Target Information
Target General Infomation | |||||
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Target ID |
T00663
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Former ID |
TTDR00928
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Target Name |
Mitogen-activated protein kinase 10
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Gene Name |
MAPK10
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Synonyms |
C-Jun N-terminal kinase 3; JNK3; MAP kinase p49 3F12; Stress-activated protein kinase JNK3; MAPK10
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Target Type |
Research
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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).
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BioChemical Class |
Kinase
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Target Validation |
T00663
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UniProt ID | |||||
EC Number |
EC 2.7.11.24
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Sequence |
MSLHFLYYCSEPTLDVKIAFCQGFDKQVDVSYIAKHYNMSKSKVDNQFYSVEVGDSTFTV
LKRYQNLKPIGSGAQGIVCAAYDAVLDRNVAIKKLSRPFQNQTHAKRAYRELVLMKCVNH KNIISLLNVFTPQKTLEEFQDVYLVMELMDANLCQVIQMELDHERMSYLLYQMLCGIKHL HSAGIIHRDLKPSNIVVKSDCTLKILDFGLARTAGTSFMMTPYVVTRYYRAPEVILGMGY KENVDIWSVGCIMGEMVRHKILFPGRDYIDQWNKVIEQLGTPCPEFMKKLQPTVRNYVEN RPKYAGLTFPKLFPDSLFPADSEHNKLKASQARDLLSKMLVIDPAKRISVDDALQHPYIN VWYDPAEVEAPPPQIYDKQLDEREHTIEEWKELIYKEVMNSEEKTKNGVVKGQPSPSGAA VNSSESLPPSSSVNDISSMSTDQTLASDTDSSLEASAGPLGCCR |
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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
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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 527722 | Bioorg 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 528237 | J 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 529213 | Proc 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 530662 | J 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 531775 | Discovery of potent and selective covalent inhibitors of JNK. Chem Biol. 2012 Jan 27;19(1):140-54. |
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