GSK3B_RAT
ID GSK3B_RAT Reviewed; 420 AA.
AC P18266;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1990, sequence version 1.
DT 03-AUG-2022, entry version 213.
DE RecName: Full=Glycogen synthase kinase-3 beta;
DE Short=GSK-3 beta;
DE EC=2.7.11.26 {ECO:0000250|UniProtKB:P49841};
DE AltName: Full=Factor A;
DE Short=FA;
DE AltName: Full=Serine/threonine-protein kinase GSK3B;
DE EC=2.7.11.1 {ECO:0000250|UniProtKB:P49841};
GN Name=Gsk3b;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RX PubMed=2164470; DOI=10.1002/j.1460-2075.1990.tb07419.x;
RA Woodgett J.R.;
RT "Molecular cloning and expression of glycogen synthase kinase-3/factor A.";
RL EMBO J. 9:2431-2438(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Brain cortex;
RX PubMed=7686508; DOI=10.1016/0014-5793(93)81066-9;
RA Ishiguro K., Shiratsuchi A., Sato S., Omori A., Arioka M., Kobayashi S.,
RA Uchida T., Imahori K.;
RT "Glycogen synthase kinase 3 beta is identical to tau protein kinase I
RT generating several epitopes of paired helical filaments.";
RL FEBS Lett. 325:167-172(1993).
RN [3]
RP PHOSPHORYLATION AT TYR-216, AND MUTAGENESIS OF TYR-216.
RX PubMed=8382613; DOI=10.1002/j.1460-2075.1993.tb05715.x;
RA Hughes K., Nikolakaki E., Plyte S.E., Totty N.F., Woodgett J.R.;
RT "Modulation of the glycogen synthase kinase-3 family by tyrosine
RT phosphorylation.";
RL EMBO J. 12:803-808(1993).
RN [4]
RP FUNCTION, AND INTERACTION WITH AXIN1.
RX PubMed=9482734; DOI=10.1093/emboj/17.5.1371;
RA Ikeda S., Kishida S., Yamamoto H., Murai H., Koyama S., Kikuchi A.;
RT "Axin, a negative regulator of the Wnt signaling pathway, forms a complex
RT with GSK-3beta and beta-catenin and promotes GSK-3beta-dependent
RT phosphorylation of beta-catenin.";
RL EMBO J. 17:1371-1384(1998).
RN [5]
RP SUBCELLULAR LOCATION, AND IDENTIFICATION IN A COMPLEX WITH MACF1; APC;
RP AXIN1 AND CTNNB1.
RX PubMed=16815997; DOI=10.1101/gad.1411206;
RA Chen H.J., Lin C.M., Lin C.S., Perez-Olle R., Leung C.L., Liem R.K.;
RT "The role of microtubule actin cross-linking factor 1 (MACF1) in the Wnt
RT signaling pathway.";
RL Genes Dev. 20:1933-1945(2006).
RN [6]
RP FUNCTION IN REGULATION OF PANCREATIC BETA-CELLS.
RX PubMed=17242403; DOI=10.1074/jbc.m609637200;
RA Mussmann R., Geese M., Harder F., Kegel S., Andag U., Lomow A., Burk U.,
RA Onichtchouk D., Dohrmann C., Austen M.;
RT "Inhibition of GSK3 promotes replication and survival of pancreatic beta
RT cells.";
RL J. Biol. Chem. 282:12030-12037(2007).
RN [7]
RP FUNCTION IN PHOSPHORYLATION OF MARK2, AND MUTAGENESIS OF SER-9.
