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Aliases for GSK3A Gene

Aliases for GSK3A Gene

  • Glycogen Synthase Kinase 3 Alpha 2 3
  • EC 2.7.11.26 4 63
  • Serine/Threonine-Protein Kinase GSK3A 4
  • GSK-3 Alpha 4
  • EC 2.7.11.1 4
  • EC 2.7.11 63

External Ids for GSK3A Gene

Summaries for GSK3A Gene

Entrez Gene Summary for GSK3A Gene

  • This gene encodes a multifunctional Ser/Thr protein kinase that is implicated in the control of several regulatory proteins including glycogen synthase, and transcription factors, such as JUN. It also plays a role in the WNT and PI3K signaling pathways, as well as regulates the production of beta-amyloid peptides associated with Alzheimer's disease. [provided by RefSeq, Oct 2011]

GeneCards Summary for GSK3A Gene

GSK3A (Glycogen Synthase Kinase 3 Alpha) is a Protein Coding gene. Diseases associated with GSK3A include alzheimer disease and schizophrenia. Among its related pathways are PI-3K cascade and PI-3K cascade. GO annotations related to this gene include protein serine/threonine kinase activity and protein kinase A catalytic subunit binding. An important paralog of this gene is GSK3B.

UniProtKB/Swiss-Prot for GSK3A Gene

  • 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.

Tocris Summary for GSK3A Gene

  • Glycogen synthase kinase 3 (GSK-3), a serine-threonine kinase with two isoforms (alpha and beta), was originally discovered as a key enzyme in glycogen metabolism. GSK-3 was subsequently shown to function in cell division, proliferation, motility and survival. GSK-3 plays a role in a number of pathological conditions including cancer and diabetes and is increasingly seen as an important component of neurological diseases. GSK-3 phosphorylates tau and presenilin-1, which are involved in the development of Alzheimers disease. Both isoforms of GSK-3 are ubiquitously expressed, although particularly high levels of GSK-3beta are found in the brain where it is involved in synaptic plasticity, possibly via regulation of NMDA receptor trafficking. GSK-3 phosphorylates over 40 different substrates including signaling proteins, transcription factors and structural proteins, and is part of the signal transduction cascade of a large number of growth factors and cytokines. The activity of GSK is regulated by phosphorylation (Akt, S6K, RSK, PKA and PKC), dephosphorylation (PP1 and PP2A), and by binding to protein complexes (with beta-catenin, axin, CK1 and the APC complex).

Gene Wiki entry for GSK3A Gene

No data available for PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for GSK3A Gene

Genomics for GSK3A Gene

Genomic Location for GSK3A Gene

Start:
42,230,186 bp from pter
End:
42,242,625 bp from pter
Size:
12,440 bases
Orientation:
Minus strand

Genomic View for GSK3A Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for GSK3A Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for GSK3A Gene

Regulatory Elements for GSK3A Gene

Proteins for GSK3A Gene

  • Protein details for GSK3A Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P49840-GSK3A_HUMAN
    Recommended name:
    Glycogen synthase kinase-3 alpha
    Protein Accession:
    P49840
    Secondary Accessions:
    • O14959

    Protein attributes for GSK3A Gene

    Size:
    483 amino acids
    Molecular mass:
    50981 Da
    Quaternary structure:
    • Monomer. Interacts with ARRB2 (By similarity). Interacts with AXIN1 and CTNNB1/beta-catenin.
    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).

    Three dimensional structures from OCA and Proteopedia for GSK3A Gene

neXtProt entry for GSK3A Gene

Proteomics data for GSK3A Gene at MOPED

Post-translational modifications for GSK3A Gene

  • 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
  • Modification sites at PhosphoSitePlus
  • Ubiquitination at Lys268, Lys355, and Lys360

Other Protein References for GSK3A Gene

ENSEMBL proteins:
Reactome Protein details:
REFSEQ proteins:

Domains for GSK3A Gene

Gene Families for GSK3A Gene

Suggested Antigen Peptide Sequences for GSK3A Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

P49840

UniProtKB/Swiss-Prot:

