FOXO1_MOUSE
ID FOXO1_MOUSE Reviewed; 652 AA.
AC Q9R1E0; Q9JJW4;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 191.
DE RecName: Full=Forkhead box protein O1;
DE AltName: Full=Forkhead box protein O1A;
DE AltName: Full=Forkhead in rhabdomyosarcoma;
GN Name=Foxo1; Synonyms=Fkhr, Foxo1a;
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], PHOSPHORYLATION AT THR-24; SER-253 AND SER-316,
RP AND MUTAGENESIS OF THR-24; SER-253 AND SER-316.
RC TISSUE=Liver;
RX PubMed=10347145; DOI=10.1074/jbc.274.23.15982;
RA Nakae J., Park B.C., Accili D.;
RT "Insulin stimulates phosphorylation of the forkhead transcription factor
RT FKHR on serine 253 through a Wortmannin-sensitive pathway.";
RL J. Biol. Chem. 274:15982-15985(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Leenders H., Benoist C., Mathis D.;
RT "The forkhead FKHR is involved in thymocyte proliferation.";
RL Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J, and NOD; TISSUE=Thymus, and Vagina;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP FUNCTION.
RX PubMed=12219087; DOI=10.1038/ng890;
RA Nakae J., Biggs W.H. III, Kitamura T., Cavenee W.K., Wright C.V.,
RA Arden K.C., Accili D.;
RT "Regulation of insulin action and pancreatic beta-cell function by mutated
RT alleles of the gene encoding forkhead transcription factor Foxo1.";
RL Nat. Genet. 32:245-253(2002).
RN [6]
RP INTERACTION WITH PPARGC1A, FUNCTION, AND PHOSPHORYLATION.
RX PubMed=12754525; DOI=10.1038/nature01667;
RA Puigserver P., Rhee J., Donovan J., Walkey C.J., Yoon J.C., Oriente F.,
RA Kitamura Y., Altomonte J., Dong H., Accili D., Spiegelman B.M.;
RT "Insulin-regulated hepatic gluconeogenesis through FOXO1-PGC-1alpha
RT interaction.";
RL Nature 423:550-555(2003).
RN [7]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=15184386; DOI=10.1074/jbc.m314214200;
RA Furuyama T., Kitayama K., Shimoda Y., Ogawa M., Sone K., Yoshida-Araki K.,
RA Hisatsune H., Nishikawa S., Nakayama K., Nakayama K., Ikeda K.,
RA Motoyama N., Mori N.;
RT "Abnormal angiogenesis in Foxo1 (Fkhr)-deficient mice.";
RL J. Biol. Chem. 279:34741-34749(2004).
RN [8]
RP ACETYLATION AT LYS-242; LYS-245 AND LYS-262, INTERACTION WITH SIRT1,
RP DEACETYLATION, FUNCTION, AND MUTAGENESIS OF LYS-242; LYS-245 AND LYS-262.
RX PubMed=15220471; DOI=10.1073/pnas.0400593101;
RA Daitoku H., Hatta M., Matsuzaki H., Aratani S., Ohshima T., Miyagishi M.,
RA Nakajima T., Fukamizu A.;
RT "Silent information regulator 2 potentiates Foxo1-mediated transcription
RT through its deacetylase activity.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:10042-10047(2004).
RN [9]
RP ACETYLATION AT LYS-242; LYS-245 AND LYS-262, PHOSPHORYLATION AT SER-253,
RP DNA-BINDING, AND MUTAGENESIS OF LYS-242; LYS-245; SER-253 AND LYS-262.
RX PubMed=16076959; DOI=10.1073/pnas.0502738102;
RA Matsuzaki H., Daitoku H., Hatta M., Aoyama H., Yoshimochi K., Fukamizu A.;
RT "Acetylation of Foxo1 alters its DNA-binding ability and sensitivity to
RT phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:11278-11283(2005).
RN [10]
RP INTERACTION WITH LRPPRC.
RX PubMed=17050673; DOI=10.1101/gad.1483906;
RA Cooper M.P., Qu L., Rohas L.M., Lin J., Yang W., Erdjument-Bromage H.,
RA Tempst P., Spiegelman B.M.;
RT "Defects in energy homeostasis in Leigh syndrome French Canadian variant
RT through PGC-1alpha/LRP130 complex.";
RL Genes Dev. 20:2996-3009(2006).
RN [11]
RP FUNCTION, INTERACTION WITH CEBPA, ACETYLATION AT LYS-242; LYS-245 AND
RP LYS-262, DEACETYLATION BY SIRT1, DNA-BINDING, AND MUTAGENESIS OF LYS-242;
RP LYS-245 AND LYS-262.
RX PubMed=17090532; DOI=10.1074/jbc.m607215200;
RA Qiao L., Shao J.;
RT "SIRT1 regulates adiponectin gene expression through Foxo1-C/enhancer-
RT binding protein alpha transcriptional complex.";
RL J. Biol. Chem. 281:39915-39924(2006).
RN [12]
RP INTERACTION WITH SIRT1, PHOSPHORYLATION, SUBCELLULAR LOCATION, FUNCTION,
RP AND MUTAGENESIS OF THR-24; SER-253; SER-316; LEU-462 AND LEU-463.
RX PubMed=16917544; DOI=10.1172/jci25518;
RA Nakae J., Cao Y., Daitoku H., Fukamizu A., Ogawa W., Yano Y., Hayashi Y.;
RT "The LXXLL motif of murine forkhead transcription factor FoxO1 mediates
RT Sirt1-dependent transcriptional activity.";
RL J. Clin. Invest. 116:2473-2483(2006).
RN [13]
RP ACETYLATION, DEACETYLATION BY SIRT2, FUNCTION IN INHIBITION OF ADIPOCYTE
RP DIFFERENTIATION, AND INTERACTION WITH SIRT2.
RX PubMed=17681146; DOI=10.1016/j.cmet.2007.07.003;
RA Jing E., Gesta S., Kahn C.R.;
RT "SIRT2 regulates adipocyte differentiation through FoxO1
RT acetylation/deacetylation.";
RL Cell Metab. 6:105-114(2007).
RN [14]
RP FUNCTION, INTERACTION WITH CEBPA, DEVELOPMENTAL STAGE, TISSUE SPECIFICITY,
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF TRP-206 AND HIS-212.
RX PubMed=17627282; DOI=10.1038/sj.emboj.7601784;
RA Sekine K., Chen Y.R., Kojima N., Ogata K., Fukamizu A., Miyajima A.;
RT "Foxo1 links insulin signaling to C/EBPalpha and regulates gluconeogenesis
RT during liver development.";
RL EMBO J. 26:3607-3615(2007).
RN [15]
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 [16]
RP INTERACTION WITH WDFY2, COMPLEX FORMATION WITH WDFY2 AND AKT1, SUBCELLULAR
RP LOCATION, INDUCTION, AND PHOSPHORYLATION AT SER-253.
RX PubMed=18388859; DOI=10.1038/emboj.2008.67;
RA Fritzius T., Moelling K.;
RT "Akt- and Foxo1-interacting WD-repeat-FYVE protein promotes adipogenesis.";
RL EMBO J. 27:1399-1410(2008).
RN [17]
RP PHOSPHORYLATION, SUBCELLULAR LOCATION, METHYLATION AT ARG-248 AND ARG-250,
RP AND MUTAGENESIS OF ARG-29; ARG-147; ARG-154; ARG-248; ARG-249; ARG-250;
RP ARG-311 AND ARG-313.
RX PubMed=18951090; DOI=10.1016/j.molcel.2008.09.013;
RA Yamagata K., Daitoku H., Takahashi Y., Namiki K., Hisatake K., Kako K.,
RA Mukai H., Kasuya Y., Fukamizu A.;
RT "Arginine methylation of FOXO transcription factors inhibits their
RT phosphorylation by Akt.";
RL Mol. Cell 32:221-231(2008).
RN [18]
RP ACETYLATION, DEACETYLATION BY SIRT2, INTERACTION WITH PPARG AND SIRT2, AND
RP SUBCELLULAR LOCATION.
RX PubMed=19037106; DOI=10.1091/mbc.e08-06-0647;
RA Wang F., Tong Q.;
RT "SIRT2 suppresses adipocyte differentiation by deacetylating FOXO1 and
RT enhancing FOXO1's repressive interaction with PPARgamma.";
RL Mol. Biol. Cell 20:801-808(2009).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-284; SER-295; SER-326 AND
RP THR-330, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Kidney, Liver, Lung, Pancreas, Spleen,
RC 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 [20]
RP INTERACTION WITH NLK, SUBCELLULAR LOCATION, PHOSPHORYLATION BY NLK, AND
RP MUTAGENESIS OF SER-284; SER-295; SER-326; SER-380; SER-391; THR-399;
RP SER-413 AND SER-415.