RX PubMed=18424437; DOI=10.1074/jbc.m706596200;
RA Timm T., Balusamy K., Li X., Biernat J., Mandelkow E., Mandelkow E.M.;
RT "Glycogen synthase kinase (GSK) 3beta directly phosphorylates Serine 212 in
RT the regulatory loop and inhibits microtubule affinity-regulating kinase
RT (MARK) 2.";
RL J. Biol. Chem. 283:18873-18882(2008).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-389, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Constitutively active protein kinase that acts as a negative
CC regulator in the hormonal control of glucose homeostasis, Wnt signaling
CC and regulation of transcription factors and microtubules, by
CC phosphorylating and inactivating glycogen synthase (GYS1 or GYS2),
CC EIF2B, CTNNB1/beta-catenin, APC, AXIN1, DPYSL2/CRMP2, JUN,
CC NFATC1/NFATC, MAPT/TAU and MACF1. Requires primed phosphorylation of
CC the majority of its substrates (PubMed:9482734). In skeletal muscle,
CC contributes to insulin regulation of glycogen synthesis by
CC phosphorylating and inhibiting GYS1 activity and hence glycogen
CC synthesis (By similarity). May also mediate the development of insulin
CC resistance by regulating activation of transcription factors (By
CC similarity). Regulates protein synthesis by controlling the activity of
CC initiation factor 2B (EIF2BE/EIF2B5) in the same manner as glycogen
CC synthase (By similarity). In Wnt signaling, GSK3B forms a multimeric
CC complex with APC, AXIN1 and CTNNB1/beta-catenin and phosphorylates the
CC N-terminus of CTNNB1 leading to its degradation mediated by
CC ubiquitin/proteasomes (PubMed:9482734). Phosphorylates JUN at sites
CC proximal to its DNA-binding domain, thereby reducing its affinity for
CC DNA. Phosphorylates NFATC1/NFATC on conserved serine residues promoting
CC NFATC1/NFATC nuclear export, shutting off NFATC1/NFATC gene regulation,
CC and thereby opposing the action of calcineurin. Phosphorylates MAPT/TAU
CC on 'Thr-548', decreasing significantly MAPT/TAU ability to bind and
CC stabilize microtubules. MAPT/TAU is the principal component of
CC neurofibrillary tangles in Alzheimer disease. Plays an important role
CC in ERBB2-dependent stabilization of microtubules at the cell cortex (By
CC similarity). Phosphorylates MACF1, inhibiting its binding to
CC microtubules which is critical for its role in bulge stem cell
CC migration and skin wound repair. Probably regulates NF-kappa-B (NFKB1)
CC at the transcriptional level and is required for the NF-kappa-B-
CC mediated anti-apoptotic response to TNF-alpha (TNF/TNFA) (By
CC similarity). Negatively regulates replication in pancreatic beta-cells,
CC resulting in apoptosis, loss of beta-cells and diabetes
CC (PubMed:17242403). Through phosphorylation of the anti-apoptotic
CC protein MCL1, may control cell apoptosis in response to growth factors
CC deprivation (By similarity). Phosphorylates MUC1 in breast cancer
CC cells, decreasing the interaction of MUC1 with CTNNB1/beta-catenin. Is
CC necessary for the establishment of neuronal polarity and axon outgrowth
CC (By similarity). Phosphorylates MARK2, leading to inhibition of its
CC activity (PubMed:18424437). Phosphorylates SIK1 at 'Thr-182', leading
CC to sustainment of its activity. Phosphorylates ZC3HAV1 which enhances
CC its antiviral activity. Phosphorylates SNAI1, leading to its BTRC-
CC triggered ubiquitination and proteasomal degradation. Phosphorylates
CC SFPQ at 'Thr-687' upon T-cell activation. Phosphorylates NR1D1 st 'Ser-
CC 55' and 'Ser-59' and stabilizes it by protecting it from proteasomal
CC degradation. Regulates the circadian clock via phosphorylation of the
CC major clock components including ARNTL/BMAL1, CLOCK and PER2.
CC Phosphorylates CLOCK AT 'Ser-427' and targets it for proteasomal
CC degradation. Phosphorylates ARNTL/BMAL1 at 'Ser-17' and 'Ser-21' and
CC primes it for ubiquitination and proteasomal degradation.
