| The protein encoded by this gene is a member of the MAP kinase family. MAP kinases act as integration points for multiple biochemical signals and are involved in a wide variety of cellular processes, such as proliferation, differentiation, transcription regulation and development. This kinase is specifically expressed in a subset of neurons in the nervous system and is activated by threonine and tyrosine phosphorylation. Targeted deletion of this gene in mice suggests that it may have a role in stress-induced neuronal apoptosis. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. A recent study provided evidence for translational readthrough in this gene and expression of an additional C-terminally extended isoform via the use of an alternative in-frame translation termination codon. [provided by RefSeq, Dec 2015],alternative products:A similar low level of binding to substrates is observed for isoform alpha-1 and isoform alpha-2. However, there is no correlation between binding and phosphorylation, which is achieved about at the same efficiency by all isoforms,catalytic activity:ATP + a protein = ADP + a phosphoprotein.,caution:The sequence shown here is derived from an Ensembl automatic analysis pipeline and should be considered as preliminary data.,cofactor:Magnesium.,disease:A chromosomal rearrangement involving MAPK10 is a cause of epileptic encephalopathy Lennox-Gastaut type [MIM:606369]. Translocation t(Y,4)(q11.2,q21) which causes MAPK10 truncation. Epileptic encephalopathies of the Lennox-Gastaut group are childhood epileptic disorders characterized by severe psychomotor delay and seizures.,domain:The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.,enzyme regulation:Activated by threonine and tyrosine phosphorylation by two dual specificity kinases, MAP2K4 and MAP2K7. MAP2K7 phosphorylates MAPK10 on Thr-221 causing a conformational change and a large increase in Vmax. MAP2K4 then phosphorylates Tyr-223 resulting in a further increase in Vmax. Inhibited by dual specificity phosphatases, such as DUSP1. Inhibited by HDAC9.,function:Responds to activation by environmental stress and pro-inflammatory cytokines by phosphorylating a number of transcription factors, primarily components of AP-1 such as c-Jun and ATF2 and thus regulates AP-1 transcriptional activity. Required for stress-induced neuronal apoptosis and the pathogenesis of glutamate excitotoxicity.,mass spectrometry: PubMed:10715136,PTM:Dually phosphorylated on Thr-221 and Tyr-223, which activates the enzyme. Weakly autophosphorylated on threonine and tyrosine residues in vitro.,similarity:Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily.,similarity:Contains 1 protein kinase domain.,subunit:Interacts with MAPKBP1 (By similarity). Binds to at least four scaffolding proteins, MAPK8IP1/JIP-1, MAPK8IP2/JIP-2, MAPK8IP3/JIP-3/JSAP1 and SPAG9/MAPK8IP4/JIP-4. These proteins also bind other components of the JNK signaling pathway. Interacts with HDAC9.,tissue specificity:Specific to a subset of neurons in the nervous system. Present in the hippocampus and areas, cerebellum, striatum, brain stem, and weakly in the spinal cord. Very weak expression in testis and kidney., |
