Glycogen synthase kinase-3 beta

Glycogen synthase kinase-3 beta, (GSK-3 beta), is an enzyme that in humans is encoded by the GSK3B gene.^[5][6] In mice, the enzyme is encoded by the Gsk3b gene.^[7] Abnormal regulation and expression of GSK-3 beta is associated with an increased susceptibility towards bipolar disorder.^[8]

GSK3B
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1GNG, 1H8F, 1I09, 1J1B, 1J1C, 1O6K, 1O6L, 1O9U, 1PYX, 1Q3D, 1Q3W, 1Q41, 1Q4L, 1Q5K, 1R0E, 1UV5, 2JDO, 2JDR, 2JLD, 2O5K, 2OW3, 2UW9, 2X39, 2XH5, 3CQU, 3CQW, 3DU8, 3E87, 3E88, 3E8D, 3F7Z, 3F88, 3GB2, 3I4B, 3L1S, 3M1S, 3MV5, 3OW4, 3PUP, 3Q3B, 3QKK, 3SAY, 3SD0, 3ZDI, 3ZRK, 3ZRL, 3ZRM, 4ACC, 4ACD, 4ACG, 4ACH, 4AFJ, 4B7T, 4DIT, 4EKK, 4IQ6, 4J1R, 4J71, 4NM0, 4NM3, 4NM5, 4NM7, 4PTC, 4PTE, 4PTG, 5F94, 5F95, 5HLP, 5HLN
Identifiers
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; OMA:GSK3B - orthologs
EC number	2.7.11.1
Gene location (Human) Chr. Chromosome 3 (human)[1] Band 3q13.33 Start 119,821,321 bp[1] End 120,094,994 bp[1]
Gene location (Mouse) Chr. Chromosome 16 (mouse)[2] Band 16|16 B3 Start 37,909,363 bp[2] End 38,066,446 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in Achilles tendon epithelium of colon sural nerve buccal mucosa cell skin of thigh ventricular zone ganglionic eminence postcentral gyrus left testis right testis Top expressed in spermatid cumulus cell ventromedial nucleus lateral septal nucleus lateral hypothalamus mammillary body retinal pigment epithelium Rostral migratory stream lateral geniculate nucleus Region I of hippocampus proper More reference expression data BioGPS More reference expression data
Gene ontology Molecular function kinase activity ATP binding protein kinase activity protein kinase A catalytic subunit binding protein serine/threonine kinase activity transferase activity NF-kappaB binding tau-protein kinase activity protein binding nucleotide binding p53 binding ubiquitin protein ligase binding protease binding beta-catenin binding protein kinase binding dynactin binding tau protein binding Cellular component cytoplasm membrane mitochondrion nucleus centrosome plasma membrane cytosol beta-catenin destruction complex postsynapse Wnt signalosome nucleoplasm axon dendrite glutamatergic synapse Biological process rhythmic process negative regulation of type B pancreatic cell development negative regulation of protein binding negative regulation of glycogen (starch) synthase activity glycogen metabolic process superior temporal gyrus development negative regulation of canonical Wnt signaling pathway chemical synaptic transmission, postsynaptic negative regulation of protein-containing complex assembly positive regulation of protein export from nucleus positive regulation of GTPase activity protein autophosphorylation cell differentiation negative regulation of protein localization to nucleus phosphorylation positive regulation of cell-matrix adhesion nervous system development dopamine receptor signaling pathway epithelial to mesenchymal transition peptidyl-threonine phosphorylation positive regulation of protein-containing complex assembly positive regulation of neuron death negative regulation of glycogen biosynthetic process multicellular organism development regulation of cellular response to heat negative regulation of signal transduction hippocampus development beta-catenin destruction complex disassembly proteasome-mediated ubiquitin-dependent protein catabolic process Wnt signaling pathway beta-catenin destruction complex assembly protein phosphorylation positive regulation of mitochondrion organization intracellular signal transduction positive regulation of protein catabolic process negative regulation of dopaminergic neuron differentiation ER overload response circadian rhythm peptidyl-serine phosphorylation positive regulation of protein binding positive regulation of proteasomal ubiquitin-dependent protein catabolic process regulation of microtubule-based process cellular response to interleukin-3 negative regulation of apoptotic process canonical Wnt signaling pathway extrinsic apoptotic signaling pathway in absence of ligand positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway carbohydrate metabolic process neuron projection development negative regulation of neuron death positive regulation of gene expression establishment of cell polarity maintenance of cell polarity regulation of axon extension negative regulation of phosphoprotein phosphatase activity regulation of dendrite morphogenesis regulation of axonogenesis excitatory postsynaptic potential regulation of microtubule cytoskeleton organization negative regulation of calcineurin-NFAT signaling cascade extrinsic apoptotic signaling pathway neuron projection retraction negative regulation of protein acetylation cellular response to amyloid-beta positive regulation of protein localization to centrosome regulation of synaptic vesicle exocytosis neuron projection organization positive regulation of autophagy regulation of circadian rhythm regulation of long-term synaptic potentiation regulation of microtubule anchoring at centrosome Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 2932 56637 Ensembl ENSG00000082701 ENSMUSG00000022812 UniProt P49841 Q9WV60 RefSeq (mRNA) NM_001146156 NM_002093 NM_001354596 NM_019827 NM_001347232 RefSeq (protein) NP_001139628 NP_002084 NP_001341525 NP_001334161 NP_062801 Location (UCSC) Chr 3: 119.82 – 120.09 Mb Chr 16: 37.91 – 38.07 Mb PubMed search [3] [4]
Wikidata
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Function

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.

Disease relevance

Homozygous disruption of the Gsk3b 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]

Signaling pathways

Pharmacological inhibition of ERK1/2 restores GSK-3 beta activity and protein synthesis levels in a model of tuberous sclerosis.^[12]

Interactions

GSK3B has been shown to interact with:

• KIAA1211L^[13]
• ATP2A2^[14]

• AKAP11,^[15]
• AXIN1,^[16][17]
• AXIN2,^[18][19]
• AR,^[20]
• CTNNB1,^[21][22]
• DNM1L,^[23]
• MACF1^[24]
• MUC1,^[25][26]
• SMAD3^[27]
• NOTCH1,^[28]
• NOTCH2,^[29]
• P53,^[30]
• PRKAR2A,^[15]
• SGK3,^[31] and
• TSC2.^[16][32]

Overview of signal transduction pathways involved in apoptosis.

See also

• Glycogen synthase kinase 3