Did you know ? If you order before Friday 14h we deliver 90PCT of the the time next Tuesday, GENTAUR another in time delivery

Forkhead box protein O1 (Forkhead box protein O1A) (Forkhead in rhabdomyosarcoma)

 FOXO1_MOUSE             Reviewed;         652 AA.
Q9R1E0; Q9JJW4;
30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
27-JUL-2011, sequence version 2.
25-OCT-2017, entry version 162.
RecName: Full=Forkhead box protein O1;
AltName: Full=Forkhead box protein O1A;
AltName: Full=Forkhead in rhabdomyosarcoma;
Name=Foxo1; Synonyms=Fkhr, Foxo1a;
Mus musculus (Mouse).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
Muroidea; Muridae; Murinae; Mus; Mus.
NCBI_TaxID=10090;
[1]
NUCLEOTIDE SEQUENCE [MRNA], PHOSPHORYLATION AT THR-24; SER-253 AND
SER-316, AND MUTAGENESIS OF THR-24; SER-253 AND SER-316.
TISSUE=Liver;
PubMed=10347145; DOI=10.1074/jbc.274.23.15982;
Nakae J., Park B.C., Accili D.;
"Insulin stimulates phosphorylation of the forkhead transcription
factor FKHR on serine 253 through a Wortmannin-sensitive pathway.";
J. Biol. Chem. 274:15982-15985(1999).
[2]
NUCLEOTIDE SEQUENCE [MRNA].
Leenders H., Benoist C., Mathis D.;
"The forkhead FKHR is involved in thymocyte proliferation.";
Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases.
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
STRAIN=C57BL/6J, and NOD; TISSUE=Thymus, and Vagina;
PubMed=16141072; DOI=10.1126/science.1112014;
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M.,
Davis M.J., Wilming L.G., Aidinis V., Allen J.E.,
Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L.,
Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M.,
Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R.,
Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G.,
di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G.,
Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M.,
Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N.,
Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T.,
Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H.,
Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K.,
Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J.,
Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L.,
Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K.,
Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P.,
Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O.,
Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G.,
Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M.,
Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B.,
Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K.,
Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A.,
Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K.,
Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C.,
Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J.,
Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y.,
Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T.,
Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N.,
Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N.,
Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S.,
Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J.,
Hayashizaki Y.;
"The transcriptional landscape of the mammalian genome.";
Science 309:1559-1563(2005).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
[5]
INTERACTION WITH PPARGC1A, FUNCTION, AND PHOSPHORYLATION.
PubMed=12754525; DOI=10.1038/nature01667;
Puigserver P., Rhee J., Donovan J., Walkey C.J., Yoon J.C.,
Oriente F., Kitamura Y., Altomonte J., Dong H., Accili D.,
Spiegelman B.M.;
"Insulin-regulated hepatic gluconeogenesis through FOXO1-PGC-1alpha
interaction.";
Nature 423:550-555(2003).
[6]
DISRUPTION PHENOTYPE, AND FUNCTION.
PubMed=15184386; DOI=10.1074/jbc.M314214200;
Furuyama T., Kitayama K., Shimoda Y., Ogawa M., Sone K.,
Yoshida-Araki K., Hisatsune H., Nishikawa S., Nakayama K.,
Nakayama K., Ikeda K., Motoyama N., Mori N.;
"Abnormal angiogenesis in Foxo1 (Fkhr)-deficient mice.";
J. Biol. Chem. 279:34741-34749(2004).
[7]
ACETYLATION AT LYS-242; LYS-245 AND LYS-262, INTERACTION WITH SIRT1,
DEACETYLATION, FUNCTION, AND MUTAGENESIS OF LYS-242; LYS-245 AND
LYS-262.
PubMed=15220471; DOI=10.1073/pnas.0400593101;
Daitoku H., Hatta M., Matsuzaki H., Aratani S., Ohshima T.,
Miyagishi M., Nakajima T., Fukamizu A.;
"Silent information regulator 2 potentiates Foxo1-mediated
transcription through its deacetylase activity.";
Proc. Natl. Acad. Sci. U.S.A. 101:10042-10047(2004).
[8]
ACETYLATION AT LYS-242; LYS-245 AND LYS-262, PHOSPHORYLATION AT
SER-253, DNA-BINDING, AND MUTAGENESIS OF LYS-242; LYS-245; SER-253 AND
LYS-262.
PubMed=16076959; DOI=10.1073/pnas.0502738102;
Matsuzaki H., Daitoku H., Hatta M., Aoyama H., Yoshimochi K.,
Fukamizu A.;
"Acetylation of Foxo1 alters its DNA-binding ability and sensitivity
to phosphorylation.";
Proc. Natl. Acad. Sci. U.S.A. 102:11278-11283(2005).
[9]
INTERACTION WITH LRPPRC.
PubMed=17050673; DOI=10.1101/gad.1483906;
Cooper M.P., Qu L., Rohas L.M., Lin J., Yang W., Erdjument-Bromage H.,
Tempst P., Spiegelman B.M.;
"Defects in energy homeostasis in Leigh syndrome French Canadian
variant through PGC-1alpha/LRP130 complex.";
Genes Dev. 20:2996-3009(2006).
[10]
FUNCTION, INTERACTION WITH CEBPA, ACETYLATION AT LYS-242; LYS-245 AND
LYS-262, DEACETYLATION BY SIRT1, DNA-BINDING, AND MUTAGENESIS OF
LYS-242; LYS-245 AND LYS-262.
PubMed=17090532; DOI=10.1074/jbc.M607215200;
Qiao L., Shao J.;
"SIRT1 regulates adiponectin gene expression through Foxo1-C/enhancer-
binding protein alpha transcriptional complex.";
J. Biol. Chem. 281:39915-39924(2006).
[11]
INTERACTION WITH SIRT1, PHOSPHORYLATION, SUBCELLULAR LOCATION,
FUNCTION, AND MUTAGENESIS OF THR-24; SER-253; SER-316; LEU-462 AND
LEU-463.
PubMed=16917544; DOI=10.1172/JCI25518;
Nakae J., Cao Y., Daitoku H., Fukamizu A., Ogawa W., Yano Y.,
Hayashi Y.;
"The LXXLL motif of murine forkhead transcription factor FoxO1
mediates Sirt1-dependent transcriptional activity.";
J. Clin. Invest. 116:2473-2483(2006).
[12]
ACETYLATION, DEACETYLATION BY SIRT2, FUNCTION IN INHIBITION OF
ADIPOCYTE DIFFERENTIATION, AND INTERACTION WITH SIRT2.
PubMed=17681146; DOI=10.1016/j.cmet.2007.07.003;
Jing E., Gesta S., Kahn C.R.;
"SIRT2 regulates adipocyte differentiation through FoxO1
acetylation/deacetylation.";
Cell Metab. 6:105-114(2007).
[13]
FUNCTION, INTERACTION WITH CEBPA, DEVELOPMENTAL STAGE, TISSUE
SPECIFICITY, SUBCELLULAR LOCATION, AND MUTAGENESIS OF TRP-206 AND
HIS-212.
PubMed=17627282; DOI=10.1038/sj.emboj.7601784;
Sekine K., Chen Y.R., Kojima N., Ogata K., Fukamizu A., Miyajima A.;
"Foxo1 links insulin signaling to C/EBPalpha and regulates
gluconeogenesis during liver development.";
EMBO J. 26:3607-3615(2007).
[14]
IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
TISSUE=Liver;
PubMed=17242355; DOI=10.1073/pnas.0609836104;
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
"Large-scale phosphorylation analysis of mouse liver.";
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
[15]
INTERACTION WITH WDFY2, COMPLEX FORMATION WITH WDFY2 AND AKT1,
SUBCELLULAR LOCATION, INDUCTION, AND PHOSPHORYLATION AT SER-253.
PubMed=18388859; DOI=10.1038/emboj.2008.67;
Fritzius T., Moelling K.;
"Akt- and Foxo1-interacting WD-repeat-FYVE protein promotes
adipogenesis.";
EMBO J. 27:1399-1410(2008).
[16]
PHOSPHORYLATION, SUBCELLULAR LOCATION, METHYLATION AT ARG-248 AND
ARG-250, AND MUTAGENESIS OF ARG-29; ARG-147; ARG-154; ARG-248;
ARG-250; ARG-311 AND ARG-313.
PubMed=18951090; DOI=10.1016/j.molcel.2008.09.013;
Yamagata K., Daitoku H., Takahashi Y., Namiki K., Hisatake K.,
Kako K., Mukai H., Kasuya Y., Fukamizu A.;
"Arginine methylation of FOXO transcription factors inhibits their
phosphorylation by Akt.";
Mol. Cell 32:221-231(2008).
[17]
ACETYLATION, DEACETYLATION BY SIRT2, INTERACTION WITH PPARG AND SIRT2,
AND SUBCELLULAR LOCATION.
