ID GSK3B_HUMAN Reviewed; 420 AA. AC P49841; D3DN89; Q9BWH3; Q9UL47; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 02-MAY-2002, sequence version 2. DT 27-MAR-2024, entry version 265. DE RecName: Full=Glycogen synthase kinase-3 beta {ECO:0000305}; DE Short=GSK-3 beta; DE EC=2.7.11.26 {ECO:0000269|PubMed:14690523}; DE AltName: Full=Serine/threonine-protein kinase GSK3B; DE EC=2.7.11.1 {ECO:0000269|PubMed:17050006, ECO:0000269|PubMed:22539723, ECO:0000269|PubMed:28992046}; GN Name=GSK3B {ECO:0000312|HGNC:HGNC:4617}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND MUTAGENESIS OF SER-9. RX PubMed=7980435; DOI=10.1042/bj3030701; RA Stambolic V., Woodgett J.R.; RT "Mitogen inactivation of glycogen synthase kinase-3 beta in intact cells RT via serine 9 phosphorylation."; RL Biochem. J. 303:701-704(1994). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Eye, and Placenta; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-28. RX PubMed=10486203; DOI=10.1006/geno.1999.5875; RA Lau K.F., Miller C.C.J., Anderton B.H., Shaw P.C.; RT "Molecular cloning and characterization of the human glycogen synthase RT kinase-3beta promoter."; RL Genomics 60:121-128(1999). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 185-202. RX PubMed=10523816; DOI=10.1038/sj.mp.4000538; RA Rhoads A.R., Karkera J.D., Detera-Wadleigh S.D.; RT "Radiation hybrid mapping of genes in the lithium-sensitive wnt signaling RT pathway."; RL Mol. Psychiatry 4:437-442(1999). RN [6] RP FUNCTION IN PHOSPHORYLATION OF JUN. RX PubMed=1846781; DOI=10.1016/0092-8674(91)90241-p; RA Boyle W.J., Smeal T., Defize L.H., Angel P., Woodgett J.R., Karin M., RA Hunter T.; RT "Activation of protein kinase C decreases phosphorylation of c-Jun at sites RT that negatively regulate its DNA-binding activity."; RL Cell 64:573-584(1991). RN [7] RP FUNCTION IN PHOSPHORYLATION OF EIF2BE/EIF2B5. RX PubMed=8397507; DOI=10.1042/bj2940625; RA Welsh G.I., Proud C.G.; RT "Glycogen synthase kinase-3 is rapidly inactivated in response to insulin RT and phosphorylates eukaryotic initiation factor eIF-2B."; RL Biochem. J. 294:625-629(1993). RN [8] RP PHOSPHORYLATION AT SER-9. RX PubMed=8250835; DOI=10.1042/bj2960015; RA Sutherland C., Leighton I.A., Cohen P.; RT "Inactivation of glycogen synthase kinase-3 beta by phosphorylation: new RT kinase connections in insulin and growth-factor signalling."; RL Biochem. J. 296:15-19(1993). RN [9] RP ACTIVITY REGULATION BY AKT1. RX PubMed=8524413; DOI=10.1038/378785a0; RA Cross D.A., Alessi D.R., Cohen P., Andjelkovich M., Hemmings B.A.; RT "Inhibition of glycogen synthase kinase-3 by insulin mediated by protein RT kinase B."; RL Nature 378:785-789(1995). RN [10] RP FUNCTION IN PHOSPHORYLATION OF NFATC1/NFATC. RX PubMed=9072970; DOI=10.1126/science.275.5308.1930; RA Beals C.R., Sheridan C.M., Turck C.W., Gardner P., Crabtree G.R.; RT "Nuclear export of NF-ATc enhanced by glycogen synthase kinase-3."; RL Science 275:1930-1934(1997). RN [11] RP INTERACTION WITH DNM1L. RC TISSUE=Liver; RX PubMed=9731200; DOI=10.1006/bbrc.1998.9253; RA Hong Y.-R., Chen C.-H., Cheng D.-S., Howng S.-L., Chow C.-C.; RT "Human dynamin-like protein interacts with the glycogen synthase kinase RT 3beta."; RL Biochem. Biophys. Res. Commun. 249:697-703(1998). RN [12] RP INTERACTION WITH MUC1, AND FUNCTION. RX PubMed=9819408; DOI=10.1128/mcb.18.12.7216; RA Li Y., Bharti A., Chen D., Gong J., Kufe D.; RT "Interaction of glycogen synthase kinase 3beta with the DF3/MUC1 carcinoma- RT associated antigen and beta-catenin."; RL Mol. Cell. Biol. 18:7216-7224(1998). RN [13] RP CHARACTERIZATION. RX PubMed=9736715; DOI=10.1073/pnas.95.19.11211; RA Delcommenne M., Tan C., Gray V., Rue L., Woodgett J.R., Dedhar S.; RT "Phosphoinositide-3-OH kinase-dependent regulation of glycogen synthase RT kinase 3 and protein kinase B/AKT by the integrin-linked kinase."; RL Proc. Natl. Acad. Sci. U.S.A. 95:11211-11216(1998). RN [14] RP INTERACTION WITH NIN. RX PubMed=11004522; DOI=10.1016/s0167-4781(00)00127-5; RA Hong Y.-R., Chen C.-H., Chang J.-H., Wang S.-K., Sy W.-D., Chou C.-K., RA Howng S.-L.; RT "Cloning and characterization of a novel human ninein protein that RT interacts with the glycogen synthase kinase 3beta."; RL Biochim. Biophys. Acta 1492:513-516(2000). RN [15] RP ASSOCIATION WITH DIABETES MELLITUS. RX PubMed=10868943; DOI=10.2337/diabetes.49.2.263; RA Nikoulina S.E., Ciaraldi T.P., Mudaliar S., Mohideen P., Carter L., RA Henry R.R.; RT "Potential role of glycogen synthase kinase-3 in skeletal muscle insulin RT resistance of type 2 diabetes."; RL Diabetes 49:263-271(2000). RN [16] RP FUNCTION, AND MUTAGENESIS OF ARG-96 AND LEU-128. RX PubMed=11430833; DOI=10.1016/s1097-2765(01)00253-2; RA Frame S., Cohen P., Biondi R.M.; RT "A common phosphate binding site explains the unique substrate specificity RT of GSK3 and its inactivation by phosphorylation."; RL Mol. Cell 7:1321-1327(2001). RN [17] RP PHOSPHORYLATION AT SER-9 BY SGK3, AND INTERACTION WITH SGK3. RX PubMed=12054501; DOI=10.1016/s0006-291x(02)00349-2; RA Dai F., Yu L., He H., Chen Y., Yu J., Yang Y., Xu Y., Ling W., Zhao S.; RT "Human serum and glucocorticoid-inducible kinase-like kinase (SGKL) RT phosphorylates glycogen syntheses kinase 3 beta (GSK-3beta) at serine-9 RT through direct interaction."; RL Biochem. Biophys. Res. Commun. 293:1191-1196(2002). RN [18] RP FUNCTION IN PHOSPHORYLATION OF MAPT/TAU. RX PubMed=14690523; DOI=10.1111/j.1471-4159.2004.02155.x; RA Cho J.H., Johnson G.V.; RT "Primed phosphorylation of tau at Thr231 by glycogen synthase kinase 3beta RT (GSK3beta) plays a critical role in regulating tau's ability to bind and RT stabilize microtubules."; RL J. Neurochem. 88:349-358(2004). RN [19] RP FUNCTION, INTERACTION WITH SNAI1, AND SUBCELLULAR LOCATION. RX PubMed=15448698; DOI=10.1038/ncb1173; RA Zhou B.P., Deng J., Xia W., Xu J., Li Y.M., Gunduz M., Hung M.C.; RT "Dual regulation of Snail by GSK-3beta-mediated phosphorylation in control RT of epithelial-mesenchymal transition."; RL Nat. Cell Biol. 6:931-940(2004). RN [20] RP INTERACTION WITH CABYR. RX PubMed=15752768; DOI=10.1016/j.bbrc.2005.02.089; RA Hsu H.-C., Lee Y.-L., Cheng T.-S., Howng S.-L., Chang L.-K., Lu P.-J., RA Hong Y.-R.; RT "Characterization of two non-testis-specific CABYR variants that bind to RT GSK3beta with a proline-rich extensin-like domain."; RL Biochem. Biophys. Res. Commun. 329:1108-1117(2005). RN [21] RP FUNCTION, AND INTERACTION WITH SNAI1. RX PubMed=15647282; DOI=10.1074/jbc.m413878200; RA Yook J.I., Li X.Y., Ota I., Fearon E.R., Weiss S.J.; RT "Wnt-dependent regulation of the E-cadherin repressor snail."; RL J. Biol. Chem. 280:11740-11748(2005). RN [22] RP INTERACTION WITH GSKIP. RX PubMed=16981698; DOI=10.1021/bi061147r; RA Chou H.-Y., Howng S.-L., Cheng T.-S., Hsiao Y.-L., Lieu A.-S., Loh J.-K., RA Hwang S.-L., Lin C.-C., Hsu C.-M., Wang C., Lee C.-I., Lu P.-J., RA Chou C.-K., Huang C.-Y., Hong Y.