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

    Gene ID: 2932, updated on 5-Jan-2025

    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; AllianceGenome:HGNC:4617
    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
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    Try the new Transcript table

    Genomic context

    See GSK3B in Genome Data Viewer
    Location:
    3q13.33
    Exon count:
    12
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (119821321..120094447, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (122541048..122814129, complement)
    RS_2024_09 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 uncharacterized LOC105374064 Neighboring gene NANOG-H3K4me1 hESC enhancer GRCh37_chr3:119421355-119422034 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20324 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20325 Neighboring gene cilia and flagella associated protein 91 Neighboring gene Sharpr-MPRA regulatory region 6912 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:119528543-119529046 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr3:119534511-119535011 Neighboring gene nuclear receptor subfamily 1 group I member 2 Neighboring gene PHB1 pseudogene 8 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20327 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20328 Neighboring gene ReSE screen-validated silencer GRCh37_chr3:119691277-119691494 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:119722393-119722919 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:119722920-119723445 Neighboring gene PARL pseudogene 1 Neighboring gene RFK pseudogene 3 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14634 Neighboring gene Sharpr-MPRA regulatory region 13833 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20330 Neighboring gene microRNA 6529 Neighboring gene GSK3B divergent transcript Neighboring gene RNA, 7SL, cytoplasmic 762, pseudogene

    Genomic regions, transcripts, and products

    Expression

    • Project title: Tissue-specific circular RNA induction during human fetal development
    • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
    • BioProject: PRJNA270632
    • Publication: PMID 26076956
    • Analysis date: Mon Apr 2 22:54:59 2018

    Bibliography

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    Phenotypes

    BioGRID CRISPR Screen Phenotypes (79 hits/1340 screens)

    EBI GWAS Catalog

    Description
    Discovery and refinement of loci associated with lipid levels.
    EBI GWAS Catalog