RX PubMed=20061393; DOI=10.1074/jbc.m110.101824;
RA Kim S., Kim Y., Lee J., Chung J.;
RT "Regulation of FOXO1 by TAK1-Nemo-like kinase pathway.";
RL J. Biol. Chem. 285:8122-8129(2010).
RN [21]
RP PHOSPHORYLATION AT THR-24 AND SER-253, ACETYLATION, SUBCELLULAR LOCATION,
RP FUNCTION, AND MUTAGENESIS OF THR-24; LYS-219; LYS-242; LYS-245; SER-253;
RP LYS-259; LYS-262; LYS-271 AND LYS-291.
RX PubMed=20519497; DOI=10.1074/jbc.m110.140228;
RA Qiang L., Banks A.S., Accili D.;
RT "Uncoupling of acetylation from phosphorylation regulates FoxO1 function
RT independent of its subcellular localization.";
RL J. Biol. Chem. 285:27396-27401(2010).
RN [22]
RP PHOSPHORYLATION AT THR-24; SER-253 AND SER-319 BY SGK1, AND SUBCELLULAR
RP LOCATION.
RX PubMed=19965929; DOI=10.1210/me.2009-0265;
RA Di Pietro N., Panel V., Hayes S., Bagattin A., Meruvu S., Pandolfi A.,
RA Hugendubler L., Fejes-Toth G., Naray-Fejes-Toth A., Mueller E.;
RT "Serum- and glucocorticoid-inducible kinase 1 (SGK1) regulates adipocyte
RT differentiation via forkhead box O1.";
RL Mol. Endocrinol. 24:370-380(2010).
RN [23]
RP FUNCTION, PHOSPHORYLATION, INTERACTION WITH SIRT1, AND INDUCTION.
RX PubMed=20668652; DOI=10.1371/journal.pone.0011786;
RA Goitre L., Balzac F., Degani S., Degan P., Marchi S., Pinton P.,
RA Retta S.F.;
RT "KRIT1 regulates the homeostasis of intracellular reactive oxygen
RT species.";
RL PLoS ONE 5:E11786-E11786(2010).
RN [24]
RP FUNCTION, SUBCELLULAR LOCATION, ACETYLATION, AND RESPONSE TO NITRIC OXIDE.
RX PubMed=21196578; DOI=10.1074/jbc.m110.204768;
RA Hughes K.J., Meares G.P., Hansen P.A., Corbett J.A.;
RT "FoxO1 and SIRT1 regulate beta-cell responses to nitric oxide.";
RL J. Biol. Chem. 286:8338-8348(2011).
RN [25]
RP SUBCELLULAR LOCATION, FUNCTION, AND DNA-BINDING.
RX PubMed=21335550; DOI=10.1074/jbc.m110.204248;
RA Meur G., Qian Q., da Silva Xavier G., Pullen T.J., Tsuboi T., McKinnon C.,
RA Fletcher L., Tavare J.M., Hughes S., Johnson P., Rutter G.A.;
RT "Nucleo-cytosolic shuttling of FoxO1 directly regulates mouse Ins2 but not
RT Ins1 gene expression in pancreatic beta cells (MIN6).";
RL J. Biol. Chem. 286:13647-13656(2011).
RN [26]
RP INTERACTION WITH RUNX2, AND FUNCTION.
RX PubMed=21471200; DOI=10.1074/jbc.m110.197905;
RA Yang S., Xu H., Yu S., Cao H., Fan J., Ge C., Fransceschi R.T., Dong H.H.,
RA Xiao G.;
RT "Foxo1 mediates insulin-like growth factor 1 (IGF1)/insulin regulation of
RT osteocalcin expression by antagonizing Runx2 in osteoblasts.";
RL J. Biol. Chem. 286:19149-19158(2011).
RN [27]
RP INTERACTION WITH XBP1, AND SUBCELLULAR LOCATION.
RX PubMed=21317886; DOI=10.1038/nm.2293;
RA Zhou Y., Lee J., Reno C.M., Sun C., Park S.W., Chung J., Lee J.,
RA Fisher S.J., White M.F., Biddinger S.B., Ozcan U.;
RT "Regulation of glucose homeostasis through a XBP-1-FoxO1 interaction.";
RL Nat. Med. 17:356-365(2011).
RN [28]
RP CHARACTERISTICS OF AN ANIMAL MODEL OF DIABETES MELLITUS TYPE 2, FUNCTION,
RP DEPHOSPHORYLATION AT THR-24 AND SER-253, AND INTERACTION WITH PPP2R1A.
RX PubMed=22417654; DOI=10.1042/bj20111606;
RA Yan L., Guo S., Brault M., Harmon J., Robertson R.P., Hamid R., Stein R.,
RA Yang E.;
RT "The B55alpha-containing PP2A holoenzyme dephosphorylates FOXO1 in islet
RT beta-cells under oxidative stress.";
RL Biochem. J. 444:239-247(2012).
RN [29]
RP FUNCTION AS A TRANSCRIPTIONAL ACTIVATOR, INTERACTION WITH FCOR AND SIRT1,
RP TISSUE SPECIFICITY, AND MUTAGENESIS OF LYS-242; LYS-245; LYS-259; LYS-262;
RP LYS-271 AND LYS-291.
RX PubMed=22510882; DOI=10.1038/emboj.2012.97;
RA Nakae J., Cao Y., Hakuno F., Takemori H., Kawano Y., Sekioka R., Abe T.,
RA Kiyonari H., Tanaka T., Sakai J., Takahashi S., Itoh H.;
RT "Novel repressor regulates insulin sensitivity through interaction with
RT Foxo1.";
RL EMBO J. 31:2275-2295(2012).
RN [30]
RP DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, INTERACTION WITH ATF4, AND
RP FUNCTION.
RX PubMed=22298775; DOI=10.1074/jbc.m111.282897;
RA Kode A., Mosialou I., Silva B.C., Joshi S., Ferron M., Rached M.T.,
RA Kousteni S.;
RT "FoxO1 protein cooperates with ATF4 protein in osteoblasts to control
RT glucose homeostasis.";
RL J. Biol. Chem. 287:8757-8768(2012).
RN [31]
RP FUNCTION, AND ACETYLATION.
RX PubMed=25009184; DOI=10.1073/pnas.1411026111;
RA Zhang P., Tu B., Wang H., Cao Z., Tang M., Zhang C., Gu B., Li Z., Wang L.,
RA Yang Y., Zhao Y., Wang H., Luo J., Deng C.X., Gao B., Roeder R.G.,
RA Zhu W.G.;
RT "Tumor suppressor p53 cooperates with SIRT6 to regulate gluconeogenesis by
RT promoting FoxO1 nuclear exclusion.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:10684-10689(2014).
RN [32]
RP FUNCTION, SUBCELLULAR LOCATION, AND DEACETYLATION BY SIRT6.
RX PubMed=27457971; DOI=10.1038/srep30321;
RA Song M.Y., Wang J., Ka S.O., Bae E.J., Park B.H.;
RT "Insulin secretion impairment in Sirt6 knockout pancreatic beta cells is
RT mediated by suppression of the FoxO1-Pdx1-Glut2 pathway.";
RL Sci. Rep. 6:30321-30321(2016).
RN [33]
RP INTERACTION WITH CRY1, UBIQUITINATION AND PROTEASOMAL DEGRADATION, AND
RP SUBCELLULAR LOCATION.
RX PubMed=28790135; DOI=10.2337/db16-1600;
RA Tong X., Zhang D., Charney N., Jin E., VanDommelen K., Stamper K.,
RA Gupta N., Saldate J., Yin L.;
RT "DDB1-mediated CRY1 degradation promotes FOXO1-driven gluconeogenesis in
RT liver.";
RL Diabetes 66:2571-2582(2017).
RN [34]
RP DEACETYLATION BY SIRT6.
RX PubMed=31442424; DOI=10.1016/j.molcel.2019.07.023;
RA Jung S.M., Hung C.M., Hildebrand S.R., Sanchez-Gurmaches J.,
RA Martinez-Pastor B., Gengatharan J.M., Wallace M., Mukhopadhyay D.,
RA Martinez Calejman C., Luciano A.K., Hsiao W.Y., Tang Y., Li H.,
RA Daniels D.L., Mostoslavsky R., Metallo C.M., Guertin D.A.;
RT "Non-canonical mTORC2 signaling regulates brown adipocyte lipid catabolism
RT through SIRT6-FoxO1.";
RL Mol. Cell 75:807-822(2019).
