GSK3B [The Human Chemical-Genetic Interaction Map Project]

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======= GSK3B =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: GSK3B
  * **<color #00a2e8>Official Name</color>**: glycogen synthase kinase 3 beta
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=2932|2932]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/P49841|P49841]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=GSK3B&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20GSK3B|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/605004|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  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]. 
  * **<color #00a2e8>UniProt Summary</color>**:  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. Phosphorylates CLOCK AT 'Ser-427' and targets it for proteasomal degradation. Phosphorylates ARNTL/BMAL1 at 'Ser-17' and 'Ser-21' and primes it for ubiquitination and proteasomal degradation. 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). {ECO:0000269|PubMed:11430833, ECO:0000269|PubMed:12554650, ECO:0000269|PubMed:14690523, ECO:0000269|PubMed:15448698, ECO:0000269|PubMed:15647282, ECO:0000269|PubMed:16484495, ECO:0000269|PubMed:18348280, ECO:0000269|PubMed:1846781, ECO:0000269|PubMed:19946213, ECO:0000269|PubMed:20932480, ECO:0000269|PubMed:20937854, ECO:0000269|PubMed:22514281, ECO:0000269|PubMed:24391509, ECO:0000269|PubMed:8397507, ECO:0000269|PubMed:9072970, ECO:0000269|PubMed:9819408}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|Pkinase Tyr|
|Pkinase|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|regulation of microtubule anchoring at centrosome|
|superior temporal gyrus development|
|negative regulation of type B pancreatic cell development|
|negative regulation of glycogen (starch) synthase activity|
|negative regulation of dopaminergic neuron differentiation|
|beta-catenin destruction complex assembly|
|negative regulation of glycogen biosynthetic process|
|cellular response to interleukin-3|
|positive regulation of protein localization to centrosome|
|response to interleukin-3|
|negative regulation of glycogen metabolic process|
|regulation of type B pancreatic cell development|
|regulation of glycogen (starch) synthase activity|
|regulation of protein localization to centrosome|
|regulation of dopaminergic neuron differentiation|
|ER overload response|
|dynactin binding|
|Wnt signalosome|
|beta-catenin destruction complex|
|protein kinase A catalytic subunit binding|
|negative regulation of calcineurin-NFAT signaling cascade|
|negative regulation of calcineurin-mediated signaling|
|maintenance of cell polarity|
|beta-catenin destruction complex disassembly|
|negative regulation of protein acetylation|
|positive regulation of protein export from nucleus|
|tau-protein kinase activity|
|regulation of glycogen biosynthetic process|
|regulation of glucan biosynthetic process|
|negative regulation of dendrite development|
|NF-kappaB binding|
|negative regulation of protein localization to nucleus|
|negative regulation of calcium-mediated signaling|
|extrinsic apoptotic signaling pathway in absence of ligand|
|signal transduction in absence of ligand|
|regulation of calcineurin-mediated signaling|
|regulation of calcineurin-NFAT signaling cascade|
|positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway|
|dopamine receptor signaling pathway|
|regulation of glycogen metabolic process|
|ER-nucleus signaling pathway|
|regulation of polysaccharide biosynthetic process|
|regulation of protein export from nucleus|
|cellular response to amyloid-beta|
|neuron projection organization|
|negative regulation of epithelial cell differentiation|
|negative regulation of cellular carbohydrate metabolic process|
|regulation of polysaccharide metabolic process|
|regulation of long-term synaptic potentiation|
|regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway|
|tau protein binding|
|negative regulation of carbohydrate metabolic process|
|glycogen metabolic process|
|response to amyloid-beta|
|cellular glucan metabolic process|
|glucan metabolic process|
|positive regulation of cell-matrix adhesion|
|negative regulation of phosphoprotein phosphatase activity|
|RNA polymerase II transcription factor binding|
|excitatory postsynaptic potential|
|positive regulation of nucleocytoplasmic transport|
|energy reserve metabolic process|
|negative regulation of protein dephosphorylation|
|p53 binding|
|chemical synaptic transmission, postsynaptic|
|epithelial to mesenchymal transition|
|regulation of protein acetylation|
|regulation of mitochondrial membrane permeability|
