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Q9R1E0

- FOXO1_MOUSE

UniProt

Q9R1E0 - FOXO1_MOUSE

Protein

Forkhead box protein O1

Gene

Foxo1

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 131 (01 Oct 2014)
      Sequence version 2 (27 Jul 2011)
      Previous versions | rss
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    Functioni

    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 syngernistically 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 to activate the expression of genes such as IGFBP1, G6PC and PPCK1. Important regulator of cell death acting downstream of CDK1, PKB/AKT1 and SKT4/MST1. Promotes neural cell death. Mediates insulin action on adipose. 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.13 Publications

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei155 – 1551DNA-bindingBy similarity
    Sitei162 – 1621DNA-bindingBy similarity
    Sitei222 – 2221DNA-bindingBy similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    DNA bindingi156 – 23277Fork-headPROSITE-ProRule annotationAdd
    BLAST

    GO - Molecular functioni

    1. DNA binding Source: MGI
    2. protein binding Source: UniProtKB
    3. protein phosphatase 2A binding Source: UniProtKB
    4. RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in negative regulation of transcription Source: MGI
    5. sequence-specific DNA binding Source: UniProtKB
    6. sequence-specific DNA binding transcription factor activity Source: MGI
    7. transcription factor binding transcription factor activity Source: MGI

    GO - Biological processi

    1. apoptotic process Source: UniProtKB-KW
    2. blood vessel development Source: MGI
    3. cellular response to DNA damage stimulus Source: UniProtKB
    4. cellular response to hyperoxia Source: UniProtKB
    5. cellular response to insulin stimulus Source: UniProtKB
    6. cellular response to nitric oxide Source: UniProtKB
    7. cellular response to oxidative stress Source: UniProtKB
    8. cellular response to starvation Source: UniProtKB
    9. endocrine pancreas development Source: Reactome
    10. glucose homeostasis Source: MGI
    11. insulin receptor signaling pathway Source: MGI
    12. negative regulation of apoptotic process Source: UniProtKB
    13. negative regulation of fat cell differentiation Source: UniProtKB
    14. negative regulation of stress-activated MAPK cascade Source: Ensembl
    15. negative regulation of transcription from RNA polymerase II promoter Source: GOC
    16. positive regulation of apoptotic process Source: UniProtKB
    17. positive regulation of autophagy Source: UniProtKB
    18. positive regulation of gluconeogenesis Source: MGI
    19. positive regulation of protein catabolic process Source: UniProtKB
    20. positive regulation of transcription, DNA-templated Source: UniProtKB
    21. positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
    22. regulation of cell proliferation Source: MGI
    23. regulation of gluconeogenesis by regulation of transcription from RNA polymerase II promoter Source: MGI
    24. regulation of transcription, DNA-templated Source: MGI

    Keywords - Molecular functioni

    Activator

    Keywords - Biological processi

    Apoptosis, Autophagy, Differentiation, Transcription, Transcription regulation

    Keywords - Ligandi

    DNA-binding

    Enzyme and pathway databases

    ReactomeiREACT_196588. Constitutive PI3K/AKT Signaling in Cancer.
    REACT_214529. Regulation of gene expression in beta cells.
    REACT_218211. AKT phosphorylates targets in the nucleus.
    REACT_221926. AKT-mediated inactivation of FOXO1A.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Forkhead box protein O1
    Alternative name(s):
    Forkhead box protein O1A
    Forkhead in rhabdomyosarcoma
    Gene namesi
    Name:Foxo1
    Synonyms:Fkhr, Foxo1a
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 3

    Organism-specific databases

    MGIiMGI:1890077. Foxo1.

