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FLASH GENE
Symbol GSK3A contributors: mct/shn - updated : 24-11-2010
HGNC name glycogen synthase kinase 3 alpha
HGNC id 4616
Location 19q13.2      Physical location : 42.734.337 - 42.746.736
EC.number 2.7.1.37
DNA
TYPE functioning gene
STRUCTURE 12.00 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
Physical map
LOC388544 19 similar to Heterogeneous nuclear ribonucleoprotein A1 (Helix-destabilizing protein) (Single-strand binding protein) (hnRNP core protein A1) (HDP-1) (Topoisomerase-inhibitor suppressed) MGC42718 19q13.31 hypothetical protein MGC42718 DMRTC2 19q13.31 DMRT-like family C2 RPS19 19q13.2 ribosomal protein S19 CD79A 19q13.2-q13.3 CD79A antigen (immunoglobulin-associated alpha) ARHGEF1 19q13,13 Rho guanine nucleotide exchange factor (GEF) 1 LOC390937 19 similar to Erf RABAC1 19q13.13-q13.2 Rab acceptor 1 (prenylated) ATP1A3 19q13.2 ATPase, Na+/K+ transporting, alpha 3 polypeptide GRIK5 19q13.2 glutamate receptor, ionotropic, kainate 5 FLJ22059 19q13.31 hypothetical protein FLJ22059 POU2F2 19q13.31 POU domain, class 2, transcription factor 2 DEDD2 19q13.31 POU domain, class 2, transcription factor 2 KIAA1951 GSK3A 19q13.2 glycogen synthase kinase 3 alpha ERF 19q13.1 Ets2 repressor factor CIC 19q13.2 capicua homolog (Drosophila) PAFAH1B3 19q13.1 platelet-activating factor acetylhydrolase, isoform Ib, gamma subunit 29kDa MGC70924 19q13.31 hypothetical LOC284338 FLJ90805 19q13.31 hypothetical protein FLJ90805 EGFL4 19q12 EGF-like-domain, multiple 4 SBP1 19q13.31 HBV pre-s2 binding protein 1 LOC84518 19q13.31 protein related with psoriasis LIPE 19q13.1-q13.2 lipase, hormone-sensitive UNQ473 19q13.31 DMC LOC388545 19 similar to Zinc finger protein 216 CEACAM1 19q13.2 carcinoembryonic antigen-related cell adhesion molecule 1 (biliary glycoprotein) CEACAMP2 19q13.2 carcinoembryonic antigen-related cell adhesion molecule pseudogene 2 CEACAM8 19q13.2 carcinoembryonic antigen-related cell adhesion molecule 8
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
Muscularstriatumskeletal  
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,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
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS development , neurogenesis
    text key regulatory enzyme in glucose metabolism
    PATHWAY
    metabolism carbohydrate
    signaling signal transduction
    wingless signaling pathway
    a component
  • inhibitory component
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • mediates BCL-3 phosphorylation
  • Eukaryotic initiation factor eIF2B
  • specific GSK3A substrates, such as APC and collapsin response mediator protein 2 (CRMP2), support axon growth by regulating the stability of axonal microtubules (MTs)
  • 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
  • dominant-negative GSK-3 Xenopus mutants induced dorsal differentiation, whereas wild-type GSK-3 induced ventralization