RN [35]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=32103177; DOI=10.1038/s41586-020-2050-1;
RA van Gastel N., Stegen S., Eelen G., Schoors S., Carlier A., Daniels V.W.,
RA Baryawno N., Przybylski D., Depypere M., Stiers P.J., Lambrechts D.,
RA Van Looveren R., Torrekens S., Sharda A., Agostinis P., Lambrechts D.,
RA Maes F., Swinnen J.V., Geris L., Van Oosterwyck H., Thienpont B.,
RA Carmeliet P., Scadden D.T., Carmeliet G.;
RT "Lipid availability determines fate of skeletal progenitor cells via
RT SOX9.";
RL Nature 579:111-117(2020).
RN [36]
RP FUNCTION, AND INTERACTION WITH TOX4.
RX PubMed=34914893; DOI=10.1016/j.cmet.2021.11.013;
RA Wang L., Yu J., Zhou Q., Wang X., Mukhanova M., Du W., Sun L.,
RA Pajvani U.B., Accili D.;
RT "TOX4, an insulin receptor-independent regulator of hepatic glucose
RT production, is activated in diabetic liver.";
RL Cell Metab. 34:158-170.e5(2022).
CC -!- FUNCTION: Transcription factor that is the main target of insulin
CC signaling and regulates metabolic homeostasis in response to oxidative
CC stress (PubMed:12219087, PubMed:12754525, PubMed:15184386,
CC PubMed:15220471, PubMed:16917544, PubMed:17090532, PubMed:17627282,
CC PubMed:17681146, PubMed:20519497, PubMed:20668652, PubMed:21196578,
CC PubMed:21335550, PubMed:21471200, PubMed:22298775, PubMed:22417654,
CC PubMed:22510882, PubMed:27457971, PubMed:34914893). Binds to the
CC insulin response element (IRE) with consensus sequence 5'-TT[G/A]TTTTG-
CC 3' and the related Daf-16 family binding element (DBE) with consensus
CC sequence 5'-TT[G/A]TTTAC-3' (PubMed:17090532, PubMed:21335550).
CC Activity suppressed by insulin (PubMed:12754525, PubMed:17627282). Main
CC regulator of redox balance and osteoblast numbers and controls bone
CC mass (PubMed:21471200, PubMed:22298775). Orchestrates the endocrine
CC function of the skeleton in regulating glucose metabolism
CC (PubMed:21471200, PubMed:22298775). Also acts as a key regulator of
CC chondrogenic commitment of skeletal progenitor cells in response to
CC lipid availability: when lipids levels are low, translocates to the
CC nucleus and promotes expression of SOX9, which induces chondrogenic
CC commitment and suppresses fatty acid oxidation (PubMed:32103177). Acts
CC synergistically with ATF4 to suppress osteocalcin/BGLAP activity,
CC increasing glucose levels and triggering glucose intolerance and
CC insulin insensitivity (PubMed:22298775). Also suppresses the
CC transcriptional activity of RUNX2, an upstream activator of
CC osteocalcin/BGLAP (PubMed:21471200). Acts as an inhibitor of glucose
CC sensing in pancreatic beta cells by acting as a transcription repressor
CC and suppressing expression of PDX1 (PubMed:12219087, PubMed:27457971).
CC In hepatocytes, promotes gluconeogenesis by acting together with
CC PPARGC1A and CEBPA to activate the expression of genes such as IGFBP1,
CC G6PC1 and PCK1 (PubMed:12754525, PubMed:25009184). Also promotes
CC gluconeogenesis by directly promoting expression of PPARGC1A and G6PC1
CC (By similarity). Important regulator of cell death acting downstream of
CC CDK1, PKB/AKT1 and STK4/MST1 (By similarity). Promotes neural cell
CC death (By similarity). Mediates insulin action on adipose tissue (By
CC similarity). Regulates the expression of adipogenic genes such as PPARG
CC during preadipocyte differentiation and, adipocyte size and adipose
CC tissue-specific gene expression in response to excessive calorie intake
CC (By similarity). Regulates the transcriptional activity of GADD45A and
CC repair of nitric oxide-damaged DNA in beta-cells (PubMed:21196578).
CC Required for the autophagic cell death induction in response to
CC starvation or oxidative stress in a transcription-independent manner
CC (By similarity). Mediates the function of MLIP in cardiomyocytes
CC hypertrophy and cardiac remodeling (By similarity). Regulates
CC endothelial cell (EC) viability and apoptosis in a PPIA/CYPA-dependent
CC manner via transcription of CCL2 and BCL2L11 which are involved in EC
CC chemotaxis and apoptosis (By similarity).
CC {ECO:0000250|UniProtKB:A4L7N3, ECO:0000250|UniProtKB:G3V7R4,
CC ECO:0000250|UniProtKB:Q12778, ECO:0000269|PubMed:12219087,
CC ECO:0000269|PubMed:12754525, ECO:0000269|PubMed:15184386,
CC ECO:0000269|PubMed:15220471, ECO:0000269|PubMed:16917544,
CC ECO:0000269|PubMed:17090532, ECO:0000269|PubMed:17627282,
CC ECO:0000269|PubMed:17681146, ECO:0000269|PubMed:20519497,
CC ECO:0000269|PubMed:20668652, ECO:0000269|PubMed:21196578,
CC ECO:0000269|PubMed:21335550, ECO:0000269|PubMed:21471200,
CC ECO:0000269|PubMed:22298775, ECO:0000269|PubMed:22417654,
CC ECO:0000269|PubMed:22510882, ECO:0000269|PubMed:25009184,
CC ECO:0000269|PubMed:27457971, ECO:0000269|PubMed:32103177,
CC ECO:0000269|PubMed:34914893}.
CC -!- SUBUNIT: Interacts with EP300 and CREBBP; the interactions acetylate
CC FOXO1. Interacts with the 14-3-3 proteins, YWHAG and YWHAZ; the
CC interactions require insulin-stimulated phosphorylation on Thr-24,
CC promote nuclear exit and loss of transcriptional activity. Interacts
CC with SKP2; the interaction ubiquitinates FOXO1 leading to its
CC proteosomal degradation. Interacts with PMRT1; methylates FOXO1,
CC prevents PKB/AKT1 phosphorylation and retains FOXO1 in the nucleus (By
CC similarity). Interacts (via an N-terminal domain) with FCOR; the
CC interaction is direct, occurs in a forskolin-independent manner and
CC prevents SIRT1 binding to FOXO1. Interacts (via the C-terminal half)
CC with ATF4 (via its DNA-binding domain); the interaction occurs in
CC osteoblasts, regulates glucose homeostasis via suppression of beta-cell
CC proliferation and subsequent decrease in insulin production. Interacts
CC with RUNX2; the interaction inhibits RUNX2 transcriptional activity and
CC mediates the IGF1/insulin-dependent BGLAP expression in osteoblasts.
CC Interacts with PPP2R1A; the interaction regulates the dephosphorylation
CC of FOXO1 at Thr-24 and Ser-253 leading to its nuclear import. Binds to
CC CDK1. Interacts with LRPPRC. Interacts with RUNX2; the interaction
CC inhibits RUNX2 transcriptional activity and mediates the IGF1/insulin-
CC dependent BGLAP expression in osteoblasts. Interacts with NLK.
CC Interacts with SIRT1; the interaction results in the deacetylation of
CC FOXO1 leading to activation of FOXO1-mediated transcription of genes
CC involved in DNA repair and stress resistance. The interaction requires
CC the presence of KRIT1 and is inhibited by FCOR. Interacts with SIRT2;
CC the interaction is disrupted in response to oxidative stress or serum
CC deprivation, leading to increased level of acetylated FOXO1, which
CC promotes stress-induced autophagy by stimulating E1-like activating
CC enzyme ATG7. Interacts (acetylated form) with ATG7; the interaction is
CC increased in response to oxidative stress or serum deprivation and
CC promotes the autophagic process leading to cell death. Interacts
CC (acetylated form) with PPARG (PubMed:12754525, PubMed:15220471,
CC PubMed:16917544, PubMed:17050673, PubMed:17681146, PubMed:19037106,
CC PubMed:20061393, PubMed:20668652, PubMed:21471200, PubMed:22298775,
CC PubMed:22417654, PubMed:22510882). Interacts with XBP1 isoform 2; this
CC interaction is direct and leads to FOXO1 ubiquitination and degradation
CC via the proteasome pathway (PubMed:21317886). Interacts (via the Fork-
CC head domain) with CEBPA; the interaction increases when FOXO1 is
CC deacetylated (PubMed:17090532, PubMed:17627282). Interacts with WDFY2
CC (PubMed:18388859). Forms a complex with WDFY2 and AKT1
CC (PubMed:18388859). Interacts with CRY1 (PubMed:28790135). Interacts
CC with PPIA/CYPA; the interaction promotes FOXO1 dephosphorylation,
CC nuclear accumulation and transcriptional activity (By similarity).
