ID GSK3B_MOUSE Reviewed; 420 AA. AC Q9WV60; DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-2000, sequence version 2. DT 27-MAR-2024, entry version 230. 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=Serine/threonine-protein kinase GSK3B; DE EC=2.7.11.1 {ECO:0000269|PubMed:22539723, ECO:0000269|PubMed:23542741, ECO:0000269|PubMed:24742671}; GN Name=Gsk3b {ECO:0000312|MGI:MGI:1861437}; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Testis; RA Salameh W.A., Guo T.B., Chan K.C., Mitchell A.P.; RT "Testicular expression and hormonal control of glycogen synthase kinase 3, RT a homologue of yeast RIM11."; RL Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=Czech II, and FVB/N; TISSUE=Mammary gland; 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 [3] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=10894547; DOI=10.1038/35017574; RA Hoeflich K.P., Luo J., Rubie E.A., Tsao M.S., Jin O., Woodgett J.R.; RT "Requirement for glycogen synthase kinase-3beta in cell survival and NF- RT kappaB activation."; RL Nature 406:86-90(2000). RN [4] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-389, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic brain; RX PubMed=15345747; DOI=10.1074/mcp.m400085-mcp200; RA Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P.; RT "Phosphoproteomic analysis of the developing mouse brain."; RL Mol. Cell. Proteomics 3:1093-1101(2004). RN [5] RP INTERACTION WITH ARRB2. RX PubMed=16051150; DOI=10.1016/j.cell.2005.05.012; RA Beaulieu J.-M., Sotnikova T.D., Marion S., Lefkowitz R.J., RA Gainetdinov R.R., Caron M.G.; RT "An Akt/beta-arrestin 2/PP2A signaling complex mediates dopaminergic RT neurotransmission and behavior."; RL Cell 122:261-273(2005). RN [6] RP FUNCTION, AND MUTAGENESIS OF SER-9. RX PubMed=15791206; DOI=10.1038/sj.emboj.7600633; RA McManus E.J., Sakamoto K., Armit L.J., Ronaldson L., Shpiro N., Marquez R., RA Alessi D.R.; RT "Role that phosphorylation of GSK3 plays in insulin and Wnt signalling RT defined by knockin analysis."; RL EMBO J. 24:1571-1583(2005). RN [7] RP FUNCTION IN MCL1 PHOSPHORYLATION. RX PubMed=16543145; DOI=10.1016/j.molcel.2006.02.009; RA Maurer U., Charvet C., Wagman A.S., Dejardin E., Green D.R.; RT "Glycogen synthase kinase-3 regulates mitochondrial outer membrane RT permeabilization and apoptosis by destabilization of MCL-1."; RL Mol. Cell 21:749-760(2006). RN [8] RP FUNCTION IN AXON FORMATION. RX PubMed=17391670; DOI=10.1016/j.febslet.2007.03.018; RA Garrido J.J., Simon D., Varea O., Wandosell F.; RT "GSK3 alpha and GSK3 beta are necessary for axon formation."; RL FEBS Lett. 581:1579-1586(2007). RN [9] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=17242355; DOI=10.1073/pnas.0609836104; RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.; RT "Large-scale phosphorylation analysis of mouse liver."; RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007). RN [10] RP FUNCTION IN REGULATION OF PANCREATIC BETA-CELLS. RX PubMed=18288891; DOI=10.1371/journal.pbio.0060037; RA Tanabe K., Liu Z., Patel S., Doble B.W., Li L., Cras-Meneur C., RA Martinez S.C., Welling C.M., White M.F., Bernal-Mizrachi E., Woodgett J.R., RA Permutt M.A.; RT "Genetic deficiency of glycogen synthase kinase-3beta corrects diabetes in RT mouse models of insulin resistance."; RL PLoS Biol. 6:E37-E37(2008). RN [11] RP INTERACTION WITH DISC1. RX PubMed=19303846; DOI=10.1016/j.cell.2008.12.044; RA Mao Y., Ge X., Frank C.L., Madison J.M., Koehler A.N., Doud M.K., Tassa C., RA Berry E.M., Soda T., Singh K.K., Biechele T., Petryshen T.L., Moon R.T., RA Haggarty S.J., Tsai L.H.; RT "Disrupted in schizophrenia 1 regulates neuronal progenitor proliferation RT via modulation of GSK3beta/beta-catenin signaling."; RL Cell 136:1017-1031(2009). RN [12] RP INTERACTION WITH AXIN1 AND ZBED3, AND MUTAGENESIS OF LYS-85. RX PubMed=19141611; DOI=10.1074/jbc.m807753200; RA Chen T., Li M., Ding Y., Zhang L.S., Xi Y., Pan W.J., Tao D.L., Wang J.Y., RA Li L.; RT "Identification of zinc-finger BED domain-containing 3 (Zbed3) as a novel RT Axin-interacting protein that activates Wnt/beta-catenin signaling."; RL J. Biol. Chem. 284:6683-6689(2009). