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Details on Person UniProt:P49840 GSK3A
| Class:Id | ReferenceGeneProduct:69666 |
|---|---|
| _chainChangeLog | initiator methionine:1 added on Fri February 6 2015;chain:2-483 added on Fri February 6 2015;initiator methionine:1 for 69666 removed on Fri Nov 03 2023;initiator methionine: for 69666 added on Fri Nov 03 2023;initiator methionine: for 69666 removed on Fri Aug 15 2025;initiator methionine:1 for 69666 added on Fri Aug 15 2025 |
| _displayName | UniProt:P49840 GSK3A |
| _timestamp | 2025-08-15 22:08:24 |
| chain | initiator methionine:1 chain:2-483 |
| checksum | F18C012C03B7D786 |
| comment | 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).CATALYTIC ACTIVITY L-seryl-[tau protein] + ATP = O-phospho-L-seryl-[tau protein] + ADP + H(+)CATALYTIC ACTIVITY L-threonyl-[tau protein] + ATP = O-phospho-L-threonyl-[tau protein] + ADP + H(+)CATALYTIC ACTIVITY L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+)CATALYTIC ACTIVITY L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+)ACTIVITY REGULATION Activated by phosphorylation at Tyr-279. In response to insulin, inhibited by phosphorylation at Ser-21 by PKB/AKT1; phosphorylation at this site causes a conformational change, preventing access of substrates to the active site. Inhibited by lithium.SUBUNIT Monomer. Interacts with ARRB2 (By similarity). Interacts with AXIN1 and CTNNB1/beta-catenin (PubMed:17229088). Interacts with CTNND2 (PubMed:19706605). Interacts with LMBR1L (PubMed:31073040). Interacts with DDX3X (PubMed:18846110). Interacts with TNFRSF10B (PubMed:18846110). Interacts with RICTOR; the interaction results in phosphorylation of RICTOR at 'Thr-1695' by GSK3A which facilitates FBXW7-mediated ubiquitination and subsequent degradation of RICTOR (PubMed:25897075).SUBUNIT (Microbial infection) Interacts with M.tuberculosis PtpA.INTERACTION Phosphorylated by AKT1 at Ser-21: upon insulin-mediated signaling, the activated PKB/AKT1 protein kinase phosphorylates and deactivates GSK3A, resulting in the dephosphorylation and activation of GYS1. Activated by phosphorylation at Tyr-279.PTM (Microbial infection) Dephosphorylated at Tyr-279 by M.tuberculosis PtpA, which leads to prevention of apoptosis during early stages of microbial infection.MISCELLANEOUS Higher expression and activity of GSK3A are found in the skeletal muscle (vastus lateralis) of patients with type 2 diabetes (PubMed:10868943). Several potent GSK3 (GSK3A and GSK3B) inhibitors have been identified and characterized in preclinical models for treatments of type 2 diabetes (PubMed:19366350).SIMILARITY Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. GSK-3 subfamily. |
| description | recommendedName: Glycogen synthase kinase-3 alpha shortName: GSK-3 alpha ecNumber: 2.7.11.26 alternativeName: Serine/threonine-protein kinase GSK3A ecNumber evidence="15 17"2.7.11.1 |
| geneName | GSK3A |
| identifier | P49840 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Acetylation Alzheimer disease ATP-binding Carbohydrate metabolism Diabetes mellitus Glycogen metabolism Kinase Neurogenesis Nucleotide-binding Phosphoprotein Proteomics identification Reference proteome Serine/threonine-protein kinase Signal transduction inhibitor Transferase Wnt signaling pathway |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9862192] Weiser, Joel, 2024-02-26 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 [InstanceEdit:9963647] Weiser, Joel, 2025-08-15 |
| name | GSK3A |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:5642241] ENSEMBL:ENSG00000105723 GSK3A [Homo sapiens] |
| secondaryIdentifier | GSK3A_HUMAN O14959 |
| sequenceLength | 483 |
| species | [Species:48887] Homo sapiens |
| (referenceEntity) | [EntityWithAccessionedSequence:198326] GSK3A [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:198352] p-S21-GSK3A [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:9635490] p-Y279-GSK3A [cytosol] [Homo sapiens] |
| (referenceSequence) | [ModifiedResidue:198353] O-phospho-L-serine at 21 [ModifiedResidue:9665113] O4'-phospho-L-tyrosine at 279 |
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No pathways have been reviewed or authored by UniProt:P49840 GSK3A (69666)
