Details of the Drug Therapeutic Target (DTT)
General Information of Drug Therapeutic Target (DTT) (ID: TTRZQE3)
DTT Name | Glycogen synthase kinase-3 alpha (GSK-3A) | ||||
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Synonyms | Serine/threonineprotein kinase GSK3A; Serine/threonine-protein kinase GSK3A; Glycogen synthase kinase3 alpha; Glycogen synthase kinase 3; GSK3 alpha; GSK-3 alpha; GSK-3 | ||||
Gene Name | GSK3A | ||||
DTT Type |
Successful target
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[1] | |||
BioChemical Class |
Kinase
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UniProt ID | |||||
TTD ID | |||||
3D Structure | |||||
EC Number |
EC 2.7.11.26
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Sequence |
MSGGGPSGGGPGGSGRARTSSFAEPGGGGGGGGGGPGGSASGPGGTGGGKASVGAMGGGV
GASSSGGGPGGSGGGGSGGPGAGTSFPPPGVKLGRDSGKVTTVVATLGQGPERSQEVAYT DIKVIGNGSFGVVYQARLAETRELVAIKKVLQDKRFKNRELQIMRKLDHCNIVRLRYFFY SSGEKKDELYLNLVLEYVPETVYRVARHFTKAKLTIPILYVKVYMYQLFRSLAYIHSQGV CHRDIKPQNLLVDPDTAVLKLCDFGSAKQLVRGEPNVSYICSRYYRAPELIFGATDYTSS IDVWSAGCVLAELLLGQPIFPGDSGVDQLVEIIKVLGTPTREQIREMNPNYTEFKFPQIK AHPWTKVFKSRTPPEAIALCSSLLEYTPSSRLSPLEACAHSFFDELRCLGTQLPNNRPLP PLFNFSAGELSIQPSLNAILIPPHLRSPAGTTTLTPSSQALTETPTSSDWQSTDATPTLT NSS |
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Function |
Requires primed phosphorylation of the majority of its substrates. Contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glycogen synthesis. Regulates glycogen metabolism in liver, but not in muscle. May also mediate the development of insulin resistance by regulating activation of transcription factors. In Wnt signaling, regulates the level and transcriptional activity of nuclear CTNNB1/beta-catenin. Facilitates amyloid precursor protein (APP) processing and the generation of APP-derived amyloid plaques found in Alzheimer disease. May be involved in the regulation of replication in pancreatic beta-cells. Is necessary for the establishment of neuronal polarity and axon outgrowth. Through phosphorylation of the anti-apoptotic protein MCL1, may control cell apoptosis in response to growth factors deprivation. Acts as a regulator of autophagy by mediating phosphorylation of KAT5/TIP60 under starvation conditions, leading to activate KAT5/TIP60 acetyltransferase activity and promote acetylation of key autophagy regulators, such as ULK1 and RUBCNL/Pacer. Constitutively active protein kinase that acts as a negative regulator in the hormonal control of glucose homeostasis, Wnt signaling and regulation of transcription factors and microtubules, by phosphorylating and inactivating glycogen synthase (GYS1 or GYS2), CTNNB1/beta-catenin, APC and AXIN1.
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KEGG Pathway | |||||
Reactome Pathway | |||||
Molecular Interaction Atlas (MIA) of This DTT
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1 Approved Drug(s) Targeting This DTT
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2 Clinical Trial Drug(s) Targeting This DTT
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29 Patented Agent(s) Targeting This DTT
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5 Investigative Drug(s) Targeting This DTT
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Molecular Expression Atlas (MEA) of This DTT
References
1 | Challenges and new opportunities in the investigation of new drug therapies to treat frontotemporal dementia. Expert Opin Ther Targets. 2008 Nov;12(11):1367-76. | ||||
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2 | The GSK3 kinase inhibitor lithium produces unexpected hyperphosphorylation of -catenin, a GSK3 substrate, in human glioblastoma cells. Biol Open. 2018 Jan 26;7(1):bio030874. | ||||
3 | Glycogen synthase kinase 3 (GSK-3) inhibitors: a patent update (2014-2015).Expert Opin Ther Pat. 2017 Jun;27(6):657-666. | ||||
4 | Stable generation of serum- and feeder-free embryonic stem cell-derived mice with full germline-competency by using a GSK3 specific inhibitor. Genesis. 2009 Jun;47(6):414-22. | ||||
5 | A zebrafish model of tauopathy allows in vivo imaging of neuronal cell death and drug evaluation. J Clin Invest. 2009 May;119(5):1382-95. | ||||
6 | From a natural product lead to the identification of potent and selective benzofuran-3-yl-(indol-3-yl)maleimides as glycogen synthase kinase 3beta inhibitors that suppress proliferation and survival of pancreatic cancer cells. J Med Chem. 2009 Apr 9;52(7):1853-63. | ||||
7 | Glycogen synthase kinase 3 beta (GSK-3 beta) as a therapeutic target in neuroAIDS. J Neuroimmune Pharmacol. 2007 Mar;2(1):93-6. | ||||
8 | Intracellular protein phosphorylation in eosinophils and the functional relevance in cytokine production. Int Arch Allergy Immunol. 2009;149 Suppl 1:45-50. | ||||