GSK3B Gene (Protein Coding)

Glycogen Synthase Kinase 3 Beta

GC03M119821
GIFtS:
51
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 ... See more...

Aliases for GSK3B Gene

Aliases for GSK3B Gene

  • Glycogen Synthase Kinase 3 Beta 2 3 5
  • Serine/Threonine-Protein Kinase GSK3B 3 4
  • Glycogen Synthase Kinase-3 Beta 3 4
  • EC 2.7.11.26 4 52
  • GSK-3 Beta 3 4
  • GSK3beta Isoform 3
  • EC 2.7.11.1 4
  • EC 2.7.11 52

External Ids for GSK3B Gene

Previous GeneCards Identifiers for GSK3B Gene

  • GC03M116184
  • GC03M119174
  • GC03M120822
  • GC03M120866
  • GC03M121028
  • GC03M119540
  • GC03M116916

Summaries for GSK3B Gene

Entrez Gene Summary for GSK3B Gene

  • 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]

GeneCards Summary for GSK3B Gene

GSK3B (Glycogen Synthase Kinase 3 Beta) is a Protein Coding gene. Diseases associated with GSK3B include Alzheimer Disease and Bipolar Disorder. Among its related pathways are MicroRNAs in cardiomyocyte hypertrophy and Downstream signaling events of B Cell Receptor (BCR). Gene Ontology (GO) annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity. An important paralog of this gene is GSK3A.

UniProtKB/Swiss-Prot Summary for GSK3B 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), EIF2B, CTNNB1/beta-catenin, APC, AXIN1, DPYSL2/CRMP2, JUN, NFATC1/NFATC, MAPT/TAU and MACF1. Requires primed phosphorylation of the majority of its substrates. In skeletal muscle, contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glycogen synthesis. May also mediate the development of insulin resistance by regulating activation of transcription factors. Regulates protein synthesis by controlling the activity of initiation factor 2B (EIF2BE/EIF2B5) in the same manner as glycogen synthase. In Wnt signaling, GSK3B forms a multimeric complex with APC, AXIN1 and CTNNB1/beta-catenin and phosphorylates the N-terminus of CTNNB1 leading to its degradation mediated by ubiquitin/proteasomes. Phosphorylates JUN at sites proximal to its DNA-binding domain, thereby reducing its affinity for DNA. Phosphorylates NFATC1/NFATC on conserved serine residues promoting NFATC1/NFATC nuclear export, shutting off NFATC1/NFATC gene regulation, and thereby opposing the action of calcineurin. Phosphorylates MAPT/TAU on 'Thr-548', decreasing significantly MAPT/TAU ability to bind and stabilize microtubules. MAPT/TAU is the principal component of neurofibrillary tangles in Alzheimer disease. Plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex. Phosphorylates MACF1, inhibiting its binding to microtubules which is critical for its role in bulge stem cell migration and skin wound repair. Probably regulates NF-kappa-B (NFKB1) at the transcriptional level and is required for the NF-kappa-B-mediated anti-apoptotic response to TNF-alpha (TNF/TNFA). Negatively regulates replication in pancreatic beta-cells, resulting in apoptosis, loss of beta-cells and diabetes. Through phosphorylation of the anti-apoptotic protein MCL1, may control cell apoptosis in response to growth factors deprivation. Phosphorylates MUC1 in breast cancer cells, decreasing the interaction of MUC1 with CTNNB1/beta-catenin. Is necessary for the establishment of neuronal polarity and axon outgrowth. Phosphorylates MARK2, leading to inhibit its activity. Phosphorylates SIK1 at 'Thr-182', leading to sustain its activity. Phosphorylates ZC3HAV1 which enhances its antiviral activity. Phosphorylates SNAI1, leading to its BTRC-triggered ubiquitination and proteasomal degradation. Phosphorylates SFPQ at 'Thr-687' upon T-cell activation. Phosphorylates NR1D1 st 'Ser-55' and 'Ser-59' and stabilizes it by protecting it from proteasomal degradation. Regulates the circadian clock via phosphorylation of the major clock components including ARNTL/BMAL1, CLOCK and PER2 (PubMed:19946213, PubMed:28903391). Phosphorylates CLOCK AT 'Ser-427' and targets it for proteasomal degradation (PubMed:19946213). Phosphorylates ARNTL/BMAL1 at 'Ser-17' and 'Ser-21' and primes it for ubiquitination and proteasomal degradation (PubMed:28903391). Phosphorylates OGT at 'Ser-3' or 'Ser-4' which positively regulates its activity. Phosphorylates MYCN in neuroblastoma cells which may promote its degradation (PubMed:24391509). Regulates the circadian rhythmicity of hippocampal long-term potentiation and ARNTL/BMLA1 and PER2 expression (By similarity). Acts as a regulator of autophagy by mediating phosphorylation of KAT5/TIP60 under starvation conditions, leading to activate KAT5/TIP60 acetyltransferase activity and promote acetylation of key autophagy regulators, such as ULK1 and RUBCNL/Pacer (PubMed:30704899). Negatively regulates extrinsic apoptotic signaling pathway via death domain receptors. Promotes the formation of an anti-apoptotic complex, made of DDX3X, BRIC2 and GSK3B, at death receptors, including TNFRSF10B. The anti-apoptotic function is most effective with weak apoptotic signals and can be overcome by stronger stimulation (PubMed:18846110).