-R.; RT "GSKIP is homologous to the axin GSK3beta interaction domain and functions RT as a negative regulator of GSK3beta."; RL Biochemistry 45:11379-11389(2006). RN [23] RP INTERACTION WITH PRUNE1. RX PubMed=16428445; DOI=10.1128/mcb.26.3.898-911.2006; RA Kobayashi T., Hino S., Oue N., Asahara T., Zollo M., Yasui W., Kikuchi A.; RT "Glycogen synthase kinase 3 and h-prune regulate cell migration by RT modulating focal adhesions."; RL Mol. Cell. Biol. 26:898-911(2006). RN [24] RP FUNCTION, AND PHOSPHORYLATION AT SER-9. RX PubMed=16484495; DOI=10.1126/science.1121613; RA Yin L., Wang J., Klein P.S., Lazar M.A.; RT "Nuclear receptor Rev-erbalpha is a critical lithium-sensitive component of RT the circadian clock."; RL Science 311:1002-1005(2006). RN [25] RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF SER-9 AND 85-LYS-LYS-86. RX PubMed=17050006; DOI=10.1016/j.bbamcr.2006.09.015; RA Garcia-Alvarez G., Ventura V., Ros O., Aligue R., Gil J., Tauler A.; RT "Glycogen synthase kinase-3beta binds to E2F1 and regulates its RT transcriptional activity."; RL Biochim. Biophys. Acta 1773:375-382(2007). RN [26] RP INTERACTION WITH AXIN1. RX PubMed=17318175; DOI=10.1038/sj.emboj.7601607; RA Luo W., Peterson A., Garcia B.A., Coombs G., Kofahl B., Heinrich R., RA Shabanowitz J., Hunt D.F., Yost H.J., Virshup D.M.; RT "Protein phosphatase 1 regulates assembly and function of the beta-catenin RT degradation complex."; RL EMBO J. 26:1511-1521(2007). RN [27] RP FUNCTION, AND INTERACTION WITH BIRC2; DDX3X AND TNFRSF10B. RX PubMed=18846110; DOI=10.1038/cdd.2008.124; RA Sun M., Song L., Li Y., Zhou T., Jope R.S.; RT "Identification of an antiapoptotic protein complex at death receptors."; RL Cell Death Differ. 15:1887-1900(2008). RN [28] RP FUNCTION IN PHOSPHORYLATION OF SIK1. RX PubMed=18348280; DOI=10.1002/jcb.21737; RA Hashimoto Y.K., Satoh T., Okamoto M., Takemori H.; RT "Importance of autophosphorylation at Ser186 in the A-loop of salt RT inducible kinase 1 for its sustained kinase activity."; RL J. Cell. Biochem. 104:1724-1739(2008). RN [29] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-402, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [30] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-390, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [31] RP INTERACTION WITH MMP2. RX PubMed=19493954; DOI=10.1093/cvr/cvp175; RA Kandasamy A.D., Schulz R.; RT "Glycogen synthase kinase-3beta is activated by matrix metalloproteinase-2 RT mediated proteolysis in cardiomyoblasts."; RL Cardiovasc. Res. 83:698-706(2009). RN [32] RP FUNCTION, AND INTERACTION WITH CLOCK-BMAL1. RX PubMed=19946213; DOI=10.4161/cc.8.24.10273; RA Spengler M.L., Kuropatwinski K.K., Schumer M., Antoch M.P.; RT "A serine cluster mediates BMAL1-dependent CLOCK phosphorylation and RT degradation."; RL Cell Cycle 8:4138-4146(2009). RN [33] RP INTERACTION WITH CTNND2. RX PubMed=19706605; DOI=10.1074/jbc.m109.002659; RA Oh M., Kim H., Yang I., Park J.H., Cong W.T., Baek M.C., Bareiss S., Ki H., RA Lu Q., No J., Kwon I., Choi J.K., Kim K.; RT "GSK-3 phosphorylates delta-catenin and negatively regulates its stability RT via ubiquitination/proteosome-mediated proteolysis."; RL J. Biol. Chem. 284:28579-28589(2009). RN [34] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200; RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., RA Mann M., Daub H.; RT "Large-scale proteomics analysis of the human kinome."; RL Mol. Cell. Proteomics 8:1751-1764(2009). RN [35] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [36] RP FUNCTION, AND ALTERNATIVE SPLICING. RX PubMed=20067585; DOI=10.1111/j.1471-4159.2010.06581.x; RA Castano Z., Gordon-Weeks P.R., Kypta R.M.; RT "The neuron-specific isoform of glycogen synthase kinase-3beta is required RT for axon growth."; RL J. Neurochem. 113:117-130(2010). RN [37] RP FUNCTION. RX PubMed=20932480; DOI=10.1016/j.molcel.2010.09.013; RA Heyd F., Lynch K.W.; RT "Phosphorylation-dependent regulation of PSF by GSK3 controls CD45 RT alternative splicing."; RL Mol. Cell 40:126-137(2010). RN [38] RP INTERACTION WITH DAB2IP AND PPP2CA. RX PubMed=20080667; DOI=10.1073/pnas.0908133107; RA Xie D., Gore C., Liu J., Pong R.C., Mason R., Hao G., Long M., Kabbani W., RA Yu L., Zhang H., Chen H., Sun X., Boothman D.A., Min W., Hsieh J.T.; RT "Role of DAB2IP in modulating epithelial-to-mesenchymal transition and RT prostate cancer metastasis."; RL Proc. Natl. Acad. Sci. U.S.A. 107:2485-2490(2010). RN [39] RP FUNCTION, SUBCELLULAR LOCATION, AND PHOSPHORYLATION AT SER-9. RX PubMed=20937854; DOI=10.1073/pnas.1000975107; RA Zaoui K., Benseddik K., Daou P., Salaun D., Badache A.; RT "ErbB2 receptor controls microtubule capture by recruiting ACF7 to the RT plasma membrane of migrating cells."; RL Proc. Natl. Acad. Sci. U.S.A. 107:18517-18522(2010). RN [40] RP REVIEW ON FUNCTION, AND ACTIVITY REGULATION. RX PubMed=11749387; DOI=10.1021/cr000110o; RA Ali A., Hoeflich K.P., Woodgett J.R.; RT "Glycogen synthase kinase-3: properties, functions, and regulation."; RL Chem. Rev. 101:2527-2540(2001). RN [41] RP REVIEW ON FUNCTION. RX PubMed=17478001; DOI=10.1016/j.diabres.2007.01.033; RA Lee J., Kim M.S.; RT "The role of GSK3 in glucose homeostasis and the development of insulin RT resistance."; RL Diabetes Res. Clin. Pract. 77:S49-S57(2007). RN [42] RP REVIEW ON FUNCTION, AND ACTIVITY REGULATION. RX PubMed=19366350; DOI=10.1111/j.1476-5381.2008.00085.x; RA Rayasam G.V., Tulasi V.K., Sodhi R., Davis J.A., Ray A.; RT "Glycogen synthase kinase 3: more than a namesake."; RL Br. J. Pharmacol. 156:885-898(2009). RN [43] RP INTERACTION WITH GSKIP, AND COMPLEX FORMATION WITH PRKAR2A AND GSKIP. RX PubMed=20007971; DOI=10.1074/jbc.m109.047944; RA Hundsrucker C., Skroblin P., Christian F., Zenn H.M., Popara V., Joshi M., RA Eichhorst J., Wiesner B., Herberg F.W., Reif B., Rosenthal W., RA Klussmann E.; RT "Glycogen synthase kinase 3beta interaction protein functions as an A- RT kinase anchoring protein."; RL J. Biol. Chem. 285:5507-5521(2010). RN [44] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [45] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [46] RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND PHOSPHORYLATION. RX PubMed=21029237; DOI=10.1111/j.1750-3639.2010.00437.x; RA Bose A., Mouton-Liger F., Paquet C., Mazot P., Vigny M., Gray F., Hugon J.; RT "Modulation of tau phosphorylation by the kinase PKR: implications in RT Alzheimer's disease."; RL Brain Pathol. 21:189-200(2011). RN [47] RP FUNCTION. RX PubMed=22514281; DOI=10.1074/jbc.m111.306373; RA Sun L., Lv F., Guo X., Gao G.; RT "Glycogen synthase kinase 3? (GSK3?) modulates antiviral activity of zinc- RT finger antiviral protein (ZAP)."; RL J. Biol. Chem. 287:22882-22888(2012). RN [48] RP CATALYTIC ACTIVITY. RX PubMed=22539723; DOI=10.1126/science.1217032; RA Lin S.Y., Li T.Y., Liu Q., Zhang C., Li X., Chen Y., Zhang S.M., Lian G., RA Liu Q., Ruan K., Wang Z., Zhang C.S., Chien K.Y., Wu J., Li Q., Han J., RA Lin S.C.; RT "GSK3-TIP60-ULK1 signaling pathway links growth factor deprivation to RT autophagy."; RL Science 336:477-481(2012). RN [49] RP ADP-RIBOSYLATION BY PARP10. RX PubMed=23332125; DOI=10.1186/1478-811x-11-5; RA Feijs K.L., Kleine H., Braczynski A., Forst A.H., Herzog N., Verheugd P., RA Linzen U., Kremmer E., Luscher B.; RT "ARTD10 substrate identification on protein microarrays: regulation of RT GSK3beta by mono-ADP-ribosylation."; RL Cell Commun. Signal. 11:5-5(2013). RN [50] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-390, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [51] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [52] RP FUNCTION, INTERACTION WITH NCYM, AND PHOSPHORYLATION AT SER-9. RX PubMed=24391509; DOI=10.1371/journal.pgen.1003996; RA Suenaga Y., Islam S.M., Alagu J., Kaneko Y., Kato M., Tanaka Y., Kawana H., RA Hossain S., Matsumoto D., Yamamoto M., Shoji W., Itami M., Shibata T., RA Nakamura Y., Ohira M., Haraguchi S., Takatori A., Nakagawara A.; RT "NCYM, a Cis-antisense gene of MYCN, encodes a de novo evolved protein that RT inhibits GSK3beta resulting in the stabilization of MYCN in human RT neuroblastomas."; RL PLoS Genet. 