PubMed=19037106; DOI=10.1091/mbc.E08-06-0647;
Wang F., Tong Q.;
"SIRT2 suppresses adipocyte differentiation by deacetylating FOXO1 and
enhancing FOXO1's repressive interaction with PPARgamma.";
Mol. Biol. Cell 20:801-808(2009).
[18]
PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-284; SER-295; SER-326
AND THR-330, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
ANALYSIS].
TISSUE=Brain, Brown adipose tissue, Kidney, Liver, Lung, Pancreas,
Spleen, and Testis;
PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
"A tissue-specific atlas of mouse protein phosphorylation and
expression.";
Cell 143:1174-1189(2010).
[19]
INTERACTION WITH NLK, SUBCELLULAR LOCATION, PHOSPHORYLATION BY NLK,
AND MUTAGENESIS OF SER-284; SER-295; SER-326; SER-380; SER-391;
THR-399; SER-413 AND SER-415.
PubMed=20061393; DOI=10.1074/jbc.M110.101824;
Kim S., Kim Y., Lee J., Chung J.;
"Regulation of FOXO1 by TAK1-Nemo-like kinase pathway.";
J. Biol. Chem. 285:8122-8129(2010).
[20]
PHOSPHORYLATION AT THR-24 AND SER-253, ACETYLATION, SUBCELLULAR
LOCATION, FUNCTION, AND MUTAGENESIS OF THR-24; LYS-219; LYS-242;
LYS-245; SER-253; LYS-259; LYS-262; LYS-271 AND LYS-291.
PubMed=20519497; DOI=10.1074/jbc.M110.140228;
Qiang L., Banks A.S., Accili D.;
"Uncoupling of acetylation from phosphorylation regulates FoxO1
function independent of its subcellular localization.";
J. Biol. Chem. 285:27396-27401(2010).
[21]
PHOSPHORYLATION AT THR-24; SER-253 AND SER-319 BY SGK1, AND
SUBCELLULAR LOCATION.
PubMed=19965929; DOI=10.1210/me.2009-0265;
Di Pietro N., Panel V., Hayes S., Bagattin A., Meruvu S., Pandolfi A.,
Hugendubler L., Fejes-Toth G., Naray-Fejes-Toth A., Mueller E.;
"Serum- and glucocorticoid-inducible kinase 1 (SGK1) regulates
adipocyte differentiation via forkhead box O1.";
Mol. Endocrinol. 24:370-380(2010).
[22]
FUNCTION, PHOSPHORYLATION, INTERACTION WITH SIRT1, AND INDUCTION.
PubMed=20668652; DOI=10.1371/journal.pone.0011786;
Goitre L., Balzac F., Degani S., Degan P., Marchi S., Pinton P.,
Retta S.F.;
"KRIT1 regulates the homeostasis of intracellular reactive oxygen
species.";
PLoS ONE 5:E11786-E11786(2010).
[23]
FUNCTION, SUBCELLULAR LOCATION, ACETYLATION, AND RESPONSE TO NITRIC
OXIDE.
PubMed=21196578; DOI=10.1074/jbc.M110.204768;
Hughes K.J., Meares G.P., Hansen P.A., Corbett J.A.;
"FoxO1 and SIRT1 regulate beta-cell responses to nitric oxide.";
J. Biol. Chem. 286:8338-8348(2011).
[24]
SUBCELLULAR LOCATION, FUNCTION, AND DNA-BINDING.
PubMed=21335550; DOI=10.1074/jbc.M110.204248;
Meur G., Qian Q., da Silva Xavier G., Pullen T.J., Tsuboi T.,
McKinnon C., Fletcher L., Tavare J.M., Hughes S., Johnson P.,
Rutter G.A.;
"Nucleo-cytosolic shuttling of FoxO1 directly regulates mouse Ins2 but
not Ins1 gene expression in pancreatic beta cells (MIN6).";
J. Biol. Chem. 286:13647-13656(2011).
[25]
INTERACTION WITH RUNX2, AND FUNCTION.
PubMed=21471200; DOI=10.1074/jbc.M110.197905;
Yang S., Xu H., Yu S., Cao H., Fan J., Ge C., Fransceschi R.T.,
Dong H.H., Xiao G.;
"Foxo1 mediates insulin-like growth factor 1 (IGF1)/insulin regulation
of osteocalcin expression by antagonizing Runx2 in osteoblasts.";
J. Biol. Chem. 286:19149-19158(2011).
[26]
INTERACTION WITH XBP1, AND SUBCELLULAR LOCATION.
PubMed=21317886; DOI=10.1038/nm.2293;
Zhou Y., Lee J., Reno C.M., Sun C., Park S.W., Chung J., Lee J.,
Fisher S.J., White M.F., Biddinger S.B., Ozcan U.;
"Regulation of glucose homeostasis through a XBP-1-FoxO1
interaction.";
Nat. Med. 17:356-365(2011).
[27]
CHARACTERISTICS OF AN ANIMAL MODEL OF DIABETES MELLITUS TYPE 2,
FUNCTION, DEPHOSPHORYLATION AT THR-24 AND SER-253, AND INTERACTION
WITH PPP2R1A.
PubMed=22417654; DOI=10.1042/BJ20111606;
Yan L., Guo S., Brault M., Harmon J., Robertson R.P., Hamid R.,
Stein R., Yang E.;
"The B55alpha-containing PP2A holoenzyme dephosphorylates FOXO1 in
islet beta-cells under oxidative stress.";
Biochem. J. 444:239-247(2012).
[28]
FUNCTION AS A TRANSCRIPTIONAL ACTIVATOR, INTERACTION WITH FCOR AND
SIRT1, TISSUE SPECIFICITY, AND MUTAGENESIS OF LYS-242; LYS-245;
LYS-259; LYS-262; LYS-271 AND LYS-291.
PubMed=22510882; DOI=10.1038/emboj.2012.97;
Nakae J., Cao Y., Hakuno F., Takemori H., Kawano Y., Sekioka R.,
Abe T., Kiyonari H., Tanaka T., Sakai J., Takahashi S., Itoh H.;
"Novel repressor regulates insulin sensitivity through interaction
with Foxo1.";
EMBO J. 31:2275-2295(2012).
[29]
DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, INTERACTION WITH ATF4, AND
FUNCTION.
PubMed=22298775; DOI=10.1074/jbc.M111.282897;
Kode A., Mosialou I., Silva B.C., Joshi S., Ferron M., Rached M.T.,
Kousteni S.;
"FoxO1 protein cooperates with ATF4 protein in osteoblasts to control
glucose homeostasis.";
J. Biol. Chem. 287:8757-8768(2012).
-!- FUNCTION: Transcription factor that is the main target of insulin
signaling and regulates metabolic homeostasis in response to
oxidative stress. Binds to the insulin response element (IRE) with
consensus sequence 5'-TT[G/A]TTTTG-3' and the related Daf-16
family binding element (DBE) with consensus sequence 5'-
TT[G/A]TTTAC-3'. Activity suppressed by insulin. Main regulator of
redox balance and osteoblast numbers and controls bone mass.
Orchestrates the endocrine function of the skeleton in regulating
glucose metabolism. Acts synergistically with ATF4 to suppress
osteocalcin/BGLAP activity, increasing glucose levels and
triggering glucose intolerance and insulin insensitivity. Also
suppresses the transcriptional activity of RUNX2, an upstream
activator of osteocalcin/BGLAP. In hepatocytes, promotes
gluconeogenesis by acting together with PPARGC1A and CEBPA to
activate the expression of genes such as IGFBP1, G6PC and PCK1.
Important regulator of cell death acting downstream of CDK1,
PKB/AKT1 and SKT4/MST1. Promotes neural cell death. Mediates
insulin action on adipose tissue. Regulates the expression of
adipogenic genes such as PPARG during preadipocyte differentiation
and, adipocyte size and adipose tissue-specific gene expression in
response to excessive calorie intake. Regulates the
transcriptional activity of GADD45A and repair of nitric oxide-
damaged DNA in beta-cells. Required for the autophagic cell death
induction in response to starvation or oxidative stress in a
transcription-independent manner. Mediates the function of MLIP in
cardiomyocytes hypertrophy and cardiac remodeling (By similarity).
{ECO:0000250|UniProtKB:G3V7R4, ECO:0000269|PubMed:12754525,
ECO:0000269|PubMed:15184386, ECO:0000269|PubMed:15220471,
ECO:0000269|PubMed:16917544, ECO:0000269|PubMed:17090532,
ECO:0000269|PubMed:17627282, ECO:0000269|PubMed:17681146,
ECO:0000269|PubMed:20519497, ECO:0000269|PubMed:20668652,
ECO:0000269|PubMed:21196578, ECO:0000269|PubMed:21335550,
ECO:0000269|PubMed:21471200, ECO:0000269|PubMed:22298775,
ECO:0000269|PubMed:22417654, ECO:0000269|PubMed:22510882}.
-!- SUBUNIT: Interacts with EP300 and CREBBP; the interactions
acetylate FOXO1. Interacts with the 14-3-3 proteins, YWHAG and
YWHAZ; the interactions require insulin-stimulated phosphorylation
on Thr-24, promote nuclear exit and loss of transcriptional
activity. Interacts with SKP2; the interaction ubiquitinates FOXO1
leading to its proteosomal degradation. Interacts with PMRT1;
methylates FOXO1, prevents PKB/AKT1 phosphorylation and retains
FOXO1 in the nucleus (By similarity). Interacts (via an N-terminal
domain) with FCOR; the interaction is direct, occurs in a
forskolin-independent manner and prevents SIRT1 binding to FOXO1.
Interacts (via the C-terminal half) with ATF4 (via its DNA-binding
domain); the interaction occurs in osteoblasts, regulates glucose
homeostasis via suppression of beta-cell proliferation and
subsequent decrease in insulin production. Interacts with RUNX2;
the interaction inhibits RUNX2 transcriptional activity and
mediates the IGF1/insulin-dependent BGLAP expression in
osteoblasts. Interacts with PPP2R1A; the interaction regulates the