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, RC Pancreas, Spleen, and Testis; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [14] RP FUNCTION. RX PubMed=20123978; DOI=10.1128/mcb.01047-09; RA Kurabayashi N., Hirota T., Sakai M., Sanada K., Fukada Y.; RT "DYRK1A and glycogen synthase kinase 3beta, a dual-kinase mechanism RT directing proteasomal degradation of CRY2 for circadian timekeeping."; RL Mol. Cell. Biol. 30:1757-1768(2010). RN [15] RP FUNCTION, AND INTERACTION WITH BMAL1. RX PubMed=20049328; DOI=10.1371/journal.pone.0008561; RA Sahar S., Zocchi L., Kinoshita C., Borrelli E., Sassone-Corsi P.; RT "Regulation of BMAL1 protein stability and circadian function by GSK3beta- RT mediated phosphorylation."; RL PLoS ONE 5:E8561-E8561(2010). RN [16] RP FUNCTION. RX PubMed=21295697; DOI=10.1016/j.cell.2010.12.033; RA Wu X., Shen Q.T., Oristian D.S., Lu C.P., Zheng Q., Wang H.W., Fuchs E.; RT "Skin stem cells orchestrate directional migration by regulating RT microtubule-ACF7 connections through GSK3beta."; RL Cell 144:341-352(2011). RN [17] RP FUNCTION IN PHOSPHORYLATION OF DPYSL2, PHOSPHORYLATION AT SER-9, AND RP MUTAGENESIS OF SER-9. RX PubMed=22057101; DOI=10.1038/ncb2373; RA Wakatsuki S., Saitoh F., Araki T.; RT "ZNRF1 promotes Wallerian degeneration by degrading AKT to induce GSK3B- RT dependent CRMP2 phosphorylation."; RL Nat. Cell Biol. 13:1415-1423(2011). RN [18] RP FUNCTION, AND 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 [19] RP FUNCTION, AND PHOSPHORYLATION AT SER-9. RX PubMed=23395175; DOI=10.1016/j.cmet.2012.12.017; RA Kaasik K., Kivimae S., Allen J.J., Chalkley R.J., Huang Y., Baer K., RA Kissel H., Burlingame A.L., Shokat K.M., Ptacek L.J., Fu Y.H.; RT "Glucose sensor O-GlcNAcylation coordinates with phosphorylation to RT regulate circadian clock."; RL Cell Metab. 17:291-302(2013). RN [20] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=23542741; DOI=10.1038/ni.2565; RA Chen B.B., Coon T.A., Glasser J.R., McVerry B.J., Zhao J., Zhao Y., Zou C., RA Ellis B., Sciurba F.C., Zhang Y., Mallampalli R.K.; RT "A combinatorial F box protein directed pathway controls TRAF adaptor RT stability to regulate inflammation."; RL Nat. Immunol. 14:470-479(2013). RN [21] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND PHOSPHORYLATION AT RP SER-9. RX PubMed=24742671; DOI=10.1074/jbc.m114.551747; RA Weathington N.M., Snavely C.A., Chen B.B., Zhao J., Zhao Y., RA Mallampalli R.K.; RT "Glycogen synthase kinase-3beta stabilizes the interleukin (IL)-22 receptor RT from proteasomal degradation in murine lung epithelia."; RL J. Biol. Chem. 289:17610-17619(2014). RN [22] RP FUNCTION IN PHOSPHORYLATION OF FXR1. RX PubMed=26240334; DOI=10.1073/pnas.1506491112; RA Del'Guidice T., Latapy C., Rampino A., Khlghatyan J., Lemasson M., RA Gelao B., Quarto T., Rizzo G., Barbeau A., Lamarre C., Bertolino A., RA Blasi G., Beaulieu J.M.; RT "FXR1P is a GSK3beta substrate regulating mood and emotion processing."; RL Proc. Natl. Acad. Sci. U.S.A. 112:E4610-E4619(2015). RN [23] RP TISSUE SPECIFICITY, AND PHOSPHORYLATION AT SER-9. RX PubMed=27827363; DOI=10.1038/ncomms13267; RA Ekim Uestuenel B., Friedrich K., Maida A., Wang X., Krones-Herzig A., RA Seibert O., Sommerfeld A., Jones A., Sijmonsma T.P., Sticht C., Gretz N., RA Fleming T., Nawroth P.P., Stremmel W., Rose A.J., Berriel-Diaz M., RA Blueher M., Herzig S.; RT "Control of diabetic hyperglycaemia and insulin resistance through RT TSC22D4."; RL Nat. Commun. 7:13267-13267(2016). RN [24] RP FUNCTION, AND PHOSPHORYLATION. RX PubMed=28556462; DOI=10.1002/hipo.22739; RA Besing R.C., Rogers C.O., Paul J.R., Hablitz L.M., Johnson R.L., RA McMahon L.L., Gamble K.L.; RT "GSK3 activity regulates rhythms in hippocampal clock gene expression and RT synaptic plasticity."; RL Hippocampus 27:890-898(2017). RN [25] RP FUNCTION. RX PubMed=29142209; DOI=10.1038/s41467-017-01199-8; RA Qie S., Majumder M., Mackiewicz K., Howley B.V., Peterson Y.K., Howe P.H., RA Palanisamy V., Diehl J.A.; RT "Fbxo4-mediated degradation of Fxr1 suppresses tumorigenesis in head and RT neck squamous cell carcinoma."; RL Nat. Commun. 8:1534-1534(2017). RN [26] RP FUNCTION, AND INTERACTION WITH BMAL1 AND PIWIL2. 