|cellular polysaccharide metabolic process|
|regulation of synaptic vesicle exocytosis|
|regulation of cellular response to heat|
|kinase activity|
|hippocampus development|
|regulation of membrane permeability|
|polysaccharide metabolic process|
|positive regulation of proteasomal ubiquitin-dependent protein catabolic process|
|peptidyl-threonine phosphorylation|
|beta-catenin binding|
|postsynapse|
|cellular response to dopamine|
|response to dopamine|
|insulin receptor signaling pathway|
|canonical Wnt signaling pathway|
|peptidyl-threonine modification|
|regulation of dendrite morphogenesis|
|positive regulation of neuron death|
|signal transduction involved in cellular response to ammonium ion|
|positive regulation of protein binding|
|regulation of carbohydrate biosynthetic process|
|regulation of calcium-mediated signaling|
|regulation of axon extension|
|extrinsic apoptotic signaling pathway|
|positive regulation of ubiquitin-dependent protein catabolic process|
|regulation of postsynaptic membrane potential|
|cellular response to monoamine stimulus|
|cellular response to catecholamine stimulus|
|protease binding|
|negative regulation of protein binding|
|positive regulation of proteasomal protein catabolic process|
|negative regulation of phosphatase activity|
|regulation of neurotransmitter secretion|
|regulation of nucleocytoplasmic transport|
|response to monoamine|
|response to catecholamine|
|limbic system development|
|regulation of extent of cell growth|
|negative regulation of dephosphorylation|
|regulation of synaptic vesicle cycle|
|negative regulation of cellular protein localization|
|regulation of glucose metabolic process|
|regulation of cell-matrix adhesion|
|regulation of circadian rhythm|
|positive regulation of mitochondrion organization|
|regulation of protein localization to nucleus|
|cerebral cortex development|
|establishment of cell polarity|
|regulation of phosphoprotein phosphatase activity|
|positive regulation of proteolysis involved in cellular protein catabolic process|
|positive regulation of autophagy|
|positive regulation of cell-substrate adhesion|
|regulation of proteasomal ubiquitin-dependent protein catabolic process|
|mitochondrial membrane organization|
|cellular response to ammonium ion|
|negative regulation of protein complex assembly|
|regulation of cellular carbohydrate metabolic process|
|regulation of protein dephosphorylation|
|positive regulation of cellular protein catabolic process|
|circadian rhythm|
|regulation of epithelial cell differentiation|
|regulation of neurotransmitter transport|
|regulation of dendrite development|
|regulation of ubiquitin-dependent protein catabolic process|
|negative regulation of neuron projection development|
|positive regulation of intracellular protein transport|
|mesenchymal cell differentiation|
|regulation of generation of precursor metabolites and energy|
|cellular response to insulin stimulus|
|regulation of regulated secretory pathway|
|negative regulation of binding|
|cellular carbohydrate metabolic process|
|pallium development|
|negative regulation of canonical Wnt signaling pathway|
|positive regulation of apoptotic signaling pathway|
|peptidyl-serine phosphorylation|
|regulation of phosphatase activity|
|positive regulation of binding|
|regulation of mitochondrion organization|
|regulation of cell size|
|negative regulation of cell projection organization|
|regulation of proteasomal protein catabolic process|
|regulation of axonogenesis|
|response to ammonium ion|
|regulation of synaptic plasticity|
|regulation of microtubule cytoskeleton organization|
|protein autophosphorylation|
|establishment or maintenance of cell polarity|
|peptidyl-serine modification|
|regulation of carbohydrate metabolic process|
|negative regulation of neuron death|
|positive regulation of intracellular transport|
|negative regulation of Wnt signaling pathway|
|regulation of dephosphorylation|
|regulation of cell-substrate adhesion|
|mitochondrial transport|
|cellular response to biotic stimulus|
|regulation of proteolysis involved in cellular protein catabolic process|
|positive regulation of protein catabolic process|
|regulation of protein binding|
|mesenchyme development|
|regulation of microtubule-based process|
|regulation of exocytosis|
|negative regulation of neuron differentiation|
|response to insulin|
|regulation of intracellular protein transport|
|energy derivation by oxidation of organic compounds|
|protein kinase activity|
|protein-containing complex disassembly|
|regulation of cellular protein catabolic process|
|positive regulation of protein complex assembly|
