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    GSK3B glycogen synthase kinase 3 beta [ Homo sapiens (human) ]

    Gene ID: 2932, updated on 13-Jun-2021

    Summary

    Official Symbol
    GSK3Bprovided by HGNC
    Official Full Name
    glycogen synthase kinase 3 betaprovided by HGNC
    Primary source
    HGNC:HGNC:4617
    See related
    Ensembl:ENSG00000082701 MIM:605004
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Summary
    The protein encoded by this gene is a serine-threonine kinase belonging to the glycogen synthase kinase subfamily. It is a negative regulator of glucose homeostasis and is involved in energy metabolism, inflammation, ER-stress, mitochondrial dysfunction, and apoptotic pathways. Defects in this gene have been associated with Parkinson disease and Alzheimer disease. [provided by RefSeq, Aug 2017]
    Expression
    Ubiquitous expression in brain (RPKM 13.9), thyroid (RPKM 9.9) and 25 other tissues See more
    Orthologs
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See GSK3B in Genome Data Viewer
    Location:
    3q13.33
    Exon count:
    13
    Annotation release Status Assembly Chr Location
    109.20210514 current GRCh38.p13 (GCF_000001405.39) 3 NC_000003.12 (119821321..120095823, complement)
    105.20201022 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (119540168..119813294, complement)

    Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene cilia and flagella associated protein 91 Neighboring gene nuclear receptor subfamily 1 group I member 2 Neighboring gene prohibitin pseudogene 8 Neighboring gene presenilin associated rhomboid like pseudogene Neighboring gene Sharpr-MPRA regulatory region 13833 Neighboring gene uncharacterized LOC107986119 Neighboring gene microRNA 6529 Neighboring gene RNA, 7SL, cytoplasmic 762, pseudogene Neighboring gene RNA, 7SL, cytoplasmic 397, pseudogene

    Genomic regions, transcripts, and products

    Expression

    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    Phenotypes

    Associated conditions

    Description Tests
    Discovery and refinement of loci associated with lipid levels.
    GeneReviews: Not available

    HIV-1 interactions

    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env PDGF protects neurons from gp120-induced cytotoxicity through an increased phosphorylation of both GSK-3beta and Bad, the downregulation of the proapoptotic protein Bax, and inhibition of gp120-induced release of mitochondrial cytochrome C PubMed
    env Insulin-like growth factor-I (IGF-I) and erythropoietin treatment protect against HIV/gp120-mediated neuronal damage in culture and in vivo, in part, through cooperative activation of phosphatidylinositol 3-kinase/Akt/GSK-3beta signaling PubMed
    Nef nef Incubation of human macrophages with exogenous HIV-1 Nef protein induces phosphorylation of Akt and GSK-3ss, and promotes IL-10 release PubMed
    Tat tat GSK-3beta inhibitors 6BIO, 6BIOder, and 18BIOder have neuroprotective effects on Tat induced cell death in rat mixed hippocampal cultures PubMed
    tat HIV-1 Tat induces phosphorylation of PI3K, AKT, PTEN, and GSK-3beta activating PI3K and AKT and inactivating PTEN and GSK-3beta in vIL-6 expressing cells PubMed
    tat PDGF-C mediated neuroprotection against HIV-1 Tat results from inactivation of the downstream mediator GSK3beta by its phosphorylation at Ser-9 in human neuroblastoma cells PubMed
    tat PI3K/Akt, TRPC, and GSK3beta signaling pathways are all involved in PDGF-C mediated neuroprotection against HIV-1 Tat in human neuroblastoma cells PubMed
    tat HIV-1 Tat associates with glycogen synthase kinase-3beta (GSK-3beta) in rat cerebellar granule neurons and increases GSK-3beta activity, suggesting dysregulation of this enzyme could contribute to HIV-induced neuronal apoptosis PubMed
    Vpr vpr Treatment of cultured dorsal root ganglion sensory neurons with HIV-1 Vpr downregulates expression of TrKA and pGSK3beta/GSK3beta proteins and pre-treatment with NGF inhibits this Vpr-induced downregulation of TrKA and pGSK3beta/GSK3beta PubMed
    Vpu vpu In vitro protein-protein interaction analysis identifies a Vpu-binding host protein glycogen synthase kinase 3 beta (GSK3B) PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
     