10:E1003996-E1003996(2014). RN [53] RP PHOSPHORYLATION AT SER-9 AND TYR-216, INTERACTION WITH JPT1, AND RP SUBCELLULAR LOCATION. RX PubMed=25169422; DOI=10.1002/jcb.24956; RA Varisli L., Ozturk B.E., Akyuz G.K., Korkmaz K.S.; RT "HN1 negatively influences the beta-catenin/E-cadherin interaction, and RT contributes to migration in prostate cells."; RL J. Cell. Biochem. 116:170-178(2015). RN [54] RP INTERACTION WITH GSKIP, AND COMPLEX FORMATION WITH PRKAR2B AND GSKIP. RX PubMed=25920809; DOI=10.1016/j.bbamcr.2015.04.013; RA Loh J.K., Lin C.C., Yang M.C., Chou C.H., Chen W.S., Hong M.C., Cho C.L., RA Hsu C.M., Cheng J.T., Chou A.K., Chang C.H., Tseng C.N., Wang C.H., RA Lieu A.S., Howng S.L., Hong Y.R.; RT "GSKIP- and GSK3-mediated anchoring strengthens cAMP/PKA/Drp1 axis RT signaling in the regulation of mitochondrial elongation."; RL Biochim. Biophys. Acta 1853:1796-1807(2015). RN [55] RP FUNCTION, AND INTERACTION WITH RICTOR. RX PubMed=25897075; DOI=10.1074/jbc.m114.633057; RA Koo J., Wu X., Mao Z., Khuri F.R., Sun S.Y.; RT "Rictor Undergoes Glycogen Synthase Kinase 3 (GSK3)-dependent, FBXW7- RT mediated Ubiquitination and Proteasomal Degradation."; RL J. Biol. Chem. 290:14120-14129(2015). RN [56] RP INTERACTION WITH GSKIP, AND COMPLEX FORMATION WITH PRKAR2A AND GSKIP. RX PubMed=27484798; DOI=10.1074/jbc.m116.738047; RA Dema A., Schroeter M.F., Perets E., Skroblin P., Moutty M.C., Deak V.A., RA Birchmeier W., Klussmann E.; RT "The A-Kinase Anchoring Protein (AKAP) Glycogen Synthase Kinase 3beta RT Interaction Protein (GSKIP) Regulates beta-Catenin through Its Interactions RT with Both Protein Kinase A (PKA) and GSK3beta."; RL J. Biol. Chem. 291:19618-19630(2016). RN [57] RP INTERACTION WITH AXIN1 AND GID8. RX PubMed=28829046; DOI=10.1038/cr.2017.107; RA Lu Y., Xie S., Zhang W., Zhang C., Gao C., Sun Q., Cai Y., Xu Z., Xiao M., RA Xu Y., Huang X., Wu X., Liu W., Wang F., Kang Y., Zhou T.; RT "Twa1/Gid8 is a beta-catenin nuclear retention factor in Wnt signaling and RT colorectal tumorigenesis."; RL Cell Res. 27:1422-1440(2017). RN [58] RP FUNCTION, AND INTERACTION WITH BMAL1. RX PubMed=28903391; DOI=10.18632/oncotarget.18973; RA Lu Y., Zheng X., Hu W., Bian S., Zhang Z., Tao D., Liu Y., Ma Y.; RT "Cancer/testis antigen PIWIL2 suppresses circadian rhythms by regulating RT the stability and activity of BMAL1 and CLOCK."; RL Oncotarget 8:54913-54924(2017). RN [59] RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF SER-9. RX PubMed=28992046; DOI=10.1093/jmcb/mjx034; RA Wang D., Zhao J., Li S., Wei J., Nan L., Mallampalli R.K., RA Weathington N.M., Ma H., Zhao Y.; RT "Phosphorylated E2F1 is stabilized by nuclear USP11 to drive Peg10 gene RT expression and activate lung epithelial cells."; RL J. Mol. Cell Biol. 10:60-73(2018). RN [60] RP FUNCTION. RX PubMed=30704899; DOI=10.1016/j.molcel.2018.12.017; RA Cheng X., Ma X., Zhu Q., Song D., Ding X., Li L., Jiang X., Wang X., RA Tian R., Su H., Shen Z., Chen S., Liu T., Gong W., Liu W., Sun Q.; RT "Pacer is a mediator of mTORC1 and GSK3-TIP60 signaling in regulation of RT autophagosome maturation and lipid metabolism."; RL Mol. Cell 73:1-15(2019). RN [61] RP INTERACTION WITH LMBR1L. RX PubMed=31073040; DOI=10.1126/science.aau0812; RA Choi J.H., Zhong X., McAlpine W., Liao T.C., Zhang D., Fang B., Russell J., RA Ludwig S., Nair-Gill E., Zhang Z., Wang K.W., Misawa T., Zhan X., Choi M., RA Wang T., Li X., Tang M., Sun Q., Yu L., Murray A.R., Moresco E.M.Y., RA Beutler B.; RT "LMBR1L regulates lymphopoiesis through Wnt/beta-catenin signaling."; RL Science 364:0-0(2019). RN [62] RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 35-386. RX PubMed=11440715; DOI=10.1016/s0092-8674(01)00374-9; RA Dajani R., Fraser E., Roe S.M., Young N., Good V., Dale T.C., Pearl L.H.; RT "Crystal structure of glycogen synthase kinase 3 beta: structural basis for RT phosphate-primed substrate specificity and autoinhibition."; RL Cell 105:721-732(2001). RN [63] RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 27-393 OF PHOSPHORYLATED GSK3B. RX PubMed=11738041; DOI=10.1016/s0969-2126(01)00679-7; RA Bax B., Carter P.S., Lewis C., Guy A.R., Bridges A., Tanner R., Pettman G., RA Mannix C., Culbert A.A., Brown M.J.B., Smith D.G., Reith A.D.; RT "The structure of phosphorylated GSK-3beta complexed with a peptide, RT FRATtide, that inhibits beta-catenin phosphorylation."; RL Structure 9:1143-1152(2001). RN [64] RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 35-384 IN COMPLEX WITH AXIN1, RP INTERACTION WITH AXIN1 AND FRAT1, FUNCTION, ACTIVITY REGULATION, AND RP PHOSPHORYLATION AT TYR-216. RX PubMed=12554650; DOI=10.1093/emboj/cdg068; RA Dajani R., Fraser E., Roe S.M., Yeo M., Good V.M., Thompson V., Dale T.C., RA Pearl L.H.; RT "Structural basis for recruitment of glycogen synthase kinase 3beta to the RT axin-APC scaffold complex."; RL EMBO J. 22:494-501(2003). 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 (PubMed:1846781, PubMed:9072970, CC PubMed:14690523, PubMed:20937854, PubMed:12554650, PubMed:11430833, CC PubMed:16484495). Requires primed phosphorylation of the majority of CC its substrates (PubMed:11430833, PubMed:16484495). In skeletal muscle, CC contributes to insulin regulation of glycogen synthesis by CC phosphorylating and inhibiting GYS1 activity and hence glycogen CC synthesis (PubMed:8397507). May also mediate the development of insulin CC resistance by regulating activation of transcription factors CC (PubMed:8397507). Regulates protein synthesis by controlling the CC activity of initiation factor 2B (EIF2BE/EIF2B5) in the same manner as CC glycogen synthase (PubMed:8397507). In Wnt signaling, GSK3B forms a CC multimeric complex with APC, AXIN1 and CTNNB1/beta-catenin and CC phosphorylates the N-terminus of CTNNB1 leading to its degradation CC mediated by ubiquitin/proteasomes (PubMed:12554650). Phosphorylates JUN CC at sites proximal to its DNA-binding domain, thereby reducing its CC affinity for DNA (PubMed:1846781). Phosphorylates NFATC1/NFATC on CC conserved serine residues promoting NFATC1/NFATC nuclear export, CC shutting off NFATC1/NFATC gene regulation, and thereby opposing the CC action of calcineurin (PubMed:9072970). Phosphorylates MAPT/TAU on CC 'Thr-548', decreasing significantly MAPT/TAU ability to bind and CC stabilize microtubules (PubMed:14690523). MAPT/TAU is the principal CC component of neurofibrillary tangles in Alzheimer disease CC (PubMed:14690523). Plays an important role in ERBB2-dependent CC stabilization of microtubules at the cell cortex (PubMed:20937854). CC Phosphorylates MACF1, inhibiting its binding to microtubules which is CC critical for its role in bulge stem cell migration and skin wound CC repair (By similarity). Probably regulates NF-kappa-B (NFKB1) at the CC transcriptional level and is required for the NF-kappa-B-mediated anti- CC apoptotic response to TNF-alpha (TNF/TNFA) (By similarity). Negatively CC regulates replication in pancreatic beta-cells, resulting in apoptosis, CC loss of beta-cells and diabetes (By similarity). Through CC phosphorylation of the anti-apoptotic protein MCL1, may control cell CC apoptosis in response to growth factors deprivation (By similarity). CC Phosphorylates MUC1 in breast cancer cells, decreasing the interaction CC of MUC1 with CTNNB1/beta-catenin (PubMed:9819408). Is necessary for the CC establishment of neuronal polarity