ID:GSK3A_HUMAN DESCRIPTION: RecName: Full=Glycogen synthase kinase-3 alpha; Short=GSK-3 alpha; EC=2.7.11.26; AltName: Full=Serine/threonine-protein kinase GSK3A; EC=2.7.11.1; FUNCTION: Constitutively active protein kinase that acts as a negative regulator in the hormonal control of glucose homeostasis, Wnt signaling and regulation of transctiption factors and microtubules, by phosphorylating and inactivating glycogen synthase (GYS1 or GYS2), CTNNB1/beta-catenin, APC and AXIN1. 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. CATALYTIC ACTIVITY: ATP + [tau protein] = ADP + [tau protein] phosphate. CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. ENZYME 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. INTERACTION: O75398:DEAF1; NbExp=2; IntAct=EBI-1044067, EBI-718185; PTM: Phosphorylated by AKT1 at Ser-21: upon insulin-mediated signaling, the activated PKB/AKT1 protein kinase phosphorylates and desactivates GSK3A, resulting in the dephosphorylation and activation of GYS1. Activated by phosphorylation at Tyr-279. 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. SIMILARITY: Contains 1 protein kinase domain.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P49840
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0003073 regulation of systemic arterial blood pressure GO:0003214 cardiac left ventricle morphogenesis GO:0005975 carbohydrate metabolic process GO:0005977 glycogen metabolic process GO:0006349 regulation of gene expression by genetic imprinting GO:0006468 protein phosphorylation GO:0007212 dopamine receptor signaling pathway GO:0007399 nervous system development GO:0007568 aging GO:0008286 insulin receptor signaling pathway GO:0009968 negative regulation of signal transduction GO:0010628 positive regulation of gene expression GO:0010800 positive regulation of peptidyl-threonine phosphorylation GO:0010905 negative regulation of UDP-glucose catabolic process GO:0016055 Wnt signaling pathway GO:0016310 phosphorylation GO:0016477 cell migration GO:0018105 peptidyl-serine phosphorylation GO:0018107 peptidyl-threonine phosphorylation GO:0031398 positive regulation of protein ubiquitination GO:0032007 negative regulation of TOR signaling GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process GO:0032869 cellular response to insulin stimulus GO:0033138 positive regulation of peptidyl-serine phosphorylation GO:0036016 cellular response to interleukin-3 GO:0036498 IRE1-mediated unfolded protein response GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process GO:0043525 positive regulation of neuron apoptotic process GO:0044027 hypermethylation of CpG island GO:0045719 negative regulation of glycogen biosynthetic process GO:0045732 positive regulation of protein catabolic process GO:0045823 positive regulation of heart contraction GO:0045944 positive regulation of transcription from RNA polymerase II promoter GO:0046325 negative regulation of glucose import GO:0046627 negative regulation of insulin receptor signaling pathway GO:0060079 excitatory postsynaptic potential GO:0061052 negative regulation of cell growth involved in cardiac muscle cell development GO:0071285 cellular response to lithium ion GO:0071407 cellular response to organic cyclic compound GO:0071879 positive regulation of adrenergic receptor signaling pathway GO:0090090 negative regulation of canonical Wnt signaling pathway GO:0097191 extrinsic apoptotic signaling pathway GO:0097192 extrinsic apoptotic signaling pathway in absence of ligand GO:1901030 positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway GO:1902004 positive regulation of beta-amyloid formation GO:1903146 regulation of mitophagy GO:1903955 positive regulation of protein targeting to mitochondrion GO:1904227 negative regulation of glycogen synthase activity, transferring glucose-1-phosphate GO:2000077 negative regulation of type B pancreatic cell development GO:2000171 negative regulation of dendrite development GO:2000466 negative regulation of glycogen (starch) synthase activity GO:2000467 positive regulation of glycogen (starch) synthase activity
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Common Gene Haplotype Alleles 