CC Interacts with TOX4; FOXO1 is required for full induction of TOX4-
CC dependent activity and the interaction is inhibited by insulin
CC (PubMed:34914893). {ECO:0000250|UniProtKB:Q12778,
CC ECO:0000269|PubMed:12754525, ECO:0000269|PubMed:15220471,
CC ECO:0000269|PubMed:16917544, ECO:0000269|PubMed:17050673,
CC ECO:0000269|PubMed:17090532, ECO:0000269|PubMed:17627282,
CC ECO:0000269|PubMed:17681146, ECO:0000269|PubMed:18388859,
CC ECO:0000269|PubMed:19037106, ECO:0000269|PubMed:20061393,
CC ECO:0000269|PubMed:20668652, ECO:0000269|PubMed:21317886,
CC ECO:0000269|PubMed:21471200, ECO:0000269|PubMed:22298775,
CC ECO:0000269|PubMed:22417654, ECO:0000269|PubMed:22510882,
CC ECO:0000269|PubMed:28790135, ECO:0000269|PubMed:34914893}.
CC -!- INTERACTION:
CC Q9R1E0; P53566: Cebpa; NbExp=5; IntAct=EBI-1371343, EBI-2644207;
CC Q9R1E0; P0DJI6: Fcor; NbExp=12; IntAct=EBI-1371343, EBI-6126630;
CC Q9R1E0; Q6PB66: Lrpprc; NbExp=2; IntAct=EBI-1371343, EBI-1371262;
CC Q9R1E0; P51450-2: Rorc; NbExp=2; IntAct=EBI-1371343, EBI-4422078;
CC Q9R1E0; P10275: AR; Xeno; NbExp=4; IntAct=EBI-1371343, EBI-608057;
CC Q9R1E0; Q96EB6: SIRT1; Xeno; NbExp=2; IntAct=EBI-1371343, EBI-1802965;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:18388859,
CC ECO:0000269|PubMed:21317886, ECO:0000269|PubMed:27457971,
CC ECO:0000269|PubMed:32103177}. Nucleus {ECO:0000269|PubMed:17627282,
CC ECO:0000269|PubMed:18388859, ECO:0000269|PubMed:19965929,
CC ECO:0000269|PubMed:20061393, ECO:0000269|PubMed:21196578,
CC ECO:0000269|PubMed:21317886, ECO:0000269|PubMed:22298775,
CC ECO:0000269|PubMed:27457971, ECO:0000269|PubMed:28790135,
CC ECO:0000269|PubMed:32103177}. Note=Shuttles between the cytoplasm and
CC nucleus (PubMed:32103177). Largely nuclear in unstimulated cells (By
CC similarity). In osteoblasts, colocalizes with ATF4 and RUNX2 in the
CC nucleus (PubMed:22298775). Serum deprivation increases localization to
CC the nucleus, leading to activate expression of SOX9 and subsequent
CC chondrogenesis (PubMed:32103177). Insulin-induced phosphorylation at
CC Ser-253 by PKB/AKT1 leads, via stimulation of Thr-24 phosphorylation,
CC to binding of 14-3-3 proteins and nuclear export to the cytoplasm where
CC it is degraded by the ubiquitin-proteosomal pathway (By similarity).
CC Phosphorylation at Ser-249 by CDK1 disrupts binding of 14-3-3 proteins
CC and promotes nuclear accumulation (By similarity). Phosphorylation by
CC NLK results in nuclear export (PubMed:20061393). Translocates to the
CC nucleus upon oxidative stress-induced phosphorylation at Ser-212 by
CC STK4/MST1 (By similarity). SGK1-mediated phosphorylation also results
CC in nuclear translocation (PubMed:19965929). Retained in the nucleus
CC under stress stimuli including oxidative stress, nutrient deprivation
CC or nitric oxide (PubMed:21196578). Methylated form is nuclear
CC (PubMed:18951090). PPIA/CYPA stimulates its nuclear accumulation (By
CC similarity). Deacetylation by SIRT6, promotes its translocation into
CC the cytoplasm (PubMed:27457971). {ECO:0000250|UniProtKB:Q12778,
CC ECO:0000269|PubMed:18951090, ECO:0000269|PubMed:19965929,
CC ECO:0000269|PubMed:20061393, ECO:0000269|PubMed:21196578,
CC ECO:0000269|PubMed:22298775, ECO:0000269|PubMed:27457971,
CC ECO:0000269|PubMed:32103177}.
CC -!- TISSUE SPECIFICITY: Expressed in liver, white and brown adipose tissues
CC (at protein level). {ECO:0000269|PubMed:17627282,
CC ECO:0000269|PubMed:22510882}.
CC -!- DEVELOPMENTAL STAGE: In liver, barely expressed at 14.5 dpc, expression
CC dramatically increases at 18.5 dpc. Abundantly expressed in neonate
CC liver but levels strongly decrease in adult liver (at protein level).
CC {ECO:0000269|PubMed:17627282}.
CC -!- INDUCTION: Expression is regulated by KRIT1 (PubMed:20668652).
CC Transiently up-regulated during adipogenesis (at protein level)
CC (PubMed:18388859). {ECO:0000269|PubMed:18388859,
CC ECO:0000269|PubMed:20668652}.
CC -!- PTM: Phosphorylation by NLK promotes nuclear export and inhibits the
CC transcriptional activity. In response to growth factors,
CC phosphorylation on Thr-24, Ser-253 and Ser-319 by PKB/AKT1 promotes
CC nuclear export and inactivation of transactivational activity.
CC Phosphorylation on Thr-24 is required for binding 14-3-3 proteins.
CC Phosphorylation of Ser-253 decreases DNA-binding activity and promotes
CC the phosphorylation of Thr-24 and Ser-316, permitting phosphorylation
CC of Ser-319 and Ser-322, probably by CDK1, leading to nuclear exclusion
CC and loss of function. Stress signals, such as response to oxygen or
CC nitric oxide, attenuate the PKB/AKT1-mediated phosphorylation leading
CC to nuclear retention. Phosphorylation of Ser-326 is independent of IGF1
CC and leads to reduced function. Dephosphorylated on Thr-24 and Ser-253
CC by PP2A in beta-cells under oxidative stress leading to nuclear
CC retention (By similarity). Phosphorylation of Ser-246 by CDK1 disrupts
CC binding of 14-3-3 proteins leading to nuclear accumulation and has no
CC effect on DNA-binding nor transcriptional activity. Phosphorylation by
CC STK4/MST1 on Ser-209, upon oxidative stress, inhibits binding to 14-3-3
CC proteins and nuclear export (By similarity). PPIA/CYPA promotes its
CC dephosphorylation on Ser-253 (By similarity).
CC {ECO:0000250|UniProtKB:Q12778, ECO:0000269|PubMed:10347145,
CC ECO:0000269|PubMed:16076959, ECO:0000269|PubMed:19965929,
CC ECO:0000269|PubMed:20519497}.
CC -!- PTM: Ubiquitinated, leading to proteasomal degradation
CC (PubMed:28790135). Ubiquitinated by SKP2 (By similarity). {ECO:0000250,
CC ECO:0000269|PubMed:28790135}.
CC -!- PTM: Methylation inhibits PKB/AKT1-mediated phosphorylation at Ser-253,
CC promoting nuclear retention and increasing the transcriptional activity
CC and cell death. Methylation increased by oxidative stress.
CC {ECO:0000269|PubMed:10347145, ECO:0000269|PubMed:16076959,
CC ECO:0000269|PubMed:18951090, ECO:0000269|PubMed:19965929,
CC ECO:0000269|PubMed:20519497}.