    Subcellular locationi

    Cytoplasm. Nucleus
    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.By similarity

    GO - Cellular componenti

    1. cytoplasm Source: UniProtKB
    2. cytosol Source: Reactome
    3. nucleoplasm Source: Reactome
    4. nucleus Source: UniProtKB

    Keywords - Cellular componenti

    Cytoplasm, Nucleus

    Pathology & Biotechi

    Disruption phenotypei

    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.2 Publications

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi24 – 241T → 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. 3 Publications
    Mutagenesisi29 – 291R → K: Little change in levels of methylation; when associated with K-147; K-154; K-311 and K-313. 1 Publication
    Mutagenesisi147 – 1471R → K: Little change in levels of methylation; when associated with K-29; K-154; K-311 and K-313. 1 Publication
    Mutagenesisi154 – 1541R → K: Little change in levels of methylation; when associated with K-29; K-147; K-311 and K-313. 1 Publication
    Mutagenesisi219 – 2191K → 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. 1 Publication
    Mutagenesisi219 – 2191K → 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. 1 Publication
    Mutagenesisi242 – 2421K → Q: Mimics acetylation. Cytoplasmic location in absence or presence of insulin. Decreased DNA-binding by about half. Enhanced phosphorylation by PKB/AKT1; 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. 4 Publications
    Mutagenesisi242 – 2421K → R: Reduced acetylation and transcriptional activity increased by about 1.5 fold. Completely abolishes acetylation 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. 4 Publications
    Mutagenesisi245 – 2451K → Q: Mimics acetylation. Decreased DNA-binding by about half. Enhanced phosphorylation by PKB/AKT1; 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. 4 Publications
    Mutagenesisi245 – 2451K → R: Reduced acetylation and transciptional activity increased by about 1.5-fold. Completely abolishes acetylation 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. 4 Publications
    Mutagenesisi248 – 2481R → K: Some decrease in levels of methylation. Greatly decreased methylation levels; when associated with K-250. 1 Publication
    Mutagenesisi249 – 2491R → K: No change in methylation levels.
    Mutagenesisi250 – 2501R → K: Some decrease in levels of methylation. Greatly decreased methylation levels; when associated with K-248. 1 Publication
    Mutagenesisi253 – 2531S → 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. 4 Publications
    Mutagenesisi259 – 2591K → 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. 2 Publications
    Mutagenesisi259 – 2591K → 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. 2 Publications
    Mutagenesisi262 – 2621K → Q: Mimics acetylation. Decreased DNA-binding by about half and enhanced phosphorylation by PKB/AKT1; 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. 4 Publications
    Mutagenesisi262 – 2621K → R: Significant reduction in acetylation and transcriptional activity increased by about 2.0 fold. Completely abolishes acetylation 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. 4 Publications
    Mutagenesisi271 – 2711K → 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. 2 Publications
    Mutagenesisi271 – 2711K → 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. 2 Publications