Tocris Summary for GSK3B Gene

  • Glycogen synthase kinase 3 (GSK-3) is a serine-threonine kinase with two isoforms (alpha and beta), that was originally discovered as an important enzyme in glycogen metabolism. GSK-3 was subsequently shown to function in cellular division, proliferation, motility and survival.

Gene Wiki entry for GSK3B Gene

Additional gene information for GSK3B Gene

No data available for CIViC Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for GSK3B Gene

Genomics for GSK3B Gene

GeneHancer (GH) Regulatory Elements for GSK3B Gene

Promoters and enhancers for GSK3B Gene
GeneHancer (GH) Identifier GH Type GH
Score		 GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites		 Gene Targets
GH03J120089 Promoter/Enhancer 2.3 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 516.3 +1.1 1065 8.3 HNRNPK ZBTB40 ZNF217 EP300 ZSCAN5C SIN3A TCF12 NRF1 POLR2G SP1 GSK3B ENSG00000242622 POGLUT1 TMEM39A B4GALT4 RPS26P21 FSTL1 MIR6529-001
GH03J120048 Enhancer 0.8 Ensembl 28.4 +43.6 43616 5.2 ZSCAN5C ZNF10 ZNF423 TRIM28 ATF2 OSR2 ZBTB17 ZNF524 SPI1 OVOL3 GSK3B ENSG00000242622 MAATS1 POGLUT1 ENSG00000241546 lnc-NR1I2-4 piR-56480-042
GH03J119825 Enhancer 1 Ensembl ENCODE 17.3 +267.8 267799 1.6 NCOR1 KDM6A ZBTB26 ZSCAN9 FOXA2 NR2F2 SAP130 ZBTB33 RBM22 ZNF205 GSK3B HSALNG0028349 RF00994-675 lnc-COX17-2
GH03J119892 Enhancer 0.8 Ensembl ENCODE 16.4 +202.1 202116 1 CTCF REST RAD21 TRIM22 SMC3 DEK FOXA2 MXI1 FOXA1 ZNF654 GSK3B B4GALT4 RF00994-676 lnc-COX17-2 RF00994-675
GH03J120143 Enhancer 1.4 FANTOM5 Ensembl ENCODE dbSUPER 9.2 -52.4 -52364 5.9 ZNF217 CTCF TEAD4 CLOCK TCF7 KLF4 RAD21 EP300 TEAD1 GATAD2B LOC105374065 GSK3B ENSG00000240661 GPR156 COX17 piR-52566
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around GSK3B on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for GSK3B

Top Transcription factor binding sites by QIAGEN in the GSK3B gene promoter:
  • CREB
  • deltaCREB
  • FOXO1
  • FOXO1a
  • FOXO4
  • HNF-4alpha1

Genomic Locations for GSK3B Gene

Genomic Locations for GSK3B Gene
chr3:119,821,321-120,094,417
(GRCh38/hg38)
Size:
273,097 bases
Orientation:
Minus strand
chr3:119,540,170-119,813,264
(GRCh37/hg19)
Size:
273,095 bases
Orientation:
Minus strand

Genomic View for GSK3B Gene

Genes around GSK3B on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
GSK3B Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for GSK3B Gene
GeneLoc Logo Genomic Neighborhood • Exon Structure • Gene Density

RefSeq DNA sequence for GSK3B Gene

Proteins for GSK3B Gene

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  • Protein details for GSK3B Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P49841-GSK3B_HUMAN
    Recommended name:
    Glycogen synthase kinase-3 beta
    Protein Accession:
    P49841
    Secondary Accessions:
    • D3DN89
    • Q9BWH3
    • Q9UL47