and axon outgrowth CC (PubMed:20067585). Phosphorylates MARK2, leading to inhibition of its CC activity (By similarity). Phosphorylates SIK1 at 'Thr-182', leading to CC sustainment of its activity (PubMed:18348280). Phosphorylates ZC3HAV1 CC which enhances its antiviral activity (PubMed:22514281). Phosphorylates CC SNAI1, leading to its BTRC-triggered ubiquitination and proteasomal CC degradation (PubMed:15448698, PubMed:15647282). Phosphorylates SFPQ at CC 'Thr-687' upon T-cell activation (PubMed:20932480). Phosphorylates CC NR1D1 st 'Ser-55' and 'Ser-59' and stabilizes it by protecting it from CC proteasomal degradation. Regulates the circadian clock via CC phosphorylation of the major clock components including BMAL1, CLOCK CC and PER2 (PubMed:19946213, PubMed:28903391). Phosphorylates FBXL2 at CC 'Thr-404' and primes it for ubiquitination by the SCF(FBXO3) complex CC and proteasomal degradation (By similarity). Phosphorylates CLOCK AT CC 'Ser-427' and targets it for proteasomal degradation (PubMed:19946213). CC Phosphorylates BMAL1 at 'Ser-17' and 'Ser-21' and primes it for CC ubiquitination and proteasomal degradation (PubMed:28903391). 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 (PubMed:24391509). Regulates the circadian rhythmicity CC of hippocampal long-term potentiation and BMAL1 and PER2 expression (By CC 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 (PubMed:30704899). CC Negatively regulates extrinsic apoptotic signaling pathway via death CC domain receptors. Promotes the formation of an anti-apoptotic complex, CC made of DDX3X, BRIC2 and GSK3B, at death receptors, including CC TNFRSF10B. The anti-apoptotic function is most effective with weak CC apoptotic signals and can be overcome by stronger stimulation CC (PubMed:18846110). Phosphorylates E2F1, promoting the interaction CC between E2F1 and USP11, stabilizing E2F1 and promoting its activity CC (PubMed:17050006, PubMed:28992046). Phosphorylates mTORC2 complex CC component RICTOR at 'Thr-1695' which facilitates FBXW7-mediated CC ubiquitination and subsequent degradation of RICTOR (PubMed:25897075). CC Phosphorylates FXR1, promoting FXR1 ubiquitination by the SCF(FBXO4) CC complex and FXR1 degradation by the proteasome (By similarity). CC Phosphorylates interleukin-22 receptor subunit IL22RA1, preventing its CC proteasomal degradation (By similarity). {ECO:0000250|UniProtKB:P18266, CC ECO:0000250|UniProtKB:Q9WV60, ECO:0000269|PubMed:11430833, CC ECO:0000269|PubMed:12554650, ECO:0000269|PubMed:14690523, CC ECO:0000269|PubMed:15448698, ECO:0000269|PubMed:15647282, CC ECO:0000269|PubMed:16484495, ECO:0000269|PubMed:17050006, CC ECO:0000269|PubMed:18348280, ECO:0000269|PubMed:1846781, CC ECO:0000269|PubMed:18846110, ECO:0000269|PubMed:19946213, CC ECO:0000269|PubMed:20067585, ECO:0000269|PubMed:20932480, CC ECO:0000269|PubMed:20937854, ECO:0000269|PubMed:22514281, CC ECO:0000269|PubMed:24391509, ECO:0000269|PubMed:25897075, CC ECO:0000269|PubMed:28903391, ECO:0000269|PubMed:28992046, CC ECO:0000269|PubMed:30704899, ECO:0000269|PubMed:8397507, CC ECO:0000269|PubMed:9072970, ECO:0000269|PubMed:9819408}. 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:0000269|PubMed:14690523}; 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:0000269|PubMed:14690523}; 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:0000269|PubMed:17050006, ECO:0000269|PubMed:22539723, CC ECO:0000269|PubMed:28992046}; 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:0000269|PubMed:17050006}; CC -!- ACTIVITY REGULATION: Activated by phosphorylation at Tyr-216. In CC response to insulin, inhibited by phosphorylation at Ser-9 by PKB/AKT1 CC and RPS6KA3; phosphorylation at this site causes a conformational CC change, preventing access of substrates to the active site. Inhibited CC by IL22 treatment which also triggers phosphorylation at Ser-9, CC promoting inactivation (By similarity). Inhibited by lithium. CC {ECO:0000250|UniProtKB:Q9WV60, ECO:0000269|PubMed:11749387, CC ECO:0000269|PubMed:12554650, ECO:0000269|PubMed:19366350, CC ECO:0000269|PubMed:8524413}. CC -!- SUBUNIT: Monomer. Interacts with ARRB2, DISC1 and ZBED3 (By CC similarity). Interacts with CABYR, MMP2, MUC1, NIN and PRUNE1. CC Interacts with AXIN1; the interaction mediates hyperphosphorylation of CC CTNNB1 leading to its ubiquitination and destruction. Interacts with CC and phosphorylates SNAI1. Interacts with DNM1L (via a C-terminal CC domain). Found in a complex composed of MACF1, APC, AXIN1, CTNNB1 and CC GSK3B (By similarity). Interacts with SGK3. Interacts with DAB2IP (via CC C2 domain); the interaction stimulates GSK3B kinase activation. CC Interacts (via C2 domain) with PPP2CA. Interacts with the CLOCK-BMAL1 CC heterodimer (PubMed:19946213). Interacts with the BMAL1 CC (PubMed:28903391). Interacts with CTNND2 (PubMed:19706605). Interacts CC with NCYM (PubMed:24391509). The complex composed, at least, of APC, CC CTNNB1 and GSK3B interacts with JPT1; the interaction requires the CC inactive form of GSK3B (phosphorylated at 'Ser-9') (PubMed:25169422). CC Forms a complex composed of PRKAR2A or PRKAR2B, GSK3B and GSKIP through CC GSKIP interaction; facilitates PKA-induced phosphorylation and CC regulates GSK3B activity (PubMed:27484798, PubMed:20007971, CC PubMed:25920809). Interacts with GSKIP (PubMed:16981698). Interacts CC with GID8 (PubMed:28829046). Interacts with PIWIL2 (By similarity). CC Interacts with LMBR1L (PubMed:31073040). Interacts with DDX3X CC (PubMed:18846110). Interacts with BIRC2 (PubMed:18846110). Interacts CC with TNFRSF10B; TNFRSF10B stimulation inhibits GSK3B kinase activity CC (PubMed:18846110). Interacts with RICTOR; the interaction results in CC phosphorylation of RICTOR at 'Thr-1695' by GSK3B which facilitates CC FBXW7-mediated ubiquitination and subsequent degradation of RICTOR CC (PubMed:25897075). Found in a complex with SLC39A6, SLC39A10 and with CC GSK3B that controls NCAM1 phosphorylation (By similarity). CC {ECO:0000250|UniProtKB:P18266, ECO:0000250|UniProtKB:Q9WV60, CC ECO:0000269|PubMed:11004522, ECO:0000269|PubMed:12054501, CC ECO:0000269|PubMed:12554650, ECO:0000269|PubMed:15448698, CC ECO:0000269|PubMed:15647282, ECO:0000269|PubMed:15752768, CC ECO:0000269|PubMed:16428445, ECO:0000269|PubMed:16981698, CC ECO:0000269|PubMed:17318175, ECO:0000269|PubMed:18846110, CC ECO:0000269|PubMed:19493954, ECO:0000269|PubMed:19706605, CC ECO:0000269|PubMed:19946213, ECO:0000269|PubMed:20007971, CC ECO:0000269|PubMed:20080667, ECO:0000269|PubMed:24391509, CC ECO:0000269|PubMed:25169422, ECO:0000269|PubMed:25897075, CC ECO:0000269|PubMed:25920809, ECO:0000269|PubMed:27484798, CC ECO:0000269|PubMed:28829046, ECO:0000269|PubMed:28903391, CC ECO:0000269|PubMed:31073040, ECO:0000269|PubMed:9731200, CC ECO:0000269|PubMed:9819408}. CC -!