Last updated
Protein GSK3B PDB 1gng.png
Available structures
PDB Ortholog search: PDBe RCSB
Aliases GSK3B , Gsk3b, 7330414F15Rik, 8430431H08Rik, C86142, GSK-3, GSK-3beta, GSK3, glycogen synthase kinase 3 beta
External IDs OMIM: 605004 MGI: 1861437 HomoloGene: 55629 GeneCards: GSK3B
EC number
Gene location (Human)
Ideogram human chromosome 3.svg
Chr. Chromosome 3 (human) [1]
Human chromosome 3 ideogram.svg
HSR 1996 II 3.5e.svg
Red rectangle 2x18.png
Band 3q13.33Start119,821,323 bp [1]
End120,094,417 bp [1]
RNA expression pattern
PBB GE GSK3B 209945 s at fs.png
More reference expression data
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC) Chr 3: 119.82 – 120.09 Mb Chr 16: 38.09 – 38.25 Mb
PubMed search [3] [4]
View/Edit Human View/Edit Mouse

Glycogen synthase kinase 3 beta, also known as GSK3B, is an enzyme that in humans is encoded by the GSK3B gene. [5] [6] In mice, the enzyme is encoded by the GSK-3β gene. [7] Abnormal regulation and expression of GSK3β is associated with an increased susceptibility towards bipolar disorder. [8]

Enzyme class of biological molecules with catalytic activity

Enzymes are macromolecular biological catalysts that accelerate chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. Almost all metabolic processes in the cell need enzyme catalysis in order to occur at rates fast enough to sustain life. Metabolic pathways depend upon enzymes to catalyze individual steps. The study of enzymes is called enzymology and a new field of pseudoenzyme analysis has recently grown up, recognising that during evolution, some enzymes have lost the ability to carry out biological catalysis, which is often reflected in their amino acid sequences and unusual 'pseudocatalytic' properties.

Gene Basic physical and functional unit of heredity

In biology, a gene is a sequence of nucleotides in DNA or RNA that codes for a molecule that has a function. During gene expression, the DNA is first copied into RNA. The RNA can be directly functional or be the intermediate template for a protein that performs a function. The transmission of genes to an organism's offspring is the basis of the inheritance of phenotypic trait. These genes make up different DNA sequences called genotypes. Genotypes along with environmental and developmental factors determine what the phenotypes will be. Most biological traits are under the influence of polygenes as well as gene–environment interactions. Some genetic traits are instantly visible, such as eye color or number of limbs, and some are not, such as blood type, risk for specific diseases, or the thousands of basic biochemical processes that constitute life.

Bipolar disorder mental disorder that causes periods of depression and periods of abnormally elevated mood

Bipolar disorder, previously known as manic depression, is a mental disorder that causes periods of depression and periods of abnormally elevated mood. The elevated mood is significant and is known as mania, or hypomania if less severe and symptoms of psychosis are absent. During mania, an individual behaves or feels abnormally energetic, happy, or irritable. Individuals often make poorly thought out decisions with little regard to the consequences. The need for sleep is usually reduced during manic phases. During periods of depression, there may be crying, a negative outlook on life, and poor eye contact with others. The risk of suicide among those with the illness is high at greater than 6 percent over 20 years, while self-harm occurs in 30–40 percent. Other mental health issues such as anxiety disorders and substance use disorder are commonly associated with bipolar disorder.


Glycogen synthase kinase-3 (GSK-3) is a proline-directed serine-threonine kinase that was initially identified as a phosphorylating and an inactivating agent of glycogen synthase. Two isoforms, alpha (GSK3A) and beta, show a high degree of amino acid homology. [5] GSK3B is involved in energy metabolism, neuronal cell development, and body pattern formation. [9] [10] It might be a new therapeutic target for ischemic stroke.