    Protein attributes for GSK3B Gene

    Size:
    420 amino acids
    Molecular mass:
    46744 Da
    Quaternary structure:
    • Monomer. Interacts with ARRB2, DISC1 and ZBED3 (By similarity). Interacts with CABYR, MMP2, MUC1, NIN and PRUNE1. Interacts with AXIN1; the interaction mediates hyperphosphorylation of CTNNB1 leading to its ubiquitination and destruction. Interacts with and phosphorylates SNAI1. Interacts with DNM1L (via a C-terminal domain). Found in a complex composed of MACF1, APC, AXIN1, CTNNB1 and GSK3B (By similarity). Interacts with SGK3. Interacts with DAB2IP (via C2 domain); the interaction stimulates GSK3B kinase activation. Interacts (via C2 domain) with PPP2CA. Interacts with the CLOCK-ARNTL/BMAL1 heterodimer (PubMed:19946213). Interacts with the ARNTL/BMAL1 (PubMed:28903391). Interacts with CTNND2 (PubMed:19706605). Interacts with NCYM (PubMed:24391509). The complex composed, at least, of APC, CTNNB1 and GSK3B interacts with JPT1; the interaction requires the inactive form of GSK3B (phosphorylated at 'Ser-9') (PubMed:25169422). Forms a complex composed of PRKAR2A or PRKAR2B, GSK3B and GSKIP through GSKIP interaction; facilitates PKA-induced phosphorylation and regulates GSK3B activity (PubMed:27484798, PubMed:20007971, PubMed:25920809). Interacts with GSKIP (PubMed:16981698). Interacts with GID8 (PubMed:28829046). Interacts with PIWIL2 (By similarity). Interacts with LMBR1L (PubMed:31073040). Interacts with DDX3X (PubMed:18846110). Interacts with BIRC2 (PubMed:18846110). Interacts with TNFRSF10B; TNFRSF10B stimulation inhibits GSK3B kinase activity (PubMed:18846110).
    Miscellaneous:
    • Higher expression and activity of GSK3B 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).
    • [Isoform 2]: May play a specific role in axon growth and neurite outgrowth. Reduced binding to AXIN1, reduced ability to phosphorylate MAPT/TAU.

    Three dimensional structures from OCA and Proteopedia for GSK3B Gene

    Alternative splice isoforms for GSK3B Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for GSK3B Gene

Protein Expression for GSK3B Gene

See protein expression from ProteomicsDB, MOPED, PaxDb, and MaxQB

Selected DME Specific Peptides for GSK3B Gene

P49841:
  • TPPEAIALCS
  • VAIKKVLQD
  • HRDIKPQNLL
  • IKVLGTPTRE
  • IFPGDSGVDQ
  • SYICSRYYRAPEL
  • PLEACAHSFFDELR
  • FAESCKP
  • YVPETVYRVARH
  • RAKQTLPV
  • ELLLGQP
  • CDFGSAK
  • YFFYSSG
  • MNPNYTEFKFPQIK
  • FPQIKAHPW
  • QEVSYTDTKVIGNGSFGVV
  • DFGSAKQL
  • VPETVYR
  • DQLVEIIK
  • YRAPELIFG

Post-translational modifications for GSK3B Gene

  • Phosphorylated by AKT1 and ILK1. Upon insulin-mediated signaling, the activated PKB/AKT1 protein kinase phosphorylates and desactivates GSK3B, resulting in the dephosphorylation and activation of GYS1. Activated by phosphorylation at Tyr-216 (PubMed:25169422). Inactivated by phosphorylation at Ser-9 (Probable). Phosphorylated in a circadian manner in the hippocampus (By similarity).
  • Mono-ADP-ribosylation by PARP10 negatively regulates kinase activity.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for GSK3B Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

Domains & Families for GSK3B Gene

Gene Families for GSK3B Gene

IUPHAR :
Human Protein Atlas (HPA):
  • Enzymes
  • Predicted intracellular proteins

Protein Domains for GSK3B Gene

InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for GSK3B Gene

GenScript: Design optimal peptide antigens:
  • Glycogen synthase kinase-3 beta (B5BUC0_HUMAN)
  • Glycogen synthase kinase-3 beta (GSK3B_HUMAN)
  • cDNA FLJ75266, highly similar to Homo sapiens glycogen synthase kinase 3 beta, mRNA (Q6FI27_HUMAN)
  • Glycogen synthase kinase 3 beta (Q86TM2_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P49841

UniProtKB/Swiss-Prot:

GSK3B_HUMAN :
  • Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. GSK-3 subfamily.
Family:
  • Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. GSK-3 subfamily.
genes like me logo Genes that share domains with GSK3B: view

Function for GSK3B Gene

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  2. CRISPR
  3. miRNA
  4. Inhibitory RNA
  5. Clone
  6. Cell Line

