Target General Infomation
Target ID
T00663
Former ID
TTDR00928
Target Name
Mitogen-activated protein kinase 10
Gene Name
MAPK10
Synonyms
C-Jun N-terminal kinase 3; JNK3; MAP kinase p49 3F12; Stress-activated protein kinase JNK3; MAPK10
Target Type
Research
Disease Central nervous system injury [ICD10: P11.9]
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. Phosphorylates the CLOCK-ARNTL/BMAL1 heterodimer and plays a role in the photic regulation of the circadian clock (PubMed:22441692).
BioChemical Class
Kinase
Target Validation
T00663
UniProt ID
EC Number
EC 2.7.11.24
Sequence
MSLHFLYYCSEPTLDVKIAFCQGFDKQVDVSYIAKHYNMSKSKVDNQFYSVEVGDSTFTV
LKRYQNLKPIGSGAQGIVCAAYDAVLDRNVAIKKLSRPFQNQTHAKRAYRELVLMKCVNH
KNIISLLNVFTPQKTLEEFQDVYLVMELMDANLCQVIQMELDHERMSYLLYQMLCGIKHL
HSAGIIHRDLKPSNIVVKSDCTLKILDFGLARTAGTSFMMTPYVVTRYYRAPEVILGMGY
KENVDIWSVGCIMGEMVRHKILFPGRDYIDQWNKVIEQLGTPCPEFMKKLQPTVRNYVEN
RPKYAGLTFPKLFPDSLFPADSEHNKLKASQARDLLSKMLVIDPAKRISVDDALQHPYIN
VWYDPAEVEAPPPQIYDKQLDEREHTIEEWKELIYKEVMNSEEKTKNGVVKGQPSPSGAA
VNSSESLPPSSSVNDISSMSTDQTLASDTDSSLEASAGPLGCCR
Structure
1JNK; 1PMN; 1PMQ; 1PMU; 1PMV; 2B1P; 2EXC; 2O0U; 2O2U; 2OK1; 2P33; 2R9S; 2WAJ; 2ZDT; 2ZDU; 3CGF; 3CGO; 3DA6; 3FI2; 3FI3; 3FV8; 3G90; 3G9L; 3G9N; 3KVX; 3OXI; 3OY1; 3PTG; 3RTP; 3TTI; 3TTJ; 3V6R; 3V6S; 4H36; 4H39; 4H3B; 4KKE; 4KKG; 4KKH; 4U79; 4WHZ
Inhibitor 2,6-Dihydroanthra/1,9-Cd/Pyrazol-6-One Drug Info [551393]
9-(4-Hydroxyphenyl)-2,7-Phenanthroline Drug Info [551393]
AC1LG8KT Drug Info [543430]
aminopyridine deriv. 2 Drug Info [528237]
AS-601245 Drug Info [529213]
ELN-864709 Drug Info [543430]
JNK-IN-8 Drug Info [531775]
N-(4-amino-5-cyano-6-ethoxypyridin-2-yl)acetamide Drug Info [528237]
N-(4-amino-5-cyano-6-phenylpyridin-2-yl)acetamide Drug Info [528237]
NSC-656158 Drug Info [530662]
Phenyl-(3-phenyl-1H-indazol-6-yl)-amine Drug Info [527722]
Phosphoaminophosphonic Acid-Adenylate Ester Drug Info [551374]
Pathways
KEGG Pathway MAPK signaling pathway
ErbB signaling pathway
Ras signaling pathway
cAMP signaling pathway
FoxO signaling pathway
Sphingolipid signaling pathway
Protein processing in endoplasmic reticulum
Wnt signaling pathway
Osteoclast differentiation
Focal adhesion
Toll-like receptor signaling pathway
NOD-like receptor signaling pathway
RIG-I-like receptor signaling pathway
Fc epsilon RI signaling pathway
TNF signaling pathway
Neurotrophin signaling pathway
Retrograde endocannabinoid signaling
Dopaminergic synapse
Inflammatory mediator regulation of TRP channels
Insulin signaling pathway
GnRH signaling pathway
Progesterone-mediated oocyte maturation
Prolactin signaling pathway
Adipocytokine signaling pathway
Type II diabetes mellitus
Non-alcoholic fatty liver disease (NAFLD)
Epithelial cell signaling in Helicobacter pylori infection
Shigellosis
Salmonella infection
Pertussis
Chagas disease (American trypanosomiasis)
Toxoplasmosis
Tuberculosis
Hepatitis C
Hepatitis B
Influenza A
Herpes simplex infection
Epstein-Barr virus infection
Pathways in cancer
Colorectal cancer
Pancreatic cancer
Choline metabolism in cancer
PANTHER Pathway Alzheimer disease-amyloid secretase pathway
Apoptosis signaling pathway
B cell activation
EGF receptor signaling pathway
FAS signaling pathway
FGF signaling pathway
Integrin signalling pathway
Interferon-gamma signaling pathway
Parkinson disease
TGF-beta signaling pathway
Ras Pathway
CCKR signaling map ST
Pathway Interaction Database Noncanonical Wnt signaling pathway
CD40/CD40L signaling
FAS (CD95) signaling pathway
Glucocorticoid receptor regulatory network
FoxO family signaling
p75(NTR)-mediated signaling
ErbB2/ErbB3 signaling events
PDGFR-beta signaling pathway
Nephrin/Neph1 signaling in the kidney podocyte
Reactome Oxidative Stress Induced Senescence
FCERI mediated MAPK activation
JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1
Activation of the AP-1 family of transcription factors
WikiPathways Toll-like receptor signaling pathway
DNA Damage Response (only ATM dependent)
G13 Signaling Pathway
Insulin Signaling
Wnt Signaling Pathway
MAPK Cascade
Oxidative Stress
Wnt Signaling Pathway and Pluripotency
Apoptosis Modulation by HSP70
MAPK Signaling Pathway
Nanoparticle-mediated activation of receptor signaling
Structural Pathway of Interleukin 1 (IL-1)
Apoptosis
BDNF signaling pathway
Integrin-mediated Cell Adhesion
Regulation of toll-like receptor signaling pathway
References
Ref 527722Bioorg Med Chem Lett. 2005 Nov 15;15(22):5095-9.Design and synthesis of 6-anilinoindazoles as selective inhibitors of c-Jun N-terminal kinase-3.
Ref 528237J Med Chem. 2006 Jun 15;49(12):3563-80.Aminopyridine-based c-Jun N-terminal kinase inhibitors with cellular activity and minimal cross-kinase activity.
Ref 529213Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20523-8. Epub 2007 Dec 11.A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases.
Ref 530662J Med Chem. 2010 Feb 25;53(4):1616-26.Synthesis and preclinical evaluations of 2-(2-fluorophenyl)-6,7-methylenedioxyquinolin-4-one monosodium phosphate (CHM-1-P-Na) as a potent antitumor agent.
Ref 531775Discovery of potent and selective covalent inhibitors of JNK. Chem Biol. 2012 Jan 27;19(1):140-54.
Ref 543430(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1498).
Ref 551374The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
Ref 551393How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
Ref 1587926URL: https://www.ebi.ac.uk/chembl/ The ChEMBL database in 2017

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