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 [27] RP IDENTIFICATION IN A COMPLEX WITH SLC39A6 AND SLC39A10. RX PubMed=28098160; DOI=10.1038/srep40313; RA Brethour D., Mehrabian M., Williams D., Wang X., Ghodrati F., Ehsani S., RA Rubie E.A., Woodgett J.R., Sevalle J., Xi Z., Rogaeva E., Schmitt-Ulms G.; RT "A ZIP6-ZIP10 heteromer controls NCAM1 phosphorylation and integration into RT focal adhesion complexes during epithelial-to-mesenchymal transition."; RL Sci. Rep. 7:40313-40313(2017). RN [28] 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). 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:15791206, PubMed:22057101, CC PubMed:23395175). Requires primed phosphorylation of the majority of CC its substrates (PubMed:15791206, PubMed:22057101, PubMed:23395175). In CC skeletal muscle, contributes to insulin regulation of glycogen CC synthesis by phosphorylating and inhibiting GYS1 activity and hence CC glycogen synthesis (By similarity). May also mediate the development of CC insulin resistance by regulating activation of transcription factors CC (By similarity). Regulates protein synthesis by controlling the CC activity of initiation factor 2B (EIF2BE/EIF2B5) in the same manner as CC glycogen synthase (By similarity). 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 (By similarity). Phosphorylates JUN CC at sites proximal to its DNA-binding domain, thereby reducing its CC affinity for DNA (By similarity). 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 (By similarity). Phosphorylates MAPT/TAU on 'Thr- CC 548', decreasing significantly MAPT/TAU ability to bind and stabilize CC microtubules (By similarity). MAPT/TAU is the principal component of CC neurofibrillary tangles in Alzheimer disease (By similarity). Plays an CC important role in ERBB2-dependent stabilization of microtubules at the CC cell cortex (By similarity). Phosphorylates MACF1, inhibiting its CC binding to microtubules which is critical for its role in bulge stem CC cell migration and skin wound repair (PubMed:21295697). Probably CC regulates NF-kappa-B (NFKB1) at the transcriptional level and is CC required for the NF-kappa-B-mediated anti-apoptotic response to TNF- CC alpha (TNF/TNFA) (PubMed:10894547). Negatively regulates replication in CC pancreatic beta-cells, resulting in apoptosis, loss of beta-cells and CC diabetes (PubMed:18288891). Through phosphorylation of the anti- CC apoptotic protein MCL1, may control cell apoptosis in response to CC growth factors deprivation (PubMed:16543145). Phosphorylates MUC1 in CC breast cancer cells, decreasing the interaction of MUC1 with CC CTNNB1/beta-catenin (By similarity). Is necessary for the establishment CC of neuronal polarity and axon outgrowth (PubMed:17391670). CC Phosphorylates MARK2, leading to inhibition of its activity (By CC similarity). Phosphorylates SIK1 at 'Thr-182', leading to sustainment CC of its activity (By similarity). Phosphorylates ZC3HAV1 which enhances CC its antiviral activity (By similarity). Phosphorylates SNAI1, leading CC to its BTRC-triggered ubiquitination and proteasomal degradation (By CC similarity). Phosphorylates SFPQ at 'Thr-687' upon T-cell activation CC (By similarity). Phosphorylates NR1D1 st 'Ser-55' and 'Ser-59' and CC stabilizes it by protecting it from proteasomal degradation (By CC similarity). Regulates the circadian clock via phosphorylation of the CC major clock components including BMAL1, CLOCK and PER2 CC (PubMed:20049328, PubMed:28556462, PubMed:28903391, PubMed:20123978). CC Phosphorylates CLOCK AT 'Ser-427' and targets it for proteasomal CC degradation (By similarity). Phosphorylates BMAL1 at 'Ser-17' and 'Ser- CC 21' and primes it for ubiquitination and proteasomal degradation CC (PubMed:20049328, PubMed:28903391). Phosphorylates FBXL2 at 'Thr-404' CC and primes it for ubiquitination by the SCF(FBXO3) complex and CC proteasomal degradation (PubMed:23542741). Phosphorylates OGT at 'Ser- CC 3' or 'Ser-4' which positively regulates its activity (By similarity). CC Phosphorylates MYCN in neuroblastoma cells which may promote its CC degradation (By similarity). Regulates the circadian rhythmicity of CC hippocampal long-term potentiation and BMAL1 and PER2 expression CC (PubMed:28556462). 