Molecular function for GSK3B Gene

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), EIF2B, CTNNB1/beta-catenin, APC, AXIN1, DPYSL2/CRMP2, JUN, NFATC1/NFATC, MAPT/TAU and MACF1. Requires primed phosphorylation of the majority of its substrates. In skeletal muscle, contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glycogen synthesis. May also mediate the development of insulin resistance by regulating activation of transcription factors. Regulates protein synthesis by controlling the activity of initiation factor 2B (EIF2BE/EIF2B5) in the same manner as glycogen synthase. In Wnt signaling, GSK3B forms a multimeric complex with APC, AXIN1 and CTNNB1/beta-catenin and phosphorylates the N-terminus of CTNNB1 leading to its degradation mediated by ubiquitin/proteasomes. Phosphorylates JUN at sites proximal to its DNA-binding domain, thereby reducing its affinity for DNA. Phosphorylates NFATC1/NFATC on conserved serine residues promoting NFATC1/NFATC nuclear export, shutting off NFATC1/NFATC gene regulation, and thereby opposing the action of calcineurin. Phosphorylates MAPT/TAU on 'Thr-548', decreasing significantly MAPT/TAU ability to bind and stabilize microtubules. MAPT/TAU is the principal component of neurofibrillary tangles in Alzheimer disease. Plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex. Phosphorylates MACF1, inhibiting its binding to microtubules which is critical for its role in bulge stem cell migration and skin wound repair. Probably regulates NF-kappa-B (NFKB1) at the transcriptional level and is required for the NF-kappa-B-mediated anti-apoptotic response to TNF-alpha (TNF/TNFA). Negatively regulates replication in pancreatic beta-cells, resulting in apoptosis, loss of beta-cells and diabetes. Through phosphorylation of the anti-apoptotic protein MCL1, may control cell apoptosis in response to growth factors deprivation. Phosphorylates MUC1 in breast cancer cells, decreasing the interaction of MUC1 with CTNNB1/beta-catenin. Is necessary for the establishment of neuronal polarity and axon outgrowth. Phosphorylates MARK2, leading to inhibit its activity. Phosphorylates SIK1 at 'Thr-182', leading to sustain its activity. Phosphorylates ZC3HAV1 which enhances its antiviral activity. Phosphorylates SNAI1, leading to its BTRC-triggered ubiquitination and proteasomal degradation. Phosphorylates SFPQ at 'Thr-687' upon T-cell activation. Phosphorylates NR1D1 st 'Ser-55' and 'Ser-59' and stabilizes it by protecting it from proteasomal degradation. Regulates the circadian clock via phosphorylation of the major clock components including ARNTL/BMAL1, CLOCK and PER2 (PubMed:19946213, PubMed:28903391). Phosphorylates CLOCK AT 'Ser-427' and targets it for proteasomal degradation (PubMed:19946213). Phosphorylates ARNTL/BMAL1 at 'Ser-17' and 'Ser-21' and primes it for ubiquitination and proteasomal degradation (PubMed:28903391). Phosphorylates OGT at 'Ser-3' or 'Ser-4' which positively regulates its activity. Phosphorylates MYCN in neuroblastoma cells which may promote its degradation (PubMed:24391509). Regulates the circadian rhythmicity of hippocampal long-term potentiation and ARNTL/BMLA1 and PER2 expression (By similarity). Acts as a regulator of autophagy by mediating phosphorylation of KAT5/TIP60 under starvation conditions, leading to activate KAT5/TIP60 acetyltransferase activity and promote acetylation of key autophagy regulators, such as ULK1 and RUBCNL/Pacer (PubMed:30704899). Negatively regulates extrinsic apoptotic signaling pathway via death domain receptors. Promotes the formation of an anti-apoptotic complex, made of DDX3X, BRIC2 and GSK3B, at death receptors, including TNFRSF10B. The anti-apoptotic function is most effective with weak apoptotic signals and can be overcome by stronger stimulation (PubMed:18846110).
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=[tau protein]-L-serine + ATP = [tau protein]-O-phospho-L-serine + ADP + H(+); Xref=Rhea:RHEA:12801, Rhea:RHEA-COMP:13701, Rhea:RHEA-COMP:13702, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.26;.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=[tau protein]-L-threonine + ATP = [tau protein]-O-phospho-L-threonine + ADP + H(+); Xref=Rhea:RHEA:53904, Rhea:RHEA-COMP:13703, Rhea:RHEA-COMP:13704, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.26;.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-[protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1; Evidence=. ;.
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.1;.
UniProtKB/Swiss-Prot EnzymeRegulation:
Activated by phosphorylation at Tyr-216. In response to insulin, inhibited by phosphorylation at Ser-9 by PKB/AKT1 and RPS6KA3; phosphorylation at this site causes a conformational change, preventing access of substrates to the active site. Inhibited by lithium.
GENATLAS Biochemistry:
glycogen synthase kinase 3 beta,dual specificity protein-kinase,regulating glycogen synthesis in skeletal muscle through Tyr activating or Ser/Thr inactivating prosphorylation,key downstream target of PI3-kinase/AKT survival signaling pathway and involved in the regulation of apoptosis,Drosophila Shaggy-Zeste-White 3 homolog,binding to APC-beta-catenin complex,