CC -!- PTM: Acetylation at Lys-259 and Lys-271 are necessary for autophagic
CC cell death induction (By similarity). Deacetylated by SIRT2 in response
CC to oxidative stress or serum deprivation, thereby negatively regulating
CC FOXO1-mediated autophagic cell death (By similarity). Once in the
CC nucleus, acetylated by CREBBP/EP300 (By similarity). Acetylation
CC diminishes the interaction with target DNA and attenuates the
CC transcriptional activity. It increases the phosphorylation at Ser-253,
CC and is required for the transcriptional inhibition by FCOR (By
CC similarity). Deacetylation by SIRT1 results in reactivation of the
CC transcriptional activity (PubMed:15220471, PubMed:16076959,
CC PubMed:17090532). Acetylation of FOXO1 diminishes its binding to PPARG
CC in adipocytes. Deacetylated by SIRT2; deacetylation of FOXO1 directly
CC increases its repressive binding to PPARG and inhibits adipocyte
CC differentiation (PubMed:17681146, PubMed:19037106, PubMed:20519497,
CC PubMed:21196578). Oxidative stress by hydrogen peroxide treatment
CC appears to promote deacetylation and uncoupling of insulin-induced
CC phosphorylation (By similarity). By contrast, resveratrol acts
CC independently of acetylation (By similarity). Acetylated at Lys-420,
CC promoting its localization to the nucleus and transcription factor
CC activity (PubMed:25009184). Deacetylation at Lys-420 by SIRT6, promotes
CC its translocation into the cytoplasm, preventing its transcription
CC factor activity (PubMed:25009184, PubMed:27457971). Deacetylation and
CC subsequent inhibition by SIRT6 has different effects depending on cell
CC types: it inhibits gluconeogenesis in hepatocytes, promotes glucose
CC sensing in pancreatic beta-cells and regulates lipid catabolism in
CC brown adipocytes (PubMed:25009184, PubMed:27457971, PubMed:31442424).
CC {ECO:0000250|UniProtKB:Q12778, ECO:0000269|PubMed:15220471,
CC ECO:0000269|PubMed:16076959, ECO:0000269|PubMed:17090532,
CC ECO:0000269|PubMed:17681146, ECO:0000269|PubMed:19037106,
CC ECO:0000269|PubMed:20519497, ECO:0000269|PubMed:21196578,
CC ECO:0000269|PubMed:25009184, ECO:0000269|PubMed:27457971,
CC ECO:0000269|PubMed:31442424}.
CC -!- DISRUPTION PHENOTYPE: Null mice die around embryonic day 11 and exhibit
CC abnormal angiogenesis. Defects are observed in branchial arches and
CC there is remarkably impaired vascular development of embryos and yolk
CC sacs. Exogeneous VEGF on FOX1-deficient endothelial cells show markedly
CC different morphological response. Active osteocalcin/BGLAP as well as
CC serum insulin and beta-cell and gonadal fat levels were increased, but
CC there is no change in total fat content, lean mass, and body weight.
CC Effect on RUNX2 activity was inhibited. FOXO1 and ATF4 double happlo-
CC insufficient mice exhibit also an increase in insulin levels and beta
CC cell proliferation, but there is an increase in insulin sensitivity
CC demonstrated by an increase in expression of insulin-sensitizing
CC hormone adiponectin. Gonadal fat levels and adipocyte numbers were
CC decreased. Osteocalcin/BGLAP levels were unchanged.
CC {ECO:0000269|PubMed:15184386, ECO:0000269|PubMed:22298775}.
CC -!- MISCELLANEOUS: In an animal model of diabetes mellitus type 2 (db/db
CC mice), beta-cell islets exhibit increased levels of PPP2R1A leading to
CC increased dephosphorylation at Thr-24 and Ser-253 and nuclear retention
CC of FOXO1.
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DR EMBL; AF126056; AAD40636.1; -; mRNA.
DR EMBL; AJ252157; CAB86873.1; -; mRNA.
DR EMBL; AK137629; BAE23437.1; -; mRNA.
DR EMBL; AK154041; BAE32333.1; -; mRNA.
DR EMBL; CH466530; EDL35224.1; -; Genomic_DNA.
DR CCDS; CCDS17343.1; -.
DR RefSeq; NP_062713.2; NM_019739.3.
DR AlphaFoldDB; Q9R1E0; -.
DR SMR; Q9R1E0; -.
DR BioGRID; 207997; 10.
DR CORUM; Q9R1E0; -.
DR IntAct; Q9R1E0; 16.
DR MINT; Q9R1E0; -.
DR STRING; 10090.ENSMUSP00000055308; -.
DR iPTMnet; Q9R1E0; -.
DR PhosphoSitePlus; Q9R1E0; -.
DR SwissPalm; Q9R1E0; -.
DR EPD; Q9R1E0; -.
DR jPOST; Q9R1E0; -.
DR MaxQB; Q9R1E0; -.
DR PaxDb; Q9R1E0; -.
DR PeptideAtlas; Q9R1E0; -.
DR PRIDE; Q9R1E0; -.
DR ProteomicsDB; 267403; -.
DR Antibodypedia; 645; 2175 antibodies from 53 providers.
DR DNASU; 56458; -.
DR Ensembl; ENSMUST00000053764; ENSMUSP00000055308; ENSMUSG00000044167.
DR GeneID; 56458; -.
DR KEGG; mmu:56458; -.
DR UCSC; uc008pei.2; mouse.
DR CTD; 2308; -.
DR MGI; MGI:1890077; Foxo1.
DR VEuPathDB; HostDB:ENSMUSG00000044167; -.
DR eggNOG; KOG2294; Eukaryota.
DR GeneTree; ENSGT00940000161558; -.
DR HOGENOM; CLU_023456_1_1_1; -.
DR InParanoid; Q9R1E0; -.
DR OMA; SMNPLPQ; -.
DR OrthoDB; 1160384at2759; -.
DR PhylomeDB; Q9R1E0; -.
DR TreeFam; TF315583; -.
DR Reactome; R-MMU-198693; AKT phosphorylates targets in the nucleus.
DR Reactome; R-MMU-211163; AKT-mediated inactivation of FOXO1A.
DR Reactome; R-MMU-5687128; MAPK6/MAPK4 signaling.
DR Reactome; R-MMU-9614399; Regulation of localization of FOXO transcription factors.
DR Reactome; R-MMU-9617629; Regulation of FOXO transcriptional activity by acetylation.
DR Reactome; R-MMU-9617828; FOXO-mediated transcription of cell cycle genes.
DR BioGRID-ORCS; 56458; 3 hits in 76 CRISPR screens.
DR ChiTaRS; Foxo1; mouse.
DR PRO; PR:Q9R1E0; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; Q9R1E0; protein.
DR Bgee; ENSMUSG00000044167; Expressed in secondary oocyte and 264 other tissues.
DR Genevisible; Q9R1E0; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0008013; F:beta-catenin binding; ISO:MGI.
DR GO; GO:0031490; F:chromatin DNA binding; IDA:MGI.
DR GO; GO:0003677; F:DNA binding; IDA:MGI.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:UniProtKB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IDA:MGI.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:UniProtKB.
DR GO; GO:1990841; F:promoter-specific chromatin binding; IDA:MGI.
DR GO; GO:0051721; F:protein phosphatase 2A binding; IDA:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:GO_Central.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:MGI.
DR GO; GO:0001223; F:transcription coactivator binding; ISO:MGI.
DR GO; GO:0008134; F:transcription factor binding; IPI:GO_Central.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0006915; P:apoptotic process; ISS:UniProtKB.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR GO; GO:0001568; P:blood vessel development; IMP:MGI.
DR GO; GO:0060070; P:canonical Wnt signaling pathway; IGI:MGI.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0071549; P:cellular response to dexamethasone stimulus; IEA:Ensembl.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:UniProtKB.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IEA:Ensembl.
DR GO; GO:0071455; P:cellular response to hyperoxia; ISS:UniProtKB.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IDA:UniProtKB.
DR GO; GO:0071732; P:cellular response to nitric oxide; IDA:UniProtKB.
DR GO; GO:0034599; P:cellular response to oxidative stress; IDA:UniProtKB.
DR GO; GO:0009267; P:cellular response to starvation; ISS:UniProtKB.
DR GO; GO:0070166; P:enamel mineralization; IEA:Ensembl.
DR GO; GO:0042593; P:glucose homeostasis; IDA:MGI.
DR GO; GO:0008286; P:insulin receptor signaling pathway; IMP:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IGI:MGI.
DR GO; GO:1903243; P:negative regulation of cardiac muscle hypertrophy in response to stress; ISS:UniProtKB.
DR GO; GO:0045599; P:negative regulation of fat cell differentiation; IMP:UniProtKB.
DR GO; GO:0046676; P:negative regulation of insulin secretion; IDA:UniProtKB.
DR GO; GO:0032873; P:negative regulation of stress-activated MAPK cascade; ISO:MGI.
DR GO; GO:0097150; P:neuronal stem cell population maintenance; IGI:MGI.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:0010508; P:positive regulation of autophagy; ISS:UniProtKB.
DR GO; GO:0045722; P:positive regulation of gluconeogenesis; IMP:MGI.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; ISS:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:MGI.
DR GO; GO:0042127; P:regulation of cell population proliferation; IMP:MGI.
DR GO; GO:0006111; P:regulation of gluconeogenesis; IMP:MGI.
DR GO; GO:2000177; P:regulation of neural precursor cell proliferation; IGI:MGI.