|response to endoplasmic reticulum stress|
|telencephalon development|
|cellular response to peptide hormone stimulus|
|rhythmic process|
|negative regulation of transferase activity|
|regulation of canonical Wnt signaling pathway|
|apoptotic signaling pathway|
|negative regulation of neurogenesis|
|ubiquitin protein ligase binding|
|axon|
|regulation of cell morphogenesis involved in differentiation|
|regulation of neuron death|
|negative regulation of nervous system development|
|positive regulation of cellular protein localization|
|cellular response to peptide|
|regulation of developmental growth|
|regulation of autophagy|
|negative regulation of cell development|
|glutamatergic synapse|
|regulation of intracellular transport|
|regulation of neurotransmitter levels|
|Wnt signaling pathway|
|cell-cell signaling by wnt|
|positive regulation of proteolysis|
|regulation of Wnt signaling pathway|
|protein serine/threonine kinase activity|
|positive regulation of cellular catabolic process|
|regulation of binding|
|regulation of cellular component size|
|regulation of protein catabolic process|
|forebrain development|
|response to peptide hormone|
|regulation of apoptotic signaling pathway|
|cellular component disassembly|
|cellular response to drug|
|positive regulation of cell adhesion|
|positive regulation of GTPase activity|
|regulation of cell growth|
|chemical synaptic transmission|
|anterograde trans-synaptic signaling|
|dendrite|
|generation of precursor metabolites and energy|
|positive regulation of protein transport|
|regulation of small molecule metabolic process|
|cell surface receptor signaling pathway involved in cell-cell signaling|
|regulation of membrane potential|
|positive regulation of catabolic process|
|trans-synaptic signaling|
|modulation of chemical synaptic transmission|
|mitochondrion organization|
|regulation of trans-synaptic signaling|
|regulation of protein complex assembly|
|negative regulation of hydrolase activity|
|positive regulation of establishment of protein localization|
|synaptic signaling|
|protein kinase binding|
|response to peptide|
|carbohydrate metabolic process|
|regulation of GTPase activity|
|regulation of cell morphogenesis|
|centrosome|
|regulation of neuron projection development|
|negative regulation of intracellular signal transduction|
|transmembrane receptor protein tyrosine kinase signaling pathway|
|regulation of anatomical structure size|
|positive regulation of cellular component biogenesis|
|regulation of cellular protein localization|
|regulation of cytoskeleton organization|
|cellular response to organic cyclic compound|
|regulation of vesicle-mediated transport|
|negative regulation of phosphate metabolic process|
|negative regulation of phosphorus metabolic process|
|negative regulation of protein modification process|
|cellular response to organonitrogen compound|
|cellular response to hormone stimulus|
|positive regulation of organelle organization|
|positive regulation of apoptotic process|
|positive regulation of programmed cell death|
|regulation of neuron differentiation|
|cellular response to nitrogen compound|
|neuron projection development|
|regulation of growth|
|regulation of cell adhesion|
|regulation of plasma membrane bounded cell projection organization|
|positive regulation of cell death|
|negative regulation of cellular component organization|
|regulation of protein transport|
|regulation of cell projection organization|
|negative regulation of cell differentiation|
|enzyme linked receptor protein signaling pathway|
|regulation of proteolysis|
|regulation of cellular response to stress|
|regulation of peptide transport|
|brain development|
|regulation of establishment of protein localization|
|regulation of secretion by cell|
|positive regulation of hydrolase activity|
|head development|
|negative regulation of catalytic activity|
|regulation of secretion|
|neuron development|
|regulation of neurogenesis|
|regulation of cellular catabolic process|
|membrane organization|
|peptidyl-amino acid modification|
|negative regulation of apoptotic process|
|negative regulation of programmed cell death|
|response to hormone|
|regulation of cellular localization|
|response to organic cyclic compound|
|apoptotic process|
|regulation of nervous system development|
|regulation of cell development|
|negative regulation of developmental process|
|regulation of cellular component biogenesis|
|oxidation-reduction process|
|protein phosphorylation|
|regulation of transferase activity|
|central nervous system development|
|positive regulation of transport|