    Mutagenesisi284 – 2841S → A: Decreases phosphorylation by NLK; when associated with A-295; A-326; A-380; A-391; A-399; A-413 and A-415. 1 Publication
    Mutagenesisi291 – 2911K → 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. 2 Publications
    Mutagenesisi291 – 2911K → 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. 2 Publications
    Mutagenesisi295 – 2951S → A: Decreases phosphorylation by NLK; when associated with A-284; A-326; A-380; A-391; A-399; A-413 and A-415. 1 Publication
    Mutagenesisi311 – 3111R → K: Little change in levels of methylation; when associated with K-29; K-147; K-154 and K-313. 1 Publication
    Mutagenesisi313 – 3131R → K: Little change in levels of methylation; when associated with K-29; K-147; K-154 and K-311. 1 Publication
    Mutagenesisi316 – 3161S → 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. 2 Publications
    Mutagenesisi326 – 3261S → A: Decreases phosphorylation by NLK; when associated with A-284; A-295; A-380; A-391; A-399; A-413 and A-415. 1 Publication
    Mutagenesisi380 – 3801S → A: Decreases phosphorylation by NLK; when associated with A-284; A-295; A-326; A-391; A-399; A-413 and A-415. 1 Publication
    Mutagenesisi391 – 3911S → A: Decreases phosphorylation by NLK; when associated with A-284; A-295; A-326; A-380; A-399; A-413 and A-415. 1 Publication
    Mutagenesisi399 – 3991T → A: Decreases phosphorylation by NLK; when associated with A-284; A-295; A-326; A-380; A-391; A-413 and A-415. 1 Publication
    Mutagenesisi413 – 4131S → A: Decreases phosphorylation by NLK; when associated with A-284; A-295; A-326; A-380; A-391; A-399 and A-415. 1 Publication
    Mutagenesisi415 – 4151S → A: Decreases phosphorylation by NLK; when associated with A-284; A-295; A-326; A-380; A-391; A-399 and A-413. 1 Publication
    Mutagenesisi462 – 4621L → 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. 1 Publication
    Mutagenesisi463 – 4631L → 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. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 652652Forkhead box protein O1PRO_0000091873Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei24 – 241Phosphothreonine; by PKB/AKT1 or PKB/AKT2 and SGK13 Publications
    Modified residuei209 – 2091Phosphoserine; by STK4/MST1By similarity
    Modified residuei215 – 2151PhosphoserineBy similarity
    Modified residuei231 – 2311PhosphoserineBy similarity
    Modified residuei232 – 2321PhosphoserineBy similarity
    Modified residuei242 – 2421N6-acetyllysine2 Publications
    Modified residuei245 – 2451N6-acetyllysine2 Publications
    Modified residuei246 – 2461Phosphoserine; by CDK1By similarity
    Modified residuei248 – 2481Omega-N-methylarginine; by PRMT11 Publication
    Modified residuei250 – 2501Omega-N-methylarginine; by PRMT11 Publication
    Modified residuei253 – 2531Phosphoserine; by PKB/AKT1 and SGK14 Publications
    Modified residuei259 – 2591N6-acetyllysineBy similarity
    Modified residuei262 – 2621N6-acetyllysine2 Publications
    Modified residuei271 – 2711N6-acetyllysineBy similarity
    Modified residuei284 – 2841PhosphoserineBy similarity
    Modified residuei316 – 3161Phosphoserine; by PKB/AKT1 or PKB/AKT21 Publication
    Modified residuei319 – 3191Phosphoserine; by CK1 and SGK11 Publication
    Modified residuei322 – 3221Phosphoserine; by CK1By similarity
    Modified residuei326 – 3261Phosphoserine; by DYRK1ABy similarity
    Modified residuei464 – 4641Phosphothreonine
    Modified residuei465 – 4651Phosphoserine