GSK3A_HUMAN
Domain:
  • Contains 1 protein kinase domain.:
    • P49840
Family:
  • Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. GSK-3 subfamily.:
    • P49840
genes like me logo Genes that share domains with GSK3A: view

Function for GSK3A Gene

Molecular function for GSK3A Gene

GENATLAS Biochemistry: glycogen synthase kinase 3 alpha,regulator of glycogen synthesis in skeletal muscle,unstabilized in response to insulin with both protein level and activity increased by heat stress
UniProtKB/Swiss-Prot CatalyticActivity: ATP + [tau protein] = ADP + [tau protein] phosphate
UniProtKB/Swiss-Prot CatalyticActivity: ATP + a protein = ADP + a phosphoprotein
UniProtKB/Swiss-Prot EnzymeRegulation: 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.
UniProtKB/Swiss-Prot Function: 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.

Enzyme Numbers (IUBMB) for GSK3A Gene

Gene Ontology (GO) - Molecular Function for GSK3A Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004672 protein kinase activity --
GO:0004674 protein serine/threonine kinase activity IDA 11035810
GO:0004713 protein tyrosine kinase activity --
GO:0005515 protein binding IPI 16365045
GO:0005524 ATP binding IEA --
genes like me logo Genes that share ontologies with GSK3A: view
genes like me logo Genes that share phenotypes with GSK3A: view

Animal Models for GSK3A Gene

MGI Knock Outs for GSK3A:

miRNA for GSK3A Gene

No data available for Transcription Factor Targeting and HOMER Transcription for GSK3A Gene

Localization for GSK3A Gene

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for GSK3A Gene COMPARTMENTS Subcellular localization image for GSK3A gene
Compartment Confidence
cytosol 4
nucleus 3
cytoskeleton 1
mitochondrion 1

Gene Ontology (GO) - Cellular Components for GSK3A Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005829 cytosol TAS 11035810
GO:0030877 beta-catenin destruction complex TAS 19366350
genes like me logo Genes that share ontologies with GSK3A: view

No data available for Subcellular locations from UniProtKB/Swiss-Prot for GSK3A Gene

Pathways for GSK3A Gene

SuperPathways for GSK3A Gene

genes like me logo Genes that share pathways with GSK3A: view

Gene Ontology (GO) - Biological Process for GSK3A Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003073 regulation of systemic arterial blood pressure ISS --
GO:0003214 cardiac left ventricle morphogenesis ISS --
GO:0005977 glycogen metabolic process IEA --
GO:0006349 regulation of gene expression by genetic imprinting --
GO:0006468 protein phosphorylation IDA 11035810
genes like me logo Genes that share ontologies with GSK3A: view

Compounds for GSK3A Gene

(6) ApexBio Compounds for GSK3A Gene

Compound Action Cas Number
AR-A014418 Cell-permeable GSK-3beta inhibitor [487021-52-3]
CHIR-98014 selective and ATP-competitive inhibitor of GSK-3beta. [252935-94-7]
CHIR-99021 (CT99021) Cell-permeable, ATP-competitive GSK-3 inhibitor [252917-06-9]
LY2090314 potent inhibitor of glycogen synthase kinase-3 [603288-22-8]
SB 216763 Potent and selective, ATP-competitive GSK-3 inhibitor. [280744-09-4]
SB 415286 Potent and selective GSK-3 inhibitor. [264218-23-7]

(5) Tocris Compounds for GSK3A Gene

Compound Action Cas Number
BIO Potent, selective GSK-3 inhibitor [667463-62-9]
BIO-acetoxime Selective GSK-3alpha/beta inhibitor [667463-85-6]
MeBIO Inactive analog of BIO (Cat. No. 3194) [667463-95-8]
SB 216763 Potent, selective GSK-3 inhibitor [280744-09-4]
TWS 119 GSK-3beta inhibitor; induces neuronal differentiation in ESCs [601514-19-6]

(2) HMDB Compounds for GSK3A Gene

Compound Synonyms Cas Number PubMed IDs
Adenosine triphosphate
  • 5'-(tetrahydrogen triphosphate) Adenosine
56-65-5
ADP
  • adenosindiphosphorsaeure
58-64-0

