Linked Life Data

P53779

Source:http://identifiers.org/uniprot/P53779

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
biopax3:comment
FUNCTION: Serine/threonine-protein kinase involved in various processes such as neuronal proliferation, differentiation, migration and programmed cell death. Extracellular stimuli such as proinflammatory 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 beta-amyloid precursor protein/APP signaling during neuronal differentiation by phosphorylating APP. Participates also in neurite growth in spiral ganglion neurons. CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. COFACTOR: Magnesium. 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. 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. Interacts with ARRB2; the interaction enhances MAPK10 activation by MAP3K5. SUBCELLULAR LOCATION: Cytoplasm. Membrane; Lipid-anchor. Nucleus. Note=Palmitoylation regulates MAPK10 trafficking to cytoskeleton. ALTERNATIVE PRODUCTS: Event=Alternative splicing; Named isoforms=4; Comment=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; Name=Alpha-2; IsoId=P53779-1; Sequence=Displayed; Name=Alpha-1; IsoId=P53779-2; Sequence=VSP_004839; Name=3; IsoId=P53779-3; Sequence=VSP_041911; Name=4; IsoId=P53779-4; Sequence=VSP_041910, VSP_004839; 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. DOMAIN: The TXY motif contains the threonine and tyrosine residues whose phosphorylation activates the MAP kinases. PTM: 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. PTM: Palmitoylation regulates subcellular location and axonal development. MASS SPECTROMETRY: Mass=44070; Method=Electrospray; Range=1-464; Source=PubMed:10715136; DISEASE: Defects in MAPK10 are a cause of epileptic encephalopathy Lennox-Gastaut type (EELG) [MIM:606369]. Epileptic encephalopathies of the Lennox-Gastaut group are childhood epileptic disorders characterized by severe psychomotor delay and seizures. Note=A chromosomal aberration involving MAPK10 has been found in a single patient. Translocation t(Y;4)(q11.2;q21) which causes MAPK10 truncation. SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MAP kinase subfamily. SIMILARITY: Contains 1 protein kinase domain. WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/JNK3ID427.html"; GENE SYNONYMS:MAPK10 JNK3 JNK3A PRKM10 SAPK1B. COPYRIGHT: Protein annotation is derived from the UniProt Consortium (http://www.uniprot.org/). Distributed under the Creative Commons Attribution-NoDerivs License., SEQUENCE 464 AA; 52585 MW; 2E20C05EB89CDA66 CRC64;
biopax3:xref
biopax3:displayName
MK10_HUMAN
biopax3:name
2.7.11.24, MAP kinase 10, MAP kinase p49 3F12, MAPK 10, MAPK10, SAPK1b, Stress-activated protein kinase 1b, Stress-activated protein kinase JNK3, c-Jun N-terminal kinase 3
biopax3:entityFeature
biopax3:organism
biopax3:sequence
MSLHFLYYCSEPTLDVKIAFCQGFDKQVDVSYIAKHYNMSKSKVDNQFYSVEVGDSTFTVLKRYQNLKPIGSGAQGIVCAAYDAVLDRNVAIKKLSRPFQNQTHAKRAYRELVLMKCVNHKNIISLLNVFTPQKTLEEFQDVYLVMELMDANLCQVIQMELDHERMSYLLYQMLCGIKHLHSAGIIHRDLKPSNIVVKSDCTLKILDFGLARTAGTSFMMTPYVVTRYYRAPEVILGMGYKENVDIWSVGCIMGEMVRHKILFPGRDYIDQWNKVIEQLGTPCPEFMKKLQPTVRNYVENRPKYAGLTFPKLFPDSLFPADSEHNKLKASQARDLLSKMLVIDPAKRISVDDALQHPYINVWYDPAEVEAPPPQIYDKQLDEREHTIEEWKELIYKEVMNSEEKTKNGVVKGQPSPSGAAVNSSESLPPSSSVNDISSMSTDQTLASDTDSSLEASAGPLGCCR
biopax3:standardName
Mitogen-activated protein kinase 10