MAPK10

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 thus 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.

mitogen-activated protein kinase 10

Serine/threonine-protein kinase involved in various processes such as neuronal proliferation, differentiation, migration and programmed cell death. Extracellular stimuli such as pro-inflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK10/JNK3. In turn, MAPK10/JNK3 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN and ATF2 and thus regulates AP-1 transcriptional activity. Plays regulatory roles in the signaling pathways during neuronal apoptosis. Phosphorylates the neuronal microtubule regulator STMN2. Acts in the regulation of the amyloid-beta precursor protein/APP signaling during neuronal differentiation by phosphorylating APP. Participates also in neurite growth in spiral ganglion neurons. Phosphorylates the CLOCK-ARNTL/BMAL1 heterodimer and plays a role in the photic regulation of the circadian clock (PubMed:22441692).
Phosphorylates JUND and this phosphorylation is inhibited in the presence of MEN1 (PubMed:22327296).

Cellular senescenceTAS:Reactome
Fc-epsilon receptor signaling pathwayTAS:Reactome
Intracellular signal transductionManual Assertion Based On ExperimentIBA:GO_Central
JNK cascadeBy SimilarityISS:UniProtKB
Protein phosphorylationManual Assertion Based On ExperimentIMP:UniProtKB
Regulation of circadian rhythmISS:UniProtKB
Regulation of DNA-binding transcription factor activityTAS:Reactome
Response to light stimulusISS:UniProtKB
Rhythmic processIEA:UniProtKB-KW
Signal transductionManual Assertion Based On ExperimentTAS:ProtInc

Cytoplasm
Membrane
Nucleus
Mitochondrion
Palmitoylation regulates MAPK10 trafficking to cytoskeleton. Recruited to the mitochondria in the presence of SARM1 (By similarity).

A chromosomal aberration involving MAPK10 has been found in a single patient with pharmacoresistant epileptic encephalopathy. Translocation t(Y;4)(q11.2;q21) which causes MAPK10 truncation.

Dually phosphorylated on Thr-221 and Tyr-223 by MAP2K4 and MAP2K7, which activates the enzyme. MAP2K7 shows a strong preference for Thr-221 while MAP2K4 phosphorylates Tyr-223 preferentially. Weakly autophosphorylated on threonine and tyrosine residues in vitro.
Palmitoylation regulates subcellular location and axonal development.