DR GO; GO:2000377; P:regulation of reactive oxygen species metabolic process; IGI:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:GO_Central.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:MGI.
DR GO; GO:0070542; P:response to fatty acid; IDA:UniProtKB.
DR GO; GO:1902617; P:response to fluoride; IEA:Ensembl.
DR CDD; cd00059; FH; 1.
DR Gene3D; 1.10.10.10; -; 1.
DR InterPro; IPR001766; Fork_head_dom.
DR InterPro; IPR032067; FOXO-TAD.
DR InterPro; IPR032068; FOXO_KIX-bd.
DR InterPro; IPR030456; TF_fork_head_CS_2.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR Pfam; PF00250; Forkhead; 1.
DR Pfam; PF16676; FOXO-TAD; 1.
DR Pfam; PF16675; FOXO_KIX_bdg; 1.
DR PRINTS; PR00053; FORKHEAD.
DR SMART; SM00339; FH; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR PROSITE; PS00658; FORK_HEAD_2; 1.
DR PROSITE; PS50039; FORK_HEAD_3; 1.
PE 1: Evidence at protein level;
KW Acetylation; Activator; Apoptosis; Autophagy; Cytoplasm; Differentiation;
KW DNA-binding; Methylation; Nucleus; Phosphoprotein; Reference proteome;
KW Transcription; Transcription regulation; Ubl conjugation.
FT CHAIN 1..652
FT /note="Forkhead box protein O1"
FT /id="PRO_0000091873"
FT DNA_BIND 156..232
FT /note="Fork-head"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00089"
FT REGION 1..62
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 112..154
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 208..215
FT /note="DNA-binding"
FT /evidence="ECO:0000250|UniProtKB:Q12778"
FT REGION 231..342
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 231..234
FT /note="DNA-binding"
FT /evidence="ECO:0000250|UniProtKB:Q12778"
FT REGION 280..562
FT /note="Sufficient for interaction with NLK"
FT /evidence="ECO:0000269|PubMed:20061393"
FT REGION 360..456
FT /note="Required for interaction with RUNX2"
FT /evidence="ECO:0000269|PubMed:21471200"
FT REGION 383..410
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 248..250
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250"
FT MOTIF 459..463
FT /note="Required for interaction with SIRT1"
FT /evidence="ECO:0000269|PubMed:15220471"
FT COMPBIAS 27..46
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 112..136
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 277..327
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 155
FT /note="DNA-binding"
FT /evidence="ECO:0000250|UniProtKB:Q12778"
FT SITE 162
FT /note="DNA-binding"
FT /evidence="ECO:0000250|UniProtKB:Q12778"
FT SITE 222
FT /note="DNA-binding"
FT /evidence="ECO:0000250|UniProtKB:Q12778"
FT MOD_RES 24
FT /note="Phosphothreonine; by PKB/AKT1 or PKB/AKT2 and SGK1"
FT /evidence="ECO:0000269|PubMed:10347145,
FT ECO:0000269|PubMed:19965929, ECO:0000269|PubMed:20519497"
FT MOD_RES 209
FT /note="Phosphoserine; by STK4/MST1"
FT /evidence="ECO:0000250|UniProtKB:Q12778"
FT MOD_RES 215
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q12778"
FT MOD_RES 231
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q12778"
FT MOD_RES 232
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q12778"
FT MOD_RES 242
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:15220471,
FT ECO:0000269|PubMed:16076959, ECO:0000269|PubMed:17090532"
FT MOD_RES 245
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:15220471,
FT ECO:0000269|PubMed:16076959, ECO:0000269|PubMed:17090532"
FT MOD_RES 246
FT /note="Phosphoserine; by CDK1"
FT /evidence="ECO:0000250|UniProtKB:Q12778"
FT MOD_RES 248
FT /note="Omega-N-methylarginine; by PRMT1"
FT /evidence="ECO:0000269|PubMed:18951090"
FT MOD_RES 250
FT /note="Omega-N-methylarginine; by PRMT1"
FT /evidence="ECO:0000269|PubMed:18951090"
FT MOD_RES 253
FT /note="Phosphoserine; by PKB/AKT1 and SGK1"
FT /evidence="ECO:0000269|PubMed:10347145,
FT ECO:0000269|PubMed:16076959, ECO:0000269|PubMed:18388859,
FT ECO:0000269|PubMed:19965929, ECO:0000269|PubMed:20519497"
FT MOD_RES 259
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q12778"
FT MOD_RES 262
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:15220471,
FT ECO:0000269|PubMed:16076959, ECO:0000269|PubMed:17090532"
FT MOD_RES 271
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q12778"
FT MOD_RES 284
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 295
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 316
FT /note="Phosphoserine; by PKB/AKT1 or PKB/AKT2"
FT /evidence="ECO:0000269|PubMed:10347145"
FT MOD_RES 319
FT /note="Phosphoserine; by CK1 and SGK1"
FT /evidence="ECO:0000269|PubMed:19965929"
FT MOD_RES 322
FT /note="Phosphoserine; by CK1"
FT /evidence="ECO:0000250|UniProtKB:Q12778"
FT MOD_RES 326
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 330
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 420
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q12778"
FT MUTAGEN 24
FT /note="T->A: Decreases insulin-induced phosphorylation by
FT approximately 30%. Nuclear location but transcriptional
FT activity decreased by about 50%. Abolishes the SIRT1
FT deacetylase binding and increases acetylation; when
FT associated with A-253; A-316; A-462 and A-463. Increased
FT insulin-induced phosphorylation at Ser-253 and binding of
FT 14-3-3 proteins; when associated with Q-219; Q-242; Q-245;
FT Q-259; Q-262; Q-271 and Q-291. Increased binding of 14-3-3
FT proteins even with decreased insulin-induced
FT phosphorylation at Ser-253; when associated with R-219; R-
FT 242; R-245; R-259; R-262; R-271 and R-291."
FT /evidence="ECO:0000269|PubMed:10347145,
FT ECO:0000269|PubMed:16917544, ECO:0000269|PubMed:20519497"
FT MUTAGEN 29
FT /note="R->K: Little change in levels of methylation; when
FT associated with K-147; K-154; K-311 and K-313."
FT /evidence="ECO:0000269|PubMed:18951090"
FT MUTAGEN 147
FT /note="R->K: Little change in levels of methylation; when
FT associated with K-29; K-154; K-311 and K-313."
FT /evidence="ECO:0000269|PubMed:18951090"
FT MUTAGEN 154
FT /note="R->K: Little change in levels of methylation; when
FT associated with K-29; K-147; K-311 and K-313."
FT /evidence="ECO:0000269|PubMed:18951090"
FT MUTAGEN 206
FT /note="W->G: Loss of interaction with CEBPA."
FT /evidence="ECO:0000269|PubMed:17627282"
FT MUTAGEN 212
FT /note="H->P: Loss of interaction with CEBPA."
FT /evidence="ECO:0000269|PubMed:17627282"
FT MUTAGEN 219
FT /note="K->Q: Mimics acetylation. Cytoplasmic location in
FT absence or presence of insulin, no change on the inhibitory
FT effect of oxidative stress on insulin-induced
FT phosphorylations, but no inhibition of these
FT phosphorylations by resveratrol; when associated with Q-
FT 242; Q-245; Q-259; Q-262; Q-271 and Q-291. Increased
FT insulin-induced phosphorylation at Ser-253 and binding of
FT 14-3-3 proteins; when associated with A-24; Q-242; Q-245;
FT Q-259; Q-262; Q-271 and Q-291."
FT /evidence="ECO:0000269|PubMed:20519497"
FT MUTAGEN 219
FT /note="K->R: Translocates to the cytoplasm after insulin-
FT stimulation. No change on the inhibitory effect of
FT oxidative stress on insulin-induced phosphorylations, but
FT no inhibition of these phosphorylations by resveratrol;
FT when associated with R-242; R-245; R-259; R-262; R-271 and
FT R-291. Increased binding of 14-3-3 proteins even with
FT decreased insulin-induced phosphorylation at Ser-253; when
FT associated with A-24; R-242; R-245; R-259; R-262; R-271 and
FT R-291."
FT /evidence="ECO:0000269|PubMed:20519497"
FT MUTAGEN 242
FT /note="K->Q,A: Mimics acetylation. Cytoplasmic location in
FT absence or presence of insulin. Decreased DNA-binding by
FT about half. Enhanced phosphorylation by PKB/AKT1, no effect
FT on interaction with CEBPA; when associated with either A-
FT 245 or Q-245 and either A-262 or Q-262. either A-262 or Q-
FT 262. Cytoplasmic location in absence or presence of
FT insulin, no change on the inhibitory effect of oxidative
FT stress on insulin-induced phosphorylations, but no
FT inhibition of these phosphorylations by resveratrol; when
FT associated with Q-219; Q-245; Q-259; Q-262; Q-271 and Q-
FT 291. Increased insulin-induced phosphorylation at Ser-253
FT and binding of 14-3-3 proteins; when associated with A-24;
FT Q-219; Q-245; Q-259; Q-262; Q-271 and Q-291."
