MAPK10

Domain

The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases.

Function

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-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).

Involvement in disease

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.

Post-translational modifications

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.

Sequence Similarities

Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily.

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.

Cellular localization

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

Alternative names

JNK3, JNK3A, PRKM10, SAPK1B, MAPK10, Mitogen-activated protein kinase 10, MAP kinase 10, MAPK 10, MAP kinase p49 3F12, Stress-activated protein kinase 1b, Stress-activated protein kinase JNK3, c-Jun N-terminal kinase 3, SAPK1b

Database links

swissprot:P53779 entrezGene:5599 omim:602896 omim:602897 omim:601158 swissprot:P45983 swissprot:P45984 entrezGene:5601 entrezGene:5602