CC Phosphorylates OGT at 'Ser-3' or 'Ser-4' which positively regulates its
CC activity. Phosphorylates MYCN in neuroblastoma cells which may promote
CC its degradation (By similarity). Regulates the circadian rhythmicity of
CC hippocampal long-term potentiation and ARNTL/BMLA1 and PER2 expression
CC (By similarity). Acts as a regulator of autophagy by mediating
CC phosphorylation of KAT5/TIP60 under starvation conditions, activating
CC KAT5/TIP60 acetyltransferase activity and promoting acetylation of key
CC autophagy regulators, such as ULK1 and RUBCNL/Pacer. Negatively
CC regulates extrinsic apoptotic signaling pathway via death domain
CC receptors. Promotes the formation of an anti-apoptotic complex, made of
CC DDX3X, BRIC2 and GSK3B, at death receptors, including TNFRSF10B. The
CC anti-apoptotic function is most effective with weak apoptotic signals
CC and can be overcome by stronger stimulation (By similarity).
CC Phosphorylates E2F1, promoting the interaction between E2F1 and USP11,
CC stabilizing E2F1 and promoting its activity (By similarity).
CC {ECO:0000250|UniProtKB:P49841, ECO:0000250|UniProtKB:Q9WV60,
CC ECO:0000269|PubMed:17242403, ECO:0000269|PubMed:18424437,
CC ECO:0000269|PubMed:9482734}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[tau protein] = ADP + H(+) + O-phospho-L-seryl-
CC [tau protein]; Xref=Rhea:RHEA:12801, Rhea:RHEA-COMP:13701, Rhea:RHEA-
CC COMP:13702, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.26;
CC Evidence={ECO:0000250|UniProtKB:P49841};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[tau protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[tau protein]; Xref=Rhea:RHEA:53904, Rhea:RHEA-COMP:13703,
CC Rhea:RHEA-COMP:13704, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.26; Evidence={ECO:0000250|UniProtKB:P49841};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000250|UniProtKB:P49841};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000250|UniProtKB:P49841};
CC -!- ACTIVITY REGULATION: Activated by phosphorylation at Tyr-216. In
CC response to insulin, inhibited by phosphorylation at Ser-9 by PKB/AKT1;
CC phosphorylation at this site causes a conformational change, preventing
CC access of substrates to the active site. Inhibited by lithium.
CC -!- SUBUNIT: Monomer (By similarity). Interacts with DAB2IP (via C2
CC domain); the interaction stimulates GSK3B kinase activation (By
CC similarity). Interacts (via C2 domain) with PPP2CA (By similarity).
CC Interacts with ARRB2, AXIN1, CABYR, DISC1, MMP2, MUC1, NIN, PRUNE1 and
CC ZBED3 (By similarity). Interacts with AXIN1; the interaction mediates
CC hyperphosphorylation of CTNNB1 leading to its ubiquitination and
CC destruction (PubMed:9482734). Interacts with and phosphorylates SNAI1
CC (By similarity). Interacts with DNM1L (via a C-terminal domain) (By
CC similarity). Found in a complex composed of MACF1, APC, AXIN1, CTNNB1
CC and GSK3B (PubMed:16815997). Interacts with SGK3 (By similarity).
CC Interacts with the CLOCK-ARNTL/BMAL1 heterodimer (By similarity).
CC Interacts with the ARNTL/BMAL1 (By similarity). Interacts with CTNND2
CC (By similarity). The complex composed, at least, of APC, CTNNB1 and
CC GSK3B interacts with JPT1; the interaction requires the inactive form
CC of GSK3B (phosphorylated at 'Ser-9') (By similarity). Forms a complex
CC composed of PRKAR2A or PRKAR2B, GSK3B and GSKIP through GSKIP
CC interaction; facilitates PKA-induced phosphorylation and regulates
CC GSK3B activity (By similarity). Interacts with GSKIP (By similarity).
CC Interacts with GID8 (By similarity). Interacts with PIWIL2 (By
CC similarity). Interacts with LMBR1L (By similarity). Interacts with
CC DDX3X (By similarity). Interacts with BIRC2 (By similarity). Interacts
CC with TNFRSF10B; TNFRSF10B stimulation inhibits GSK3B kinase activity
CC (By similarity). {ECO:0000250|UniProtKB:P49841,
CC ECO:0000250|UniProtKB:Q9WV60, ECO:0000269|PubMed:16815997,
CC ECO:0000269|PubMed:9482734}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P49841}. Nucleus
CC {ECO:0000250|UniProtKB:P49841}. Membrane {ECO:0000269|PubMed:16815997}.