FT /evidence="ECO:0000269|PubMed:15220471,
FT ECO:0000269|PubMed:16076959, ECO:0000269|PubMed:17090532,
FT ECO:0000269|PubMed:20519497, ECO:0000269|PubMed:22510882"
FT MUTAGEN 242
FT /note="K->R: Reduced acetylation and transcriptional
FT activity increased by about 1.5 fold. Completely abolishes
FT acetylation, increases interaction with CEBPA and
FT transcriptional activity increased by about 3-fold; when
FT associated with R-245 and R-262. Transcriptional activity
FT not inhibited by FCOR; when associated with R-245; R-259;
FT R-262; R-271 and R-291. Predominantly nuclear and
FT translocates to the cytoplasm on insulin-stimulation. No
FT change on the inhibitory effect of oxidative stress on
FT insulin-induced phosphorylations, but no inhibition of
FT these phosphorylations by resveratrol; when associated with
FT R-219; R-245; R-259; R-262; R-271 and R-291. Increased
FT binding of 14-3-3 proteins even with decreased insulin-
FT induced phosphorylation at Ser-253; when associated with A-
FT 24; R-219; R-245; R-259; R-262; R-271 and R-291."
FT /evidence="ECO:0000269|PubMed:15220471,
FT ECO:0000269|PubMed:16076959, ECO:0000269|PubMed:17090532,
FT ECO:0000269|PubMed:20519497, ECO:0000269|PubMed:22510882"
FT MUTAGEN 245
FT /note="K->Q,A: Mimics acetylation. Decreased DNA-binding by
FT about half. Enhanced phosphorylation by PKB/AKT1, no effect
FT on interaction with CEBPA; when associated with either A-
FT 242 or Q-242 and either A-262 or Q-262. Cytoplasmic
FT location in absence or presence of insulin, no change on
FT the inhibitory effect of oxidative stress on insulin-
FT induced phosphorylations, but no inhibition of these
FT phosphorylations by resveratrol; when associated with Q-
FT 219; Q-242; Q-259; Q-262; Q-271 and Q-291. Increased
FT insulin-induced phosphorylation at Ser-253 and binding of
FT 14-3-3 proteins; when associated with A-24; Q-219; Q-242;
FT Q-259; Q-262; Q-271 and Q-291."
FT /evidence="ECO:0000269|PubMed:15220471,
FT ECO:0000269|PubMed:16076959, ECO:0000269|PubMed:17090532,
FT ECO:0000269|PubMed:20519497, ECO:0000269|PubMed:22510882"
FT MUTAGEN 245
FT /note="K->R: Reduced acetylation and transcriptional
FT activity increased by about 1.5-fold. Completely abolishes
FT acetylation, increases interaction with CEBPA and
FT transcriptional activity increased by about 3-fold; when
FT associated with R-242 and R-262. Transcriptional activity
FT not inhibited by FCOR; when associated with R-242; R-259;
FT R-262; R-271 and R-291. Predominantly nuclear and
FT translocates to the cytoplasm on insulin-stimulation. No
FT change on the inhibitory effect of oxidative stress on
FT insulin-induced phosphorylations, but no inhibition of
FT these phosphorylations by resveratrol; when associated with
FT R-219; R-242; R-259; R-262; R-271 and R-291. Increased
FT binding of 14-3-3 proteins even with decreased insulin-
FT induced phosphorylation at Ser-253; when associated with A-
FT 24; R-219; R-242; R-259; R-262; R-271 and R-291."
FT /evidence="ECO:0000269|PubMed:15220471,
FT ECO:0000269|PubMed:16076959, ECO:0000269|PubMed:17090532,
FT ECO:0000269|PubMed:20519497, ECO:0000269|PubMed:22510882"
FT MUTAGEN 248
FT /note="R->K: Some decrease in levels of methylation.
FT Greatly decreased methylation levels; when associated with
FT K-250."
FT /evidence="ECO:0000269|PubMed:18951090"
FT MUTAGEN 249
FT /note="R->K: No change in methylation levels."
FT /evidence="ECO:0000269|PubMed:18951090"
FT MUTAGEN 250
FT /note="R->K: Some decrease in levels of methylation.
FT Greatly decreased methylation levels; when associated with
FT K-248."
FT /evidence="ECO:0000269|PubMed:18951090"
FT MUTAGEN 253
FT /note="S->A: Abolishes insulin-induced phosphorylation when
FT associated with A-463. Nuclear location but transcriptional
FT activity decreased by about 50%. Abolishes the SIRT1
FT deacetylase binding and increases acetylation; when
FT associated with A-24; A-316; A-462 and A-463."
FT /evidence="ECO:0000269|PubMed:10347145,
FT ECO:0000269|PubMed:16076959, ECO:0000269|PubMed:16917544,
FT ECO:0000269|PubMed:20519497"
FT MUTAGEN 259
FT /note="K->Q: Mimics acetylation. Cytoplasmic location in
FT absence or presence of insulin, no change on the inhibitory
FT effect of oxidative stress on insulin-induced
FT phosphorylations, but no inhibition of these
FT phosphorylations by resveratrol; when associated with Q-
FT 219; Q-242; Q-245; Q-262; Q-271 and Q-291. Increased
FT insulin-induced phosphorylation at Ser-253 and binding of
FT 14-3-3 proteins; when associated with A-24; Q-219; Q-242;
FT Q-245; Q-262; Q-271 and Q-291."
FT /evidence="ECO:0000269|PubMed:20519497,
FT ECO:0000269|PubMed:22510882"
FT MUTAGEN 259
FT /note="K->R: Transcriptional activity not inhibited by
FT FCOR; when associated with R-242; R-245; R-262; R-271 and
FT R-291. Predominantly nuclear and translocates to the
FT cytoplasm on insulin-stimulation. No change on the
FT inhibitory effect of oxidative stress on insulin-induced
FT phosphorylations, but no inhibition of these
FT phosphorylations by resveratrol; when associated with R-
FT 219; R-242; R-245; R-262; R-271 and R-291. Increased
FT binding of 14-3-3 proteins even with decreased insulin-
FT induced phosphorylation at Ser-253; when associated with A-
FT 24; R-219; R-242; R-245; R-262; R-271 and R-291."
FT /evidence="ECO:0000269|PubMed:20519497,
FT ECO:0000269|PubMed:22510882"
FT MUTAGEN 262
FT /note="K->Q,A: Mimics acetylation. Decreased DNA-binding by
FT about half and enhanced phosphorylation by PKB/AKT1, no
FT effect on interaction with CEBPA; when associated with
FT either A-242 or Q-242 and either A-245 or Q-245.
FT Cytoplasmic location in absence or presence of insulin, no
FT change on the inhibitory effect of oxidative stress on
FT insulin-induced phosphorylations, but no inhibition of
FT these phosphorylations by resveratrol; when associated with
FT Q-219; Q-242; Q-245; Q-259; Q-271 and Q-291. Increased
FT insulin-induced phosphorylation at Ser-253 and binding of
FT 14-3-3 proteins; when associated with A-24; Q-219; Q-242;
FT Q-245; Q-259; Q-271 and Q-291."
FT /evidence="ECO:0000269|PubMed:15220471,
FT ECO:0000269|PubMed:16076959, ECO:0000269|PubMed:17090532,
FT ECO:0000269|PubMed:20519497, ECO:0000269|PubMed:22510882"
FT MUTAGEN 262
FT /note="K->R: Significant reduction in acetylation and
FT transcriptional activity increased by about 2.0 fold.
FT Completely abolishes acetylation, increases interaction
FT with CEBPA and transcriptional activity increased by about
FT 3-fold; when associated with R-242 and R-245.
FT Transcriptional activity not inhibited by FCOR; when
FT associated with R-242; R-245; R-259; R-271 and R-291.
FT Predominantly nuclear and translocates to the cytoplasm on
FT insulin-stimulation. No change on the inhibitory effect of
FT oxidative stress on insulin-induced phosphorylations, but
FT no inhibition of these phosphorylations by resveratrol;
FT when associated with R-219; R-242; R-245; R-259; R-271 and
FT R-291. Increased binding of 14-3-3 proteins even with
FT decreased insulin-induced phosphorylation at Ser-253; when
FT associated with A-24; R-219; R-242; R-245; R-259; R-271 and
FT R-291."