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:22539723). CC Negatively regulates extrinsic apoptotic signaling pathway via death CC domain receptors (By similarity). Promotes the formation of an anti- CC apoptotic complex, made of DDX3X, BRIC2 and GSK3B, at death receptors, CC including TNFRSF10B (By similarity). The anti-apoptotic function is CC most effective with weak apoptotic signals and can be overcome by CC stronger stimulation (By similarity). Phosphorylates E2F1, promoting CC the interaction between E2F1 and USP11, stabilizing E2F1 and promoting CC its activity (By similarity). Phosphorylates FXR1, promoting FXR1 CC ubiquitination by the SCF(FBXO4) complex and FXR1 degradation by the CC proteasome (PubMed:26240334, PubMed:29142209). Phosphorylates CC interleukin-22 receptor subunit IL22RA1, preventing its proteasomal CC degradation (PubMed:24742671). {ECO:0000250|UniProtKB:P18266, CC ECO:0000250|UniProtKB:P49841, ECO:0000269|PubMed:10894547, CC ECO:0000269|PubMed:15791206, ECO:0000269|PubMed:16543145, CC ECO:0000269|PubMed:17391670, ECO:0000269|PubMed:18288891, CC ECO:0000269|PubMed:20049328, ECO:0000269|PubMed:20123978, CC ECO:0000269|PubMed:21295697, ECO:0000269|PubMed:22057101, CC ECO:0000269|PubMed:22539723, ECO:0000269|PubMed:23395175, CC ECO:0000269|PubMed:23542741, ECO:0000269|PubMed:24742671, CC ECO:0000269|PubMed:26240334, ECO:0000269|PubMed:28556462, CC ECO:0000269|PubMed:28903391, ECO:0000269|PubMed:29142209}. 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:0000269|PubMed:22539723, ECO:0000269|PubMed:24742671}; 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:23542741}; 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 (By CC similarity). Inhibited by IL22 treatment which also triggers CC phosphorylation at Ser-9, promoting inactivation (PubMed:24742671). CC Inhibited by lithium (By similarity). {ECO:0000250|UniProtKB:P49841, CC ECO:0000269|PubMed:24742671}. 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 CABYR, MMP2, MUC1, NIN and PRUNE1 (By similarity). CC Interacts with AXIN1; the interaction mediates hyperphosphorylation of CC CTNNB1 leading to its ubiquitination and destruction (PubMed:19141611). CC Interacts with and phosphorylates SNAI1 (By similarity). Interacts with CC DNM1L (via a C-terminal domain) (By similarity). Interacts with ARRB2 CC (PubMed:16051150). Interacts with DISC1 (PubMed:19303846). Found in a CC complex composed of MACF1, APC, AXIN1, CTNNB1 and GSK3B (By CC similarity). Interacts with SGK3 (By similarity). Interacts with the CC CLOCK-BMAL1 heterodimer (By similarity). Interacts with ZBED3 CC (PubMed:19141611). Interacts with the BMAL1 (PubMed:20049328, CC PubMed:28903391). 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 CC (PubMed:28903391). Interacts with LMBR1L (PubMed:31073040). Interacts CC with DDX3X (By similarity). Interacts with BIRC2 (By similarity). CC Interacts with TNFRSF10B; TNFRSF10B stimulation inhibits GSK3B kinase CC activity (By similarity). Found in a complex with SLC39A6, SLC39A10 and CC with GSK3B that controls NCAM1 phosphorylation (PubMed:28098160). CC {ECO:0000250|UniProtKB:P49841, ECO:0000269|PubMed:16051150, CC ECO:0000269|PubMed:19141611, ECO:0000269|PubMed:19303846, CC ECO:0000269|PubMed:20049328, ECO:0000269|PubMed:28098160, CC ECO:0000269|PubMed:28903391, ECO:0000269|PubMed:31073040}. CC -!- INTERACTION: CC Q9WV60; Q02248: Ctnnb1; NbExp=2; IntAct=EBI-400793, EBI-397872; CC Q9WV60; Q9WUA5: Epm2a; NbExp=2; IntAct=EBI-400793, EBI-1040928; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P49841}. Nucleus CC {ECO:0000250|UniProtKB:P49841}. Cell membrane CC {ECO:0000250|UniProtKB:P49841}. Note=The phosphorylated form shows CC localization to cytoplasm and cell membrane. The MEMO1-RHOA-DIAPH1 CC signaling pathway controls localization of the phosphorylated form to CC the cell membrane (By similarity). {ECO:0000250|UniProtKB:P49841}. CC -!- TISSUE SPECIFICITY: Expressed in the liver (at protein level). CC {ECO:0000269|PubMed:27827363}. 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. Phosphorylation of Ser-9 in CC the hippocampus peaks at CT0, whereas in the liver it peaks at CT12. CC Inactivated by phosphorylation at Ser-9 (By similarity). Phosphorylated CC in a circadian manner in the hippocampus (PubMed:28556462). CC {ECO:0000250|UniProtKB:P49841, ECO:0000269|PubMed:22057101, CC ECO:0000269|PubMed:23395175, ECO:0000269|PubMed:28556462}. CC -!- PTM: Mono-ADP-ribosylation by PARP10 negatively regulates kinase CC activity. {ECO:0000250|UniProtKB:P49841}. CC -!