CC Cell membrane {ECO:0000250|UniProtKB:P49841}. Note=The phosphorylated
CC form shows localization to cytoplasm and cell membrane. The MEMO1-RHOA-
CC DIAPH1 signaling pathway controls localization of the phosphorylated
CC form to the cell membrane (By similarity).
CC {ECO:0000250|UniProtKB:P49841}.
CC -!- PTM: Phosphorylated by AKT1 and ILK1. Upon insulin-mediated signaling,
CC the activated PKB/AKT1 and RPS6KA3 protein kinases phosphorylate and
CC deactivate GSK3B, resulting in the dephosphorylation and activation of
CC GYS1. Activated by phosphorylation at Tyr-216 (By similarity).
CC Inactivated by phosphorylation at Ser-9 (By similarity). Phosphorylated
CC in a circadian manner in the hippocampus (By similarity).
CC {ECO:0000250|UniProtKB:P49841, ECO:0000250|UniProtKB:Q9WV60}.
CC -!- PTM: Mono-ADP-ribosylation by PARP10 negatively regulates kinase
CC activity. {ECO:0000250|UniProtKB:P49841}.
CC -!- MISCELLANEOUS: Simultaneous silencing of GSK3A and GSK3B by RNAi
CC stimulates replication and promotes survival of INS-1E pancreatic beta
CC cells. {ECO:0000305|PubMed:17242403}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC protein kinase family. GSK-3 subfamily. {ECO:0000305}.
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DR EMBL; X53428; CAA37519.1; -; mRNA.
DR EMBL; X73653; CAA52020.1; -; mRNA.
DR PIR; S14708; TVRTKB.
DR RefSeq; NP_114469.1; NM_032080.1.
DR AlphaFoldDB; P18266; -.
DR SMR; P18266; -.
DR BioGRID; 249893; 12.
DR CORUM; P18266; -.
DR DIP; DIP-40957N; -.
DR IntAct; P18266; 1.
DR MINT; P18266; -.
DR STRING; 10116.ENSRNOP00000003867; -.
DR BindingDB; P18266; -.
DR ChEMBL; CHEMBL3669; -.
DR iPTMnet; P18266; -.
DR PhosphoSitePlus; P18266; -.
DR jPOST; P18266; -.
DR PaxDb; P18266; -.
DR PRIDE; P18266; -.
DR GeneID; 84027; -.
DR KEGG; rno:84027; -.
DR UCSC; RGD:70982; rat.
DR CTD; 2932; -.
DR RGD; 70982; Gsk3b.
DR eggNOG; KOG0658; Eukaryota.
DR InParanoid; P18266; -.
DR OrthoDB; 990896at2759; -.
DR PhylomeDB; P18266; -.
DR TreeFam; TF101104; -.
DR BRENDA; 2.7.11.1; 5301.
DR BRENDA; 2.7.11.26; 5301.
DR Reactome; R-RNO-195253; Degradation of beta-catenin by the destruction complex.
DR Reactome; R-RNO-196299; Beta-catenin phosphorylation cascade.
DR Reactome; R-RNO-3371453; Regulation of HSF1-mediated heat shock response.
DR Reactome; R-RNO-399956; CRMPs in Sema3A signaling.
DR Reactome; R-RNO-4641262; Disassembly of the destruction complex and recruitment of AXIN to the membrane.
DR Reactome; R-RNO-5250924; B-WICH complex positively regulates rRNA expression.
DR Reactome; R-RNO-5610785; GLI3 is processed to GLI3R by the proteasome.
DR Reactome; R-RNO-9762114; GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2.
DR PRO; PR:P18266; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0030424; C:axon; IDA:RGD.
DR GO; GO:0030877; C:beta-catenin destruction complex; IDA:BHF-UCL.
DR GO; GO:0044297; C:cell body; ISO:RGD.