FT /evidence="ECO:0000269|PubMed:15220471,
FT ECO:0000269|PubMed:16076959, ECO:0000269|PubMed:17090532,
FT ECO:0000269|PubMed:20519497, ECO:0000269|PubMed:22510882"
FT MUTAGEN 271
FT /note="K->Q: Mimics acetylation. Cytoplasmic location in
FT absence or presence of insulin, no change on the inhibitory
FT effect of oxidative stress on insulin-induced
FT phosphorylations, but no inhibition of these
FT phosphorylations by resveratrol; when associated with Q-
FT 219; Q-242; Q-245; Q-259; Q-262 and Q-291. Increased
FT insulin-induced phosphorylation at Ser-253 and binding of
FT 14-3-3 proteins; when associated with A-24; Q-219; Q-242;
FT Q-245; Q-259; Q-262 and Q-291."
FT /evidence="ECO:0000269|PubMed:20519497,
FT ECO:0000269|PubMed:22510882"
FT MUTAGEN 271
FT /note="K->R: Transcriptional activity not inhibited by
FT FCOR; when associated with R-242; R-245; R-259; R-262 and
FT R-291. Predominantly nuclear and translocates to the
FT cytoplasm on insulin-stimulation. No inhibitory effect of
FT oxidative stress on insulin-induced phosphorylations, but
FT no inhibition of these phosphorylations by resveratrol;
FT when associated with R-219; R-242; R-245; R-259; R-262 and
FT R-291. Increased binding of 14-3-3 proteins even with
FT decreased insulin-induced phosphorylation at Ser-253; when
FT associated with A-24; R-219; R-242; R-245; R-259; R-262 and
FT R-291."
FT /evidence="ECO:0000269|PubMed:20519497,
FT ECO:0000269|PubMed:22510882"
FT MUTAGEN 284
FT /note="S->A: Decreases phosphorylation by NLK; when
FT associated with A-295; A-326; A-380; A-391; A-399; A-413
FT and A-415."
FT /evidence="ECO:0000269|PubMed:20061393"
FT MUTAGEN 291
FT /note="K->Q: Mimics acetylation. Cytoplasmic location in
FT absence or presence of insulin, no change on the inhibitory
FT effect of oxidative stress on insulin-induced
FT phosphorylations, but no inhibition of these
FT phosphorylations by resveratrol; when associated with Q-
FT 219; Q-242; Q-245; Q-259; Q-262 and Q-271. Increased
FT insulin-induced phosphorylation at Ser-253 and binding of
FT 14-3-3 proteins; when associated with A-24: Q-219; Q-242;
FT Q-245; Q-259; Q-262 and Q-271."
FT /evidence="ECO:0000269|PubMed:20519497,
FT ECO:0000269|PubMed:22510882"
FT MUTAGEN 291
FT /note="K->R: Transcriptional activity not inhibited by
FT FCOR; when associated with R-242; R-245; R-259; R-262 and
FT R-271. Predominantly nuclear and translocates to the
FT cytoplasm on insulin-stimulation. No inhibitory effect of
FT oxidative stress on insulin-induced phosphorylations, but
FT no inhibition of these phosphorylations by resveratrol;
FT when associated with R-219; R-242; R-245; R-259; R-262 and
FT R-271. Increased binding of 14-3-3 proteins even with
FT decreased insulin-induced phosphorylation at Ser-253; when
FT associated with A-24; R-219; R-242; R-245; R-259; R-262 and
FT R-271."
FT /evidence="ECO:0000269|PubMed:20519497,
FT ECO:0000269|PubMed:22510882"
FT MUTAGEN 295
FT /note="S->A: Decreases phosphorylation by NLK; when
FT associated with A-284; A-326; A-380; A-391; A-399; A-413
FT and A-415."
FT /evidence="ECO:0000269|PubMed:20061393"
FT MUTAGEN 311
FT /note="R->K: Little change in levels of methylation; when
FT associated with K-29; K-147; K-154 and K-313."
FT /evidence="ECO:0000269|PubMed:18951090"
FT MUTAGEN 313
FT /note="R->K: Little change in levels of methylation; when
FT associated with K-29; K-147; K-154 and K-311."
FT /evidence="ECO:0000269|PubMed:18951090"
FT MUTAGEN 316
FT /note="S->A: Decreases insulin-induced phosphorylation by
FT approximately 30%. Abolishes the SIRT1 deacetylase binding
FT and increases acetylation; when associated with A-24; A-
FT 253; A-462 and A-463."
FT /evidence="ECO:0000269|PubMed:10347145,
FT ECO:0000269|PubMed:16917544"
FT MUTAGEN 326
FT /note="S->A: Decreases phosphorylation by NLK; when
FT associated with A-284; A-295; A-380; A-391; A-399; A-413
FT and A-415."
FT /evidence="ECO:0000269|PubMed:20061393"
FT MUTAGEN 380
FT /note="S->A: Decreases phosphorylation by NLK; when
FT associated with A-284; A-295; A-326; A-391; A-399; A-413
FT and A-415."
FT /evidence="ECO:0000269|PubMed:20061393"
FT MUTAGEN 391
FT /note="S->A: Decreases phosphorylation by NLK; when
FT associated with A-284; A-295; A-326; A-380; A-399; A-413
FT and A-415."
FT /evidence="ECO:0000269|PubMed:20061393"
FT MUTAGEN 399
FT /note="T->A: Decreases phosphorylation by NLK; when
FT associated with A-284; A-295; A-326; A-380; A-391; A-413
FT and A-415."
FT /evidence="ECO:0000269|PubMed:20061393"
FT MUTAGEN 413
FT /note="S->A: Decreases phosphorylation by NLK; when
FT associated with A-284; A-295; A-326; A-380; A-391; A-399
FT and A-415."
FT /evidence="ECO:0000269|PubMed:20061393"
FT MUTAGEN 415
FT /note="S->A: Decreases phosphorylation by NLK; when
FT associated with A-284; A-295; A-326; A-380; A-391; A-399
FT and A-413."
FT /evidence="ECO:0000269|PubMed:20061393"
FT MUTAGEN 462
FT /note="L->A: Decreased transcriptional activity by about 2-
FT fold in the absence of serum; when associated with A-463.
FT Nuclear location but transcriptional activity decreased by
FT about 50%. Abolishes the SIRT1 deacetylase binding and
FT increases acetylation; when associated with A-24; A-253; A-
FT 316 and A-463."
FT /evidence="ECO:0000269|PubMed:16917544"
FT MUTAGEN 463
FT /note="L->A: Decreased transcriptional activity by about 2-
FT fold in the absence of serum; when associated with A-463.
FT Nuclear location but transcriptional activity decreased by
FT about 50%. Abolishes the SIRT1 deacetylase binding and
FT increases acetylation; when associated with A-24; A-253; A-
FT 316 and A-462."
FT /evidence="ECO:0000269|PubMed:16917544"
FT CONFLICT 619
FT /note="L -> P (in Ref. 1; AAD40636)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 652 AA; 69518 MW; 3FF58636EA85205F CRC64;
MAEAPQVVET DPDFEPLPRQ RSCTWPLPRP EFNQSNSTTS SPAPSGGAAA NPDAAASLAS
ASAVSTDFMS NLSLLEESED FARAPGCVAV AAAAAASRGL CGDFQGPEAG CVHPAPPQPP
PTGPLSQPPP VPPSAAAAAG PLAGQPRKTS SSRRNAWGNL SYADLITKAI ESSAEKRLTL
SQIYEWMVKS VPYFKDKGDS NSSAGWKNSI RHNLSLHSKF IRVQNEGTGK SSWWMLNPEG
GKSGKSPRRR AASMDNNSKF AKSRGRAAKK KASLQSGQEG PGDSPGSQFS KWPASPGSHS
NDDFDNWSTF RPRTSSNAST ISGRLSPIMT EQDDLGDGDV HSLVYPPSAA KMASTLPSLS
EISNPENMEN LLDNLNLLSS PTSLTVSTQS SPGSMMQQTP CYSFAPPNTS LNSPSPNYSK
YTYGQSSMSP LPQMPMQTLQ DSKSSYGGLN QYNCAPGLLK ELLTSDSPPH NDIMSPVDPG
VAQPNSRVLG QNVMMGPNSV MPAYGSQASH NKMMNPSSHT HPGHAQQTAS VNGRTLPHVV
NTMPHTSAMN RLTPVKTPLQ VPLSHPMQMS ALGSYSSVSS CNGYGRMGVL HQEKLPSDLD
GMFIERLDCD MESIIRNDLM DGDTLDFNFD NVLPNQSFPH SVKTTTHSWV SG