dephosphorylation of FOXO1 at Thr-24 and Ser-253 leading to its
nuclear import. Binds to CDK1. Interacts with LRPPRC. Interacts
with RUNX2; the interaction inhibits RUNX2 transcriptional
activity and mediates the IGF1/insulin-dependent BGLAP expression
in osteoblasts. Interacts with NLK. Interacts with SIRT1; the
interaction results in the deacetylation of FOXO1 leading to
activation of FOXO1-mediated transcription of genes involved in
DNA repair and stress resistance. The interaction requires the
presence of KRIT1 and is inhibited by FCOR. Interacts with SIRT2;
the interaction is disrupted in response to oxidative stress or
serum deprivation, leading to increased level of acetylated FOXO1,
which promotes stress-induced autophagy by stimulating E1-like
activating enzyme ATG7. Interacts (acetylated form) with ATG7; the
interaction is increased in response to oxidative stress or serum
deprivation and promotes the autophagic process leading to cell
death. Interacts (acetylated form) with PPARG (PubMed:12754525,
PubMed:15220471, PubMed:16917544, PubMed:17050673,
PubMed:17681146, PubMed:19037106, PubMed:20061393,
PubMed:20668652, PubMed:21471200, PubMed:22298775,
PubMed:22417654, PubMed:22510882). Interacts with XBP1 isoform 2;
this interaction is direct and leads to FOXO1 ubiquitination and
degradation via the proteasome pathway (PubMed:21317886).
Interacts (via the Fork-head domain) with CEBPA; the interaction
increases when FOXO1 is deacetylated (PubMed:17090532,
PubMed:17627282). Interacts with WDFY2 (PubMed:18388859). Forms a
complex with WDFY2 and AKT1 (PubMed:18388859).
{ECO:0000250|UniProtKB:Q12778, ECO:0000269|PubMed:12754525,
ECO:0000269|PubMed:15220471, ECO:0000269|PubMed:16917544,
ECO:0000269|PubMed:17050673, ECO:0000269|PubMed:17090532,
ECO:0000269|PubMed:17627282, ECO:0000269|PubMed:17681146,
ECO:0000269|PubMed:18388859, ECO:0000269|PubMed:19037106,
ECO:0000269|PubMed:20061393, ECO:0000269|PubMed:20668652,
ECO:0000269|PubMed:21317886, ECO:0000269|PubMed:21471200,
ECO:0000269|PubMed:22298775, ECO:0000269|PubMed:22417654,
ECO:0000269|PubMed:22510882}.
-!- INTERACTION:
P10275:AR (xeno); NbExp=4; IntAct=EBI-1371343, EBI-608057;
P53566:Cebpa; NbExp=5; IntAct=EBI-1371343, EBI-2644207;
P0DJI6:Fcor; NbExp=12; IntAct=EBI-1371343, EBI-6126630;
Q6PB66:Lrpprc; NbExp=2; IntAct=EBI-1371343, EBI-1371262;
P51450-2:Rorc; NbExp=2; IntAct=EBI-1371343, EBI-4422078;
Q96EB6:SIRT1 (xeno); NbExp=2; IntAct=EBI-1371343, EBI-1802965;
-!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:18388859,
ECO:0000269|PubMed:21317886}. Nucleus
{ECO:0000269|PubMed:17627282, ECO:0000269|PubMed:18388859,
ECO:0000269|PubMed:21317886}. Note=Shuttles between the cytoplasm
and nucleus. Largely nuclear in unstimulated cells. In
osteoblasts, colocalizes with ATF4 and RUNX2 in the nucleus (By
similarity). Insulin-induced phosphorylation at Ser-253 by
PKB/AKT1 leads, via stimulation of Thr-24 phosphorylation, to
binding of 14-3-3 proteins and nuclear export to the cytoplasm
where it is degraded by the ubiquitin-proteosomal pathway.
Phosphorylation at Ser-249 by CDK1 disrupts binding of 14-3-3
proteins and promotes nuclear accumulation. Phosphorylation by NLK
results in nuclear export. Translocates to the nucleus upon
oxidative stress-induced phosphorylation at Ser-212 by STK4/MST1.
SGK1-mediated phosphorylation also results in nuclear
translocation. Retained in the nucleus under stress stimuli
including oxidative stress, nutrient deprivation or nitric oxide.
Methylated form is nuclear. {ECO:0000250}.
-!- TISSUE SPECIFICITY: Expressed in liver, white and brown adipose
tissues (at protein level). {ECO:0000269|PubMed:17627282,
ECO:0000269|PubMed:22510882}.
-!- DEVELOPMENTAL STAGE: In liver, barely expressed at E14.5,
expression dramatically increases at E18.5. Abundantly expressed
in neonate liver but levels strongly decrease in adult liver (at
protein level). {ECO:0000269|PubMed:17627282}.
-!- INDUCTION: Expression is regulated by KRIT1 (PubMed:20668652).
Transiently up-regulated during adipogenesis (at protein level)
(PubMed:18388859). {ECO:0000269|PubMed:18388859,
ECO:0000269|PubMed:20668652}.
-!- PTM: Phosphorylation by NLK promotes nuclear export and inhibits
the transcriptional activity. In response to growth factors,
phosphorylation on Thr-24, Ser-253 and Ser-319 by PKB/AKT1
promotes nuclear export and inactivation of transactivational
activity. Phosphorylation on Thr-24 is required for binding 14-3-3
proteins. Phosphorylation of Ser-253 decreases DNA-binding
activity and promotes the phosphorylation of Thr-24 and Ser-316,
permitting phosphorylation of Ser-319 and Ser-322, probably by
CDK1, leading to nuclear exclusion and loss of function. Stress
signals, such as response to oxygen or nitric oxide, attenuate the
PKB/AKT1-mediated phosphorylation leading to nuclear retention.
Phosphorylation of Ser-326 is independent of IGF1 and leads to
reduced function. Dephosphorylated on Thr-24 and Ser-253 by PP2A
in beta-cells under oxidative stress leading to nuclear retention
(By similarity). Phosphorylation of Ser-246 by CDK1 disrupts
binding of 14-3-3 proteins leading to nuclear accumulation and has
no effect on DNA-binding nor transcriptional activity.
Phosphorylation by STK4/MST1 on Ser-209, upon oxidative stress,
inhibits binding to 14-3-3 proteins and nuclear export.
{ECO:0000250, ECO:0000269|PubMed:10347145,
ECO:0000269|PubMed:16076959, ECO:0000269|PubMed:19965929,
ECO:0000269|PubMed:20519497}.
-!- PTM: Ubiquitinated by SRT2. Ubiquitination leads to proteasomal
degradation (By similarity). {ECO:0000250}.
-!- PTM: Methylation inhibits PKB/AKT1-mediated phosphorylation at
Ser-253, promoting nuclear retention and increasing the
transcriptional activity and cell death. Methylation increased by
oxidative stress. {ECO:0000269|PubMed:10347145,
ECO:0000269|PubMed:16076959, ECO:0000269|PubMed:18951090,
ECO:0000269|PubMed:19965929, ECO:0000269|PubMed:20519497}.
-!- PTM: Acetylation at Lys-259 and Lys-271 are necessary for
autophagic cell death induction. Deacetylated by SIRT2 in response
to oxidative stress or serum deprivation, thereby negatively
regulating FOXO1-mediated autophagic cell death (By similarity).
Once in the nucleus, acetylated by CREBBP/EP300. Acetylation
diminishes the interaction with target DNA and attenuates the
transcriptional activity. It increases the phosphorylation at Ser-
253, and is required for the transcriptional inhibition by FCOR.
Deacetylation by SIRT1 results in reactivation of the
transcriptional activity (PubMed:17090532). Acetylation of FOXO1
diminishes its binding to PPARG in adipocytes. Deacetylated by
SIRT2; deacetylation of FOXO1 directly increases its repressive
binding to PPARG and inhibits adipocyte differentiation. Oxidative
stress by hydrogen peroxide treatment appears to promote
deacetylation and uncoupling of insulin-induced phosphorylation.
By contrast, resveratrol acts independently of acetylation.
{ECO:0000250, ECO:0000269|PubMed:10347145,
ECO:0000269|PubMed:15220471, ECO:0000269|PubMed:16076959,
ECO:0000269|PubMed:17090532, ECO:0000269|PubMed:17681146,
ECO:0000269|PubMed:19037106, ECO:0000269|PubMed:19965929,
ECO:0000269|PubMed:20519497, ECO:0000269|PubMed:21196578}.
-!- DISRUPTION PHENOTYPE: Null mice die around embryonic day 11 and
exhibit abnormal angiogenesis. Defects are observed in branchial
arches and there is remarkably impaired vascular development of
embryos and yolk sacs. Exogeneous VEGF on FOX1-deficient
endothelial cells show markedly different morphological response.
Active osteocalcin/BGLAP as well as serum insulin and beta-cell
and gonadal fat levels were increased, but there is no change in
total fat content, lean mass, and body weight. Effect on RUNX2
activity was inhibited. FOXO1 and ATF4 double happlo-insufficient