    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

    General gene information

    Gene Ontology Provided by GOA

    Items 1 - 25 of 47
    Function Evidence Code Pubs
    enables 3-phosphoinositide-dependent protein kinase activity  
    enables AMP-activated protein kinase activity  
    enables ATP binding  
    enables DNA-dependent protein kinase activity  
    enables NF-kappaB binding PubMed 
    enables RNA polymerase II-specific DNA-binding transcription factor binding PubMed 
    enables Rho-dependent protein serine/threonine kinase activity  
    enables beta-catenin binding  
    enables beta-catenin binding PubMed 
    enables dynactin binding PubMed 
    enables eukaryotic translation initiation factor 2alpha kinase activity  
    enables histone H2AS1 kinase activity  
    enables histone H2AS121 kinase activity  
    enables histone H2AT120 kinase activity  
    enables histone H2AXS139 kinase activity  
    enables histone H2BS14 kinase activity  
    enables histone H2BS36 kinase activity  
    enables histone H3S10 kinase activity  
    enables histone H3S28 kinase activity  
    enables histone H3S57 kinase activity  
    enables histone H3T11 kinase activity  
    enables histone H3T3 kinase activity  
    enables histone H3T45 kinase activity  
    enables histone H3T6 kinase activity  
    enables histone H4S1 kinase activity  
    enables kinase activity PubMed 
    enables p53 binding PubMed 
    enables protease binding PubMed 
    enables protein binding PubMed 
    enables protein kinase A catalytic subunit binding PubMed 
    enables protein kinase activity PubMed 
    enables protein kinase activity PubMed 
    enables protein kinase binding PubMed 
    enables protein serine kinase activity PubMed 
    enables protein serine/threonine kinase activity  
    enables protein serine/threonine kinase activity PubMed 
    enables protein serine/threonine kinase activity PubMed 
    enables protein serine/threonine kinase activity  
    enables protein serine/threonine kinase activity PubMed 
    enables protein serine/threonine kinase activity  
    enables ribosomal protein S6 kinase activity  
    enables scaffold protein binding PubMed 
    enables tau protein binding PubMed 
    enables tau-protein kinase activity  
    enables tau-protein kinase activity PubMed 
    enables tau-protein kinase activity PubMed 
    enables ubiquitin protein ligase binding PubMed 
    Items 1 - 25 of 47
    Items 1 - 25 of 97
    Process Evidence Code Pubs
    acts_upstream_of_or_within ER overload response PubMed 
    involved_in G protein-coupled dopamine receptor signaling pathway PubMed 
    involved_in beta-catenin destruction complex disassembly  
    involved_in canonical Wnt signaling pathway PubMed 
    involved_in canonical Wnt signaling pathway  
    involved_in cell differentiation  
    involved_in cellular response to amyloid-beta  
    involved_in cellular response to interleukin-3  
    involved_in cellular response to retinoic acid PubMed 
    involved_in chromatin remodeling  
    involved_in circadian rhythm  
    involved_in epithelial to mesenchymal transition PubMed 
    involved_in establishment of cell polarity  
    involved_in establishment of cell polarity PubMed 
    involved_in excitatory postsynaptic potential PubMed 
    involved_in extrinsic apoptotic signaling pathway  
    involved_in extrinsic apoptotic signaling pathway in absence of ligand  
    involved_in glycogen metabolic process PubMed 
    involved_in hippocampus development PubMed 
    involved_in insulin receptor signaling pathway  
    acts_upstream_of_or_within intracellular signal transduction PubMed 
    involved_in intracellular signal transduction PubMed 
    involved_in maintenance of cell polarity  
    involved_in maintenance of cell polarity PubMed 
    involved_in mitochondrion organization PubMed 
    involved_in negative regulation of TOR signaling  
    involved_in negative regulation of TORC2 signaling PubMed 
    acts_upstream_of_or_within negative regulation of apoptotic process PubMed 
    involved_in negative regulation of calcineurin-NFAT signaling cascade PubMed 
    involved_in negative regulation of canonical Wnt signaling pathway  
    involved_in negative regulation of canonical Wnt signaling pathway PubMed 
    involved_in negative regulation of canonical Wnt signaling pathway PubMed 
    involved_in negative regulation of canonical Wnt signaling pathway PubMed 
    involved_in negative regulation of canonical Wnt signaling pathway  
    involved_in negative regulation of canonical Wnt signaling pathway PubMed 
    involved_in negative regulation of cell migration PubMed 
    involved_in negative regulation of dopaminergic neuron differentiation PubMed 
    involved_in negative regulation of epithelial to mesenchymal transition PubMed 
    involved_in negative regulation of extrinsic apoptotic signaling pathway via death domain receptors PubMed 
    acts_upstream_of negative regulation of gene expression PubMed 
    involved_in negative regulation of glycogen (starch) synthase activity PubMed 
    involved_in negative regulation of glycogen biosynthetic process PubMed 
    involved_in negative regulation of mesenchymal stem cell differentiation PubMed 
    involved_in negative regulation of osteoblast differentiation PubMed 
    involved_in negative regulation of protein acetylation  
    involved_in negative regulation of protein localization to nucleus  
    involved_in negative regulation of protein-containing complex assembly PubMed 
    involved_in negative regulation of type B pancreatic cell development PubMed 
    involved_in neuron projection development PubMed 
    involved_in neuron projection organization  
    acts_upstream_of_or_within peptidyl-serine phosphorylation PubMed 
    involved_in peptidyl-serine phosphorylation PubMed 
    involved_in peptidyl-threonine phosphorylation PubMed 
    involved_in positive regulation of GTPase activity PubMed 
    involved_in positive regulation of autophagy  
    involved_in positive regulation of autophagy  
    involved_in positive regulation of cell differentiation PubMed 
    involved_in positive regulation of cell-matrix adhesion PubMed 
    involved_in positive regulation of cilium assembly  
    acts_upstream_of positive regulation of gene expression PubMed 
    involved_in positive regulation of gene expression  
    involved_in positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway  
    involved_in positive regulation of neuron apoptotic process  
    involved_in positive regulation of proteasomal ubiquitin-dependent protein catabolic process  
    involved_in positive regulation of proteasomal ubiquitin-dependent protein catabolic process PubMed 
    involved_in positive regulation of proteasomal ubiquitin-dependent protein catabolic process PubMed 
    involved_in positive regulation of proteasomal ubiquitin-dependent protein catabolic process PubMed 
    involved_in positive regulation of protein binding  
    involved_in positive regulation of protein catabolic process PubMed 
    acts_upstream_of_or_within positive regulation of protein export from nucleus PubMed 
    involved_in positive regulation of protein localization to centrosome PubMed 
    involved_in positive regulation of protein localization to cilium  
    involved_in positive regulation of protein ubiquitination PubMed 
    involved_in positive regulation of protein-containing complex assembly PubMed 
    involved_in presynaptic modulation of chemical synaptic transmission PubMed 
    involved_in presynaptic modulation of chemical synaptic transmission PubMed 
    involved_in presynaptic modulation of chemical synaptic transmission PubMed 
    involved_in proteasome-mediated ubiquitin-dependent protein catabolic process PubMed 
    involved_in protein autophosphorylation PubMed 
    involved_in protein phosphorylation PubMed 
    involved_in protein phosphorylation PubMed 
    involved_in protein phosphorylation PubMed 
    involved_in regulation of axon extension  
    involved_in regulation of axonogenesis  
    involved_in regulation of cellular response to heat  
    involved_in regulation of circadian rhythm  
    involved_in regulation of dendrite morphogenesis  
    involved_in regulation of long-term synaptic potentiation  
    involved_in regulation of microtubule anchoring at centrosome PubMed 
    involved_in regulation of microtubule cytoskeleton organization  
    involved_in regulation of microtubule cytoskeleton organization  
    involved_in regulation of microtubule-based process PubMed 
    involved_in regulation of neuron projection development  
    involved_in regulation of protein export from nucleus PubMed 
    involved_in regulation of protein export from nucleus  
    involved_in superior temporal gyrus development PubMed 
    involved_in viral protein processing  
    Items 1 - 25 of 97
    Items 1 - 20 of 27
    Component Evidence Code Pubs
    part_of Wnt signalosome PubMed 
    is_active_in axon  
    located_in axon  
    part_of beta-catenin destruction complex  
    part_of beta-catenin destruction complex PubMed 
    part_of beta-catenin destruction complex PubMed 
    part_of beta-catenin destruction complex PubMed 
    located_in centrosome PubMed 
    is_active_in cytoplasm  
    located_in cytoplasm PubMed 
    located_in cytoplasm  
    is_active_in cytosol  
    located_in cytosol  
    located_in dendrite  
    is_active_in glutamatergic synapse PubMed 
    is_active_in glutamatergic synapse  
    is_active_in glutamatergic synapse PubMed 
    is_active_in glutamatergic synapse PubMed 
    located_in mitochondrion  
    located_in nucleoplasm  
    located_in nucleoplasm  
    is_active_in nucleus  
    located_in nucleus PubMed 
    located_in nucleus  
    located_in plasma membrane PubMed 
    located_in postsynapse  
    located_in presynapse  
    Items 1 - 20 of 27