- INTERACTION: CC P49841; P31749: AKT1; NbExp=4; IntAct=EBI-373586, EBI-296087; CC P49841; P31751: AKT2; NbExp=2; IntAct=EBI-373586, EBI-296058; CC P49841; PRO_0000000093 [P05067]: APP; NbExp=2; IntAct=EBI-373586, EBI-2431589; CC P49841; O15169: AXIN1; NbExp=51; IntAct=EBI-373586, EBI-710484; CC P49841; Q96G01: BICD1; NbExp=7; IntAct=EBI-373586, EBI-1104509; CC P49841; O75952-3: CABYR; NbExp=3; IntAct=EBI-373586, EBI-10900795; CC P49841; O75952-5: CABYR; NbExp=3; IntAct=EBI-373586, EBI-10898671; CC P49841; P35222: CTNNB1; NbExp=19; IntAct=EBI-373586, EBI-491549; CC P49841; Q5VWQ8: DAB2IP; NbExp=2; IntAct=EBI-373586, EBI-2871881; CC P49841; Q5VWQ8-2: DAB2IP; NbExp=2; IntAct=EBI-373586, EBI-9543020; CC P49841; Q9NYF0: DACT1; NbExp=3; IntAct=EBI-373586, EBI-3951744; CC P49841; O75398: DEAF1; NbExp=2; IntAct=EBI-373586, EBI-718185; CC P49841; Q13144: EIF2B5; NbExp=2; IntAct=EBI-373586, EBI-4401110; CC P49841; Q92837: FRAT1; NbExp=5; IntAct=EBI-373586, EBI-3934879; CC P49841; P13807: GYS1; NbExp=4; IntAct=EBI-373586, EBI-740553; CC P49841; O75581: LRP6; NbExp=4; IntAct=EBI-373586, EBI-910915; CC P49841; Q5S007: LRRK2; NbExp=7; IntAct=EBI-373586, EBI-5323863; CC P49841; P10636: MAPT; NbExp=4; IntAct=EBI-373586, EBI-366182; CC P49841; P10636-8: MAPT; NbExp=12; IntAct=EBI-373586, EBI-366233; CC P49841; Q14596: NBR1; NbExp=4; IntAct=EBI-373586, EBI-742698; CC P49841; Q8N4C6: NIN; NbExp=3; IntAct=EBI-373586, EBI-1164022; CC P49841; P17612: PRKACA; NbExp=7; IntAct=EBI-373586, EBI-476586; CC P49841; Q01201: RELB; NbExp=4; IntAct=EBI-373586, EBI-357837; CC P49841; O95863: SNAI1; NbExp=5; IntAct=EBI-373586, EBI-1045459; CC P49841; P37840: SNCA; NbExp=2; IntAct=EBI-373586, EBI-985879; CC P49841; Q6J9G0: STYK1; NbExp=2; IntAct=EBI-373586, EBI-6424915; CC P49841; P04637: TP53; NbExp=3; IntAct=EBI-373586, EBI-366083; CC P49841; Q14134: TRIM29; NbExp=2; IntAct=EBI-373586, EBI-702370; CC P49841; O95071: UBR5; NbExp=8; IntAct=EBI-373586, EBI-358329; CC P49841; P63104: YWHAZ; NbExp=4; IntAct=EBI-373586, EBI-347088; CC P49841; Q8IX07: ZFPM1; NbExp=2; IntAct=EBI-373586, EBI-3942619; CC P49841; O35625: Axin1; Xeno; NbExp=5; IntAct=EBI-373586, EBI-2365912; CC P49841; Q14DJ8: Axin1; Xeno; NbExp=2; IntAct=EBI-373586, EBI-4312125; CC P49841; Q02248: Ctnnb1; Xeno; NbExp=3; IntAct=EBI-373586, EBI-397872; CC P49841; Q811T9: Disc1; Xeno; NbExp=4; IntAct=EBI-373586, EBI-2298259; CC P49841; P63085: Mapk1; Xeno; NbExp=2; IntAct=EBI-373586, EBI-397697; CC P49841; P0DTC9: N; Xeno; NbExp=3; IntAct=EBI-373586, EBI-25475856; CC P49841-2; P05067: APP; NbExp=3; IntAct=EBI-15870655, EBI-77613; CC P49841-2; P35637: FUS; NbExp=3; IntAct=EBI-15870655, EBI-400434; CC P49841-2; P01106: MYC; NbExp=3; IntAct=EBI-15870655, EBI-447544; CC P49841-2; Q8BMD2-1: Dzip1; Xeno; NbExp=3; IntAct=EBI-15870655, EBI-16153101; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:21029237, CC ECO:0000269|PubMed:25169422}. Nucleus {ECO:0000269|PubMed:15448698, CC ECO:0000269|PubMed:21029237}. Cell membrane CC {ECO:0000269|PubMed:20937854}. Note=The phosphorylated form shows CC localization to cytoplasm and cell membrane (PubMed:20937854). The CC MEMO1-RHOA-DIAPH1 signaling pathway controls localization of the CC phosphorylated form to the cell membrane (PubMed:20937854). CC {ECO:0000269|PubMed:20937854}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; Synonyms=GSK-3beta1; CC IsoId=P49841-1; Sequence=Displayed; CC Name=2; Synonyms=GSK-3beta2, neuron-specific; CC IsoId=P49841-2; Sequence=VSP_004790; CC -!- TISSUE SPECIFICITY: Expressed in testis, thymus, prostate and ovary and CC weakly expressed in lung, brain and kidney. Colocalizes with CC EIF2AK2/PKR and TAU in the Alzheimer disease (AD) brain. CC {ECO:0000269|PubMed:21029237}. CC -!- PTM: Phosphorylated by AKT1 and ILK1. Upon insulin-mediated signaling, CC the activated PKB/AKT1 protein kinase phosphorylates and deactivates CC GSK3B, resulting in the dephosphorylation and activation of GYS1. CC Activated by phosphorylation at Tyr-216 (PubMed:25169422). Inactivated CC by phosphorylation at Ser-9 (Probable). Phosphorylated in a circadian CC manner in the hippocampus (By similarity). CC {ECO:0000250|UniProtKB:Q9WV60, ECO:0000269|PubMed:12054501, CC ECO:0000269|PubMed:12554650, ECO:0000269|PubMed:16484495, CC ECO:0000269|PubMed:20937854, ECO:0000269|PubMed:21029237, CC ECO:0000269|PubMed:25169422, ECO:0000269|PubMed:8250835, CC ECO:0000305|PubMed:25169422}. CC -!- PTM: Mono-ADP-ribosylation by PARP10 negatively regulates kinase CC activity. {ECO:0000269|PubMed:23332125}. CC -!- MISCELLANEOUS: Higher expression and activity of GSK3B are found in the CC skeletal muscle (vastus lateralis) of patients with type 2 diabetes CC (PubMed:10868943). Several potent GSK3 (GSK3A and GSK3B) inhibitors CC have been identified and characterized in preclinical models for CC treatments of type 2 diabetes (PubMed:19366350). CC {ECO:0000305|PubMed:10868943, ECO:0000305|PubMed:19366350}. CC -!- MISCELLANEOUS: [Isoform 2]: May play a specific role in axon growth and CC neurite outgrowth. Reduced binding to AXIN1, reduced ability to CC phosphorylate MAPT/TAU. {ECO:0000269|PubMed:20067585}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr CC protein kinase family. GSK-3 subfamily. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/40761/GSK3B"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; L33801; AAA66475.1; -; mRNA. DR EMBL; CH471052; EAW79533.1; -; Genomic_DNA. DR EMBL; CH471052; EAW79536.1; -; Genomic_DNA. DR EMBL; BC000251; AAH00251.1; -; mRNA. DR EMBL; BC012760; AAH12760.1; -; mRNA. DR EMBL; AF074333; AAD48517.1; -; Genomic_DNA. DR EMBL; AF098789; AAC69340.1; -; Genomic_DNA. DR CCDS; CCDS2996.1; -. [P49841-2] DR CCDS; CCDS54628.1; -. [P49841-1] DR PIR; S53324; S53324. DR RefSeq; NP_001139628.1; NM_001146156.1. [P49841-1] DR RefSeq; NP_002084.2; NM_002093.3. [P49841-2] DR PDB; 1GNG; X-ray; 2.60 A; A/B=27-393. DR PDB; 1H8F; X-ray; 2.80 A; A/B=35-386. DR PDB; 1I09; X-ray; 2.70 A; A/B=1-420. DR PDB; 1J1B; X-ray; 1.80 A; A/B=1-420. DR PDB; 1J1C; X-ray; 2.10 A; A/B=1-420. DR PDB; 1O6K; X-ray; 1.70 A; C=3-12. DR PDB; 1O6L; X-ray; 1.60 A; C=3-12. DR PDB; 1O9U; X-ray; 2.40 A; A=35-384. DR PDB; 1PYX; X-ray; 2.40 A; A/B=1-420. DR PDB; 1Q3D; X-ray; 2.20 A; A/B=2-420. DR PDB; 1Q3W; X-ray; 2.30 A; A/B=2-420. DR PDB; 1Q41; X-ray; 2.10 A; A/B=2-420. DR PDB; 1Q4L; X-ray; 2.77 A; A/B=2-420. DR PDB; 1Q5K; X-ray; 1.94 A; A/B=7-420. DR PDB; 1R0E; X-ray; 2.25 A; A/B=35-420. DR PDB; 1UV5; X-ray; 2.80 A; A=35-384. DR PDB; 2JDO; X-ray; 1.80 A; C=3-12. DR PDB; 2JDR; X-ray; 2.30 A; C=3-12. DR PDB; 2JLD; X-ray; 2.35 A; A/B=1-420. DR PDB; 2O5K; X-ray; 3.20 A; A=29-393. DR PDB; 2OW3; X-ray; 2.80 A; A/B=35-386. DR PDB; 2UW9; X-ray; 2.10 A; C=3-12. DR PDB; 2X39; X-ray; 1.93 A; C=3-12. DR PDB; 2XH5; X-ray; 2.72 A; C=3-12. DR PDB; 3CQU; X-ray; 2.20 A; C=3-12. DR PDB; 3CQW; X-ray; 2.00 A; C=3-12. DR PDB; 3DU8; X-ray; 2.20 A; A/B=1-420. DR PDB; 3E87; X-ray; 2.30 A; C/D=3-12. DR PDB; 3E88; X-ray; 2.50 A; C/D=3-12. DR PDB; 3E8D; X-ray; 2.70 A; C/D=3-12. DR PDB; 3F7Z; X-ray; 2.40 A; A/B=35-383. DR PDB; 3F88; X-ray; 2.60 A; A/B=35-383. DR PDB; 3GB2; X-ray; 2.40 A; A=34-383. DR PDB; 3I4B; X-ray; 2.30 A; A/B=7-420. DR PDB; 3L1S; X-ray; 2.90 A; A/B=7-420. DR PDB; 3M1S; X-ray; 3.13 A; A/B=1-420. DR PDB; 3MV5; X-ray; 2.47 A; C=3-12. DR PDB; 3OW4; X-ray; 2.60 A; C/D=3-12. DR PDB; 3PUP; X-ray; 2.99 A; A/B=1-420. DR PDB; 3Q3B; X-ray; 2.70 A; A/B=2-420. DR PDB; 3QKK; X-ray; 2.30 A; C=3-12. DR PDB; 3SAY; X-ray; 2.23 A; A/B=1-420. DR PDB; 3SD0; X-ray; 2.70 A; A/B=35-384. DR PDB; 3ZDI; X-ray; 2.64 A; A=35-384. DR PDB; 3ZRK; X-ray; 2.37 A; A/B=23-393. DR PDB; 3ZRL; X-ray; 2.48 A; A/B=23-393. DR PDB; 3ZRM; X-ray; 2.49 A; A/B=23-393. DR PDB; 4ACC; X-ray; 2.21 A; A/B=1-420. DR PDB; 4ACD; X-ray; 2.60 A; A/B=1-420. DR PDB; 4ACG; X-ray; 2.60 A; A/B=1-420. DR PDB; 4ACH; X-ray; 2.60 A; A/B=1-420. DR PDB; 4AFJ; X-ray; 1.98 A; A/B=27-393. DR PDB; 4B7T; X-ray; 2.77 A; A=35-384. DR PDB; 4DIT; X-ray; 2.60 A; A=27-393. DR PDB; 4EKK; X-ray; 2.80 A; C/D=3-12. DR PDB; 4IQ6; X-ray; 3.12 A; A/B=1-420. DR PDB; 4J1R; X-ray; 2.70 A; A/B/C/D=1-420. DR PDB; 4J71; X-ray; 2.31 A; A/B=1-420. DR PDB; 4NM0; X-ray; 