:LRRK2; NbExp=3; IntAct=EBI-492605, EBI-5323863; O43318:MAP3K7; NbExp=3; IntAct=EBI-492605, EBI-358684; P45983:MAPK8; NbExp=3; IntAct=EBI-492627, EBI-286483; Q9UQF2:MAPK8IP1; NbExp=5; IntAct=EBI-492605, EBI-78404;
PtmActivated by phosphorylation on Ser-271 and Thr-275 by MAP kinase kinase kinases (MAP3Ks). {ECO:0000250}.
Sequence CautionSequence=AAB97813.1; Type=Erroneous termination; Positions=420; Note=Translated as stop.; Evidence={ECO:0000305}; Sequence=AAB97813.1; Type=Frameshift; Positions=402, 410; Evidence={ECO:0000305};
SimilarityBelongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase subfamily. {ECO:0000305}.
SimilarityContains 1 protein kinase domain. {ECO:0000255|PROSITE-ProRule:PRU00159}.
Subcellular LocationNucleus. Cytoplasm {ECO:0000250}.
SubunitInteracts 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. {ECO:0000250, ECO:0000269|PubMed:10490659, ECO:0000269|PubMed:12189133, ECO:0000269|PubMed:18286207, ECO:0000269|PubMed:21278800}.
Tissue SpecificityUbiquitous; with highest level of expression in skeletal muscle. Isoform 3 is found at low levels in placenta, fetal liver, and skeletal muscle. {ECO:0000269|PubMed:16442502, ECO:0000269|PubMed:9372971, ECO:0000269|PubMed:9535930}.
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