Glycogen synthase kinase 3 is a serine/threonine protein kinase that mediates the addition of phosphate molecules onto serine and threonine amino acid residues. First discovered in 1980 as a regulatory kinase for its namesake, Glycogen synthase, GSK-3 has since been identified as a kinase for over forty different proteins in a variety of different pathways. In mammals GSK-3 is encoded by two paralogous genes, GSK-3 alpha (GSK3A) and GSK-3 beta (GSK3B). GSK-3 has recently been the subject of much research because it has been implicated in a number of diseases, including Type II diabetes, Alzheimer's Disease, inflammation, cancer, and bipolar disorder.

Serine/threonine-specific protein kinase

A serine/threonine protein kinase is a kinase enzyme that phosphorylates the OH group of serine or threonine. At least 125 of the 500+ human protein kinases are serine/threonine kinases (STK).

Phosphorylation the process of introducing a phosphate group into a molecule, usually with the formation of a phosphoric ester, a phosphoric anhydride or a phosphoric amide.

In chemistry, phosphorylation of a molecule is the attachment of a phosphoryl group. Together with its counterpart, dephosphorylation, it is critical for many cellular processes in biology. Phosphorylation is especially important for protein function; for example, this modification activates almost half of the enzymes present in yeast, thereby regulating their function. Many proteins are phosphorylated temporarily, as are many sugars, lipids, and other biologically-relevant molecules.

Disease relevance

Homozygous disruption of the GSK-3β locus in mice results in embryonic lethality during mid-gestation. [7] This lethality phenotype could be rescued by inhibition of tumor necrosis factor. [7]

Two SNPs at this gene, rs334558 (-50T/C) and rs3755557 (-1727A/T), are associated with efficacy of lithium treatment in bipolar disorder. [11]

Lithium (medication) primarily used as a psychiatric medication

Lithium compounds, also known as lithium salts, are primarily used as a psychiatric medication. This includes the treatment of major depressive disorder that does not improve following the use of other antidepressants, and bipolar disorder. In these disorders, it reduces the risk of suicide. Lithium is taken by mouth.

Signaling pathways

Pharmacological inhibition of ERK1/2 restores GSK3β activity and protein synthesis levels in a model of tuberous sclerosis. [12]

MAPK3 protein-coding gene in the species Homo sapiens

Mitogen-activated protein kinase 3, also known as p44MAPK and ERK1, is an enzyme that in humans is encoded by the MAPK3 gene.

Tuberous sclerosis rare multisystem genetic disease that causes benign tumors to grow in the brain and on other vital organs

Tuberous sclerosis complex (TSC) is a rare multisystem autosomal dominant genetic disease that causes non-cancerous tumours to grow in the brain and on other vital organs such as the kidneys, heart, liver, eyes, lungs and skin. A combination of symptoms may include seizures, intellectual disability, developmental delay, behavioral problems, skin abnormalities, lung disease, and kidney disease.


GSK3B has been shown to interact with:

AKAP11 protein-coding gene in the species Homo sapiens

A-kinase anchor protein 11 is an enzyme that in humans is encoded by the AKAP11 gene.

AXIN1 protein-coding gene in the species Homo sapiens

Axin-1 is a protein that in humans is encoded by the AXIN1 gene.

AXIN2 protein-coding gene in the species Homo sapiens

Axin-2 also known as axin-like protein (Axil) or axis inhibition protein 2 (AXIN2) or conductin is a protein that in humans is encoded by the AXIN2 gene.

Overview of signal transduction pathways involved in apoptosis. Signal transduction v1.png
Overview of signal transduction pathways involved in apoptosis.

See also

Related Research Articles

The Wnt signaling pathways are a group of signal transduction pathways which begin with proteins that pass signals into a cell through cell surface receptors. The name Wnt is a portmanteau created from the name Wingless and the name Int-1.

Adenomatous polyposis coli protein-coding gene in the species Homo sapiens

Adenomatous polyposis coli (APC) also known as deleted in polyposis 2.5 (DP2.5) is a protein that in humans is encoded by the APC gene. The APC protein is a negative regulator that controls beta-catenin concentrations and interacts with E-cadherin, which are involved in cell adhesion. Mutations in the APC gene may result in colorectal cancer.