2.50 A; A=1-383. DR PDB; 4NM3; X-ray; 2.10 A; A=1-383. DR PDB; 4NM5; X-ray; 2.30 A; A=13-383. DR PDB; 4NM7; X-ray; 2.30 A; A=13-383. DR PDB; 4PTC; X-ray; 2.71 A; A/B=1-420. DR PDB; 4PTE; X-ray; 2.03 A; A/B=1-420. DR PDB; 4PTG; X-ray; 2.36 A; A/B=1-420. DR PDB; 5F94; X-ray; 2.51 A; A/B=36-385. DR PDB; 5F95; X-ray; 2.52 A; A/B=36-385. DR PDB; 5HLN; X-ray; 3.10 A; A/B=1-420. DR PDB; 5HLP; X-ray; 2.45 A; A/B=1-420. DR PDB; 5K5N; X-ray; 2.20 A; A/B=28-384. DR PDB; 5KPK; X-ray; 2.40 A; A/B=1-420. DR PDB; 5KPL; X-ray; 2.60 A; A/B=1-420. DR PDB; 5KPM; X-ray; 2.69 A; A/B=1-420. DR PDB; 5OY4; X-ray; 3.20 A; A/B=1-420. DR PDB; 5T31; X-ray; 2.85 A; A/B=1-420. DR PDB; 6B8J; X-ray; 2.60 A; A=1-420. DR PDB; 6BUU; X-ray; 2.40 A; F/G=3-12. DR PDB; 6GJO; X-ray; 2.91 A; A/B=7-420. DR PDB; 6GN1; X-ray; 2.60 A; A/B=27-393. DR PDB; 6H0U; X-ray; 2.30 A; A/B=1-420. DR PDB; 6HK3; X-ray; 2.35 A; A/B=35-384. DR PDB; 6HK4; X-ray; 2.50 A; A/B=35-384. DR PDB; 6HK7; X-ray; 3.20 A; A=36-382. DR PDB; 6NPZ; X-ray; 2.12 A; F/G=3-12. DR PDB; 6TCU; X-ray; 2.14 A; A=35-386. DR PDB; 6V6L; X-ray; 2.19 A; A=1-420. DR PDB; 6Y9R; X-ray; 2.08 A; A=35-384. DR PDB; 6Y9S; X-ray; 2.03 A; A/B=35-384. DR PDB; 7B6F; X-ray; 2.05 A; A=26-383. DR PDB; 7OY5; X-ray; 2.57 A; A/B=35-385. DR PDB; 7SXH; X-ray; 2.09 A; A=37-383. DR PDB; 7SXJ; X-ray; 1.85 A; A=34-383. DR PDB; 7U2Z; X-ray; 2.21 A; A/B=35-382. DR PDB; 7U31; X-ray; 2.38 A; A/B=36-385. DR PDB; 7U33; X-ray; 2.60 A; A/B=35-385. DR PDB; 7U36; X-ray; 2.75 A; A/B=35-385. DR PDB; 7Z1F; X-ray; 3.00 A; A/B=26-383. DR PDB; 7Z1G; X-ray; 2.85 A; A=26-383. DR PDB; 8AUZ; X-ray; 2.66 A; A/B=26-383. DR PDB; 8AV1; X-ray; 2.15 A; A/B=26-383. DR PDB; 8DJC; X-ray; 2.46 A; A/B=1-420. DR PDB; 8DJD; X-ray; 2.21 A; A/B=1-420. DR PDB; 8DJE; X-ray; 2.37 A; A/B=1-420. DR PDB; 8FF8; X-ray; 2.33 A; A/B=1-420. DR PDBsum; 1GNG; -. DR PDBsum; 1H8F; -. DR PDBsum; 1I09; -. DR PDBsum; 1J1B; -. DR PDBsum; 1J1C; -. DR PDBsum; 1O6K; -. DR PDBsum; 1O6L; -. DR PDBsum; 1O9U; -. DR PDBsum; 1PYX; -. DR PDBsum; 1Q3D; -. DR PDBsum; 1Q3W; -. DR PDBsum; 1Q41; -. DR PDBsum; 1Q4L; -. DR PDBsum; 1Q5K; -. DR PDBsum; 1R0E; -. DR PDBsum; 1UV5; -. DR PDBsum; 2JDO; -. DR PDBsum; 2JDR; -. DR PDBsum; 2JLD; -. DR PDBsum; 2O5K; -. DR PDBsum; 2OW3; -. DR PDBsum; 2UW9; -. DR PDBsum; 2X39; -. DR PDBsum; 2XH5; -. DR PDBsum; 3CQU; -. DR PDBsum; 3CQW; -. DR PDBsum; 3DU8; -. DR PDBsum; 3E87; -. DR PDBsum; 3E88; -. DR PDBsum; 3E8D; -. DR PDBsum; 3F7Z; -. DR PDBsum; 3F88; -. DR PDBsum; 3GB2; -. DR PDBsum; 3I4B; -. DR PDBsum; 3L1S; -. DR PDBsum; 3M1S; -. DR PDBsum; 3MV5; -. DR PDBsum; 3OW4; -. DR PDBsum; 3PUP; -. DR PDBsum; 3Q3B; -. DR PDBsum; 3QKK; -. DR PDBsum; 3SAY; -. DR PDBsum; 3SD0; -. DR PDBsum; 3ZDI; -. DR PDBsum; 3ZRK; -. DR PDBsum; 3ZRL; -. DR PDBsum; 3ZRM; -. DR PDBsum; 4ACC; -. DR PDBsum; 4ACD; -. DR PDBsum; 4ACG; -. DR PDBsum; 4ACH; -. DR PDBsum; 4AFJ; -. DR PDBsum; 4B7T; -. DR PDBsum; 4DIT; -. DR PDBsum; 4EKK; -. DR PDBsum; 4IQ6; -. DR PDBsum; 4J1R; -. DR PDBsum; 4J71; -. DR PDBsum; 4NM0; -. DR PDBsum; 4NM3; -. DR PDBsum; 4NM5; -. DR PDBsum; 4NM7; -. DR PDBsum; 4PTC; -. DR PDBsum; 4PTE; -. DR PDBsum; 4PTG; -. DR PDBsum; 5F94; -. DR PDBsum; 5F95; -. DR PDBsum; 5HLN; -. DR PDBsum; 5HLP; -. DR PDBsum; 5K5N; -. DR PDBsum; 5KPK; -. DR PDBsum; 5KPL; -. DR PDBsum; 5KPM; -. DR PDBsum; 5OY4; -. DR PDBsum; 5T31; -. DR PDBsum; 6B8J; -. DR PDBsum; 6BUU; -. DR PDBsum; 6GJO; -. DR PDBsum; 6GN1; -. DR PDBsum; 6H0U; -. DR PDBsum; 6HK3; -. DR PDBsum; 6HK4; -. DR PDBsum; 6HK7; -. DR PDBsum; 6NPZ; -. DR PDBsum; 6TCU; -. DR PDBsum; 6V6L; -. DR PDBsum; 6Y9R; -. DR PDBsum; 6Y9S; -. DR PDBsum; 7B6F; -. DR PDBsum; 7OY5; -. DR PDBsum; 7SXH; -. DR PDBsum; 7SXJ; -. DR PDBsum; 7U2Z; -. DR PDBsum; 7U31; -. DR PDBsum; 7U33; -. DR PDBsum; 7U36; -. DR PDBsum; 7Z1F; -. DR PDBsum; 7Z1G; -. DR PDBsum; 8AUZ; -. DR PDBsum; 8AV1; -. DR PDBsum; 8DJC; -. DR PDBsum; 8DJD; -. DR PDBsum; 8DJE; -. DR PDBsum; 8FF8; -. DR AlphaFoldDB; P49841; -. DR SMR; P49841; -. DR BioGRID; 109187; 848. DR ComplexPortal; CPX-109; Beta-catenin destruction core complex, APC-AXIN1-GSK3B variant. DR ComplexPortal; CPX-439; Beta-catenin destruction core complex, APC-AXIN2-GSK3B variant. DR ComplexPortal; CPX-440; Beta-catenin destruction core complex, APC2-AXIN2-GSK3B variant. DR ComplexPortal; CPX-459; Nuclear export complex FRAT1-GSK3B. DR ComplexPortal; CPX-462; Nuclear export complex FRAT2-GSK3B. DR ComplexPortal; CPX-99; Beta-catenin destruction core complex, APC2-AXIN1-GSK3B variant. DR CORUM; P49841; -. DR DIP; DIP-878N; -. DR ELM; P49841; -. DR IntAct; P49841; 348. DR MINT; P49841; -. DR STRING; 9606.ENSP00000324806; -. DR BindingDB; P49841; -. DR ChEMBL; CHEMBL262; -. DR DrugBank; DB08073; (2S)-1-(1H-INDOL-3-YL)-3-{[5-(3-METHYL-1H-INDAZOL-5-YL)PYRIDIN-3-YL]OXY}PROPAN-2-AMINE. DR DrugBank; DB07149; (7S)-2-(2-aminopyrimidin-4-yl)-7-(2-fluoroethyl)-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one. DR DrugBank; DB07014; 2-(1,3-benzodioxol-5-yl)-5-[(3-fluoro-4-methoxybenzyl)sulfanyl]-1,3,4-oxadiazole. DR DrugBank; DB07676; 3-({[(3S)-3,4-dihydroxybutyl]oxy}amino)-1H,2'H-2,3'-biindol-2'-one. DR DrugBank; DB01772; 3-[3-(2,3-Dihydroxy-Propylamino)-Phenyl]-4-(5-Fluoro-1-Methyl-1h-Indol-3-Yl)-Pyrrole-2,5-Dione. DR DrugBank; DB07859; 4-(4-CHLOROPHENYL)-4-[4-(1H-PYRAZOL-4-YL)PHENYL]PIPERIDINE. DR DrugBank; DB07585; 5-(5-chloro-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine. DR DrugBank; DB07058; 5-[1-(4-methoxyphenyl)-1H-benzimidazol-6-yl]-1,3,4-oxadiazole-2(3H)-thione. DR DrugBank; DB03444; 6-bromoindirubin-3'-oxime. DR DrugBank; DB04014; Alsterpaullone. DR DrugBank; DB01950; AR-AO-14418. DR DrugBank; DB12010; Fostamatinib. DR DrugBank; DB02052; Indirubin-3'-monoxime. DR DrugBank; DB07947; ISOQUINOLINE-5-SULFONIC ACID (2-(2-(4-CHLOROBENZYLOXY)ETHYLAMINO)ETHYL)AMIDE. DR DrugBank; DB14509; Lithium carbonate. DR DrugBank; DB01356; Lithium cation. DR DrugBank; DB14507; Lithium citrate. DR DrugBank; DB14508; Lithium succinate. DR DrugBank; DB07812; N-[(1S)-2-amino-1-phenylethyl]-5-(1H-pyrrolo[2,3-b]pyridin-4-yl)thiophene-2-carboxamide. DR DrugBank; DB07584; N-[2-(5-methyl-4H-1,2,4-triazol-3-yl)phenyl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine. DR DrugBank; DB04395; Phosphoaminophosphonic Acid-Adenylate Ester. DR DrugBank; DB01793; SB-409513. DR DrugBank; DB02010; Staurosporine. DR DrugBank; DB12129; Tideglusib. DR DrugCentral; P49841; -. DR GuidetoPHARMACOLOGY; 2030; -. DR GlyCosmos; P49841; 3 sites, 1 glycan. DR GlyGen; P49841; 3 sites, 1 O-linked glycan (3 sites). DR iPTMnet; P49841; -. DR PhosphoSitePlus; P49841; -. DR SwissPalm; P49841; -. DR BioMuta; GSK3B; -. DR DMDM; 20455502; -. DR CPTAC; CPTAC-3038; -. DR CPTAC; CPTAC-3039; -. DR CPTAC; CPTAC-5749; -. DR CPTAC; CPTAC-5750; -. DR CPTAC; CPTAC-5751; -. DR CPTAC; CPTAC-5790; -. DR CPTAC; CPTAC-5791; -. DR CPTAC; CPTAC-804; -. DR CPTAC; non-CPTAC-5401; -. DR CPTAC; non-CPTAC-5403; -. DR CPTAC; non-CPTAC-5404; -. DR CPTAC; non-CPTAC-5554; -. DR CPTAC; non-CPTAC-5556; -. DR CPTAC; non-CPTAC-5705; -. DR EPD; P49841; -. DR jPOST; P49841; -. DR MassIVE; P49841; -. DR MaxQB; P49841; -. DR PaxDb; 9606-ENSP00000324806; -. DR PeptideAtlas; P49841; -. DR ProteomicsDB; 56151; -. [P49841-1] DR ProteomicsDB; 56152; -. [P49841-2] DR Pumba; P49841; -. DR Antibodypedia; 4266; 1850 antibodies from 53 providers. DR CPTC; P49841; 10 antibodies. DR DNASU; 2932; -. DR Ensembl; ENST00000264235.13; ENSP00000264235.9; ENSG00000082701.17. [P49841-1] DR Ensembl; ENST00000316626.6; ENSP00000324806.5; ENSG00000082701.17. [P49841-2] DR