    enables NF-kappaB binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables RNA polymerase II-specific DNA-binding transcription factor binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables beta-catenin binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    enables beta-catenin binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables dynactin binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables kinase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables p53 binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables protease binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein kinase A catalytic subunit binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein kinase activity IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    enables protein kinase activity TAS
    Traceable Author Statement
    more info
    PubMed 
    enables protein kinase binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein serine kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables protein serine/threonine kinase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    enables protein serine/threonine kinase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables protein serine/threonine kinase activity IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    enables protein serine/threonine kinase activity ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    enables protein serine/threonine kinase activity NAS
    Non-traceable Author Statement
    more info
    PubMed 
    enables protein threonine kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    enables tau protein binding NAS
    Non-traceable Author Statement
    more info
    PubMed 
    enables tau-protein kinase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    enables tau-protein kinase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables tau-protein kinase activity NAS
    Non-traceable Author Statement
    more info
    PubMed 
    enables ubiquitin protein ligase binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    Process Evidence Code Pubs
    acts_upstream_of_or_within ER overload response IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in Wnt signaling pathway TAS
    Traceable Author Statement
    more info
     
    involved_in beta-catenin destruction complex assembly TAS
    Traceable Author Statement
    more info
     
    involved_in beta-catenin destruction complex disassembly TAS
    Traceable Author Statement
    more info
     
    involved_in cellular response to amyloid-beta ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in cellular response to interleukin-3 ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in circadian rhythm ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in dopamine receptor signaling pathway NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in epithelial to mesenchymal transition IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in establishment of cell polarity ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in establishment of cell polarity TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in excitatory postsynaptic potential NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in extrinsic apoptotic signaling pathway ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in extrinsic apoptotic signaling pathway in absence of ligand IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    involved_in extrinsic apoptotic signaling pathway in absence of ligand ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in glycogen metabolic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in hippocampus development IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in insulin receptor signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    acts_upstream_of_or_within intracellular signal transduction IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in intracellular signal transduction TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in maintenance of cell polarity ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in maintenance of cell polarity TAS
    Traceable Author Statement
    more info
    PubMed 
    acts_upstream_of_or_within negative regulation of apoptotic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in negative regulation of calcineurin-NFAT signaling cascade IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in negative regulation of canonical Wnt signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    involved_in negative regulation of canonical Wnt signaling pathway IC
    Inferred by Curator
    more info
    PubMed 
    involved_in negative regulation of canonical Wnt signaling pathway ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in negative regulation of canonical Wnt signaling pathway TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in negative regulation of dopaminergic neuron differentiation TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in negative regulation of extrinsic apoptotic signaling pathway via death domain receptors IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in negative regulation of glycogen (starch) synthase activity TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in negative regulation of glycogen biosynthetic process TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in negative regulation of neuron death IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in negative regulation of phosphoprotein phosphatase activity TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in negative regulation of protein acetylation ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in negative regulation of protein binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in negative regulation of protein localization to nucleus ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in negative regulation of protein-containing complex assembly IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in negative regulation of type B pancreatic cell development TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in neuron projection development IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in neuron projection organization ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    acts_upstream_of_or_within peptidyl-serine phosphorylation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in peptidyl-serine phosphorylation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in peptidyl-threonine phosphorylation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of GTPase activity IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of autophagy ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in positive regulation of cell-matrix adhesion IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of gene expression ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in positive regulation of mitochondrion organization IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of neuron death IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of proteasomal ubiquitin-dependent protein catabolic process IC
    Inferred by Curator
    more info
    PubMed 
    involved_in positive regulation of proteasomal ubiquitin-dependent protein catabolic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of proteasomal ubiquitin-dependent protein catabolic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of protein binding ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in positive regulation of protein catabolic process IC
    Inferred by Curator
    more info
    PubMed 
    acts_upstream_of_or_within positive regulation of protein export from nucleus IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of protein localization to centrosome IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of protein-containing complex assembly IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in protein autophosphorylation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in protein phosphorylation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in protein phosphorylation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in protein phosphorylation TAS
    Traceable Author Statement
    more info
    PubMed 
    involved_in regulation of axon extension ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in regulation of axonogenesis ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in regulation of cellular response to heat TAS
    Traceable Author Statement
    more info
     
    involved_in regulation of circadian rhythm ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in regulation of dendrite morphogenesis ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in regulation of long-term synaptic potentiation ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in regulation of microtubule anchoring at centrosome IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in regulation of microtubule cytoskeleton organization IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    involved_in regulation of microtubule cytoskeleton organization ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    involved_in regulation of microtubule-based process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in regulation of neuron projection development IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    involved_in regulation of synaptic vesicle exocytosis EXP
    Inferred from Experiment
    more info
    PubMed 
    involved_in regulation of synaptic vesicle exocytosis IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in regulation of synaptic vesicle exocytosis IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in signal transduction IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    involved_in superior temporal gyrus development IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in viral protein processing TAS
    Traceable Author Statement
    more info
     