- DISRUPTION PHENOTYPE: Embryonic lethality at 16 dpc due to hepatocyte CC apoptosis. {ECO:0000269|PubMed:10894547}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr CC protein kinase family. GSK-3 subfamily. {ECO:0000305}. 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; AF156099; AAD39258.2; -; mRNA. DR EMBL; BC006936; AAH06936.1; -; mRNA. DR EMBL; BC060743; AAH60743.1; -; mRNA. DR CCDS; CCDS28163.1; -. DR RefSeq; NP_062801.1; NM_019827.6. DR PDB; 4NU1; X-ray; 2.50 A; A=1-383. DR PDB; 5AIR; X-ray; 2.53 A; A/B=4-420. DR PDB; 6AE3; X-ray; 2.14 A; A/B/C/D=1-420. DR PDBsum; 4NU1; -. DR PDBsum; 5AIR; -. DR PDBsum; 6AE3; -. DR AlphaFoldDB; Q9WV60; -. DR SMR; Q9WV60; -. DR BioGRID; 208115; 104. DR ComplexPortal; CPX-103; Beta-catenin destruction core complex, Apc-Axin1-Gsk3b variant. DR ComplexPortal; CPX-108; Nuclear export complex Frat1-Gsk3b. DR ComplexPortal; CPX-110; Nuclear export complex Frat2-Gsk3b. DR ComplexPortal; CPX-448; Beta-catenin destruction core complex, Apc2-Axin1-Gsk3b variant. DR ComplexPortal; CPX-449; Beta-catenin destruction core complex, Apc-Axin2-Gsk3b variant. DR ComplexPortal; CPX-452; Beta-catenin destruction core complex, Apc2-Axin2-Gsk3b. DR ComplexPortal; CPX-464; Nuclear export complex Frat3-Gsk3b. DR CORUM; Q9WV60; -. DR DIP; DIP-32446N; -. DR ELM; Q9WV60; -. DR IntAct; Q9WV60; 54. DR MINT; Q9WV60; -. DR STRING; 10090.ENSMUSP00000110398; -. DR BindingDB; Q9WV60; -. DR ChEMBL; CHEMBL1075321; -. DR GlyGen; Q9WV60; 3 sites, 1 O-linked glycan (3 sites). DR iPTMnet; Q9WV60; -. DR PhosphoSitePlus; Q9WV60; -. DR SwissPalm; Q9WV60; -. DR EPD; Q9WV60; -. DR jPOST; Q9WV60; -. DR MaxQB; Q9WV60; -. DR PaxDb; 10090-ENSMUSP00000023507; -. DR ProteomicsDB; 270899; -. DR Pumba; Q9WV60; -. DR Antibodypedia; 4266; 1850 antibodies from 53 providers. DR DNASU; 56637; -. DR Ensembl; ENSMUST00000023507.13; ENSMUSP00000023507.7; ENSMUSG00000022812.15. DR GeneID; 56637; -. DR KEGG; mmu:56637; -. DR UCSC; uc007zen.1; mouse. DR AGR; MGI:1861437; -. DR CTD; 2932; -. DR MGI; MGI:1861437; Gsk3b. DR VEuPathDB; HostDB:ENSMUSG00000022812; -. DR eggNOG; KOG0658; Eukaryota. DR GeneTree; ENSGT00520000055635; -. DR HOGENOM; CLU_000288_181_20_1; -. DR InParanoid; Q9WV60; -. DR OMA; MKTTMPM; -. DR OrthoDB; 2872909at2759; -. DR PhylomeDB; Q9WV60; -. DR TreeFam; TF101104; -. DR BRENDA; 2.7.11.26; 3474. DR Reactome; R-MMU-195253; Degradation of beta-catenin by the destruction complex. DR Reactome; R-MMU-196299; Beta-catenin phosphorylation cascade. DR Reactome; R-MMU-3371453; Regulation of HSF1-mediated heat shock response. DR Reactome; R-MMU-399956; CRMPs in Sema3A signaling. DR Reactome; R-MMU-4641262; Disassembly of the destruction complex and recruitment of AXIN to the membrane. DR Reactome; R-MMU-5250924; B-WICH complex positively regulates rRNA expression. DR Reactome; R-MMU-5610785; GLI3 is processed to GLI3R by the proteasome. DR Reactome; R-MMU-9762114; GSK3B and BTRC:CUL1-mediated-degradation of NFE2L2. DR BioGRID-ORCS; 56637; 13 hits in 81 CRISPR screens. DR ChiTaRS; Gsk3b; mouse. DR PRO; PR:Q9WV60; -. DR Proteomes; UP000000589; Chromosome 16. DR RNAct; Q9WV60; Protein. DR Bgee; ENSMUSG00000022812; Expressed in spermatid and 251 other cell types or tissues. DR ExpressionAtlas; Q9WV60; baseline and differential. DR GO; GO:0030424; C:axon; ISO:MGI. DR GO; GO:0030877; C:beta-catenin destruction complex; IDA:MGI. DR GO; GO:0005813; C:centrosome; ISO:MGI. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:MGI. DR GO; GO:0030425; C:dendrite; ISO:MGI. DR GO; GO:0043198; C:dendritic shaft; IDA:MGI. DR GO; GO:0043197; C:dendritic spine; ISO:MGI. DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO. DR GO; GO:0030426; C:growth cone; IDA:MGI. DR GO; GO:0072687; C:meiotic spindle; IDA:MGI. DR GO; GO:0016020; C:membrane; ISS:UniProtKB. DR GO; GO:0043227; C:membrane-bounded organelle; IDA:MGI. DR GO; GO:0005874; C:microtubule; ISO:MGI. DR GO; GO:0005739; C:mitochondrion; IEA:GOC. DR GO; GO:0043025; C:neuronal cell body; IDA:MGI. DR GO; GO:0005654; C:nucleoplasm; ISO:MGI. DR GO; GO:0005634; C:nucleus; IDA:MGI. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:BHF-UCL. DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB. DR GO; GO:0014069; C:postsynaptic density; IDA:MGI. DR GO; GO:0098793; C:presynapse; IEA:GOC. DR GO; GO:0032991; C:protein-containing complex; ISO:MGI. DR GO; GO:1990904; C:ribonucleoprotein complex; IDA:MGI. DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; ISO:MGI. DR GO; GO:1990909; C:Wnt signalosome; IDA:ParkinsonsUK-UCL. DR GO; GO:0005524; F:ATP binding; ISO:MGI. DR GO; GO:0008013; F:beta-catenin binding; IPI:MGI. DR GO; GO:0034452; F:dynactin binding; ISO:MGI. DR GO; GO:0070840; F:dynein complex binding; IPI:CAFA. DR GO; GO:0005178; F:integrin binding; ISO:MGI. DR GO; GO:0035255; F:ionotropic glutamate receptor binding; ISO:MGI. DR GO; GO:0016301; F:kinase activity; ISS:UniProtKB. DR GO; GO:0051059; F:NF-kappaB binding; ISO:MGI. DR GO; GO:0002039; F:p53 binding; ISO:MGI. DR GO; GO:0002020; F:protease binding; ISO:MGI. DR GO; GO:0034236; F:protein kinase A catalytic subunit binding; ISO:MGI. DR GO; GO:0004672; F:protein kinase activity; IDA:UniProtKB. DR GO; GO:0019901; F:protein kinase binding; IPI:ParkinsonsUK-UCL. DR GO; GO:0106310; F:protein serine kinase activity; ISO:MGI. DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB. DR GO; GO:0120283; F:protein serine/threonine kinase binding; ISO:MGI. DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISO:MGI. DR GO; GO:0048156; F:tau protein binding; ISO:MGI. DR GO; GO:0050321; F:tau-protein kinase activity; IDA:MGI. DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI. DR GO; GO:0009887; P:animal organ morphogenesis; IMP:MGI. DR GO; GO:0141068; P:autosome genomic imprinting; IMP:BHF-UCL. DR GO; GO:0048675; P:axon extension; IGI:MGI. DR GO; GO:0007409; P:axonogenesis; IGI:MGI. DR GO; GO:1904886; P:beta-catenin destruction complex disassembly; ISO:MGI. DR GO; GO:0046849; P:bone remodeling; ISO:MGI. DR GO; GO:0060070; P:canonical Wnt signaling pathway; IDA:MGI. DR GO; GO:0061049; P:cell growth involved in cardiac muscle cell development; ISO:MGI. DR GO; GO:0016477; P:cell migration; IGI:MGI. DR GO; GO:1904646; P:cellular response to amyloid-beta; ISO:MGI. DR GO; GO:0071385; P:cellular response to glucocorticoid stimulus; IGI:ARUK-UCL. DR GO; GO:0035729; P:cellular response to hepatocyte growth factor stimulus; IDA:MGI. DR GO; GO:0036016; P:cellular response to interleukin-3; IDA:UniProtKB. DR GO; GO:0071260; P:cellular response to mechanical stimulus; ISO:MGI. DR GO; GO:0071300; P:cellular response to retinoic acid; ISO:MGI. DR GO; GO:0007623; P:circadian rhythm; IMP:UniProtKB. DR GO; GO:0007010; P:cytoskeleton organization; TAS:UniProtKB. DR GO; GO:0001837; P:epithelial to mesenchymal transition; ISS:UniProtKB. DR GO; GO:0006983; P:ER overload response; IDA:MGI. DR GO; GO:0030010; P:establishment of cell polarity; ISO:MGI. DR GO; GO:0007163; P:establishment or maintenance of cell polarity; ISO:MGI. DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; IGI:ARUK-UCL. DR GO; GO:0097192; P:extrinsic apoptotic signaling pathway in absence of ligand; IDA:UniProtKB. DR GO; GO:0045444; P:fat cell differentiation; IDA:MGI. DR GO; GO:0005977; P:glycogen metabolic process; ISO:MGI. DR GO; GO:0035733; P:hepatic stellate cell activation; ISO:MGI. DR GO; GO:0097284; P:hepatocyte apoptotic process; ISO:MGI. DR GO; GO:0021766; P:hippocampus development; ISO:MGI. DR GO; GO:0008286; P:insulin receptor signaling pathway; IDA:CAFA. DR GO; GO:0035556; P:intracellular signal transduction; ISO:MGI. DR GO; GO:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; IDA:CACAO. DR GO; GO:0030011; P:maintenance of cell polarity; ISO:MGI. DR GO; GO:0007127; P:meiosis I; IMP:MGI. DR GO; GO:0007520; P:myoblast fusion; IDA:MGI. DR GO; GO:0014902; P:myotube differentiation; IGI:MGI. DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:MGI. 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; IMP:BHF-UCL. DR GO; GO:0010614; P:negative regulation of cardiac muscle hypertrophy; IDA:MGI. DR GO; GO:2000171; P:negative regulation of dendrite development; ISO:MGI. DR GO; GO:0050774; P:negative regulation of dendrite morphogenesis; ISO:MGI. DR GO; GO:1904339; P:negative regulation of dopaminergic neuron differentiation; ISO:MGI. 