mice exhibit also an increase in insulin levels and beta cell
proliferation, but there is an increase in insulin sensitivity
demonstrated by an increase in expression of insulin-sensitizing
hormone adiponectin. Gonadal fat levels and adipocyte numbers were
decreased. Osteocalcin/BGLAP levels were unchanged.
{ECO:0000269|PubMed:15184386, ECO:0000269|PubMed:22298775}.
-!- MISCELLANEOUS: In an animal model of diabetes mellitus type 2
(db/db mice), beta-cell islets exhibit increased levels of PPP2R1A
leading to increased dephosphorylation at Thr-24 and Ser-253 and
nuclear retention of FOXO1.
-----------------------------------------------------------------------
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
Distributed under the Creative Commons Attribution-NoDerivs License
-----------------------------------------------------------------------
EMBL; AF126056; AAD40636.1; -; mRNA.
EMBL; AJ252157; CAB86873.1; -; mRNA.
EMBL; AK137629; BAE23437.1; -; mRNA.
EMBL; AK154041; BAE32333.1; -; mRNA.
EMBL; CH466530; EDL35224.1; -; Genomic_DNA.
CCDS; CCDS17343.1; -.
RefSeq; NP_062713.2; NM_019739.3.
UniGene; Mm.29891; -.
ProteinModelPortal; Q9R1E0; -.
SMR; Q9R1E0; -.
BioGrid; 207997; 10.
CORUM; Q9R1E0; -.
IntAct; Q9R1E0; 17.
MINT; MINT-5112421; -.
STRING; 10090.ENSMUSP00000055308; -.
iPTMnet; Q9R1E0; -.
PhosphoSitePlus; Q9R1E0; -.
SwissPalm; Q9R1E0; -.
EPD; Q9R1E0; -.
MaxQB; Q9R1E0; -.
PaxDb; Q9R1E0; -.
PeptideAtlas; Q9R1E0; -.
PRIDE; Q9R1E0; -.
DNASU; 56458; -.
Ensembl; ENSMUST00000053764; ENSMUSP00000055308; ENSMUSG00000044167.
GeneID; 56458; -.
KEGG; mmu:56458; -.
UCSC; uc008pei.2; mouse.
CTD; 2308; -.
MGI; MGI:1890077; Foxo1.
eggNOG; KOG2294; Eukaryota.
eggNOG; COG5025; LUCA.
GeneTree; ENSGT00790000123003; -.
HOGENOM; HOG000251635; -.
HOVERGEN; HBG057789; -.
InParanoid; Q9R1E0; -.
KO; K07201; -.
OMA; KWPGSPN; -.
OrthoDB; EOG091G06K3; -.
TreeFam; TF315583; -.
Reactome; R-MMU-198693; AKT phosphorylates targets in the nucleus.
Reactome; R-MMU-210745; Regulation of gene expression in beta cells.
Reactome; R-MMU-211163; AKT-mediated inactivation of FOXO1A.
Reactome; R-MMU-5687128; MAPK6/MAPK4 signaling.
PRO; PR:Q9R1E0; -.
Proteomes; UP000000589; Chromosome 3.
Bgee; ENSMUSG00000044167; -.
CleanEx; MM_FOXO1; -.
Genevisible; Q9R1E0; MM.
GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
GO; GO:0005829; C:cytosol; TAS:Reactome.
GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
GO; GO:0005634; C:nucleus; IDA:UniProtKB.
GO; GO:0008013; F:beta-catenin binding; ISO:MGI.
GO; GO:0003677; F:DNA binding; IDA:MGI.
GO; GO:0051721; F:protein phosphatase 2A binding; IDA:UniProtKB.
GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB.
GO; GO:0001223; F:transcription coactivator binding; IEA:Ensembl.
GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; IDA:MGI.
GO; GO:0000989; F:transcription factor activity, transcription factor binding; IPI:MGI.
GO; GO:0008134; F:transcription factor binding; IPI:UniProtKB.
GO; GO:0001078; F:transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding; IDA:MGI.
GO; GO:0001227; F:transcriptional repressor activity, RNA polymerase II transcription regulatory region sequence-specific binding; IGI:MGI.
GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
GO; GO:0009653; P:anatomical structure morphogenesis; IBA:GO_Central.
GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
GO; GO:0001568; P:blood vessel development; IMP:MGI.
GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
GO; GO:0071549; P:cellular response to dexamethasone stimulus; IEA:Ensembl.
GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:UniProtKB.
GO; GO:0070301; P:cellular response to hydrogen peroxide; IEA:Ensembl.
GO; GO:0071455; P:cellular response to hyperoxia; ISS:UniProtKB.
GO; GO:0032869; P:cellular response to insulin stimulus; IDA:UniProtKB.
GO; GO:0071732; P:cellular response to nitric oxide; IDA:UniProtKB.
GO; GO:0034599; P:cellular response to oxidative stress; IDA:UniProtKB.
GO; GO:0009267; P:cellular response to starvation; ISS:UniProtKB.
GO; GO:0070166; P:enamel mineralization; IEA:Ensembl.
GO; GO:0042593; P:glucose homeostasis; IDA:MGI.
GO; GO:0008286; P:insulin receptor signaling pathway; IMP:MGI.
GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IGI:MGI.
GO; GO:1903243; P:negative regulation of cardiac muscle hypertrophy in response to stress; ISS:UniProtKB.
GO; GO:0045599; P:negative regulation of fat cell differentiation; IMP:UniProtKB.
GO; GO:0032873; P:negative regulation of stress-activated MAPK cascade; ISO:MGI.
GO; GO:0097150; P:neuronal stem cell population maintenance; IGI:MGI.
GO; GO:0043065; P:positive regulation of apoptotic process; ISS:UniProtKB.
GO; GO:0010508; P:positive regulation of autophagy; ISS:UniProtKB.
GO; GO:0045722; P:positive regulation of gluconeogenesis; IMP:MGI.
GO; GO:0045732; P:positive regulation of protein catabolic process; ISS:UniProtKB.
GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IMP:MGI.
GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
GO; GO:0042127; P:regulation of cell proliferation; IMP:MGI.
GO; GO:0035947; P:regulation of gluconeogenesis by regulation of transcription from RNA polymerase II promoter; IMP:MGI.
GO; GO:2000177; P:regulation of neural precursor cell proliferation; IGI:MGI.
GO; GO:2000377; P:regulation of reactive oxygen species metabolic process; IGI:MGI.
GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:MGI.
GO; GO:1902617; P:response to fluoride; IEA:Ensembl.
GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW.
CDD; cd00059; FH; 1.
Gene3D; 1.10.10.10; -; 1.
InterPro; IPR001766; Fork_head_dom.
InterPro; IPR032067; FOXO-TAD.
InterPro; IPR032068; FOXO_KIX-bd.
InterPro; IPR030456; TF_fork_head_CS_2.
InterPro; IPR036388; WH-like_DNA-bd_sf.
InterPro; IPR036390; WH_DNA-bd_sf.
Pfam; PF00250; Forkhead; 1.
Pfam; PF16676; FOXO-TAD; 1.
Pfam; PF16675; FOXO_KIX_bdg; 1.
PRINTS; PR00053; FORKHEAD.
SMART; SM00339; FH; 1.
SUPFAM; SSF46785; SSF46785; 1.
PROSITE; PS00658; FORK_HEAD_2; 1.
PROSITE; PS50039; FORK_HEAD_3; 1.
1: Evidence at protein level;
Acetylation; Activator; Apoptosis; Autophagy; Complete proteome;
Cytoplasm; Differentiation; DNA-binding; Methylation; Nucleus;
Phosphoprotein; Reference proteome; Transcription;
Transcription regulation; Ubl conjugation.
CHAIN 1 652 Forkhead box protein O1.
/FTId=PRO_0000091873.
DNA_BIND 156 232 Fork-head. {ECO:0000255|PROSITE-
ProRule:PRU00089}.
REGION 208 215 DNA-binding. {ECO:0000250}.
REGION 231 234 DNA-binding. {ECO:0000250}.
REGION 280 562 Sufficient for interaction with NLK.
{ECO:0000269|PubMed:20061393}.
REGION 360 456 Required for interaction with RUNX2.
{ECO:0000269|PubMed:21471200}.
MOTIF 248 250 Nuclear localization signal.
{ECO:0000250}.
MOTIF 459 463 Required for interaction with SIRT1.
COMPBIAS 89 96 Poly-Ala.
COMPBIAS 135 139 Poly-Ala.
COMPBIAS 149 152 Poly-Ser.
SITE 155 155 DNA-binding. {ECO:0000250}.
SITE 162 162 DNA-binding. {ECO:0000250}.
SITE 222 222 DNA-binding. {ECO:0000250}.
MOD_RES 24 24 Phosphothreonine; by PKB/AKT1 or PKB/AKT2
and SGK1. {ECO:0000269|PubMed:10347145,
ECO:0000269|PubMed:19965929,
ECO:0000269|PubMed:20519497}.
MOD_RES 209 209 Phosphoserine; by STK4/MST1.
{ECO:0000250|UniProtKB:Q12778}.
MOD_RES 215 215 Phosphoserine.
{ECO:0000250|UniProtKB:Q12778}.
MOD_RES 231 231 Phosphoserine.
{ECO:0000250|UniProtKB:Q12778}.
MOD_RES 232 232 Phosphoserine.
{ECO:0000250|UniProtKB:Q12778}.
MOD_RES 242 242 N6-acetyllysine.
{ECO:0000269|PubMed:15220471,
ECO:0000269|PubMed:16076959,
ECO:0000269|PubMed:17090532}.
MOD_RES 245 245 N6-acetyllysine.
{ECO:0000269|PubMed:15220471,
ECO:0000269|PubMed:16076959,
ECO:0000269|PubMed:17090532}.
MOD_RES 246 246 Phosphoserine; by CDK1.
{ECO:0000250|UniProtKB:Q12778}.
MOD_RES 248 248 Omega-N-methylarginine; by PRMT1.
{ECO:0000269|PubMed:18951090}.
MOD_RES 250 250 Omega-N-methylarginine; by PRMT1.
{ECO:0000269|PubMed:18951090}.