GeneID; 2932; -. DR KEGG; hsa:2932; -. DR MANE-Select; ENST00000264235.13; ENSP00000264235.9; NM_001146156.2; NP_001139628.1. DR UCSC; uc003edn.4; human. [P49841-1] DR AGR; HGNC:4617; -. DR CTD; 2932; -. DR DisGeNET; 2932; -. DR GeneCards; GSK3B; -. DR HGNC; HGNC:4617; GSK3B. DR HPA; ENSG00000082701; Low tissue specificity. DR MIM; 605004; gene. DR neXtProt; NX_P49841; -. DR OpenTargets; ENSG00000082701; -. DR PharmGKB; PA29009; -. DR VEuPathDB; HostDB:ENSG00000082701; -. DR eggNOG; KOG0658; Eukaryota. DR GeneTree; ENSGT00520000055635; -. DR HOGENOM; CLU_000288_181_20_1; -. DR InParanoid; P49841; -. DR OMA; MKTTMPM; -. DR OrthoDB; 2872909at2759; -. DR PhylomeDB; P49841; -. DR TreeFam; TF101104; -. DR BRENDA; 2.7.11.26; 2681. DR PathwayCommons; P49841; -. DR Reactome; R-HSA-195253; Degradation of beta-catenin by the destruction complex. DR Reactome; R-HSA-196299; Beta-catenin phosphorylation cascade. DR Reactome; R-HSA-198323; AKT phosphorylates targets in the cytosol. DR Reactome; R-HSA-3371453; Regulation of HSF1-mediated heat shock response. DR Reactome; R-HSA-399956; CRMPs in Sema3A signaling. DR Reactome; R-HSA-4641262; Disassembly of the destruction complex and recruitment of AXIN to the membrane. DR Reactome; R-HSA-5250924; B-WICH complex positively regulates rRNA expression. DR Reactome; R-HSA-5339716; Signaling by GSK3beta mutants. DR Reactome; R-HSA-5358747; CTNNB1 S33 mutants aren't phosphorylated. DR Reactome; R-HSA-5358749; CTNNB1 S37 mutants aren't phosphorylated. DR Reactome; R-HSA-5358751; CTNNB1 S45 mutants aren't phosphorylated. DR Reactome; R-HSA-5358752; CTNNB1 T41 mutants aren't phosphorylated. DR Reactome; R-HSA-5467337; APC truncation mutants have impaired AXIN binding. DR Reactome; R-HSA-5467340; AXIN missense mutants destabilize the destruction complex. DR Reactome; R-HSA-5467348; Truncations of AMER1 destabilize the destruction complex. DR Reactome; R-HSA-5610783; Degradation of GLI2 by the proteasome. DR Reactome; R-HSA-5610785; GLI3 is processed to GLI3R by the proteasome. DR Reactome; R-HSA-5674400; Constitutive Signaling by AKT1 E17K in Cancer. DR Reactome; R-HSA-75815; Ubiquitin-dependent degradation of Cyclin D. DR Reactome; R-HSA-8939902; Regulation of RUNX2 expression and activity. DR Reactome; R-HSA-9683610; Maturation of nucleoprotein. DR Reactome; R-HSA-9694631; Maturation of nucleoprotein. DR Reactome; R-HSA-9762114; GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2. DR SignaLink; P49841; -. DR SIGNOR; P49841; -. DR BioGRID-ORCS; 2932; 75 hits in 1226 CRISPR screens. DR ChiTaRS; GSK3B; human. DR EvolutionaryTrace; P49841; -. DR GeneWiki; GSK3B; -. DR GenomeRNAi; 2932; -. DR Pharos; P49841; Tclin. DR PRO; PR:P49841; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; P49841; Protein. DR Bgee; ENSG00000082701; Expressed in calcaneal tendon and 197 other cell types or tissues. DR ExpressionAtlas; P49841; baseline and differential. DR GO; GO:0030424; C:axon; ISS:ARUK-UCL. DR GO; GO:0030877; C:beta-catenin destruction complex; IDA:UniProtKB. DR GO; GO:0005813; C:centrosome; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IBA:GO_Central. DR GO; GO:0030425; C:dendrite; ISS:ARUK-UCL. DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO. DR GO; GO:0005739; C:mitochondrion; IEA:GOC. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0098794; C:postsynapse; IEA:GOC. DR GO; GO:0098793; C:presynapse; IEA:GOC. DR GO; GO:1990909; C:Wnt signalosome; TAS:ParkinsonsUK-UCL. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0008013; F:beta-catenin binding; IPI:BHF-UCL. DR GO; GO:0034452; F:dynactin binding; IPI:ARUK-UCL. DR GO; GO:0016301; F:kinase activity; IDA:UniProtKB. DR GO; GO:0051059; F:NF-kappaB binding; IPI:UniProtKB. DR GO; GO:0002039; F:p53 binding; IDA:MGI. DR GO; GO:0002020; F:protease binding; IPI:ParkinsonsUK-UCL. DR GO; GO:0034236; F:protein kinase A catalytic subunit binding; IPI:BHF-UCL. DR GO; GO:0004672; F:protein kinase activity; IMP:UniProtKB. DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB. DR GO; GO:0106310; F:protein serine kinase activity; IGI:ARUK-UCL. DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB. DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:UniProtKB. DR GO; GO:0048156; F:tau protein binding; NAS:ARUK-UCL. DR GO; GO:0050321; F:tau-protein kinase activity; IDA:UniProtKB. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:BHF-UCL. DR GO; GO:1904886; P:beta-catenin destruction complex disassembly; IDA:ComplexPortal. DR GO; GO:0060070; P:canonical Wnt signaling pathway; IDA:BHF-UCL. DR GO; GO:1904646; P:cellular response to amyloid-beta; ISS:ARUK-UCL. DR GO; GO:0036016; P:cellular response to interleukin-3; ISS:UniProtKB. DR GO; GO:0071300; P:cellular response to retinoic acid; IMP:ARUK-UCL. DR GO; GO:0007623; P:circadian rhythm; ISS:UniProtKB. DR GO; GO:0007212; P:dopamine receptor signaling pathway; NAS:ParkinsonsUK-UCL. DR GO; GO:0001837; P:epithelial to mesenchymal transition; IMP:UniProtKB. DR GO; GO:0006983; P:ER overload response; IDA:MGI. DR GO; GO:0030010; P:establishment of cell polarity; ISS:ARUK-UCL. DR GO; GO:0060079; P:excitatory postsynaptic potential; NAS:ParkinsonsUK-UCL. DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; ISS:ARUK-UCL. DR GO; GO:0097192; P:extrinsic apoptotic signaling pathway in absence of ligand; ISS:UniProtKB. DR GO; GO:0005977; P:glycogen metabolic process; IDA:BHF-UCL. DR GO; GO:0003170; P:heart valve development; ISS:BHF-UCL. DR GO; GO:0021766; P:hippocampus development; IMP:BHF-UCL. DR GO; GO:0008286; P:insulin receptor signaling pathway; IBA:GO_Central. DR GO; GO:0035556; P:intracellular signal transduction; IDA:MGI. DR GO; GO:0030011; P:maintenance of cell polarity; ISS:ARUK-UCL. DR GO; GO:0043066; P:negative regulation of apoptotic process; IDA:MGI. DR GO; GO:0070885; P:negative regulation of calcineurin-NFAT signaling cascade; IMP:UniProtKB. DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IMP:ARUK-UCL. DR GO; GO:1904339; P:negative regulation of dopaminergic neuron differentiation; TAS:ParkinsonsUK-UCL. DR GO; GO:1902042; P:negative regulation of extrinsic apoptotic signaling pathway via death domain receptors; IMP:UniProtKB. DR GO; GO:0010629; P:negative regulation of gene expression; IMP:ARUK-UCL. DR GO; GO:2000466; P:negative regulation of glycogen (starch) synthase activity; TAS:UniProtKB. DR GO; GO:0045719; P:negative regulation of glycogen biosynthetic process; TAS:UniProtKB. DR GO; GO:2000740; P:negative regulation of mesenchymal stem cell differentiation; IMP:ARUK-UCL. DR GO; GO:0045668; P:negative regulation of osteoblast differentiation; IMP:ARUK-UCL. DR GO; GO:0032515; P:negative regulation of phosphoprotein phosphatase activity; TAS:ARUK-UCL. DR GO; GO:1901984; P:negative regulation of protein acetylation; ISS:ARUK-UCL. DR GO; GO:1900181; P:negative regulation of protein localization to nucleus; ISS:BHF-UCL. DR GO; GO:0031333; P:negative regulation of protein-containing complex assembly; IMP:BHF-UCL. DR GO; GO:2000077; P:negative regulation of type B pancreatic cell development; TAS:UniProtKB. DR GO; GO:0031175; P:neuron projection development; IDA:UniProtKB. DR GO; GO:0106027; P:neuron projection organization; ISS:ARUK-UCL. DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:MGI. DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IDA:ParkinsonsUK-UCL. DR GO; GO:0010508; P:positive regulation of autophagy; ISS:UniProtKB. DR GO; GO:0045597; P:positive regulation of cell differentiation; IMP:ARUK-UCL. DR GO; GO:0001954; P:positive regulation of cell-matrix adhesion; IMP:BHF-UCL. DR GO; GO:0045724; P:positive regulation of cilium assembly; ISS:UniProtKB. DR GO; GO:0010628; P:positive regulation of gene expression; IMP:ARUK-UCL. DR GO; GO:0043547; P:positive regulation of GTPase activity; IMP:BHF-UCL. 