GSK3A - Glycogen synthase kinase-3 alpha - human protein (Function)
 
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GSK3A »  Glycogen synthase kinase-3 alpha   [ EC 2.7.11.26 ]  (GSK-3 alpha)
 
Protein also known as:  Serine/threonine-protein kinase GSK3A [EC 2.7.11.1].
Gene name:  GSK3A
Entry whose protein(s) existence is based on evidence at protein level
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GENE REF ISO

Function

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Overview 
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. 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. Through phosphorylation of the anti-apoptotic protein MCL1, may control cell apoptosis in response to growth factors deprivation.  
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  • CuratedUniProtKB
GO molecular function 
ATP bindingdefinition[GO:0005524]  
  • IEAUniProtKB KW
Protein bindingdefinition[GO:0005515]  
5
  • IPIIntAct
Protein kinase A catalytic subunit bindingdefinition[GO:0034236]  
1
  • IPIBHF-UCL
Protein serine/threonine kinase activitydefinition[GO:0004674]  
1
  • IDABHF-UCL
Tau-protein kinase activitydefinition[GO:0050321]  
1
  • TASUniProtKB
GO biological process 
Cardiac left ventricle morphogenesisdefinition[GO:0003214]  
  • ISSOrtholog Curator
Cellular response to insulin stimulusdefinition[GO:0032869]  
1
  • IMPBHF-UCL
Cellular response to interleukin-3definition[GO:0036016]  
  • ISSOrtholog Curator
Extrinsic apoptotic signaling pathway in absence of liganddefinition[GO:0097192]  
  • ISSOrtholog Curator
Glycogen metabolic processdefinition[GO:0005977]  
  • IEAUniProtKB KW
Insulin receptor signaling pathwaydefinition[GO:0008286]  
1
  • ISSBHF-UCL
Negative regulation of canonical Wnt signaling pathwaydefinition[GO:0090090]  
1
  • TASUniProtKB
Negative regulation of cell growth involved in cardiac muscle cell developmentdefinition[GO:0061052]  
  • ISSOrtholog Curator
Negative regulation of glucose importdefinition[GO:0046325]  
1
  • IMPBHF-UCL
Negative regulation of glycogen (starch) synthase activitydefinition[GO:2000466]  
1
  • TASUniProtKB
Negative regulation of glycogen biosynthetic processdefinition[GO:0045719]  
1
  • TASUniProtKB
Negative regulation of insulin receptor signaling pathwaydefinition[GO:0046627]  
1
  • IMPBHF-UCL
Negative regulation of TOR signalingdefinition[GO:0032007]  
  • ISSOrtholog Curator
Negative regulation of transferase activitydefinition[GO:0051348]  
1
  • IMPBHF-UCL
Negative regulation of type B pancreatic cell developmentdefinition[GO:2000077]  
1
  • TASUniProtKB
Negative regulation of UDP-glucose catabolic processdefinition[GO:0010905]  
1
  • ICUniProtKB
Nervous system developmentdefinition[GO:0007399]  
  • IEAUniProtKB KW
Positive regulation of adrenergic receptor signaling pathwaydefinition[GO:0071879]  
  • ISSOrtholog Curator
Positive regulation of cAMP biosynthetic processdefinition[GO:0030819]  
  • ISSOrtholog Curator
Positive regulation of glycogen (starch) synthase activitydefinition[GO:2000467]  
  • ISSOrtholog Curator
Positive regulation of heart contractiondefinition[GO:0045823]  
  • ISSOrtholog Curator
Positive regulation of mitochondrial outer membrane permeabilizationdefinition[GO:1901030]  
  • ISSOrtholog Curator
Positive regulation of protein catabolic processdefinition[GO:0045732]  
1
  • NASBHF-UCL
Proteasome-mediated ubiquitin-dependent protein catabolic processdefinition[GO:0043161]  
  • ISSOrtholog Curator
Protein phosphorylationdefinition[GO:0006468]  
1
  • IDABHF-UCL
Regulation of systemic arterial blood pressuredefinition[GO:0003073]  
  • ISSOrtholog Curator
Wnt signaling pathwaydefinition[GO:0016055]  
  • IEAUniProtKB KW
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reactions
EC 2.7.11.26: ATP + [tau protein] ADP + [tau protein] phosphate.  
  • CuratedUniProtKB
EC 2.7.11.1: ATP + a protein ADP + a phosphoprotein.  
  • CuratedUniProtKB
It is regulated in the following manner
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.  
  • CuratedUniProtKB
Pathways 
According to KEGG, this protein belongs to the following pathways:
Chemokine signaling pathway  hsa04062+2931  
Dopaminergic synapse  hsa04728+2931  
According to Reactome, this protein belongs to the following pathways:
Disease  REACT_116125  
Immune System  REACT_6900  
Metabolism of proteins  REACT_17015  
Signal Transduction  REACT_111102  
Note 
Higher expression and activity of GSK3A are found in the skeletal muscle (vastus lateralis) of patients with type 2 diabetes (PubMed10868943). Several potent GSK3 (GSK3A and GSK3B) inhibitors have been identified and characterized in preclinical models for treatments of type 2 diabetes (PubMed19366350).  
2
  • CuratedUniProtKB
 

Keywords

Biological process 
Carbohydrate metabolism  definition   [KW-0119]
Glycogen metabolism  definition   [KW-0321]
Neurogenesis  definition   [KW-0524]
Wnt signaling pathway  definition   [KW-0879]
Molecular function 
Kinase  definition   [KW-0418]
Serine/threonine-protein kinase  definition   [KW-0723]
Signal transduction inhibitor  definition   [KW-0734]
Transferase  definition   [KW-0808]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: GSK3A
GenomeRNAi: 2931
PRO: PR:P49840
Chemistry
GuidetoPHARMACOLOGY: 2029