General Information of the Protein
Protein ID |
PT00931
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Protein Name |
Glycogen synthase kinase-3 alpha
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Secondarily Protein Name |
Serine/threonine-protein kinase GSK3A
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Gene Name |
GSK3A
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Sequence |
MSGGGPSGGGPGGSGRARTSSFAEPGGGGGGGGGGPGGSASGPGGTGGGKASVGAMGGGVGASSSGGGPGGSGGGGSGGPGAGTSFPPPGVKLGRDSGKVTTVVATLGQGPERSQEVAYTDIKVIGNGSFGVVYQARLAETRELVAIKKVLQDKRFKNRELQIMRKLDHCNIVRLRYFFYSSGEKKDELYLNLVLEYVPETVYRVARHFTKAKLTIPILYVKVYMYQLFRSLAYIHSQGVCHRDIKPQNLLVDPDTAVLKLCDFGSAKQLVRGEPNVSYICSRYYRAPELIFGATDYTSSIDVWSAGCVLAELLLGQPIFPGDSGVDQLVEIIKVLGTPTREQIREMNPNYTEFKFPQIKAHPWTKVFKSRTPPEAIALCSSLLEYTPSSRLSPLEACAHSFFDELRCLGTQLPNNRPLPPLFNFSAGELSIQPSLNAILIPPHLRSPAGTTTLTPSSQALTETPTSSDWQSTDATPTLTNSS
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Organism |
Homo sapiens, Human
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Protein Classification |
Enzyme
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Kinase
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Protein Kinase
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CMGC protein kinase group
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CMGC protein kinase GSK family
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Function |
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 (PubMed:11749387, PubMed:17478001, PubMed:19366350). Requires primed phosphorylation of the majority of its substrates (PubMed:11749387, PubMed:17478001, PubMed:19366350). Contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glycogen synthesis (PubMed:11749387, PubMed:17478001, PubMed:19366350). Regulates glycogen metabolism in liver, but not in muscle (By similarity). May also mediate the development of insulin resistance by regulating activation of transcription factors (PubMed:10868943, PubMed:17478001). In Wnt signaling, regulates the level and transcriptional activity of nuclear CTNNB1/beta-catenin (PubMed:17229088). Facilitates amyloid precursor protein (APP) processing and the generation of APP-derived amyloid plaques found in Alzheimer disease (PubMed:12761548). May be involved in the regulation of replication in pancreatic beta-cells (By similarity). Is necessary for the establishment of neuronal polarity and axon outgrowth (By similarity). Through phosphorylation of the anti-apoptotic protein MCL1, may control cell apoptosis in response to growth factors deprivation (By similarity). Acts as a regulator of autophagy by mediating phosphorylation of KAT5/TIP60 under starvation conditions which activates KAT5/TIP60 acetyltransferase activity and promotes acetylation of key autophagy regulators, such as ULK1 and RUBCNL/Pacer (PubMed:30704899). Negatively regulates extrinsic apoptotic signaling pathway via death domain receptors. Promotes the formation of an anti-apoptotic complex, made of DDX3X, BRIC2 and GSK3B, at death receptors, including TNFRSF10B. The anti-apoptotic function is most effective with weak apoptotic signals and can be overcome by stronger stimulation (By similarity). Phosphorylates mTORC2 complex component RICTOR at 'Thr-1695' which facilitates FBXW7-mediated ubiquitination and subsequent degradation of RICTOR (PubMed:25897075).
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Uniprot ID |
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HGNC ID |
Map of Molecular Bioactivity Related to the Protein
Map of Molecular Bioactivity Related to the Protein Protein Cell Line Compound Bioactivity Value: <= 0.1 μM > 0.1 μM and <= 10 μM > 10 μM Imprecise Activity |
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Table of Molecular Bioactivities Related to the Protein
Cell Line ID: CL000025 , HEK-293T
Cell Line ID: CL000013 , Sf9
Biochemical Assays
Clinical Information about the Protein
Target 1 ( Glycogen synthase kinase-3 alpha (GSK-3A) )
Target Type | Successful Target | ||||
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Disease | 5 Target-related Diseases | 5 | |||
1 | Epilepsy [ICD-11: 8A60-8A68] | ||||
2 | Acute myeloid leukaemia [ICD-11: 2A60] | ||||
3 | Ovarian cancer [ICD-11: 2C73] | ||||
4 | Graft rejection [ICD-11: NE84] | ||||
5 | Malignant glioma [ICD-11: 2A00.0] | ||||
Approved Drug(s) | 1 Approved Drug | 1 | |||
1 | Valproate | Approved | |||
Clinical Trial Drug(s) | 1 Clinical Trial Drug | 1 | |||
1 | LY2090314 | Phase 2 | |||
Patented Agent(s) | 3 Patented Agents | 3 | |||
1 | AR-A014418 | Patented | |||
2 | CHIR-99021 | Patented | |||
3 | TDZD-8 | Patented |
Target 2 ( GSK3A messenger RNA (GSK3A mRNA) )
Target Type | Literature-reported Target |
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