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; IMP:ParkinsonsUK-UCL. DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IDA:FlyBase. DR GO; GO:0032092; P:positive regulation of protein binding; ISS:UniProtKB. DR GO; GO:0045732; P:positive regulation of protein catabolic process; IC:BHF-UCL. DR GO; GO:0046827; P:positive regulation of protein export from nucleus; IDA:MGI. DR GO; GO:1904781; P:positive regulation of protein localization to centrosome; IMP:ARUK-UCL. DR GO; GO:1903566; P:positive regulation of protein localization to cilium; ISS:UniProtKB. DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IDA:UniProt. DR GO; GO:0031334; P:positive regulation of protein-containing complex assembly; IDA:BHF-UCL. DR GO; GO:0099171; P:presynaptic modulation of chemical synaptic transmission; IDA:SynGO. DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; NAS:ComplexPortal. DR GO; GO:0046777; P:protein autophosphorylation; IDA:UniProtKB. DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB. DR GO; GO:0030516; P:regulation of axon extension; ISS:ARUK-UCL. DR GO; GO:0050770; P:regulation of axonogenesis; ISS:ARUK-UCL. DR GO; GO:1900034; P:regulation of cellular response to heat; TAS:Reactome. DR GO; GO:0042752; P:regulation of circadian rhythm; ISS:UniProtKB. DR GO; GO:0048814; P:regulation of dendrite morphogenesis; ISS:ARUK-UCL. DR GO; GO:1900271; P:regulation of long-term synaptic potentiation; ISS:UniProtKB. DR GO; GO:0150101; P:regulation of microtubule anchoring at centrosome; IMP:ARUK-UCL. DR GO; GO:0070507; P:regulation of microtubule cytoskeleton organization; ISS:ARUK-UCL. DR GO; GO:0032886; P:regulation of microtubule-based process; IMP:UniProtKB. DR GO; GO:0010975; P:regulation of neuron projection development; IBA:GO_Central. DR GO; GO:0046825; P:regulation of protein export from nucleus; IDA:ComplexPortal. DR GO; GO:0071109; P:superior temporal gyrus development; IMP:BHF-UCL. DR GO; GO:0019082; P:viral protein processing; TAS:Reactome. DR CDD; cd14137; STKc_GSK3; 1. DR DisProt; DP00385; -. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR IDEAL; IID00052; -. 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; GLYCOGEN SYNTHASE KINASE-3 ALPHA; 1. DR PANTHER; PTHR24057:SF8; GLYCOGEN SYNTHASE KINASE-3 BETA; 1. DR Pfam; PF00069; Pkinase; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. DR Genevisible; P49841; HS. PE 1: Evidence at protein level; KW 3D-structure; ADP-ribosylation; Alternative splicing; Alzheimer disease; KW ATP-binding; Biological rhythms; Carbohydrate metabolism; Cell membrane; KW Cytoplasm; Developmental protein; Diabetes mellitus; 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_0000085980" 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 386..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 ACT_SITE 181 FT /note="Proton acceptor" 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 ECO:0000305|PubMed:17050006" FT MOD_RES 9 FT /note="Phosphoserine; by PKB/AKT1, RPS6KA3 and SGK3" FT /evidence="ECO:0000269|PubMed:12054501, FT ECO:0000269|PubMed:16484495, ECO:0000269|PubMed:20937854, FT ECO:0000269|PubMed:24391509, ECO:0000269|PubMed:25169422, FT ECO:0000269|PubMed:8250835" FT MOD_RES 216 FT /note="Phosphotyrosine" FT /evidence="ECO:0000269|PubMed:12554650, FT ECO:0000269|PubMed:25169422" FT MOD_RES 389 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9WV60" FT MOD_RES 390 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 402 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18691976" FT VAR_SEQ 303 FT /note="K -> KDSSGTGHFTSGVR (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_004790" FT MUTAGEN 9 FT /note="S->A: Loss of phosphorylation; abolished inhibition FT of activity, leading to constitutively active." FT /evidence="ECO:0000269|PubMed:17050006, FT ECO:0000269|PubMed:28992046, ECO:0000269|PubMed:7980435" FT MUTAGEN 85..86 FT /note="KK->AA: Abolished serine/threonine-protein kinase FT activity." FT /evidence="ECO:0000269|PubMed:17050006" FT MUTAGEN 96 FT /note="R->A: Prevents the phosphorylation of FT phosphate-primed glycogen synthase." FT /evidence="ECO:0000269|PubMed:11430833" FT MUTAGEN 128 FT /note="L->A: Abolishes activity toward AXIN1." FT /evidence="ECO:0000269|PubMed:11430833" FT CONFLICT 28 FT /note="V -> G (in Ref. 4; AAD48517)" FT /evidence="ECO:0000305" FT CONFLICT 350 FT /note="L -> H (in Ref. 1; AAA66475)" FT /evidence="ECO:0000305" FT STRAND 10..12 FT /evidence="ECO:0007829|PDB:2JDO" FT STRAND 26..30 FT /evidence="ECO:0007829|PDB:1J1B" FT STRAND 32..34 FT /evidence="ECO:0007829|PDB:4NM5" FT STRAND 38..48 FT /evidence="ECO:0007829|PDB:1J1B" FT STRAND 52..64 FT /evidence="ECO:0007829|PDB:1J1B" FT STRAND 66..75 FT /evidence="ECO:0007829|PDB:1J1B" FT TURN 76..78 FT /evidence="ECO:0007829|PDB:1J1B" FT STRAND 81..88 FT /evidence="ECO:0007829|PDB:1J1B" FT STRAND 91..93 FT /evidence="ECO:0007829|PDB:1Q5K" FT HELIX 96..102 FT /evidence="ECO:0007829|PDB:1J1B" FT STRAND 112..120 FT /evidence="ECO:0007829|PDB:1J1B" FT TURN 121..124 FT /evidence="ECO:0007829|PDB:1J1B" FT STRAND 125..133 FT /evidence="ECO:0007829|PDB:1J1B" FT STRAND 136..138 FT /evidence="ECO:0007829|PDB:7SXJ" FT HELIX 139..148 FT /evidence="ECO:0007829|PDB:1J1B" FT HELIX 155..173 FT /evidence="ECO:0007829|PDB:1J1B" FT TURN 174..176 FT /evidence="ECO:0007829|PDB:1J1B" FT HELIX 184..186 FT /evidence="ECO:0007829|PDB:1J1B" FT STRAND 187..190 FT /evidence="ECO:0007829|PDB:1J1B" FT TURN 191..194 FT /evidence="ECO:0007829|PDB:1J1B" FT STRAND 195..198 FT /evidence="ECO:0007829|PDB:1J1B" FT HELIX 201..203 FT /evidence="ECO:0007829|PDB:7SXJ" FT STRAND 209..211 FT /evidence="ECO:0007829|PDB:6HK4" FT HELIX 220..222 FT /evidence="ECO:0007829|PDB:7SXJ" FT HELIX 225..228 FT /evidence="ECO:0007829|PDB:1J1B" FT HELIX 237..252 FT /evidence="ECO:0007829|PDB:1J1B" FT HELIX 262..273 FT /evidence="ECO:0007829|PDB:1J1B" FT HELIX 278..284 FT /evidence="ECO:0007829|PDB:1J1B" FT HELIX 286..288 FT /evidence="ECO:0007829|PDB:7B6F" FT STRAND 289..291 FT /evidence="ECO:0007829|PDB:4ACC" FT HELIX 301..304 FT /evidence="ECO:0007829|PDB:1J1B" FT HELIX 311..320 FT /evidence="ECO:0007829|PDB:1J1B" FT HELIX 325..327 FT /evidence="ECO:0007829|PDB:1J1B" FT HELIX 331..335 FT /evidence="ECO:0007829|PDB:1J1B" FT HELIX 338..344 FT /evidence="ECO:0007829|PDB:1J1B" FT STRAND 345..347 FT /evidence="ECO:0007829|PDB:1UV5" FT STRAND 353..355 FT /evidence="ECO:0007829|PDB:6HK4" FT HELIX 364..367 FT /evidence="ECO:0007829|PDB:1J1B" FT HELIX 371..373 FT /evidence="ECO:0007829|PDB:1J1B" FT HELIX 374..377 FT /evidence="ECO:0007829|PDB:1J1B" FT TURN 380..383 FT /evidence="ECO:0007829|PDB:1J1B" SQ SEQUENCE 420 AA; 46744 MW; 4ACC24D00CDBB9C3 CRC64; MSGRPRTTSF AESCKPVQQP SAFGSMKVSR DKDGSKVTTV VATPGQGPDR PQEVSYTDTK VIGNGSFGVV YQAKLCDSGE LVAIKKVLQD KRFKNRELQI MRKLDHCNIV RLRYFFYSSG EKKDEVYLNL VLDYVPETVY RVARHYSRAK QTLPVIYVKL YMYQLFRSLA YIHSFGICHR DIKPQNLLLD PDTAVLKLCD FGSAKQLVRG EPNVSYICSR YYRAPELIFG ATDYTSSIDV WSAGCVLAEL LLGQPIFPGD SGVDQLVEII KVLGTPTREQ IREMNPNYTE FKFPQIKAHP WTKVFRPRTP PEAIALCSRL LEYTPTARLT PLEACAHSFF DELRDPNVKL PNGRDTPALF NFTTQELSSN PPLATILIPP HARIQAAAST PTNATAASDA NTGDRGQTNN AASASASNST //