MOD_RES 253 253 Phosphoserine; by PKB/AKT1 and SGK1.
{ECO:0000269|PubMed:10347145,
ECO:0000269|PubMed:16076959,
ECO:0000269|PubMed:18388859,
ECO:0000269|PubMed:19965929,
ECO:0000269|PubMed:20519497}.
MOD_RES 259 259 N6-acetyllysine.
{ECO:0000250|UniProtKB:Q12778}.
MOD_RES 262 262 N6-acetyllysine.
{ECO:0000269|PubMed:15220471,
ECO:0000269|PubMed:16076959,
ECO:0000269|PubMed:17090532}.
MOD_RES 271 271 N6-acetyllysine.
{ECO:0000250|UniProtKB:Q12778}.
MOD_RES 284 284 Phosphoserine.
{ECO:0000244|PubMed:21183079}.
MOD_RES 295 295 Phosphoserine.
{ECO:0000244|PubMed:21183079}.
MOD_RES 316 316 Phosphoserine; by PKB/AKT1 or PKB/AKT2.
{ECO:0000269|PubMed:10347145}.
MOD_RES 319 319 Phosphoserine; by CK1 and SGK1.
{ECO:0000269|PubMed:19965929}.
MOD_RES 322 322 Phosphoserine; by CK1.
{ECO:0000250|UniProtKB:Q12778}.
MOD_RES 326 326 Phosphoserine.
{ECO:0000244|PubMed:21183079}.
MOD_RES 330 330 Phosphothreonine.
{ECO:0000244|PubMed:21183079}.
MUTAGEN 24 24 T->A: Decreases insulin-induced
phosphorylation by approximately 30%.
Nuclear location but transcriptional
activity decreased by about 50%.
Abolishes the SIRT1 deacetylase binding
and increases acetylation; when
associated with A-253; A-316; A-462 and
A-463. Increased insulin-induced
phosphorylation at Ser-253 and binding of
14-3-3 proteins; when associated with Q-
219; Q-242; Q-245; Q-259; Q-262; Q-271
and Q-291. Increased binding of 14-3-3
proteins even with decreased insulin-
induced phosphorylation at Ser-253; when
associated with R-219; R-242; R-245; R-
259; R-262; R-271 and R-291.
{ECO:0000269|PubMed:10347145,
ECO:0000269|PubMed:16917544,
ECO:0000269|PubMed:20519497}.
MUTAGEN 29 29 R->K: Little change in levels of
methylation; when associated with K-147;
K-154; K-311 and K-313.
{ECO:0000269|PubMed:18951090}.
MUTAGEN 147 147 R->K: Little change in levels of
methylation; when associated with K-29;
K-154; K-311 and K-313.
{ECO:0000269|PubMed:18951090}.
MUTAGEN 154 154 R->K: Little change in levels of
methylation; when associated with K-29;
K-147; K-311 and K-313.
{ECO:0000269|PubMed:18951090}.
MUTAGEN 206 206 W->G: Loss of interaction with CEBPA.
{ECO:0000269|PubMed:17627282}.
MUTAGEN 212 212 H->P: Loss of interaction with CEBPA.
{ECO:0000269|PubMed:17627282}.
MUTAGEN 219 219 K->Q: Mimics acetylation. Cytoplasmic
location in absence or presence of
insulin, no change on the inhibitory
effect of oxidative stress on insulin-
induced phosphorylations, but no
inhibition of these phosphorylations by
resveratrol; when associated with Q-242;
Q-245; Q-259; Q-262; Q-271 and Q-291.
Increased insulin-induced phosphorylation
at Ser-253 and binding of 14-3-3
proteins; when associated with A-24; Q-
242; Q-245; Q-259; Q-262; Q-271 and Q-
291. {ECO:0000269|PubMed:20519497}.
MUTAGEN 219 219 K->R: Translocates to the cytoplasm after
insulin-stimulation. No change on the
inhibitory effect of oxidative stress on
insulin-induced phosphorylations, but no
inhibition of these phosphorylations by
resveratrol; when associated with R-242;
R-245; R-259; R-262; R-271 and R-291.
Increased binding of 14-3-3 proteins even
with decreased insulin-induced
phosphorylation at Ser-253; when
associated with A-24; R-242; R-245; R-
259; R-262; R-271 and R-291.
{ECO:0000269|PubMed:20519497}.
MUTAGEN 242 242 K->Q,A: Mimics acetylation. Cytoplasmic
location in absence or presence of
insulin. Decreased DNA-binding by about
half. Enhanced phosphorylation by
PKB/AKT1, no effect on interaction with
CEBPA; when associated with either A-245
or Q-245 and either A-262 or Q-262.
either A-262 or Q-262. Cytoplasmic
location in absence or presence of
insulin, no change on the inhibitory
effect of oxidative stress on insulin-
induced phosphorylations, but no
inhibition of these phosphorylations by
resveratrol; when associated with Q-219;
Q-245; Q-259; Q-262; Q-271 and Q-291.
Increased insulin-induced phosphorylation
at Ser-253 and binding of 14-3-3
proteins; when associated with A-24; Q-
219; Q-245; Q-259; Q-262; Q-271 and Q-
291. {ECO:0000269|PubMed:15220471,
ECO:0000269|PubMed:16076959,
ECO:0000269|PubMed:17090532,
ECO:0000269|PubMed:20519497,
ECO:0000269|PubMed:22510882}.
MUTAGEN 242 242 K->R: Reduced acetylation and
transcriptional activity increased by
about 1.5 fold. Completely abolishes
acetylation, increases interaction with
CEBPA and transcriptional activity
increased by about 3-fold; when
associated with R-245 and R-262.
Transcriptional activity not inhibited by
FCOR; when associated with R-245; R-259;
R-262; R-271 and R-291. Predominantly
nuclear and translocates to the cytoplasm
on insulin-stimulation. No change on the
inhibitory effect of oxidative stress on
insulin-induced phosphorylations, but no
inhibition of these phosphorylations by
resveratrol; when associated with R-219;
R-245; R-259; R-262; R-271 and R-291.
Increased binding of 14-3-3 proteins even
with decreased insulin-induced
phosphorylation at Ser-253; when
associated with A-24; R-219; R-245; R-
259; R-262; R-271 and R-291.
{ECO:0000269|PubMed:15220471,
ECO:0000269|PubMed:16076959,
ECO:0000269|PubMed:17090532,
ECO:0000269|PubMed:20519497,
ECO:0000269|PubMed:22510882}.
MUTAGEN 245 245 K->Q,A: Mimics acetylation. Decreased
DNA-binding by about half. Enhanced
phosphorylation by PKB/AKT1, no effect on
interaction with CEBPA; when associated
with either A-242 or Q-242 and either A-
262 or Q-262. Cytoplasmic location in
absence or presence of insulin, no change
on the inhibitory effect of oxidative
stress on insulin-induced
phosphorylations, but no inhibition of
these phosphorylations by resveratrol;
when associated with Q-219; Q-242; Q-259;
Q-262; Q-271 and Q-291. Increased
insulin-induced phosphorylation at Ser-
253 and binding of 14-3-3 proteins; when
associated with A-24; Q-219; Q-242; Q-
259; Q-262; Q-271 and Q-291.
{ECO:0000269|PubMed:15220471,
ECO:0000269|PubMed:16076959,
ECO:0000269|PubMed:17090532,
ECO:0000269|PubMed:20519497,
ECO:0000269|PubMed:22510882}.
MUTAGEN 245 245 K->R: Reduced acetylation and
transcriptional activity increased by
about 1.5-fold. Completely abolishes
acetylation, increases interaction with
CEBPA and transcriptional activity
increased by about 3-fold; when
associated with R-242 and R-262.
Transcriptional activity not inhibited by
FCOR; when associated with R-242; R-259;
R-262; R-271 and R-291. Predominantly
nuclear and translocates to the cytoplasm
on insulin-stimulation. No change on the
inhibitory effect of oxidative stress on
insulin-induced phosphorylations, but no
inhibition of these phosphorylations by
resveratrol; when associated with R-219;
R-242; R-259; R-262; R-271 and R-291.
Increased binding of 14-3-3 proteins even
with decreased insulin-induced
phosphorylation at Ser-253; when
associated with A-24; R-219; R-242; R-
259; R-262; R-271 and R-291.
{ECO:0000269|PubMed:15220471,
ECO:0000269|PubMed:16076959,
ECO:0000269|PubMed:17090532,
ECO:0000269|PubMed:20519497,
ECO:0000269|PubMed:22510882}.
MUTAGEN 248 248 R->K: Some decrease in levels of
methylation. Greatly decreased
methylation levels; when associated with
K-250. {ECO:0000269|PubMed:18951090}.
MUTAGEN 249 249 R->K: No change in methylation levels.
MUTAGEN 250 250 R->K: Some decrease in levels of
methylation. Greatly decreased
methylation levels; when associated with
K-248. {ECO:0000269|PubMed:18951090}.
MUTAGEN 253 253 S->A: Abolishes insulin-induced
phosphorylation when associated with A-
463. Nuclear location but transcriptional
activity decreased by about 50%.
Abolishes the SIRT1 deacetylase binding
and increases acetylation; when
associated with A-24; A-316; A-462 and A-
463. {ECO:0000269|PubMed:10347145,
ECO:0000269|PubMed:16076959,
ECO:0000269|PubMed:16917544,
ECO:0000269|PubMed:20519497}.
MUTAGEN 259 259 K->Q: Mimics acetylation. Cytoplasmic
location in absence or presence of
insulin, no change on the inhibitory
effect of oxidative stress on insulin-