DR GO; GO:0005813; C:centrosome; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0030425; C:dendrite; IDA:RGD.
DR GO; GO:0043198; C:dendritic shaft; ISO:RGD.
DR GO; GO:0043197; C:dendritic spine; IDA:RGD.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0030426; C:growth cone; ISO:RGD.
DR GO; GO:0016020; C:membrane; IDA:UniProtKB.
DR GO; GO:0045121; C:membrane raft; IDA:RGD.
DR GO; GO:0043227; C:membrane-bounded organelle; ISO:RGD.
DR GO; GO:0005874; C:microtubule; IDA:RGD.
DR GO; GO:0005739; C:mitochondrion; IDA:RGD.
DR GO; GO:0043025; C:neuronal cell body; ISO:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0014069; C:postsynaptic density; ISO:RGD.
DR GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR GO; GO:1990904; C:ribonucleoprotein complex; ISO:RGD.
DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; IDA:SynGO.
DR GO; GO:1990909; C:Wnt signalosome; ISO:RGD.
DR GO; GO:0005524; F:ATP binding; IDA:RGD.
DR GO; GO:0008013; F:beta-catenin binding; ISO:RGD.
DR GO; GO:0034452; F:dynactin binding; ISO:RGD.
DR GO; GO:0070840; F:dynein complex binding; ISO:RGD.
DR GO; GO:0005178; F:integrin binding; IPI:RGD.
DR GO; GO:0035255; F:ionotropic glutamate receptor binding; IPI:RGD.
DR GO; GO:0016301; F:kinase activity; IDA:RGD.
DR GO; GO:0051059; F:NF-kappaB binding; ISO:RGD.
DR GO; GO:0002039; F:p53 binding; ISO:RGD.
DR GO; GO:0002020; F:protease binding; ISO:RGD.
DR GO; GO:0034236; F:protein kinase A catalytic subunit binding; ISO:RGD.
DR GO; GO:0004672; F:protein kinase activity; ISS:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IPI:RGD.
DR GO; GO:0106310; F:protein serine kinase activity; ISO:RGD.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:BHF-UCL.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISO:RGD.
DR GO; GO:0048156; F:tau protein binding; IDA:RGD.
DR GO; GO:0050321; F:tau-protein kinase activity; IDA:RGD.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:RGD.
DR GO; GO:0007568; P:aging; IEP:RGD.
DR GO; GO:0009887; P:animal organ morphogenesis; ISO:RGD.
DR GO; GO:0007409; P:axonogenesis; ISO:RGD.
DR GO; GO:1904886; P:beta-catenin destruction complex disassembly; ISO:RGD.
DR GO; GO:0046849; P:bone remodeling; IDA:RGD.
DR GO; GO:0060070; P:canonical Wnt signaling pathway; ISO:RGD.
DR GO; GO:0061049; P:cell growth involved in cardiac muscle cell development; IDA:RGD.
DR GO; GO:0016477; P:cell migration; ISO:RGD.
DR GO; GO:1904646; P:cellular response to amyloid-beta; IDA:ARUK-UCL.
DR GO; GO:1903351; P:cellular response to dopamine; IEP:RGD.
DR GO; GO:0036018; P:cellular response to erythropoietin; IEP:RGD.
DR GO; GO:0071385; P:cellular response to glucocorticoid stimulus; ISO:RGD.
DR GO; GO:0035729; P:cellular response to hepatocyte growth factor stimulus; ISO:RGD.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IEP:RGD.
DR GO; GO:0036016; P:cellular response to interleukin-3; ISS:UniProtKB.
DR GO; GO:0071282; P:cellular response to iron(II) ion; IEP:RGD.
DR GO; GO:0071285; P:cellular response to lithium ion; IEP:RGD.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IDA:RGD.
DR GO; GO:0071300; P:cellular response to retinoic acid; ISO:RGD.
DR GO; GO:0007623; P:circadian rhythm; ISS:UniProtKB.
DR GO; GO:0001837; P:epithelial to mesenchymal transition; ISS:UniProtKB.
DR GO; GO:0006983; P:ER overload response; ISO:RGD.
