Mitogen-activated protein kinase 10

UniProt P53779 Organism Homo sapiens Gene JNK3, JNK3A, MAPK10, PRKM10, SAPK1B EC 2.7.11.24

Also known as: JNK3, JNK3A, MAPK10, PRKM10, SAPK1B

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. Also participates in neurite growth in spiral ganglion neurons. Phosphorylates the CLOCK-BMAL1 heterodimer and plays a role in the photic regulation of the circadian clock. Phosphorylates JUND and this phosphorylation is inhibited in the presence of MEN1.

Classification

Family (Pfam): PF00069 Pkinase
InterPro: Kinase-like_dom_sf, MAP_kinase_CS, MAPK, MAPK_JNK, Prot_kinase_dom, Ser/Thr_kinase_AS
Functional cluster: Phosphoribosyltransferases & related

Experimental structures · PDB · 65

1JNK X-ray 2.30A
1PMN X-ray 2.20A
1PMU X-ray 2.70A
1PMV X-ray 2.50A
2B1P X-ray 1.90A
2EXC X-ray 2.75A
2O0U X-ray 2.10A
2O2U X-ray 2.45A
2OK1 X-ray 2.40A
2P33 X-ray 2.40A
2R9S X-ray 2.40A
2WAJ X-ray 2.40A
… and 53 more

A predicted model is available from AlphaFold.

Gene Ontology · 18

Drugs targeting this protein · 5

CC-401 inhibitor
TANZISERTIB inhibitor
BENTAMAPIMOD inhibitor
BRIMAPITIDE, C-TERMINAL ACID inhibitor
BRIMAPITIDE inhibitor

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Mitogen-activated protein kinase 9 4 shared papers
Mitogen-activated protein kinase 8 5 shared papers
Mitogen-activated protein kinase 10 2 shared papers
C-Jun-amino-terminal kinase-interacting protein 4 1 shared papers
Histone deacetylase 9 1 shared papers
Beta-arrestin-2 1 shared papers
Transcription factor JunD 1 shared papers
Histone deacetylase 9 1 shared papers
Mitogen-activated protein kinase 9 1 shared papers
Mitogen-activated protein kinase 3 1 shared papers
PC4 and SFRS1-interacting protein 1 shared papers
Mitogen-activated protein kinase 1 1 shared papers

Literature · 17 cited papers

JNK regulates the photic response of the mammalian circadian clock. EMBO Rep. · 2012
The same pocket in menin binds both MLL and JUND but has opposite effects on transcription. Nature · 2012
Isoform-specific palmitoylation of JNK regulates axonal development. Cell Death Differ. · 2012
Mutations of beta-arrestin 2 that limit self-association also interfere with interactions with the beta2-adrenoceptor and the ERK1/2 MAPKs: implications for beta2-adrenoceptor signalling via the ERK1/2 MAPKs. Biochem. J. · 2008
Visual and both non-visual arrestins in their 'inactive' conformation bind JNK3 and Mdm2 and relocalize them from the nucleus to the cytoplasm. J. Biol. Chem. · 2006
Neuroprotection by histone deacetylase-related protein. Mol. Cell. Biol. · 2006
Truncation of the CNS-expressed JNK3 in a patient with a severe developmental epileptic encephalopathy. Hum. Genet. · 2006
Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Nature · 2005
Characterization of a novel human sperm-associated antigen 9 (SPAG9) having structural homology with c-Jun N-terminal kinase-interacting protein. Biochem. J. · 2005
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat. Genet. · 2004
c-Jun N-terminal kinase-3 (JNK3)/stress-activated protein kinase-beta (SAPKbeta) binds and phosphorylates the neuronal microtubule regulator SCG10. FEBS Lett. · 2001
… and 5 more in the literature graph

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