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FLASH GENE
Symbol GSK3A contributors: mct/shn - updated : 06-03-2019
HGNC name glycogen synthase kinase 3 alpha
HGNC id 4616
Location 19q13.2      Physical location : 42.734.337 - 42.746.736
Synonym symbol(s) GSK3
EC.number 2.7.1.37/ 2.7.11.26/2.7.11.26
DNA
TYPE functioning gene
STRUCTURE 13.14 kb     11 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked   status confirmed
Map cen - D19S198 - D19S423 - GSK3A - D19S872 - D19S211 - tel
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
11 - 2200 51 483 heart, liver, spleen, and highly expressed in lung, ovary, kidney and testis 1990 2164470
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Cardiovascularheart   highly
Lymphoid/Immunespleen   moderately
 thymus   predominantly
Nervousbrain   highly
Reproductivefemale systemovary  predominantly
 male systemprostate  predominantly
 male systemtestis  predominantly
Respiratorylung   highly
Urinarykidney   highly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Blood / hematopoieticplasma  predominantly Homo sapiens
Muscularstriatumskeletal  
cells
SystemCellPubmedSpeciesStageRna symbol
Blood/Hematopoieticneutrophil Homo sapiens
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
protein kinase domains
conjugated
mono polymer monomer
HOMOLOGY
interspecies homolog to shaggy' (zeste-white3), Drosophila
ortholog to Gsk3a, Mus musculus
ortholog to Gsk3a, Rattus norvegicus
ortholog to gsk3a, Danio rerio
ortholog to GSK3A, Pan troglodytes
Homologene
FAMILY
  • protein kinase superfamily
  • CMGC Ser/Thr protein kinase family
  • GSK-3 subfamily
    • CATEGORY enzyme , receptor membrane serine/threonine tyrosine
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,mitochondria
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    text
  • nuclear localization induced by proapoptotic stimuli
  • localized at the growth cone of developing axons
    • basic FUNCTION
  • glycogen synthase kinase, dual-specificity protein-kinase
  • an important regulator of muscle insulin action
  • regulator of glycogen synthesis in skeletal muscle through Tyr (activating) or Ser/Thr (inactivating) phosphorylation
  • key downstream target of PI3-kinase/AKT survival sognaling pathway and involved in regulation of apoptosis
  • regulates mitochondrial outer membrane permeabilization and apoptosis by destabilization of MCL-1
  • regulates microtubule growth and stability, phosphorylating many microtubule associated proteins such as tau, MAP1b and CRMP-2 or APC
  • playing an essential role for axon outgrowth
  • implicated in the control of several regulatory proteins including glycogen synthase
  • plays a role in the WNT and PI3K signaling pathways
  • a downstream effector of PI3K that phosphorylates proteins involved in regulating microtubule dynamics and microtubule-based transport
  • role in NK cell cytotoxicity and X-linked lymphoproliferative disease
  • regulates production of Alzheimer's disease amyloid-beta peptides
  • role in control neurogenesis, neuronal polarization and axon growth and guidance during brain development
  • negatively regulates the expression of the adherens junction protein CDH1, thereby influencing barrier function and inhibiting epithelial–mesenchymal transition (EMT)
  • controls axon growth via CLASP1-mediated regulation of growth cone microtubules
  • new role of GSK3A, GSK3B as regulators of lysosomal biogenesis which could have important consequences in neurodegenerative diseases, such as AD
  • GSK3A is a multifunctional serine/threonine protein kinase that plays a role in the Wnt signaling pathways and is implicated in the control of several regulatory proteins and transcription factors
  • GSK3A contributed to the neuronal architecture of the hippocampal CA1 sub-region that is most vulnerable in Alzheimer disease
  • GSK3A, GSK3B were regulated independently, but that they acted on the same physiological functions in learning and memory, in mobility and in behavior
  • GSK3A is the main isoform expressed in neutrophils and many different pathways can converge to inhibit GSK3A activity via Ser21-phosphorylation
  • GSK3B, but not GSK3A, negatively controls the neuronal differentiation of progenitor cells and GSK3B may act downstream of the mammalian target of rapamycin complex1 signaling pathway
  • cardiac myocyte GSK3A, GSK3B3 is required to maintain normal cardiac homeostasis, and its loss is incompatible with life because of cell cycle dysregulation that ultimately results in a severe fatal dilated cardiomyopathy
  • isoform-specific GSK3A activity is negatively correlated with human sperm motility
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS development , neurogenesis
    text key regulatory enzyme in glucose metabolism
    PATHWAY
    metabolism carbohydrate
    signaling signal transduction
  • wingless signaling pathway
  • autophagy-activating pathway that comprises GSK3A, GSK3B, KAT5, and ULK1
  • novel GSK3A, GSK3B/DPYSL2 pathway that connects neuronal activity to dendritic growth
    • a component
  • inhibitory component
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • Eukaryotic initiation factor eIF2B
  • mediates BCL-3 phosphorylation
  • specific GSK3A substrates, such as APC and collapsin response mediator protein 2 (CRMP2), support axon growth by regulating the stability of axonal microtubules (MTs)
  • redundant functions of GSK3A and GSK3B through phosphorylation of RELA at Thr-254 play a crucial role in early stages of chondrocyte differentiation
  • PRKCA and AKT1 modulate platelet function by phosphorylating and inhibiting GSK3A/GSK3B, thereby relieving the negative effect of GSK3A/GSK3B on thrombin-mediated platelet activation
  • GSK3A regulates osteogenic activity of SP7
  • GSK3A, GSK3B activity status is regulated by the circadian clock and GSK3A, GSK3B feeds back to regulate the molecular clock amplitude in the
  • GSK3A, and PRMT1 cooperate to orchestrate a series of posttranslational modifications on the Intermediate filament (IF) -anchoring protein desmoplakin (DSP) that play an essential role in coordinating cytoskeletal dynamics and cellular adhesion
  • GSK3A is regulated by CREB1 in lung cancer and is required for the cell viability
  • RABEP2 is a novel primed substrate of GSK3A, and thus a potential biomarker for GSK3A activity
    • cell & other
    REGULATION
    inhibited by serine phosphorylation in response to extracellular cues
    GSK-3 binding protein GBP
    insulin mediated by protein kinase B
    repressed by protein kinase A
    Other may be regulated by multiple mechanisms and its basal activity subjected to activation or inhibition
    phosphorylated and inactivated by AKT
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
  • Inhibition of GSK3 in a preclinical murine model of MLL leukaemia provides promising evidence of efficacy and earmarks GSK3 as a candidate cancer drug target
    • ANIMAL & CELL MODELS
  • alterations of GSK3 profoundly affect neuronal morphology in culture
  • knockdown of both GSK3B markedly reduced axon growth in dissociated cultures
  • concomitant loss of Gsk3a and Gsk3b in the oocyte significantly increased neonatal death rate due to congestive heart failure secondary to ventricular hyperplasia
  • dominant-negative GSK-3 Xenopus mutants induced dorsal differentiation, whereas wild-type GSK-3 induced ventralization
  • disruption of the Gsk3a gene in testis results in normal spermatogenesis, but mature sperm present a reduced motility, rendering male mice infertile