DR GO; GO:0030010; P:establishment of cell polarity; IDA:RGD.
DR GO; GO:0007163; P:establishment or maintenance of cell polarity; IDA:RGD.
DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; ISO:RGD.
DR GO; GO:0097192; P:extrinsic apoptotic signaling pathway in absence of ligand; ISS:UniProtKB.
DR GO; GO:0045444; P:fat cell differentiation; ISO:RGD.
DR GO; GO:0005977; P:glycogen metabolic process; ISO:RGD.
DR GO; GO:0035733; P:hepatic stellate cell activation; IMP:RGD.
DR GO; GO:0097284; P:hepatocyte apoptotic process; IDA:RGD.
DR GO; GO:0021766; P:hippocampus development; ISO:RGD.
DR GO; GO:0044027; P:hypermethylation of CpG island; ISO:RGD.
DR GO; GO:0008286; P:insulin receptor signaling pathway; ISO:RGD.
DR GO; GO:0035556; P:intracellular signal transduction; ISO:RGD.
DR GO; GO:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; ISO:RGD.
DR GO; GO:0030011; P:maintenance of cell polarity; IMP:ARUK-UCL.
DR GO; GO:0007520; P:myoblast fusion; ISO:RGD.
DR GO; GO:0014902; P:myotube differentiation; ISO:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:RGD.
DR GO; GO:0070885; P:negative regulation of calcineurin-NFAT signaling cascade; ISS:UniProtKB.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; ISO:RGD.
DR GO; GO:1905240; P:negative regulation of canonical Wnt signaling pathway involved in osteoblast differentiation; ISO:RGD.
DR GO; GO:0010614; P:negative regulation of cardiac muscle hypertrophy; ISO:RGD.
DR GO; GO:2000171; P:negative regulation of dendrite development; IMP:RGD.
DR GO; GO:0050774; P:negative regulation of dendrite morphogenesis; IMP:RGD.
DR GO; GO:1904339; P:negative regulation of dopaminergic neuron differentiation; IMP:RGD.
DR GO; GO:1902042; P:negative regulation of extrinsic apoptotic signaling pathway via death domain receptors; ISS:UniProtKB.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:RGD.
DR GO; GO:0043407; P:negative regulation of MAP kinase activity; IMP:RGD.
DR GO; GO:2000740; P:negative regulation of mesenchymal stem cell differentiation; ISO:RGD.
DR GO; GO:1901215; P:negative regulation of neuron death; ISS:UniProtKB.
DR GO; GO:0014043; P:negative regulation of neuron maturation; ISO:RGD.
DR GO; GO:2001223; P:negative regulation of neuron migration; IMP:RGD.
DR GO; GO:0010977; P:negative regulation of neuron projection development; ISO:RGD.
DR GO; GO:0051001; P:negative regulation of nitric-oxide synthase activity; IMP:RGD.
DR GO; GO:1901984; P:negative regulation of protein acetylation; IMP:ARUK-UCL.
DR GO; GO:0032091; P:negative regulation of protein binding; ISO:RGD.
DR GO; GO:1904780; P:negative regulation of protein localization to centrosome; ISO:RGD.
DR GO; GO:1900181; P:negative regulation of protein localization to nucleus; IMP:BHF-UCL.
DR GO; GO:0031333; P:negative regulation of protein-containing complex assembly; ISO:RGD.
DR GO; GO:0034392; P:negative regulation of smooth muscle cell apoptotic process; IMP:RGD.
DR GO; GO:0045886; P:negative regulation of synaptic assembly at neuromuscular junction; IMP:CACAO.
DR GO; GO:0032007; P:negative regulation of TOR signaling; ISO:RGD.
DR GO; GO:0031175; P:neuron projection development; ISS:UniProtKB.
DR GO; GO:0106027; P:neuron projection organization; IMP:ARUK-UCL.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; ISS:UniProtKB.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; ISO:RGD.
DR GO; GO:0016310; P:phosphorylation; ISO:RGD.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:RGD.
DR GO; GO:0010508; P:positive regulation of autophagy; ISS:UniProtKB.