Enzyme Numbers (IUBMB) for GSK3B Gene

Phenotypes From GWAS Catalog for GSK3B Gene

Gene Ontology (GO) - Molecular Function for GSK3B Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001085 RNA polymerase II transcription factor binding IPI 20864106
GO:0002020 protease binding IPI 25118933
GO:0002039 p53 binding IDA 14744935
GO:0004672 protein kinase activity IEA,TAS 22988876
GO:0004674 protein serine/threonine kinase activity IEA,TAS --
genes like me logo Genes that share ontologies with GSK3B: view
genes like me logo Genes that share phenotypes with GSK3B: view

Animal Models for GSK3B Gene

MGI Knock Outs for GSK3B:

Animal Model Products

CRISPR Products

miRNA for GSK3B Gene

miRTarBase miRNAs that target GSK3B

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for GSK3B

Clone Products

  • Addgene plasmids for GSK3B

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for GSK3B Gene

Localization for GSK3B Gene

Subcellular locations from UniProtKB/Swiss-Prot for GSK3B Gene

Cytoplasm. Nucleus. Cell membrane. Note=The phosphorylated form shows localization to cytoplasm and cell membrane. The MEMO1-RHOA-DIAPH1 signaling pathway controls localization of the phosphorylated form to the cell membrane.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for GSK3B gene
Compartment Confidence
plasma membrane 5
cytoskeleton 5
nucleus 5
mitochondrion 4
cytosol 4
extracellular 2
endoplasmic reticulum 2
lysosome 2
peroxisome 1
endosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Nucleoplasm (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for GSK3B Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IBA,IDA 14744935
GO:0005654 nucleoplasm TAS --
GO:0005737 cytoplasm IEA,IDA 14744935
GO:0005739 mitochondrion IEA --
GO:0005813 centrosome IDA 17139249
genes like me logo Genes that share ontologies with GSK3B: view

Pathways & Interactions for GSK3B Gene

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SuperPathways for GSK3B Gene

SuperPathway Contained pathways
1 S45 mutants of beta-catenin arent phosphorylated
APC truncation mutants have impaired AXIN binding
.93
S45 mutants of beta-catenin arent phosphorylated
.93
Disassembly of the destruction complex and recruitment of AXIN to the membrane
.47
Signaling by WNT in cancer
.43
Canonical Wnt signaling pathway
.31
AMER1 mutants destabilize the destruction complex
.01
AXIN missense mutants destabilize the destruction complex
.01
AXIN mutants destabilize the destruction complex, activating WNT signaling
.01
Beta-catenin phosphorylation cascade
.01
Misspliced GSK3beta mutants stabilize beta-catenin
.01
phosphorylation site mutants of CTNNB1 are not targeted to the proteasome by the destruction complex
.01
S33 mutants of beta-catenin arent phosphorylated
.01
S37 mutants of beta-catenin arent phosphorylated
.01
T41 mutants of beta-catenin arent phosphorylated
.01
truncated APC mutants destabilize the destruction complex
.01
Truncations of AMER1 destabilize the destruction complex
.01
2 Common Cytokine Receptor Gamma-Chain Family Signaling Pathways
IL-21 Signaling Pathways
.90
IL-7 Signaling Pathways
.90
IL-9 Signaling Pathways
.90
Common Cytokine Receptor Gamma-Chain Family Signaling Pathways
.90
IL-15 Signaling Pathways
.88
IL-2 Signaling Pathways
.88
IL-4 Signaling Pathways
.84
Development Thrombopoietin-regulated cell processes
.38
Adipokines and Insulin Signaling Pathways
.34
3 RET signaling
Downstream signal transduction
.94
Signaling by PDGF
.94
DAP12 signaling
.92
Signaling by EGFR
.90
DAP12 interactions
.89
NGF signalling via TRKA from the plasma membrane
.87
Signaling by SCF-KIT
.85
Signalling by NGF
.81
Fc epsilon receptor (FCERI) signaling
.79
4 Regulation of lipid metabolism Insulin signaling-generic cascades
Regulation of lipid metabolism Insulin signaling-generic cascades
.59
Translation Insulin regulation of translation
.59
Translation Regulation of EIF2 activity
.47
Development Growth hormone signaling via PI3K/AKT and MAPK cascades
.34
Insulin signaling pathway
.32
5 GAB1 signalosome
PIP3 activates AKT signaling
.91
Role of LAT2/NTAL/LAB on calcium mobilization
.91
GAB1 signalosome
.89
PI3K/AKT activation
.89
PI3K/AKT Signaling in Cancer
.72
genes like me logo Genes that share pathways with GSK3B: view