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:MGI. DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; ISO:MGI. DR GO; GO:2000740; P:negative regulation of mesenchymal stem cell differentiation; ISO:MGI. DR GO; GO:0014043; P:negative regulation of neuron maturation; IGI:MGI. DR GO; GO:2001223; P:negative regulation of neuron migration; ISO:MGI. DR GO; GO:0010977; P:negative regulation of neuron projection development; IMP:MGI. DR GO; GO:0045668; P:negative regulation of osteoblast differentiation; ISO:MGI. DR GO; GO:1901984; P:negative regulation of protein acetylation; ISO:MGI. DR GO; GO:1904780; P:negative regulation of protein localization to centrosome; IMP:CAFA. DR GO; GO:1900181; P:negative regulation of protein localization to nucleus; ISO:MGI. DR GO; GO:0031333; P:negative regulation of protein-containing complex assembly; ISO:MGI. DR GO; GO:0034392; P:negative regulation of smooth muscle cell apoptotic process; ISO:MGI. DR GO; GO:0045886; P:negative regulation of synaptic assembly at neuromuscular junction; ISO:MGI. DR GO; GO:0032007; P:negative regulation of TOR signaling; IGI:BHF-UCL. DR GO; GO:0031175; P:neuron projection development; ISS:UniProtKB. DR GO; GO:0106027; P:neuron projection organization; ISO:MGI. DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:UniProtKB. DR GO; GO:0043491; P:phosphatidylinositol 3-kinase/protein kinase B signal transduction; IMP:MGI. DR GO; GO:0016310; P:phosphorylation; IMP:UniProtKB. DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI. DR GO; GO:0010508; P:positive regulation of autophagy; IDA:UniProtKB. DR GO; GO:0045773; P:positive regulation of axon extension; IGI:MGI. DR GO; GO:2000727; P:positive regulation of cardiac muscle cell differentiation; IMP:BHF-UCL. DR GO; GO:0045597; P:positive regulation of cell differentiation; ISO:MGI. DR GO; GO:0001954; P:positive regulation of cell-matrix adhesion; ISO:MGI. DR GO; GO:0045724; P:positive regulation of cilium assembly; IMP:UniProtKB. DR GO; GO:2000573; P:positive regulation of DNA biosynthetic process; ISO:MGI. DR GO; GO:2000463; P:positive regulation of excitatory postsynaptic potential; ISO:MGI. DR GO; GO:0010628; P:positive regulation of gene expression; IMP:BHF-UCL. DR GO; GO:0010918; P:positive regulation of mitochondrial membrane potential; ISO:MGI. DR GO; GO:1901030; P:positive regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway; IDA:UniProtKB. DR GO; GO:0010822; P:positive regulation of mitochondrion organization; ISO:MGI. DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; ISO:MGI. DR GO; GO:0033690; P:positive regulation of osteoblast proliferation; ISO:MGI. DR GO; GO:0045672; P:positive regulation of osteoclast differentiation; ISO:MGI. DR GO; GO:0090290; P:positive regulation of osteoclast proliferation; ISO:MGI. DR GO; GO:0010800; P:positive regulation of peptidyl-threonine phosphorylation; IDA:MGI. DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IGI:MGI. DR GO; GO:0045732; P:positive regulation of protein catabolic process; ISO:MGI. DR GO; GO:0046827; P:positive regulation of protein export from nucleus; ISO:MGI. DR GO; GO:1904781; P:positive regulation of protein localization to centrosome; ISO:MGI. DR GO; GO:1903566; P:positive regulation of protein localization to cilium; IMP:UniProtKB. DR GO; GO:0031398; P:positive regulation of protein ubiquitination; ISO:MGI. DR GO; GO:0031334; P:positive regulation of protein-containing complex assembly; ISO:MGI. DR GO; GO:0048661; P:positive regulation of smooth muscle cell proliferation; ISO:MGI. DR GO; GO:2000738; P:positive regulation of stem cell differentiation; IMP:MGI. DR GO; GO:0045887; P:positive regulation of synaptic assembly at neuromuscular junction; ISO:MGI. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:BHF-UCL. DR GO; GO:0099171; P:presynaptic modulation of chemical synaptic transmission; ISO:MGI. DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; NAS:ComplexPortal. DR GO; GO:0006611; P:protein export from nucleus; IDA:MGI. DR GO; GO:0035372; P:protein localization to microtubule; IGI:MGI. DR GO; GO:0006468; P:protein phosphorylation; IMP:UniProtKB. DR GO; GO:0000320; P:re-entry into mitotic cell cycle; IDA:MGI. DR GO; GO:0042981; P:regulation of apoptotic process; IMP:BHF-UCL. DR GO; GO:0030516; P:regulation of axon extension; ISO:MGI. DR GO; GO:0050770; P:regulation of axonogenesis; ISO:MGI. DR GO; GO:0001558; P:regulation of cell growth; IMP:MGI. DR GO; GO:0042752; P:regulation of circadian rhythm; IMP:UniProtKB. DR