DR GO; GO:0045773; P:positive regulation of axon extension; ISO:RGD.
DR GO; GO:2000727; P:positive regulation of cardiac muscle cell differentiation; ISO:RGD.
DR GO; GO:0045597; P:positive regulation of cell differentiation; ISO:RGD.
DR GO; GO:0001954; P:positive regulation of cell-matrix adhesion; ISO:RGD.
DR GO; GO:0045724; P:positive regulation of cilium assembly; ISS:UniProtKB.
DR GO; GO:2000573; P:positive regulation of DNA biosynthetic process; IMP:RGD.
DR GO; GO:2000463; P:positive regulation of excitatory postsynaptic potential; IMP:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
DR GO; GO:0043547; P:positive regulation of GTPase activity; ISO:RGD.
DR GO; GO:0010918; P:positive regulation of mitochondrial membrane potential; IMP:RGD.
DR GO; GO:1901030; P:positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway; ISS:UniProtKB.
DR GO; GO:0010822; P:positive regulation of mitochondrion organization; ISO:RGD.
DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IMP:RGD.
DR GO; GO:1901216; P:positive regulation of neuron death; ISO:RGD.
DR GO; GO:0033690; P:positive regulation of osteoblast proliferation; IMP:RGD.
DR GO; GO:0045672; P:positive regulation of osteoclast differentiation; IMP:RGD.
DR GO; GO:0090290; P:positive regulation of osteoclast proliferation; IMP:RGD.
DR GO; GO:0010800; P:positive regulation of peptidyl-threonine phosphorylation; ISO:RGD.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; ISO:RGD.
DR GO; GO:0032092; P:positive regulation of protein binding; ISS:UniProtKB.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; IMP:RGD.
DR GO; GO:0046827; P:positive regulation of protein export from nucleus; ISO:RGD.
DR GO; GO:1904781; P:positive regulation of protein localization to centrosome; ISO:RGD.
DR GO; GO:1903566; P:positive regulation of protein localization to cilium; ISS:UniProtKB.
DR GO; GO:0031334; P:positive regulation of protein-containing complex assembly; ISO:RGD.
DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; IMP:RGD.
DR GO; GO:2000738; P:positive regulation of stem cell differentiation; ISO:RGD.
DR GO; GO:0045887; P:positive regulation of synaptic assembly at neuromuscular junction; IMP:CACAO.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0046777; P:protein autophosphorylation; ISO:RGD.
DR GO; GO:0006611; P:protein export from nucleus; ISO:RGD.
DR GO; GO:0035372; P:protein localization to microtubule; ISO:RGD.
DR GO; GO:0006468; P:protein phosphorylation; IDA:BHF-UCL.
DR GO; GO:0000320; P:re-entry into mitotic cell cycle; ISO:RGD.
DR GO; GO:0042981; P:regulation of apoptotic process; ISO:RGD.
DR GO; GO:0030516; P:regulation of axon extension; IMP:RGD.
DR GO; GO:0050770; P:regulation of axonogenesis; IMP:RGD.
DR GO; GO:0001558; P:regulation of cell growth; ISO:RGD.
DR GO; GO:0042752; P:regulation of circadian rhythm; ISS:UniProtKB.
DR GO; GO:0048814; P:regulation of dendrite morphogenesis; IMP:RGD.
DR GO; GO:0006349; P:regulation of gene expression by genomic imprinting; ISO:RGD.
DR GO; GO:1900271; P:regulation of long-term synaptic potentiation; ISS:UniProtKB.
DR GO; GO:0150101; P:regulation of microtubule anchoring at centrosome; ISO:RGD.
DR GO; GO:0070507; P:regulation of microtubule cytoskeleton organization; IMP:ARUK-UCL.
DR GO; GO:0032886; P:regulation of microtubule-based process; ISS:UniProtKB.
DR GO; GO:0099159; P:regulation of modification of postsynaptic structure; IDA:SynGO.
DR GO; GO:0010975; P:regulation of neuron projection development; ISO:RGD.