Pathways by source for GSK3B Gene

30 GeneGo (Thomson Reuters) pathways for GSK3B Gene
  • Cell cycle Regulation of G1/S transition (part 1)
  • Cell cycle Regulation of G1/S transition (part 2)
  • Cytoskeleton remodeling FAK signaling
  • Cytoskeleton remodeling Integrin outside-in signaling
  • Cytoskeleton remodeling Reverse signaling by ephrin B
37 Qiagen pathways for GSK3B Gene
  • 14-3-3 Induced Intracellular Signaling
  • Activation of cAMP-Dependent PKA
  • Activation of PKA through GPCR
  • Akt Signaling
  • Alzheimers Disease Pathway
4 Cell Signaling Technology pathways for GSK3B Gene
2 GeneTex pathways for GSK3B Gene

SIGNOR curated interactions for GSK3B Gene

Activates:
Inactivates:
Is activated by:
Is inactivated by:
Other effect:

Gene Ontology (GO) - Biological Process for GSK3B Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001837 epithelial to mesenchymal transition IMP 15448698
GO:0001954 positive regulation of cell-matrix adhesion IMP 18156211
GO:0005975 carbohydrate metabolic process IEA --
GO:0005977 glycogen metabolic process IDA 8638126
GO:0006468 protein phosphorylation TAS,IEA 26049140
genes like me logo Genes that share ontologies with GSK3B: view

Drugs & Compounds for GSK3B Gene

Products:

  1. Drug

(81) Drugs for GSK3B Gene - From: DrugBank, PharmGKB, ApexBio, DGIdb, HMDB, Tocris, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
fostamatinib Approved, Investigational Pharma Target, inhibitor Kinase Inhibitors 0
Lithium carbonate Approved Pharma Target Mood stabilizer; inhibits Na+/K+ ATPase pump activity 289
Lithium citrate Approved Pharma Target 0
Citalopram Approved Pharma 582
Fluoxetine Approved, Vet_approved Pharma Channel blocker, Antagonist, Inhibition, Inhibitor 272

(7) Additional Compounds for GSK3B Gene - From: Novoseek and HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
ADP
  • 5'-Adenylphosphoric acid
  • Adenosine 5'-diphosphate
  • ADENOSINE-5'-diphosphATE
  • H3ADP
  • 5'-Adenylphosphate
 Full agonist, Agonist, Partial agonist, Antagonist, Gating inhibitor 58-64-0

(3) Tocris Compounds for GSK3B Gene

Compound Action Cas Number
Indirubin-3'-oxime GSK-3beta inhibitor. Also inhibits other protein kinases 160807-49-8
MeBIO Inactive analog of BIO (Cat. No. 3194) 667463-95-8
SB 216763 Potent, selective GSK-3 inhibitor 280744-09-4

(29) ApexBio Compounds for GSK3B Gene

Compound Action Cas Number
1-Azakenpaullone GSK-3β inhibitor,potent and selective,cell-permeable 676596-65-9
3F8 GSK-3β inhibitor 159109-11-2
A 1070722 1384424-80-9
AR-A014418 GSK3β inhibitor, ATP-competitive and selective 487021-52-3
AZD1080 GSK3βinhibitor 612487-72-6
AZD2858 GSK-3 inhibitor,potent and selective 486424-20-8
Bikinin GSK3 inhibitor and Brassinosteroid activator 188011-69-0
BIO-acetoxime 667463-85-6
CHIR 99021 trihydrochloride
CHIR-98014 GSK-3β inhibitor,selective and ATP-competitive 252935-94-7
CHIR-99021 (CT99021) GSK-3 inhibitor, Cell-permeable, ATP-competitive 252917-06-9
CHIR-99021 (CT99021) HCl GSK-3α/β inhibitor 252917-06-9
FRATide 251087-38-4
GSK-3 inhibitor 1 603272-51-1
GSK-3 Inhibitor IX (BIO) 667463-62-9
IM-12 1129669-05-1
Indirubin 479-41-4
Indirubin-3'-oxime 160807-49-8
L803-mts 1043881-55-5
LY2090314 Potent GSK-3 inhibitor 603288-22-8
SB 216763 GSK-3 inhibitor,ATP-competitive,potent and selective 280744-09-4
SB 415286 GSK-3 inhibitor,potent and selective 264218-23-7
TC-G 24 1257256-44-2
TCS 183
TCS 184 1315378-71-2
TCS 2002 GSK -3β inhibitor, potent 1005201-24-0
TDZD-8 GSK-3β inhibitor 327036-89-5
Tideglusib 865854-05-3
TWS119 GSK-3β inhibitor 601514-19-6
genes like me logo Genes that share compounds with GSK3B: view