GO; GO:0048814; P:regulation of dendrite morphogenesis; ISO:MGI. DR GO; GO:1900271; P:regulation of long-term synaptic potentiation; IMP:UniProtKB. DR GO; GO:0150101; P:regulation of microtubule anchoring at centrosome; ISO:MGI. DR GO; GO:0070507; P:regulation of microtubule cytoskeleton organization; ISO:MGI. DR GO; GO:0032886; P:regulation of microtubule-based process; IDA:UniProtKB. DR GO; GO:0099159; P:regulation of modification of postsynaptic structure; ISO:MGI. DR GO; GO:0010975; P:regulation of neuron projection development; IGI:MGI. DR GO; GO:0048168; P:regulation of neuronal synaptic plasticity; ISO:MGI. DR GO; GO:0098696; P:regulation of neurotransmitter receptor localization to postsynaptic specialization membrane; ISO:MGI. DR GO; GO:0045667; P:regulation of osteoblast differentiation; ISO:MGI. DR GO; GO:0046825; P:regulation of protein export from nucleus; ISO:MGI. DR GO; GO:0010043; P:response to zinc ion; ISO:MGI. DR GO; GO:0048863; P:stem cell differentiation; IMP:MGI. DR GO; GO:0071109; P:superior temporal gyrus development; ISO:MGI. DR GO; GO:0006366; P:transcription by RNA polymerase II; IMP:MGI. DR GO; GO:0016055; P:Wnt signaling pathway; IGI:MGI. DR CDD; cd14137; STKc_GSK3; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR IDEAL; IID50236; -. 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; Q9WV60; MM. PE 1: Evidence at protein level; KW 3D-structure; ADP-ribosylation; ATP-binding; Biological rhythms; KW Carbohydrate metabolism; Cell membrane; Cytoplasm; Developmental protein; KW Differentiation; Glycogen metabolism; Kinase; Membrane; Neurogenesis; KW Nucleotide-binding; 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_0000085981" 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:0000269|PubMed:22057101, FT ECO:0000269|PubMed:23395175, ECO:0000269|PubMed:24742671, FT ECO:0000269|PubMed:27827363" FT MOD_RES 216 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P49841" FT MOD_RES 389 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:15345747" FT MUTAGEN 9 FT /note="S->A: Loss of phosphorylation; No inhibition of FT activity and constitutively active." FT /evidence="ECO:0000269|PubMed:15791206, FT ECO:0000269|PubMed:22057101" FT MUTAGEN 85 FT /note="K->R: Inhibits interaction with AXIN1 and ZBED3." FT /evidence="ECO:0000269|PubMed:19141611" FT STRAND 27..29 FT /evidence="ECO:0007829|PDB:5AIR" FT STRAND 37..47 FT /evidence="ECO:0007829|PDB:6AE3" FT STRAND 52..64 FT /evidence="ECO:0007829|PDB:6AE3" FT STRAND 66..75 FT /evidence="ECO:0007829|PDB:6AE3" FT TURN 76..78 FT /evidence="ECO:0007829|PDB:6AE3" FT STRAND 81..88 FT /evidence="ECO:0007829|PDB:6AE3" FT HELIX 96..102 FT /evidence="ECO:0007829|PDB:6AE3" FT STRAND 112..119 FT /evidence="ECO:0007829|PDB:6AE3" FT STRAND 121..124 FT /evidence="ECO:0007829|PDB:5AIR" FT STRAND 126..133 FT /evidence="ECO:0007829|PDB:6AE3" FT HELIX 139..148 FT /evidence="ECO:0007829|PDB:6AE3" FT HELIX 155..173 FT /evidence="ECO:0007829|PDB:6AE3" FT TURN 174..176 FT /evidence="ECO:0007829|PDB:6AE3" FT HELIX 184..186 FT /evidence="ECO:0007829|PDB:6AE3" FT STRAND 187..189 FT /evidence="ECO:0007829|PDB:6AE3" FT TURN 191..193 FT /evidence="ECO:0007829|PDB:6AE3" FT STRAND 196..198 FT /evidence="ECO:0007829|PDB:6AE3" FT HELIX 201..203 FT /evidence="ECO:0007829|PDB:6AE3" FT HELIX 220..222 FT /evidence="ECO:0007829|PDB:6AE3" FT HELIX 225..228 FT /evidence="ECO:0007829|PDB:6AE3" FT HELIX 237..252 FT /evidence="ECO:0007829|PDB:6AE3" FT TURN 261..263 FT /evidence="ECO:0007829|PDB:6AE3" FT HELIX 264..273 FT /evidence="ECO:0007829|PDB:6AE3" FT HELIX 278..284 FT /evidence="ECO:0007829|PDB:6AE3" FT HELIX 286..288 FT /evidence="ECO:0007829|PDB:4NU1" FT HELIX 301..304 FT /evidence="ECO:0007829|PDB:6AE3" FT HELIX 311..320 FT /evidence="ECO:0007829|PDB:6AE3" FT HELIX 325..327 FT /evidence="ECO:0007829|PDB:6AE3" FT HELIX 331..335 FT /evidence="ECO:0007829|PDB:6AE3" FT HELIX 338..344 FT /evidence="ECO:0007829|PDB:6AE3" FT HELIX 364..367 FT /evidence="ECO:0007829|PDB:6AE3" FT HELIX 371..373 FT /evidence="ECO:0007829|PDB:6AE3" FT HELIX 374..377 FT /evidence="ECO:0007829|PDB:6AE3" FT HELIX 380..382 FT /evidence="ECO:0007829|PDB:6AE3" SQ SEQUENCE 420 AA; 46710 MW; 200C3FD1B38B4883 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 HARIQAAASP PANATAASDT NAGDRGQTNN AASASASNST //