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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

GSK3B Gene

protein-coding GIFtS: 74
GCID: GC03M119540

glycogen synthase kinase 3 beta

Explore 91 diseases affiliated with
GSK3B via

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(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
Glycogen Synthase Kinase 3 Beta¹ ²		Glycogen Synthase Kinase-3 Beta²
Serine/Threonine-Protein Kinase GSK3B² ³		GSK3beta Isoform²
GSK-3 Beta² ³		EC 2.7.11.1³
EC 2.7.11.26³ ⁸		EC 2.7.11⁸

External Ids:	HGNC: 4617¹	Entrez Gene: 2932²	Ensembl: ENSG00000082701⁷	OMIM: 605004⁵	UniProtKB: P49841³

Export aliases for GSK3B gene to outside databases

Previous GC identifers: GC03M116184 GC03M119174 GC03M120822 GC03M120866 GC03M121028 GC03M116916

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for GSK3B:

The protein encoded by this gene is a serine-threonine kinase, belonging to the glycogen synthase kinase subfamily. It

is involved in energy metabolism, neuronal cell development, and body pattern formation. Polymorphisms in this gene

have been implicated in modifying risk of Parkinson disease, and studies in mice show that overexpression of this gene

may be relevant to the pathogenesis of Alzheimer disease. Alternatively spliced transcript variants encoding different

isoforms have been found for this gene.(provided by RefSeq, Sep 2009)

UniProtKB/Swiss-Prot: GSK3B_HUMAN, P49841

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. 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

summary for GSK3B:

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 Alzheimer's

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 GSK3B

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000003.11 NC_018914.1 NT_005612.16

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the GSK3B gene promoter:
CREB FOXO4 deltaCREB FOXO1a FOXO1 HNF-4alpha1
Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: GSK3B promoter sequence

Search SABiosciences Chromatin IP Primers for GSK3B

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat GSK3B

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 3q13.3 Ensembl cytogenetic band: 3q13.33 HGNC cytogenetic band: 3q13.3

GSK3B Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
GSK3B gene location

GeneLoc information about chromosome 3 GeneLoc Exon Structure

GeneLoc location for GC03M119540: view genomic region (about GC identifiers)

Start:	119,540,170 bp from pter	End:	119,813,264 bp from pter
Size:	273,095 bases	Orientation:	minus strand

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: GSK3B_HUMAN, P49841 (See protein sequence)

Recommended Name: Glycogen synthase kinase-3 beta

Size: 420 amino acids; 46744 Da

Subunit: Monomer. Interacts with ARRB2, DISC1 and ZBED3 (By similarity). Interacts with CABYR, MMP2, MUC1, NIN and

PRUNE 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

Subcellular location: 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

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)

6/50 PDB 3D structures from and Proteopedia for GSK3B (see all 50):

1GNG (3D)

1H8F (3D)

1I09 (3D)

1J1B (3D)

1J1C (3D)

1O9U (3D)

Secondary accessions: D3DN89 Q9BWH3 Q9UL47

Alternative splicing: 2 isoforms: P49841-1 P49841-2 (No experimental confirmation available)

Explore the universe of human proteins at neXtProt for GSK3B: NX_P49841

Post-translational modifications:

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-216¹

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_P49841

4/20 DME Specific Peptides for GSK3B (P49841) (see all 20)

CDFGSAK

FAESCKP

YFFYSSG

VPETVYR

GSK3B Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins (2 alternative transcripts):

NP_001139628.1 NP_002084.2

ENSEMBL proteins:

ENSP00000264235 ENSP00000324806

Reactome Protein details: P49841
Human Recombinant Protein Products:

	EMD Millipore Purified and/or Recombinant GSK3B Protein
	R&D Systems Recombinant & Natural Proteins for GSK3B (GSK-3 beta)
	Enzo Life Sciences proteins for GSK3B
	OriGene Purified Protein: GSK3B OriGene Protein Over-expression Lysate: GSK3B OriGene Custom Protein Services for GSK3B
	GenScript Custom Purified and Recombinant Proteins Services for GSK3B
	Novus Biologicals GSK3B Proteins Novus Biologicals GSK3B Lysates
	Sino Biological Recombinant Protein for GSK3B
	Browse ProSpec Recombinant Proteins
	Browse Proteins at Uscn

Gene Ontology (GO): 5/18 cellular component terms (GO ID links to tree view) (see all 18): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005625	soluble fraction	--	--
GO:0005634	nucleus	IDA	--
GO:0005730	NOT nucleolus	IDA	--
GO:0005737	cytoplasm	IDA	19038973
GO:0005813	centrosome	IDA	--

GSK3B for ontologies About GeneDecksing

GSK3B Antibody Products:

	EMD Millipore Mono- and Polyclonal Antibodies for the study of GSK3B
	R&D Systems Antibodies for GSK3B (GSK-3 beta)
	Cell Signaling Technology (CST) Antibodies for GSK3B
	OriGene Antibodies (see all 2): GSK3B OriGene Custom Antibody Services for GSK3B
	GenScript Superior Antibodies for GSK3B
	Novus Biologicals GSK3B Antibodies
	Abcam antibodies for GSK3B
	Browse Antibodies at Uscn
	ThermoFisher Antibody for GSK3B

Assay Products for GSK3B:

	EMD Millipore Kits and Assays for the Analysis of GSK3B
	OriGene Custom Immunoassay Development Browse OriGene Fluorogenic Cell Assay Kits
	R&D Systems ELISAs for GSK3B (GSK-3 beta) (see all)
	GenScript GSK3B-Activity-based Kinase Assay for Compound Screening
	Cell Signaling Technology (CST) Sandwich ELISA Kits for GSK3B
	Enzo Life Sciences assays for GSK3B
	Browse ELISAs and CLIAs at Uscn

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

GSK3B for domains About GeneDecksing

5 InterPro domains/families:

IPR017441 Protein_kinase_ATP_BS

IPR002290 Ser/Thr_dual-sp_kinase_dom

IPR011009 Kinase-like_dom

IPR008271 Ser/Thr_kinase_AS

IPR000719 Prot_kinase_cat_dom

Graphical View of Domain Structure for InterPro Entry P49841

ProtoNet protein and cluster: P49841

UniProtKB/Swiss-Prot: GSK3B_HUMAN, P49841

Similarity: Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. GSK-3 subfamily

Similarity: Contains 1 protein kinase domain

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary: