Glycogen synthase kinase-3 beta, (GSK-3 beta), is an

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

that in humans is encoded by the ''GSK3B''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

. In mice, the enzyme is encoded by the Gsk3b gene. Abnormal regulation and expression of GSK-3 beta is associated with an increased susceptibility towards

bipolar disorder Bipolar disorder (BD), previously known as manic depression, is a mental disorder characterized by periods of Depression (mood), depression and periods of abnormally elevated Mood (psychology), mood that each last from days to weeks, and in ...

Function

Glycogen synthase kinase-3 (

GSK-3 Glycogen synthase kinase 3 (GSK-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 ...

) is a proline-directed

serine-threonine kinase A serine/threonine protein kinase () is a kinase enzyme, in particular a protein kinase, that phosphorylates the OH group of the amino-acid residues serine or threonine, which have similar side chains. At least 350 of the 500+ human prote ...

that was initially identified as a

phosphorylating In biochemistry, phosphorylation is described as the "transfer of a phosphate group" from a donor to an acceptor. A common phosphorylating agent (phosphate donor) is ATP and a common family of acceptor are alcohols: : This equation can be writt ...

and an inactivating agent of

glycogen synthase Glycogen synthase (UDP-glucose-glycogen glucosyltransferase) is a key enzyme in glycogenesis, the conversion of glucose into glycogen. It is a glycosyltransferase () that catalyses the reaction of UDP-glucose and (1,4--D-glucosyl)n to yield UD ...

. Two isoforms, alpha (

GSK3A Glycogen synthase kinase-3 alpha is an enzyme that in humans is encoded by the ''GSK3A'' gene. Glycogen synthase kinase 3-alpha is a multifunctional protein serine kinase, homologous to ''Drosophila melanogaster, Drosophila'' 'shaggy' (zeste-whi ...

) and beta, show a high degree of amino acid homology. GSK3B is involved in energy metabolism, neuronal cell development, and body pattern formation. It might be a new therapeutic target for ischemic stroke.

Disease relevance

Homozygous Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mos ...

disruption of the Gsk3b locus in mice results in embryonic lethality during mid-gestation. This lethality phenotype could be rescued by inhibition of

tumor necrosis factor Tumor necrosis factor (TNF), formerly known as TNF-α, is a chemical messenger produced by the immune system that induces inflammation. TNF is produced primarily by activated macrophages, and induces inflammation by binding to its receptors o ...

. Two SNPs at this gene, rs334558 (-50T/C) and rs3755557 (-1727A/T), are associated with efficacy of

lithium Lithium (from , , ) is a chemical element; it has chemical symbol, symbol Li and atomic number 3. It is a soft, silvery-white alkali metal. Under standard temperature and pressure, standard conditions, it is the least dense metal and the ...

treatment in

Signaling pathways

Pharmacological inhibition of ERK1/2 restores GSK-3 beta activity and protein synthesis levels in a model of

tuberous sclerosis 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 combinatio ...

Interactions

GSK3B has been shown to

interact Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization advocating for the legal and human rights of children with intersex traits. The organization was founded in 2006 and fo ...

with: * KIAA1211L * ATP2A2 *

AKAP11 A-kinase anchor protein 11 is an enzyme that in humans is encoded by the ''AKAP11'' gene. Function The A-kinase anchor proteins (AKAPs) are a group of structurally diverse proteins, which have the common function of binding to the regulatory s ...

, *

AXIN1 Axin-1 is a protein that in humans is encoded by the ''AXIN1'' gene. Function This gene encodes a cytoplasmic protein which contains a regulation of G-protein signaling (RGS) domain and a dishevelled and axin (DIX) domain. The encoded protei ...

, *

AXIN2 Axin-2, also known as axin-like protein (Axil), axis inhibition protein 2 (AXIN2), or conductin, is a protein that in humans is encoded by the ''AXIN2'' gene. Function The Axin-related protein, Axin2, presumably plays an important role in the ...

, * AR, *

CTNNB1 Catenin beta-1, also known as β-catenin (''beta''-catenin), is a protein that in humans is encoded by the ''CTNNB1'' gene. β-Catenin is a dual function protein, involved in regulation and coordination of cell–cell adhesion and gene transcr ...

, *

DNM1L Dynamin-1-like protein is a GTPase that regulates mitochondrial fission. In humans, dynamin-1-like protein, which is typically referred to as dynamin-related protein 1 (Drp1), is encoded by the ''DNM1L'' gene and is part of the dynamin superfamil ...

, *

MACF1 Microtubule-actin cross-linking factor 1, isoforms 1/2/3/5 is a protein that in humans is encoded by the ''MACF1'' gene. MACF1 encodes a large protein containing numerous spectrin and leucine-rich repeat (LRR) domains. MACF1 is a member of a fami ...

MUC1 Mucin short variant S1, also called polymorphic epithelial mucin (PEM) or epithelial membrane antigen (EMA), is a mucin encoded by the ''MUC1'' gene in humans. Mucin short variant S1 is a glycoprotein with extensive O-linked glycosylation of its ...

, *

SMAD3 Mothers against decapentaplegic homolog 3 also known as SMAD family member 3 or SMAD3 is a protein that in humans is encoded by the SMAD3 gene. SMAD3 is a member of the SMAD (protein), SMAD family of proteins. It acts as a mediator of the signal ...

NOTCH1 Neurogenic locus notch homolog protein 1 (Notch 1) is a protein encoded in humans by the ''NOTCH1'' gene. Notch 1 is a single-pass transmembrane receptor. Function This gene encodes a member of the Notch family. Members of this type 1 transm ...

, *

NOTCH2 Neurogenic locus notch homolog protein 2 (Notch 2) is a protein that in humans is encoded by the ''NOTCH2'' gene. NOTCH2 is associated with Alagille syndrome and Hajdu–Cheney syndrome. Function Notch 2 is a member of the notch family. Me ...

, *

P53 p53, also known as tumor protein p53, cellular tumor antigen p53 (UniProt name), or transformation-related protein 53 (TRP53) is a regulatory transcription factor protein that is often mutated in human cancers. The p53 proteins (originally thou ...

, *

PRKAR2A cAMP-dependent protein kinase type II-alpha regulatory subunit is an enzyme that in humans is encoded by the ''PRKAR2A'' gene. Function cAMP is a signaling molecule important for a variety of cellular functions. cAMP exerts its effects by act ...

, *

SGK3 Serine/threonine-protein kinase Sgk3 is an enzyme that in humans is encoded by the ''SGK3'' gene. Function This gene is a member of the serine/threonine protein kinase family and encodes a phosphoprotein with a PX (phox homology) domain. The ...

, and *

TSC2 Tuberous sclerosis complex 2 (TSC2), also known as tuberin, is a protein that in humans is encoded by the ''TSC2'' gene. Function Mutations in this gene lead to tuberous sclerosis. Its gene product is believed to be a tumor suppressor and is ...

References

External links

PDBe-KB
provides an overview of all the structure information available in the PDB for Human Glycogen synthase kinase-3 beta (GSK3B) {{Portal bar, Biology, border=no Protein kinases EC 2.7.11