induced phosphorylations, but no
inhibition of these phosphorylations by
resveratrol; when associated with Q-219;
Q-242; Q-245; Q-262; Q-271 and Q-291.
Increased insulin-induced phosphorylation
at Ser-253 and binding of 14-3-3
proteins; when associated with A-24; Q-
219; Q-242; Q-245; Q-262; Q-271 and Q-
291. {ECO:0000269|PubMed:20519497,
ECO:0000269|PubMed:22510882}.
MUTAGEN 259 259 K->R: Transcriptional activity not
inhibited by FCOR; when associated with
R-242; R-245; R-262; R-271 and R-291.
Predominantly nuclear and translocates to
the cytoplasm on insulin-stimulation. No
change on the inhibitory effect of
oxidative stress on insulin-induced
phosphorylations, but no inhibition of
these phosphorylations by resveratrol;
when associated with R-219; R-242; R-245;
R-262; R-271 and R-291. Increased binding
of 14-3-3 proteins even with decreased
insulin-induced phosphorylation at Ser-
253; when associated with A-24; R-219; R-
242; R-245; R-262; R-271 and R-291.
{ECO:0000269|PubMed:20519497,
ECO:0000269|PubMed:22510882}.
MUTAGEN 262 262 K->Q,A: Mimics acetylation. Decreased
DNA-binding by about half and enhanced
phosphorylation by PKB/AKT1, no effect on
interaction with CEBPA; when associated
with either A-242 or Q-242 and either A-
245 or Q-245. Cytoplasmic location in
absence or presence of insulin, no change
on the inhibitory effect of oxidative
stress on insulin-induced
phosphorylations, but no inhibition of
these phosphorylations by resveratrol;
when associated with Q-219; Q-242; Q-245;
Q-259; Q-271 and Q-291. Increased
insulin-induced phosphorylation at Ser-
253 and binding of 14-3-3 proteins; when
associated with A-24; Q-219; Q-242; Q-
245; Q-259; Q-271 and Q-291.
{ECO:0000269|PubMed:15220471,
ECO:0000269|PubMed:16076959,
ECO:0000269|PubMed:17090532,
ECO:0000269|PubMed:20519497,
ECO:0000269|PubMed:22510882}.
MUTAGEN 262 262 K->R: Significant reduction in
acetylation and transcriptional activity
increased by about 2.0 fold. Completely
abolishes acetylation, increases
interaction with CEBPA and
transcriptional activity increased by
about 3-fold; when associated with R-242
and R-245. Transcriptional activity not
inhibited by FCOR; when associated with
R-242; R-245; R-259; R-271 and R-291.
Predominantly nuclear and translocates to
the cytoplasm on insulin-stimulation. No
change on the inhibitory effect of
oxidative stress on insulin-induced
phosphorylations, but no inhibition of
these phosphorylations by resveratrol;
when associated with R-219; R-242; R-245;
R-259; R-271 and R-291. Increased binding
of 14-3-3 proteins even with decreased
insulin-induced phosphorylation at Ser-
253; when associated with A-24; R-219; R-
242; R-245; R-259; R-271 and R-291.
{ECO:0000269|PubMed:15220471,
ECO:0000269|PubMed:16076959,
ECO:0000269|PubMed:17090532,
ECO:0000269|PubMed:20519497,
ECO:0000269|PubMed:22510882}.
MUTAGEN 271 271 K->Q: Mimics acetylation. Cytoplasmic
location in absence or presence of
insulin, no change on the inhibitory
effect of oxidative stress on insulin-
induced phosphorylations, but no
inhibition of these phosphorylations by
resveratrol; when associated with Q-219;
Q-242; Q-245; Q-259; Q-262 and Q-291.
Increased insulin-induced phosphorylation
at Ser-253 and binding of 14-3-3
proteins; when associated with A-24; Q-
219; Q-242; Q-245; Q-259; Q-262 and Q-
291. {ECO:0000269|PubMed:20519497,
ECO:0000269|PubMed:22510882}.
MUTAGEN 271 271 K->R: Transcriptional activity not
inhibited by FCOR; when associated with
R-242; R-245; R-259; R-262 and R-291.
Predominantly nuclear and translocates to
the cytoplasm on insulin-stimulation. No
inhibitory effect of oxidative stress on
insulin-induced phosphorylations, but no
inhibition of these phosphorylations by
resveratrol; when associated with R-219;
R-242; R-245; R-259; R-262 and R-291.
Increased binding of 14-3-3 proteins even
with decreased insulin-induced
phosphorylation at Ser-253; when
associated with A-24; R-219; R-242; R-
245; R-259; R-262 and R-291.
{ECO:0000269|PubMed:20519497,
ECO:0000269|PubMed:22510882}.
MUTAGEN 284 284 S->A: Decreases phosphorylation by NLK;
when associated with A-295; A-326; A-380;
A-391; A-399; A-413 and A-415.
{ECO:0000269|PubMed:20061393}.
MUTAGEN 291 291 K->Q: Mimics acetylation. Cytoplasmic
location in absence or presence of
insulin, no change on the inhibitory
effect of oxidative stress on insulin-
induced phosphorylations, but no
inhibition of these phosphorylations by
resveratrol; when associated with Q-219;
Q-242; Q-245; Q-259; Q-262 and Q-271.
Increased insulin-induced phosphorylation
at Ser-253 and binding of 14-3-3
proteins; when associated with A-24: Q-
219; Q-242; Q-245; Q-259; Q-262 and Q-
271. {ECO:0000269|PubMed:20519497,
ECO:0000269|PubMed:22510882}.
MUTAGEN 291 291 K->R: Transcriptional activity not
inhibited by FCOR; when associated with
R-242; R-245; R-259; R-262 and R-271.
Predominantly nuclear and translocates to
the cytoplasm on insulin-stimulation. No
inhibitory effect of oxidative stress on
insulin-induced phosphorylations, but no
inhibition of these phosphorylations by
resveratrol; when associated with R-219;
R-242; R-245; R-259; R-262 and R-271.
Increased binding of 14-3-3 proteins even
with decreased insulin-induced
phosphorylation at Ser-253; when
associated with A-24; R-219; R-242; R-
245; R-259; R-262 and R-271.
{ECO:0000269|PubMed:20519497,
ECO:0000269|PubMed:22510882}.
MUTAGEN 295 295 S->A: Decreases phosphorylation by NLK;
when associated with A-284; A-326; A-380;
A-391; A-399; A-413 and A-415.
{ECO:0000269|PubMed:20061393}.
MUTAGEN 311 311 R->K: Little change in levels of
methylation; when associated with K-29;
K-147; K-154 and K-313.
{ECO:0000269|PubMed:18951090}.
MUTAGEN 313 313 R->K: Little change in levels of
methylation; when associated with K-29;
K-147; K-154 and K-311.
{ECO:0000269|PubMed:18951090}.
MUTAGEN 316 316 S->A: Decreases insulin-induced
phosphorylation by approximately 30%.
Abolishes the SIRT1 deacetylase binding
and increases acetylation; when
associated with A-24; A-253; A-462 and A-
463. {ECO:0000269|PubMed:10347145,
ECO:0000269|PubMed:16917544}.
MUTAGEN 326 326 S->A: Decreases phosphorylation by NLK;
when associated with A-284; A-295; A-380;
A-391; A-399; A-413 and A-415.
{ECO:0000269|PubMed:20061393}.
MUTAGEN 380 380 S->A: Decreases phosphorylation by NLK;
when associated with A-284; A-295; A-326;
A-391; A-399; A-413 and A-415.
{ECO:0000269|PubMed:20061393}.
MUTAGEN 391 391 S->A: Decreases phosphorylation by NLK;
when associated with A-284; A-295; A-326;
A-380; A-399; A-413 and A-415.
{ECO:0000269|PubMed:20061393}.
MUTAGEN 399 399 T->A: Decreases phosphorylation by NLK;
when associated with A-284; A-295; A-326;
A-380; A-391; A-413 and A-415.
{ECO:0000269|PubMed:20061393}.
MUTAGEN 413 413 S->A: Decreases phosphorylation by NLK;
when associated with A-284; A-295; A-326;
A-380; A-391; A-399 and A-415.
{ECO:0000269|PubMed:20061393}.
MUTAGEN 415 415 S->A: Decreases phosphorylation by NLK;
when associated with A-284; A-295; A-326;
A-380; A-391; A-399 and A-413.
{ECO:0000269|PubMed:20061393}.
MUTAGEN 462 462 L->A: Decreased transcriptional activity
by about 2-fold in the absence of serum;
when associated with A-463. Nuclear
location but transcriptional activity
decreased by about 50%. Abolishes the
SIRT1 deacetylase binding and increases
acetylation; when associated with A-24;
A-253; A-316 and A-463.
{ECO:0000269|PubMed:16917544}.
MUTAGEN 463 463 L->A: Decreased transcriptional activity
by about 2-fold in the absence of serum;
when associated with A-463. Nuclear
location but transcriptional activity
decreased by about 50%. Abolishes the
SIRT1 deacetylase binding and increases
acetylation; when associated with A-24;
A-253; A-316 and A-462.
{ECO:0000269|PubMed:16917544}.
CONFLICT 619 619 L -> P (in Ref. 1; AAD40636).
{ECO:0000305}.
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