Drug Products

Transcripts for GSK3B Gene

Products:

  1. CRISPR
  2. miRNA
  3. Inhibitory RNA
  4. Clone

mRNA/cDNA for GSK3B Gene

3 REFSEQ mRNAs :
11 NCBI additional mRNA sequence :
5 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for GSK3B

Clone Products

  • Addgene plasmids for GSK3B

Alternative Splicing Database (ASD) splice patterns (SP) for GSK3B Gene

No ASD Table

Relevant External Links for GSK3B Gene

GeneLoc Exon Structure for
GSK3B

Expression for GSK3B Gene

Products:

  1. Primer
  2. Gene Expression Assay

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for GSK3B Gene

mRNA expression in normal human tissues for GSK3B Gene
mRNA expression by GTEx for GSK3B GenemRNA expression by BioGPS for GSK3B Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for GSK3B Gene

This gene is overexpressed in Fetal Brain (10.4).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for GSK3B Gene



Protein tissue co-expression partners for GSK3B Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for GSK3B

SOURCE GeneReport for Unigene cluster for GSK3B Gene:

Hs.445733

mRNA Expression by UniProt/SwissProt for GSK3B Gene:

P49841-GSK3B_HUMAN
Tissue specificity: Expressed in testis, thymus, prostate and ovary and weakly expressed in lung, brain and kidney. Colocalizes with EIF2AK2/PKR and TAU in the Alzheimer disease (AD) brain.

Evidence on tissue expression from TISSUES for GSK3B Gene

  • Liver(4.5)
  • Eye(4.3)
  • Nervous system(4)
  • Muscle(3)
  • Heart(2.9)
  • Intestine(2.6)
  • Kidney(2.6)
  • Blood(2.4)
  • Lung(2.4)
  • Adrenal gland(2.3)
  • Skin(2.1)
genes like me logo Genes that share expression patterns with GSK3B: view

No data available for mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for GSK3B Gene

Orthologs for GSK3B Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for GSK3B Gene

Organism Taxonomy Gene Similarity Type Details
oppossum
(Monodelphis domestica)
 Mammalia GSK3B 31
  • 100 (a)
 OneToOne
chimpanzee
(Pan troglodytes)
 Mammalia GSK3B 31 30
  • 98.46 (n)
 OneToOne
platypus
(Ornithorhynchus anatinus)
 Mammalia GSK3B 31
  • 98 (a)
 OneToOne
dog
(Canis familiaris)
 Mammalia GSK3B 31 30
  • 97 (n)
 OneToOne
cow
(Bos Taurus)
 Mammalia GSK3B 31 30
  • 96.37 (n)
 OneToOne
mouse
(Mus musculus)
 Mammalia Gsk3b 17 31 30
  • 92.73 (n)
rat
(Rattus norvegicus)
 Mammalia Gsk3b 30
  • 92.4 (n)
chicken
(Gallus gallus)
 Aves GSK3B 31 30
  • 88.52 (n)
 OneToOne
lizard
(Anolis carolinensis)
 Reptilia GSK3B 31
  • 92 (a)
 OneToOne
tropical clawed frog
(Silurana tropicalis)
 Amphibia gsk3b 30
  • 77.09 (n)
Str.19775 30
African clawed frog
(Xenopus laevis)
 Amphibia Xgsk-3 30
zebrafish
(Danio rerio)
 Actinopterygii GSK3B (2 of 2) 31
  • 90 (a)
 OneToMany
gsk3b 31 30 30
  • 79.82 (n)
 OneToMany
fruit fly
(Drosophila melanogaster)
 Insecta gskt 31 32
  • 49 (a)
 ManyToMany
Pk34A 32
  • 39 (a)
sgg 31 32
  • 26 (a)
 ManyToMany
worm
(Caenorhabditis elegans)
 Secernentea Y18D10A.5 32
  • 74 (a)
gsk-3 31 30
  • 64.84 (n)
 OneToMany
C44H4.6 32
  • 42 (a)
R03D7.5 32
  • 38 (a)
F21F3.2 32
  • 32 (a)
C36B1.10 32
  • 31 (a)
Y106G6D.4 32
  • 31 (a)
baker's yeast
(Saccharomyces cerevisiae)
 Saccharomycetes RIM11 33 31
  • 48 (a)
MRK1 31
  • 35 (a)
 ManyToMany
thale cress
(Arabidopsis thaliana)
 eudicotyledons SK13 30
  • 63.58 (n)
Alicante grape
(Vitis vinifera)
 eudicotyledons Vvi.7461 30
rice
(Oryza sativa)
 Liliopsida Os05g0134000 30
  • 61.67 (n)
corn
(Zea mays)
 Liliopsida Zm.6802 30
sea squirt
(Ciona savignyi)
 Ascidiacea -- 31
  • 78 (a)
 OneToMany
Species where no ortholog for GSK3B was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • 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)
  • wheat (Triticum aestivum)