(7) Novoseek inferred chemical compound relationships for GSK3A Gene

Compound -log(P) Hits PubMed IDs
glycogen 83.2 27
lithium 54.2 2
serine 52.7 5
threonine 47.2 4
okadaic acid 32.2 5
genes like me logo Genes that share compounds with GSK3A: view

Transcripts for GSK3A Gene

mRNA/cDNA for GSK3A Gene

Unigene Clusters for GSK3A Gene

Glycogen synthase kinase 3 alpha:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for GSK3A Gene

ExUns: 1a · 1b ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10a · 10b ^ 11 ^ 12
SP1: -
SP2:
SP3:

Relevant External Links for GSK3A Gene

GeneLoc Exon Structure for
GSK3A
ECgene alternative splicing isoforms for
GSK3A

Expression for GSK3A Gene

mRNA expression in normal human tissues for GSK3A Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for GSK3A Gene

SOURCE GeneReport for Unigene cluster for GSK3A Gene Hs.466828

genes like me logo Genes that share expressions with GSK3A: view

No data available for mRNA differential expression in normal tissues and mRNA Expression by UniProt/SwissProt for GSK3A Gene

Orthologs for GSK3A Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for GSK3A Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia GSK3A 35
  • 99.59 (n)
  • 99.59 (a)
GSK3A 36
  • 100 (a)
OneToMany
cow
(Bos Taurus)
Mammalia GSK3A 35
  • 93.52 (n)
  • 96.21 (a)
GSK3A 36
  • 92 (a)
OneToMany
dog
(Canis familiaris)
Mammalia -- 36
  • 93 (a)
OneToMany
GSK3A 35
  • 93.22 (n)
  • 96.48 (a)
mouse
(Mus musculus)
Mammalia Gsk3a 35
  • 89.53 (n)
  • 95.09 (a)
Gsk3a 16
Gsk3a 36
  • 93 (a)
OneToMany
rat
(Rattus norvegicus)
Mammalia Gsk3a 35
  • 91.52 (n)
  • 97.01 (a)
lizard
(Anolis carolinensis)
Reptilia -- 36
  • 83 (a)
OneToMany
tropical clawed frog
(Silurana tropicalis)
Amphibia gsk3a 35
  • 75.37 (n)
  • 86.26 (a)
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.1135 35
zebrafish
(Danio rerio)
Actinopterygii gsk3a 35
gsk3aa 35
  • 76.75 (n)
  • 88.52 (a)
gsk3aa 36
  • 74 (a)
ManyToMany
gsk3ab 36
  • 79 (a)
ManyToMany
fruit fly
(Drosophila melanogaster)
Insecta gskt 36
  • 47 (a)
ManyToMany
Pk34A 36
  • 36 (a)
ManyToMany
sgg 36
  • 25 (a)
ManyToMany
sgg 37
  • 78 (a)
Pk34A 37
  • 40 (a)
gskt 37
  • 61 (a)
CG6800 37
  • 35 (a)
worm
(Caenorhabditis elegans)
Secernentea gsk-3 36
  • 69 (a)
OneToMany
C44H4.6 37
  • 44 (a)
Y18D10A.5 37
  • 76 (a)
Y106G6D.4 37
  • 31 (a)
F21F3.2 37
  • 32 (a)
R03D7.5 37
  • 37 (a)
C36B1.10 37
  • 30 (a)
A. gosspyii yeast
(Ashbya gossypii)
Saccharomycetes AGOS_ADR253W 35
  • 61.92 (n)
  • 60.6 (a)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes MCK1 38
MRK1 36
  • 37 (a)
ManyToMany
RIM11 35
  • 58.76 (n)
  • 59.32 (a)
RIM11 36
  • 49 (a)
ManyToMany
K. lactis yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0F17006g 35
  • 54.53 (n)
  • 54.63 (a)
Alicante grape
(Vitis vinifera)
eudicotyledons Vvi.3400 35
thale cress
(Arabidopsis thaliana)
eudicotyledons ATSK12 35
  • 62.75 (n)
  • 67.05 (a)
rice
(Oryza sativa)
Liliopsida Os01g0252100 35
  • 63.82 (n)
  • 67.24 (a)
wheat
(Triticum aestivum)
Liliopsida Ta.3019 35
bread mold
(Neurospora crassa)
Ascomycetes NCU04185 35
  • 67.57 (n)
  • 69.88 (a)
fission yeast
(Schizosaccharomyces pombe)
Schizosaccharomycetes gsk3 35
  • 55.28 (n)
  • 61.9 (a)
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.5080 35
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 75 (a)
OneToMany
Species with no ortholog for GSK3A:
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • chicken (Gallus gallus)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • oppossum (Monodelphis domestica)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • platypus (Ornithorhynchus anatinus)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)

