KinaseMD - GSK3A

GSK3A 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, leading to activate KAT5/TIP60 acetyltransferase activity and promote 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). View more >>

GO - Biological processes (BP): aging, cardiac left ventricle morphogenesis, cell migration, cellular response to insulin stimulus, cellular response to interleukin-3, cellular response to lithium ion, dopamine receptor signaling pathway, excitatory postsynaptic potential, extrinsic apoptotic signaling pathway, extrinsic apoptotic signaling pathway in absence of ligand, glycogen metabolic process, hypermethylation of CpG island, insulin receptor signaling pathway, IRE1-mediated unfolded protein response, negative regulation of canonical Wnt signaling pathway, negative regulation of cell growth involved in cardiac muscle cell development, negative regulation of dendrite development, negative regulation of glucose import, negative regulation of glycogen (starch) synthase activity, negative regulation of glycogen biosynthetic process, negative regulation of glycogen synthase activity, transferring glucose-1-phosphate, negative regulation of insulin receptor signaling pathway, negative regulation of TOR signaling, negative regulation of type B pancreatic cell development, negative regulation of UDP-glucose catabolic process, peptidyl-serine phosphorylation, peptidyl-threonine phosphorylation, positive regulation of adenylate cyclase-activating adrenergic receptor signaling pathway, positive regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway, positive regulation of amyloid-beta formation, positive regulation of autophagy, positive regulation of gene expression, positive regulation of glycogen (starch) synthase activity, positive regulation of heart contraction, positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway, positive regulation of neuron apoptotic process, positive regulation of peptidyl-serine phosphorylation, positive regulation of peptidyl-threonine phosphorylation, positive regulation of proteasomal ubiquitin-dependent protein catabolic process, positive regulation of protein catabolic process, positive regulation of protein targeting to mitochondrion, positive regulation of protein ubiquitination, positive regulation of transcription by RNA polymerase II, proteasome-mediated ubiquitin-dependent protein catabolic process, protein phosphorylation, regulation of autophagy of mitochondrion, regulation of gene expression by genetic imprinting, regulation of neuron projection development, regulation of systemic arterial blood pressure, signal transduction, Wnt signaling pathway View more >>

GO - Molecular function (MF): View more >>

GO - Cellular component (CC): View more >>

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KinaseMD: Kinase mutations and drug responses

GSK3A

Entrez ID: 2931

Full name: glycogen synthase kinase 3 alpha

External links: HGNC UniprotKB Ensembl RefSeq COSMIC

Family: CMGC: GSK: GSK

Chromosomal location: 19q13.2

Substructure location: Gatekeeper: 195 A-loop: 262...272, 274...284 G-loop: [N/A] αC-helix: [N/A]

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Kaplan plot for GSK3A in