Related products :

Catalog number Product name Quantity
E0764h ELISA FKHR,Forkhead box protein O1,Forkhead box protein O1A,Forkhead in rhabdomyosarcoma,FOXO1,FOXO1A,Homo sapiens,Human 96T
E0764h ELISA kit FKHR,Forkhead box protein O1,Forkhead box protein O1A,Forkhead in rhabdomyosarcoma,FOXO1,FOXO1A,Homo sapiens,Human 96T
U0764h CLIA FKHR,Forkhead box protein O1,Forkhead box protein O1A,Forkhead in rhabdomyosarcoma,FOXO1,FOXO1A,Homo sapiens,Human 96T
U0764m CLIA Fkhr,Forkhead box protein O1,Forkhead box protein O1A,Forkhead in rhabdomyosarcoma,Foxo1,Foxo1a,Mouse,Mus musculus 96T
E0764m ELISA Fkhr,Forkhead box protein O1,Forkhead box protein O1A,Forkhead in rhabdomyosarcoma,Foxo1,Foxo1a,Mouse,Mus musculus 96T
E0764m ELISA kit Fkhr,Forkhead box protein O1,Forkhead box protein O1A,Forkhead in rhabdomyosarcoma,Foxo1,Foxo1a,Mouse,Mus musculus 96T
E0762h ELISA AF6q21 protein,FKHRL1,Forkhead box protein O3,Forkhead in rhabdomyosarcoma-like 1,FOXO3,FOXO3A,Homo sapiens,Human 96T
U0762h CLIA AF6q21 protein,FKHRL1,Forkhead box protein O3,Forkhead in rhabdomyosarcoma-like 1,FOXO3,FOXO3A,Homo sapiens,Human 96T
E0762h ELISA kit AF6q21 protein,FKHRL1,Forkhead box protein O3,Forkhead in rhabdomyosarcoma-like 1,FOXO3,FOXO3A,Homo sapiens,Human 96T
18-003-43185 Forkhead box protein O1A - Forkhead in rhabdomyosarcoma Polyclonal 0.1 mg Protein A
18-003-42082 Forkhead box protein F1 - Forkhead-related protein FKHL5; Forkhead-related transcription factor 1; FREAC-1; Forkhead-related activator 1 Polyclonal 0.1 mg Protein A
18-003-42083 Forkhead box protein F2 - Forkhead-related protein FKHL6; Forkhead-related transcription factor 2; FREAC-2; Forkhead-related activator 2 Polyclonal 0.1 mg Protein A
18-003-42174 Forkhead box protein F1 - Forkhead-related protein FKHL5; Forkhead-related transcription factor 1; FREAC-1; Forkhead-related activator 1 Polyclonal 0.1 mg Protein A
18-003-43334 Forkhead box protein J1 - Forkhead-related protein FKHL13; Hepatocyte nuclear factor 3 forkhead homolog 4; HFH-4 Polyclonal 0.05 mg Aff Pur
18-003-43076 Forkhead box protein I1 - Forkhead-related protein FKHL10; Forkhead-related transcription factor 6; FREAC-6; Hepatocyte nuclear factor 3 forkhead homolog 3; HNF-3_fork-head homolog 3; HFH-3 Polyclonal 0.05 mg Aff Pur
18-003-42177 Forkhead box protein L1 - Forkhead-related protein FKHL11; Forkhead-related transcription factor 7; FREAC-7 Polyclonal 0.1 mg Protein A
18-003-42178 Forkhead box protein E3 - Forkhead-related protein FKHL12; Forkhead-related transcription factor 8; FREAC-8 Polyclonal 0.05 mg Aff Pur
18-003-42175 Forkhead box protein C1 - Forkhead-related protein FKHL7; Forkhead-related transcription factor 3; FREAC-3 Polyclonal 0.1 mg Protein A
18-003-43801 Forkhead box protein D2 - Forkhead-related protein FKHL17; Forkhead-related transcription factor 9; FREAC-9 Polyclonal 0.1 mg Protein A
18-003-43151 Forkhead box protein D1 - Forkhead-related protein FKHL8; Forkhead-related transcription factor 4; FREAC-4; Brain factor 2; HFH-BF-2 Polyclonal 0.05 mg Aff Pur
18-003-43800 Forkhead box protein C2 - Forkhead-related protein FKHL14; Mesenchyme fork head protein 1; MFH-1 protein; Transcription factor FKH-14 Polyclonal 0.1 mg Protein A
18-003-42180 Forkhead box protein C2 - Forkhead-related protein FKHL14; Mesenchyme fork head protein 1; MFH-1 protein; Transcription factor FKH-14 Polyclonal 0.1 mg Protein A
27-546 Forkhead Box Protein E3 (FOXE3, forkhead-related protein FKHL12, forkhead-related transcription factor 8) is a forkhead_winged helix transcription factor, which is expressed in the developing lens fro 0.05 mg
18-003-43387 Forkhead box protein Q1 - Hepatocyte nuclear factor 3 forkhead homolog 1; HNF-3_forkhead-like protein 1; HFH-1 Polyclonal 0.1 mg Protein A
31-247 Forkhead-related protein FKHL2 (brain factor 2, FOXG1A, Forkhead box protein G1A, HFK2 ) is a member of the fork head gene family of transcription factors. 0.1 mg