    Post-translational modificationi

    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.By similarity4 Publications
    Ubiquitinated by SRT2. Ubiquitination leads to proteasomal degradation By similarity.By similarity
    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.5 Publications
    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. 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.By similarity8 Publications

    Keywords - PTMi

    Acetylation, Methylation, Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiQ9R1E0.
    PaxDbiQ9R1E0.
    PRIDEiQ9R1E0.

    PTM databases

    PhosphoSiteiQ9R1E0.

    Expressioni

    Tissue specificityi

    Expressed in white and brown adipose tissues (at protein level).1 Publication

    Inductioni

    Expression is regulated by KRIT1.1 Publication

    Gene expression databases

    ArrayExpressiQ9R1E0.
    BgeeiQ9R1E0.
    CleanExiMM_FOXO1.
    GenevestigatoriQ9R1E0.

    Interactioni

    Subunit structurei

    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.By similarity12 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    ARP102754EBI-1371343,EBI-608057From a different organism.
    CebpaP535665EBI-1371343,EBI-2644207
    FcorP0DJI612EBI-1371343,EBI-6126630
    LrpprcQ6PB662EBI-1371343,EBI-1371262
    SIRT1Q96EB62EBI-1371343,EBI-1802965From a different organism.

    Protein-protein interaction databases

    BioGridi207997. 4 interactions.
    IntActiQ9R1E0. 13 interactions.
    MINTiMINT-5112421.
    STRINGi10090.ENSMUSP00000055308.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9R1E0.
    SMRiQ9R1E0. Positions 151-266.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni208 – 2158DNA-bindingBy similarity
    Regioni231 – 2344DNA-bindingBy similarity
    Regioni280 – 562283Sufficient for interaction with NLKAdd
    BLAST
    Regioni360 – 45697Required for interaction with RUNX2Add
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi248 – 2503Nuclear localization signalBy similarity
    Motifi459 – 4635Required for interaction with SIRT1

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi89 – 968Poly-Ala
    Compositional biasi135 – 1395Poly-Ala
    Compositional biasi149 – 1524Poly-Ser

    Sequence similaritiesi

    Contains 1 fork-head DNA-binding domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiCOG5025.
    GeneTreeiENSGT00390000000589.
    HOGENOMiHOG000251635.
    HOVERGENiHBG057789.
    InParanoidiQ9JJW4.
    KOiK07201.
    OMAiGVKTTTH.
    OrthoDBiEOG7SJD45.
    TreeFamiTF315583.

    Family and domain databases

    Gene3Di1.10.10.10. 1 hit.
    InterProiIPR001766. TF_fork_head.
    IPR018122. TF_fork_head_CS.
    IPR011991. WHTH_DNA-bd_dom.
    [Graphical view]
    PfamiPF00250. Fork_head. 1 hit.
    [Graphical view]
    PRINTSiPR00053. FORKHEAD.
    SMARTiSM00339. FH. 1 hit.
    [Graphical view]
    PROSITEiPS00658. FORK_HEAD_2. 1 hit.
    PS50039. FORK_HEAD_3. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q9R1E0-1 [UniParc]FASTAAdd to Basket

    « Hide

    MAEAPQVVET DPDFEPLPRQ RSCTWPLPRP EFNQSNSTTS SPAPSGGAAA    50
    NPDAAASLAS ASAVSTDFMS NLSLLEESED FARAPGCVAV AAAAAASRGL 100
    CGDFQGPEAG CVHPAPPQPP PTGPLSQPPP VPPSAAAAAG PLAGQPRKTS 150
    SSRRNAWGNL SYADLITKAI ESSAEKRLTL SQIYEWMVKS VPYFKDKGDS 200
    NSSAGWKNSI RHNLSLHSKF IRVQNEGTGK SSWWMLNPEG GKSGKSPRRR 250
    AASMDNNSKF AKSRGRAAKK KASLQSGQEG PGDSPGSQFS KWPASPGSHS 300
    NDDFDNWSTF RPRTSSNAST ISGRLSPIMT EQDDLGDGDV HSLVYPPSAA 350
    KMASTLPSLS EISNPENMEN LLDNLNLLSS PTSLTVSTQS SPGSMMQQTP 400
    CYSFAPPNTS LNSPSPNYSK YTYGQSSMSP LPQMPMQTLQ DSKSSYGGLN 450
    QYNCAPGLLK ELLTSDSPPH NDIMSPVDPG VAQPNSRVLG QNVMMGPNSV 500
    MPAYGSQASH NKMMNPSSHT HPGHAQQTAS VNGRTLPHVV NTMPHTSAMN 550
    RLTPVKTPLQ VPLSHPMQMS ALGSYSSVSS CNGYGRMGVL HQEKLPSDLD 600
    GMFIERLDCD MESIIRNDLM DGDTLDFNFD NVLPNQSFPH SVKTTTHSWV 650
    SG 652
    Length:652
    Mass (Da):69,518
    Last modified:July 27, 2011 - v2
    Checksum:i3FF58636EA85205F
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti619 – 6191L → P in AAD40636. (PubMed:10347145)Curated

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF126056 mRNA. Translation: AAD40636.1.
    AJ252157 mRNA. Translation: CAB86873.1.
    AK137629 mRNA. Translation: BAE23437.1.
    AK154041 mRNA. Translation: BAE32333.1.
    CH466530 Genomic DNA. Translation: EDL35224.1.
    CCDSiCCDS17343.1.
    RefSeqiNP_062713.2. NM_019739.3.
    UniGeneiMm.29891.