|negative regulation of cell death|
|regulation of catabolic process|
|response to organonitrogen compound|
|cellular response to cytokine stimulus|
|neuron differentiation|
|response to drug|
|regulation of protein localization|
|negative regulation of cellular protein metabolic process|
|programmed cell death|
|cellular response to oxygen-containing compound|
|regulation of anatomical structure morphogenesis|
|response to nitrogen compound|
|cell death|
|response to cytokine|
|negative regulation of protein metabolic process|
|cell-cell signaling|
|plasma membrane bounded cell projection organization|
|negative regulation of molecular function|
|cell projection organization|
|negative regulation of multicellular organismal process|
|positive regulation of cellular component organization|
|cellular response to endogenous stimulus|
|mitochondrion|
|negative regulation of signal transduction|
|regulation of hydrolase activity|
|phosphorylation|
|regulation of organelle organization|
|response to biotic stimulus|
|negative regulation of cell communication|
|negative regulation of signaling|
|nervous system process|
|negative regulation of cellular macromolecule biosynthetic process|
|positive regulation of catalytic activity|
|negative regulation of macromolecule biosynthetic process|
|response to endogenous stimulus|
|regulation of response to stress|
|ATP binding|
|negative regulation of cellular biosynthetic process|
|generation of neurons|
|regulation of apoptotic process|
|negative regulation of biosynthetic process|
|response to oxygen-containing compound|
|protein-containing complex assembly|
|regulation of programmed cell death|
|positive regulation of cellular protein metabolic process|
|negative regulation of response to stimulus|
|neurogenesis|
|cell development|
|positive regulation of signal transduction|
|regulation of cell death|
|intracellular signal transduction|
|cellular response to stress|
|positive regulation of protein metabolic process|
|tissue development|
|positive regulation of molecular function|
|regulation of phosphate metabolic process|
|regulation of phosphorus metabolic process|
|regulation of cell differentiation|
|positive regulation of cell communication|
|positive regulation of signaling|
|regulation of intracellular signal transduction|
|regulation of protein modification process|
|protein-containing complex subunit organization|
|regulation of transport|
|system process|
|positive regulation of gene expression|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='primary' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
^Screen^Score^
|[[:results:exp500|LY2090314 0.003μM R08 exp500 no dilution day6]]|-5.52|
|[[:results:exp499|LY2090314 0.003μM R08 exp499]]|-5.48|
|[[:results:exp379|MSC2530818 10μM R07 exp379]]|-3.13|
|[[:results:exp217|Mdivi-1 15μM R05 exp217]]|-2.67|
|[[:results:exp282|Fluvastatin 2.2μM R06 exp282]]|-2.6|
|[[:results:exp59|UMK57 1μM R01 exp59]]|-2.36|
|[[:results:exp458|Bisphenol S 100μM R08 exp458]]|-1.95|
|[[:results:exp301|VER-155008 3.9μM R06 exp301]]|-1.84|
|[[:results:exp30|Rapamycin 10μM R00 exp30]]|1.79|
|[[:results:exp365|I-BRD9 4μM R07 exp365]]|1.8|
|[[:results:exp342|Calcium Ionophore 0.4μM R07 exp342]]|1.86|
|[[:results:exp240|Pyridostatin 4μM R05 exp240]]|2.09|
|[[:results:exp306|Rapamycin 2μM R07 exp306]]|2.19|
|[[:results:exp351|Dexamethasone 0.006μM R07 exp351]]|2.32|
|[[:results:exp414|Tozasertib 0.1μM R07 exp414]]|2.41|
|[[:results:exp82|Torin1 0.08μM R02 exp82]]|2.53|
|[[:results:exp308|Rapamycin 2μM plus FK-506 5μM R07 exp308]]|2.84|
|[[:results:exp29|Rapamycin 1μM R00 exp29]]|3.04|
|[[:results:exp307|Rapamycin 2μM plus Cyclosporin-A 3μM R07 exp307]]|3.17|
|[[:results:exp352|Dexamethasone 0.006 to 0.015μM on day4 R07 exp352]]|3.82|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:y:ypel5|YPEL5]]|0.515|
|[[:human genes:g:gsk3a|GSK3A]]|0.475|
|[[:human genes:g:gskip|GSKIP]]|0.464|
|[[:human genes:t:tsc2|TSC2]]|0.434|
|[[:human genes:g:glyr1|GLYR1]]|0.415|
|[[:human genes:w:wdr26|WDR26]]|0.41|
|[[:human genes:t:tsc1|TSC1]]|0.407|
|[[:human genes:n:nans|NANS]]|0.407|
|[[:human genes:f:fam122a|FAM122A]]|0.401|
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 0/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/26|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/16|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/16|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 18808
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 5.59 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='GSK3B Expression in NALM6 Cells: 5.59'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>