 

GENTAUR Belgium BVBA BE0473327336
Voortstraat 49, 1910 Kampenhout BELGIUM
Tel 0032 16 58 90 45

Fax 0032 16 50 90 45
info@gentaur.com | Gentaur





GENTAUR Ltd.
Howard Frank Turnberry House
1404-1410 High Road
Whetstone London N20 9BH
Tel 020 3393 8531 Fax 020 8445 9411
uk@gentaur.com | Gentaur

 

 




GENTAUR France SARL
9, rue Lagrange, 75005 Paris
Tel 01 43 25 01 50

Fax 01 43 25 01 60
RCS Paris B 484 237 888

SIRET 48423788800017

BNP PARIBAS PARIS PL MAUBERT BIC BNPAFRPPPRG

france@gentaur.com | Gentaur

GENTAUR GmbH
Marienbongard 20
52062 Aachen Deutschland
Support Karolina Elandt
Tel: 0035929830070
Fax: (+49) 241 56 00 47 88

Logistic :0241 40 08 90 86
Bankleitzahl 39050000
IBAN lautet DE8839050000107569353
Handelsregister Aachen HR B 16058
Umsatzsteuer-Identifikationsnummer *** DE 815175831
Steuernummer 201/5961/3925
de@gentaur.com | Gentaur

GENTAUR U.S.A
Genprice Inc, Logistics
547, Yurok Circle
San Jose, CA 95123
CA 95123
Tel (408) 780-0908,
Fax (408) 780-0908,
sales@genprice.com

Genprice Inc, Invoices and accounting
6017 Snell Ave, Ste 357
San Jose, CA 95123




GENTAUR Nederland BV
NL850396268B01 KVK nummer 52327027
Kuiper 1
5521 DG Eersel Nederland
Tel:  0208-080893  Fax: 0497-517897
nl@gentaur.com | Gentaur
IBAN: NL04 RABO 0156 9854 62   SWIFT RABONL2U






GENTAUR Spain
tel:0911876558
spain@gentaur.com | Gentaur






ГЕНТАУЪР БЪЛГАРИЯ
ID # 201 358 931 /BULSTAT
София 1000, ул. "Граф Игнатиев" 53 вх. В, ет. 2
Tel 0035924682280 Fax 0035924808322
e-mail: Sofia@gentaur.com | Gentaur
IBAN: BG11FINV91501014771636
BIC: FINVBGSF

GENTAUR Poland Sp. z o.o.


ul. Grunwaldzka 88/A m.2
81-771 Sopot, Poland
TEL Gdansk 058 710 33 44 FAX  058 710 33 48              

poland@gentaur.com | Gentaur

Other countries

Österreich +43720880899

Canada Montreal +15149077481

Ceská republika Praha +420246019719

Danmark +4569918806

Finland Helsset +358942419041

Magyarország Budapest +3619980547

Ireland Dublin+35316526556

Luxembourg+35220880274

Norge Oslo+4721031366

Sverige Stockholm+46852503438

Schweiz Züri+41435006251

US New York+17185132983

GENTAUR Italy
SRL IVA IT03841300167
Piazza Giacomo Matteotti, 6
24122 Bergamo Tel 02 36 00 65 93
Fax 02 36 00 65 94
italia@gentaur.com | Gentaur