    Component Evidence Code Pubs
    part_of Wnt signalosome TAS
    Traceable Author Statement
    more info
    PubMed 
    is_active_in axon IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    located_in axon ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    part_of beta-catenin destruction complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    part_of beta-catenin destruction complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    part_of beta-catenin destruction complex TAS
    Traceable Author Statement
    more info
    PubMed 
    located_in centrosome IDA
    Inferred from Direct Assay
    more info
    PubMed 
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    PubMed 
    is_active_in cytosol IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    located_in cytosol TAS
    Traceable Author Statement
    more info
     
    located_in dendrite ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    located_in glutamatergic synapse EXP
    Inferred from Experiment
    more info
    PubMed 
    is_active_in glutamatergic synapse IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    located_in glutamatergic synapse IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in glutamatergic synapse IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    located_in mitochondrion IEA
    Inferred from Electronic Annotation
    more info
     
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
     
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
     
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in plasma membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in postsynapse IEA
    Inferred from Electronic Annotation
    more info
     

    General protein information

    Preferred Names
    glycogen synthase kinase-3 beta
    Names
    GSK-3 beta
    serine/threonine-protein kinase GSK3B
    NP_001139628.1
    NP_001341525.1
    NP_002084.2
    XP_006713673.1

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_012922.1 RefSeqGene

      Range
      4971..278097
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001146156.2NP_001139628.1  glycogen synthase kinase-3 beta isoform 2

      See identical proteins and their annotated locations for NP_001139628.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (2) has the same N- and C-termini but is shorter compared to isoform 1.
      Source sequence(s)
      AC069444, AC092910, BC012760, CA312249, DA477189
      Consensus CDS
      CCDS54628.1
      UniProtKB/Swiss-Prot
      P49841
      UniProtKB/TrEMBL
      Q6FI27
      Related
      ENSP00000264235.9, ENST00000264235.13
      Conserved Domains (1) summary
      cd14137
      Location:51343
      STKc_GSK3; The catalytic domain of the Serine/Threonine Kinase, Glycogen Synthase Kinase 3
    2. NM_001354596.2NP_001341525.1  glycogen synthase kinase-3 beta isoform 3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks two alternate in-frame exons compared to variant 1. The resulting isoform (3) has the same N- and C-termini but is shorter compared to isoform 1.
      Source sequence(s)
      AC069444, AC078856, AC092910
      Related
      ENSP00000497956.2, ENST00000650344.2
      Conserved Domains (1) summary
      cd14137
      Location:51343
      STKc_GSK3; The catalytic domain of the Serine/Threonine Kinase, Glycogen Synthase Kinase 3
    3. NM_002093.4NP_002084.2  glycogen synthase kinase-3 beta isoform 1

      See identical proteins and their annotated locations for NP_002084.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
      Source sequence(s)
      AC069444, AC092910, BC000251, BC012760, CA312249, DA477189
      Consensus CDS
      CCDS2996.1
      UniProtKB/Swiss-Prot
      P49841
      Related
      ENSP00000324806.5, ENST00000316626.6
      Conserved Domains (1) summary
      cd14137
      Location:51356
      STKc_GSK3; The catalytic domain of the Serine/Threonine Kinase, Glycogen Synthase Kinase 3

    RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20210514

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p13 Primary Assembly

    Genomic

    1. NC_000003.12 Reference GRCh38.p13 Primary Assembly

      Range
      119821321..120095823 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_006713610.3XP_006713673.1  glycogen synthase kinase-3 beta isoform X1

      See identical proteins and their annotated locations for XP_006713673.1

      Conserved Domains (1) summary
      cd14137
      Location:51356
      STKc_GSK3; The catalytic domain of the Serine/Threonine Kinase, Glycogen Synthase Kinase 3

    RNA

    1. XR_002959518.1 RNA Sequence

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