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GSK3A a constitutively active proline-directed protein kinase of the GSK family. A negative regulator in the hormonal control of glucose homeostasis, Wnt signaling and regulation of transcription factors and microtubule. Phosphorylates and inactivates glycogen synthase (GYS1 or GYS2), CTNNB1/beta-catenin, APC and AXIN1. Generally requires primed phosphorylation sites C-terminal to the targeted serine or threonine residues in its substrate. 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 factor deprivation. A GSK3 promoter SNP effects progression of bipolar disorder. The GSK3 inhibitor, lithium, is used to treat bipolar disorder and is seen to block plaque formation. GSK3 generally opposes the action of insulin, and GSK3 hyperactivity is thought to contribute to insulin resistant (type II) diabetes. GSK3 also negatively regulates cardiac hypertrophy. A tumor suppressor role is indicated by the oncogenic potential of stabilized b-catenin mutants that lack GSK3 phosphorylation sites. Note: This description may include information from UniProtKB.
Protein type: CMGC group; EC; EC; GSK family; GSK subfamily; Kinase, protein; Protein kinase, CMGC; Protein kinase, Ser/Thr (non-receptor)
Chromosomal Location of Human Ortholog: 19q13.2
Cellular Component: beta-catenin destruction complex; cell soma; cytosol; microtubule; mitochondrion; postsynapse; proximal dendrite
Molecular Function: ATP binding; protein binding; protein serine/threonine kinase activity; tau-protein kinase activity
Biological Process: aging; cardiac left ventricle morphogenesis; cell migration; cellular response to insulin stimulus; cellular response to lithium ion; cellular response to organic cyclic compound; dopamine receptor signaling pathway; genetic imprinting; glycogen metabolic process; insulin receptor signaling pathway; IRE1-mediated unfolded protein response; negative regulation of canonical Wnt signaling pathway; 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; positive regulation of adrenergic receptor signaling pathway; positive regulation of amyloid-beta formation; positive regulation of cAMP biosynthetic process; 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 protein catabolic process; positive regulation of protein targeting to mitochondrion; positive regulation of transcription from RNA polymerase II promoter; proteasomal ubiquitin-dependent protein catabolic process; protein amino acid phosphorylation; regulation of systemic arterial blood pressure; Wnt signaling pathway
Reference #:  P49840 (UniProtKB)
Alt. Names/Synonyms: DKFZp686D0638; glycogen synthase kinase 3 alpha; Glycogen synthase kinase-3 alpha; GSK-3 alpha; GSK3A
Gene Symbols: GSK3A
Molecular weight: 50,981 Da
Basal Isoelectric point: 8.95  Predict pI for various phosphorylation states
CST Pathways:  Adherens Junction Dynamics  |  Alzheimer's Disease  |  B Cell Receptor Signaling  |  ErbB/HER Signaling  |  ESC Pluripotency and Differentiation  |  Growth And Differentiation Control by MAPKs  |  Inhibition of Apoptosis  |  Insulin Receptor Signaling  |  mTOR Signaling  |  PI3K/Akt Signaling  |  Translation: eIF4E and p70S6K  |  Wnt/ß-Catenin Signaling
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