Evolution for GSK3B Gene

ENSEMBL:
Gene Tree for GSK3B (if available)
TreeFam:
Gene Tree for GSK3B (if available)
Aminode:
Evolutionary constrained regions (ECRs) for GSK3B: view image

Paralogs for GSK3B Gene

Paralogs for GSK3B Gene

(23) SIMAP similar genes for GSK3B Gene using alignment to 4 proteins:

  • GSK3B_HUMAN
  • B5BUC0_HUMAN
  • Q6FI27_HUMAN
  • Q86TM2_HUMAN

Pseudogenes.org Pseudogenes for GSK3B Gene

genes like me logo Genes that share paralogs with GSK3B: view

Variants for GSK3B Gene

Products:

  1. SNP Genotyping and Copy Number Assay

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for GSK3B Gene

SNP ID Clinical significance and condition Chr 03 pos Variation AA Info Type
718992 Likely Benign: not provided 120,002,229(-) G/A SYNONYMOUS_VARIANT
721176 Benign: not provided 119,923,394(-) C/T SYNONYMOUS_VARIANT
784016 Benign: not provided 119,863,444(-) A/G SYNONYMOUS_VARIANT
791946 Benign: not provided 119,843,259(-) C/T SYNONYMOUS_VARIANT,INTRON_VARIANT

Additional dbSNP identifiers (rs#s) for GSK3B Gene

Structural Variations from Database of Genomic Variants (DGV) for GSK3B Gene

Variant ID Type Subtype PubMed ID
dgv883e199 CNV deletion 23128226
esv22981 CNV loss 19812545
esv2516850 CNV deletion 19546169
esv2631534 CNV deletion 19546169
esv2666502 CNV deletion 23128226
esv3562450 CNV deletion 23714750
esv3568979 CNV loss 25503493
esv3597569 CNV loss 21293372
nsv1073239 CNV deletion 25765185
nsv3964 CNV deletion 18451855
nsv478074 CNV novel sequence insertion 20440878
nsv478327 CNV novel sequence insertion 20440878
nsv507120 OTHER sequence alteration 20534489
nsv829696 CNV gain 17160897
nsv829697 CNV loss 17160897
nsv955330 CNV duplication 24416366

Variation tolerance for GSK3B Gene

Residual Variation Intolerance Score: 20.5% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.61; 13.12% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for GSK3B Gene

Human Gene Mutation Database (HGMD)
GSK3B
SNPedia medical, phenotypic, and genealogical associations of SNPs for
GSK3B

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for GSK3B Gene

Disorders for GSK3B Gene

MalaCards: The human disease database

(33) MalaCards diseases for GSK3B Gene - From: DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
alzheimer disease
  • ad
bipolar disorder
  • major affective disorder 1
familial adenomatous polyposis
  • fap
usher syndrome, type iia
  • ush2a
aneurysmal bone cysts
  • aneurysmal bone cyst
- elite association - COSMIC cancer census association via MalaCards
Search GSK3B in MalaCards View complete list of genes associated with diseases

Additional Disease Information for GSK3B

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with GSK3B: view

No data available for UniProtKB/Swiss-Prot and Genatlas for GSK3B Gene

Publications for GSK3B Gene

  1. First evidence of genetic association between AKT2 and polycystic ovary syndrome. (PMID: 18768676) Goodarzi MO … Azziz R (Diabetes care 2008) 3 23 41 54
  2. Glycogen synthase kinase-3beta and tau genes interact in Alzheimer's disease. (PMID: 18991351) Kwok JB … Schofield PR (Annals of neurology 2008) 3 23 41 54
  3. No significant association between the genetic polymorphisms in the GSK-3 beta gene and schizophrenia in the Chinese population. (PMID: 17368486) Meng J … He L (Journal of psychiatric research 2008) 3 23 41 54
  4. Response to lithium augmentation in depression is associated with the glycogen synthase kinase 3-beta -50T/C single nucleotide polymorphism. (PMID: 17628506) Adli M … Bauer M (Biological psychiatry 2007) 3 23 26 54
  5. Preliminary evidence of glycogen synthase kinase 3 beta as a genetic determinant of polycystic ovary syndrome. (PMID: 17270183) Goodarzi MO … Azziz R (Fertility and sterility 2007) 3 23 41 54

ExternalLinks

View latest publications for GSK3B gene in Mastermind

Products for GSK3B Gene