DR GO; GO:0048168; P:regulation of neuronal synaptic plasticity; IMP:RGD.
DR GO; GO:0098696; P:regulation of neurotransmitter receptor localization to postsynaptic specialization membrane; IDA:SynGO.
DR GO; GO:0045667; P:regulation of osteoblast differentiation; IMP:RGD.
DR GO; GO:0046825; P:regulation of protein export from nucleus; ISO:RGD.
DR GO; GO:2000300; P:regulation of synaptic vesicle exocytosis; ISO:RGD.
DR GO; GO:0014823; P:response to activity; IEP:RGD.
DR GO; GO:1990776; P:response to angiotensin; IEP:RGD.
DR GO; GO:0071871; P:response to epinephrine; IEP:RGD.
DR GO; GO:0032355; P:response to estradiol; IEP:RGD.
DR GO; GO:0032868; P:response to insulin; IEP:RGD.
DR GO; GO:1990418; P:response to insulin-like growth factor stimulus; IEP:RGD.
DR GO; GO:1902065; P:response to L-glutamate; IEP:RGD.
DR GO; GO:0010226; P:response to lithium ion; IEP:RGD.
DR GO; GO:1990478; P:response to ultrasound; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
DR GO; GO:0010043; P:response to zinc ion; IDA:RGD.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0071109; P:superior temporal gyrus development; ISO:RGD.
DR GO; GO:0016055; P:Wnt signaling pathway; ISO:RGD.
DR CDD; cd14137; STKc_GSK3; 1.
DR InterPro; IPR033573; GSK3B.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR InterPro; IPR039192; STKc_GSK3.
DR PANTHER; PTHR24057:SF8; PTHR24057:SF8; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW ADP-ribosylation; ATP-binding; Biological rhythms; Carbohydrate metabolism;
KW Cell membrane; Cytoplasm; Developmental protein; Differentiation;
KW Glycogen metabolism; Kinase; Membrane; Neurogenesis; Nucleotide-binding;
KW Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Signal transduction inhibitor;
KW Transferase; Wnt signaling pathway.
FT CHAIN 1..420
FT /note="Glycogen synthase kinase-3 beta"
FT /id="PRO_0000085982"
FT DOMAIN 56..340
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..53
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 385..420
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..25
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 391..420
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 181
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 62..70
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 85
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 9
FT /note="Phosphoserine; by PKB/AKT1, RPS6KA3 and SGK3"
FT /evidence="ECO:0000250|UniProtKB:P49841"
FT MOD_RES 216
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:8382613"
FT MOD_RES 389
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MUTAGEN 9
FT /note="S->A: Loss of phosphorylation; No inhibition of
FT activity."
FT /evidence="ECO:0000269|PubMed:18424437"
FT MUTAGEN 216
FT /note="Y->F: Loss of phosphorylation and strong reduction
FT of activity."
FT /evidence="ECO:0000269|PubMed:8382613"
FT CONFLICT 240
FT /note="M -> V (in Ref. 2; CAA52020)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 420 AA; 46742 MW; 2F473FCAB89B4398 CRC64;
MSGRPRTTSF AESCKPVQQP SAFGSMKVSR DKDGSKVTTV VATPGQGPDR PQEVSYTDTK
VIGNGSFGVV YQAKLCDSGE LVAIKKVLQD KRFKNRELQI MRKLDHCNIV RLRYFFYSSG
EKKDEVYLNL VLDYVPETVY RVARHYSRAK QTLPVIYVKL YMYQLFRSLA YIHSFGICHR
DIKPQNLLLD PDTAVLKLCD FGSAKQLVRG EPNVSYICSR YYRAPELIFG ATDYTSSIDM
WSAGCVLAEL LLGQPIFPGD SGVDQLVEII KVLGTPTREQ IREMNPNYTE FKFPQIKAHP
WTKVFRPRTP PEAIALCSRL LEYTPTARLT PLEACAHSFF DELRDPNVKL PNGRDTPALF
NFTTQELSSN PPLATILIPP HARIQAAASP PANATAASDT NAGDRGQTNN AASASASNST