Evolution for GSK3A Gene

ENSEMBL:
Gene Tree for GSK3A (if available)
TreeFam:
Gene Tree for GSK3A (if available)

Paralogs for GSK3A Gene

Paralogs for GSK3A Gene

genes like me logo Genes that share paralogs with GSK3A: view

Variants for GSK3A Gene

Sequence variations from dbSNP and Humsavar for GSK3A Gene

SNP ID Clin Chr 19 pos Sequence Context AA Info Type MAF
rs708598 -- 42,241,771(+) GACAG(C/G)GAATG intron-variant
rs851609 -- 42,232,115(+) GGGAT(A/G)AGAAT reference, synonymous-codon
rs851610 -- 42,235,531(+) TGACA(C/T)GGCTG intron-variant
rs860387 -- 42,237,997(+) gcctc(A/G)ggctc intron-variant
rs1054311 -- 42,230,530(-) GCCCC(C/T)TCCCC utr-variant-3-prime

Structural Variations from Database of Genomic Variants (DGV) for GSK3A Gene

Variant ID Type Subtype PubMed ID
nsv522854 CNV Gain 19592680
nsv520239 CNV Loss 19592680
nsv911782 CNV Loss 21882294
nsv833833 CNV Loss 17160897
nsv526186 CNV Gain 19592680
esv2422471 CNV Deletion 17116639
nsv833834 CNV Loss 17160897
dgv3884n71 CNV Loss 21882294
nsv911785 CNV Loss 21882294

Relevant External Links for GSK3A Gene

HapMap Linkage Disequilibrium report
GSK3A

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for GSK3A Gene

Disorders for GSK3A Gene

(8) Novoseek inferred disease relationships for GSK3A Gene

Disease -log(P) Hits PubMed IDs
neurofibrillary tangles 51.3 1
brain diseases 42.4 3
alzheimers disease 41 5
neoplastic transformation 34.8 1
shock 12.2 1

Relevant External Links for GSK3A

Genetic Association Database (GAD)
GSK3A
Human Genome Epidemiology (HuGE) Navigator
GSK3A
genes like me logo Genes that share disorders with GSK3A: view

No data available for UniProtKB/Swiss-Prot for GSK3A Gene

Publications for GSK3A Gene

  1. Isolation and chromosomal mapping of human glycogen synthase kinase-3 alpha and -3 beta encoding genes. (PMID: 9809441) Shaw P.C. … Anderton B.H. (Genome 1998) 2 3 23
  2. Phosphorylation and inactivation of glycogen synthase kinase 3 by protein kinase A. (PMID: 11035810) Fang X. … Mills G.B. (Proc. Natl. Acad. Sci. U.S.A. 2000) 3 23
  3. Protein kinase FA/glycogen synthase kinase-3 alpha after heparin potentiation phosphorylates tau on sites abnormally phosphorylated in Alzheimer's disease brain. (PMID: 7931292) Yang S.D. … Huang J.J. (J. Neurochem. 1994) 3 23
  4. Insulin receptor substrate-2 phosphorylation is necessary for protein kinase C zeta activation by insulin in L6hIR cells. (PMID: 11481324) Oriente F. … Beguinot F. (J. Biol. Chem. 2001) 3 23
  5. GSK-3 parameters in lymphocytes of schizophrenic patients. (PMID: 12379450) Nadri C. … Bersudsky Y. (Psychiatry Res 2002) 3 23

Products for GSK3A Gene

  • Addgene plasmids for GSK3A

Sources for GSK3A Gene

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