    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
    XP_054202359.1

    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_001146156.2 → NP_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
      D3DN89, P49841, Q9BWH3, Q9UL47
      UniProtKB/TrEMBL
      B5BUC0, D3DN88, Q6FI27
      Related
      ENSP00000264235.9, ENST00000264235.13
      Conserved Domains (1) summary
      cd14137
      Location:51 → 343
      STKc_GSK3; The catalytic domain of the Serine/Threonine Kinase, Glycogen Synthase Kinase 3
    2. NM_001354596.2 → NP_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
      Consensus CDS
      CCDS93346.1
      UniProtKB/TrEMBL
      A0A3B3ITW1, B5BUC0
      Related
      ENSP00000497956.2, ENST00000650344.2
      Conserved Domains (1) summary
      cd14137
      Location:51 → 343
      STKc_GSK3; The catalytic domain of the Serine/Threonine Kinase, Glycogen Synthase Kinase 3
    3. NM_002093.4 → NP_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/TrEMBL
      B5BUC0
      Related
      ENSP00000324806.5, ENST00000316626.6
      Conserved Domains (1) summary
      cd14137
      Location:51 → 356
      STKc_GSK3; The catalytic domain of the Serine/Threonine Kinase, Glycogen Synthase Kinase 3

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000003.12 Reference GRCh38.p14 Primary Assembly

      Range
      119821321..120094447 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_006713610.4 → XP_006713673.1  glycogen synthase kinase-3 beta isoform X1

      See identical proteins and their annotated locations for XP_006713673.1

      UniProtKB/TrEMBL
      B5BUC0
      Conserved Domains (1) summary
      cd14137
      Location:51 → 356
      STKc_GSK3; The catalytic domain of the Serine/Threonine Kinase, Glycogen Synthase Kinase 3

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060927.1 Alternate T2T-CHM13v2.0

      Range
      122541048..122814129 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054346384.1 → XP_054202359.1  glycogen synthase kinase-3 beta isoform X1

      UniProtKB/TrEMBL
      B5BUC0
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