Beta-catenin protein-coding gene in the species Homo sapiens

Catenin beta-1, also known as β-catenin, is a protein that in humans is encoded by the CTNNB1 gene.

Plakoglobin protein-coding gene in the species Homo sapiens

Plakoglobin, also known as junction plakoglobin or gamma-catenin, is a protein that in humans is encoded by the JUP gene. Plakoglobin is a member of the catenin protein family and homologous to β-catenin. Plakoglobin is a cytoplasmic component of desmosomes and adherens junctions structures located within intercalated discs of cardiac muscle that function to anchor sarcomeres and join adjacent cells in cardiac muscle. Mutations in plakoglobin are associated with arrhythmogenic right ventricular dysplasia.

GSK3A protein-coding gene in the species Homo sapiens

Glycogen synthase kinase-3 alpha is an enzyme that in humans is encoded by the GSK3A gene.

Tau-protein kinase

In enzymology, a tau-protein kinase is an enzyme that catalyzes the chemical reaction

DVL1 protein-coding gene in the species Homo sapiens

Segment polarity protein dishevelled homolog DVL-1 is a protein that in humans is encoded by the DVL1 gene.

SGK3 protein-coding gene in the species Homo sapiens

Serine/threonine-protein kinase Sgk3 is an enzyme that in humans is encoded by the SGK3 gene.

PRKD3 protein-coding gene in the species Homo sapiens

Serine/threonine-protein kinase D3 (PKD3) or PKC-nu is an enzyme that in humans is encoded by the PRKD3 gene.

LRP6 protein-coding gene in the species Homo sapiens

Low-density lipoprotein receptor-related protein 6 is a protein that in humans is encoded by the LRP6 gene. LRP6 is a key component of the LRP5/LRP6/Frizzled co-receptor group that is involved in canonical Wnt pathway.

WNT3A protein-coding gene in the species Homo sapiens

Protein Wnt-3a is a protein that in humans is encoded by the WNT3A gene.

NLK mammalian protein found in Homo sapiens

Serine/threonine protein kinase NLK is an enzyme that in humans is encoded by the NLK gene. Its name is an abbreviation for Nemo-Like Kinase, Nemo (nmo) being the Drosophila ortholog of the mammalian NLK gene. This enzyme is a member of the Mitogen-activated protein kinase (MAPK) family, although not explicitly designated as such. It is a highly divergent, atypical member of the MAPK group, lacking most features so characteristic of most mitogen-activated protein kinases. Its activation mechanism and downstream targets are still not well characterized.

DVL2 protein-coding gene in the species Homo sapiens

Segment polarity protein dishevelled homolog DVL-2 is a protein that in humans is encoded by the DVL2 gene.

FRAT1 protein-coding gene in the species Homo sapiens

Proto-oncogene FRAT1 is a protein that in humans is encoded by the FRAT1 gene.

FRAT2 protein-coding gene in the species Homo sapiens

GSK-3-binding protein FRAT2 is a protein that in humans is encoded by the FRAT2 gene.

ILKAP protein-coding gene in the species Homo sapiens

Integrin-linked kinase-associated serine/threonine phosphatase 2C is an enzyme that in humans is encoded by the ILKAP gene.


Dishevelled (Dsh) is a family of proteins involved in canonical and non-canonical Wnt signalling pathways. Dsh is a cytoplasmic phosphoprotein that acts directly downstream of frizzled receptors. It takes its name from its initial discovery in flies, where a mutation in the dishevelled gene was observed to cause improper orientation of body and wing hairs. There are vertebrate homologs in zebrafish, Xenopus (Xdsh), mice and humans. Dsh relays complex Wnt signals in tissues and cells, in normal and abnormal contexts. It is thought to interact with the novel protein, SPATS1, when regulating the Wnt Signalling pathway.


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Further reading