    Genome annotation databases

    EnsembliENSMUST00000053764; ENSMUSP00000055308; ENSMUSG00000044167.
    GeneIDi56458.
    KEGGimmu:56458.
    UCSCiuc008pei.2. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF126056 mRNA. Translation: AAD40636.1 .
    AJ252157 mRNA. Translation: CAB86873.1 .
    AK137629 mRNA. Translation: BAE23437.1 .
    AK154041 mRNA. Translation: BAE32333.1 .
    CH466530 Genomic DNA. Translation: EDL35224.1 .
    CCDSi CCDS17343.1.
    RefSeqi NP_062713.2. NM_019739.3.
    UniGenei Mm.29891.

    3D structure databases

    ProteinModelPortali Q9R1E0.
    SMRi Q9R1E0. Positions 151-266.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 207997. 4 interactions.
    IntActi Q9R1E0. 13 interactions.
    MINTi MINT-5112421.
    STRINGi 10090.ENSMUSP00000055308.

    PTM databases

    PhosphoSitei Q9R1E0.

    Proteomic databases

    MaxQBi Q9R1E0.
    PaxDbi Q9R1E0.
    PRIDEi Q9R1E0.

    Protocols and materials databases

    DNASUi 56458.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000053764 ; ENSMUSP00000055308 ; ENSMUSG00000044167 .
    GeneIDi 56458.
    KEGGi mmu:56458.
    UCSCi uc008pei.2. mouse.

    Organism-specific databases

    CTDi 2308.
    MGIi MGI:1890077. Foxo1.

    Phylogenomic databases

    eggNOGi COG5025.
    GeneTreei ENSGT00390000000589.
    HOGENOMi HOG000251635.
    HOVERGENi HBG057789.
    InParanoidi Q9JJW4.
    KOi K07201.
    OMAi GVKTTTH.
    OrthoDBi EOG7SJD45.
    TreeFami TF315583.

    Enzyme and pathway databases

    Reactomei REACT_196588. Constitutive PI3K/AKT Signaling in Cancer.
    REACT_214529. Regulation of gene expression in beta cells.
    REACT_218211. AKT phosphorylates targets in the nucleus.
    REACT_221926. AKT-mediated inactivation of FOXO1A.

    Miscellaneous databases

    NextBioi 312698.
    PROi Q9R1E0.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q9R1E0.
    Bgeei Q9R1E0.
    CleanExi MM_FOXO1.
    Genevestigatori Q9R1E0.

    Family and domain databases

    Gene3Di 1.10.10.10. 1 hit.
    InterProi IPR001766. TF_fork_head.
    IPR018122. TF_fork_head_CS.
    IPR011991. WHTH_DNA-bd_dom.
    [Graphical view ]
    Pfami PF00250. Fork_head. 1 hit.
    [Graphical view ]
    PRINTSi PR00053. FORKHEAD.
    SMARTi SM00339. FH. 1 hit.
    [Graphical view ]
    PROSITEi PS00658. FORK_HEAD_2. 1 hit.
    PS50039. FORK_HEAD_3. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Insulin stimulates phosphorylation of the forkhead transcription factor FKHR on serine 253 through a Wortmannin-sensitive pathway."
      Nakae J., Park B.C., Accili D.
      J. Biol. Chem. 274:15982-15985(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], PHOSPHORYLATION AT THR-24; SER-253 AND SER-316, MUTAGENESIS OF THR-24; SER-253 AND SER-316.
      Tissue: Liver.
    2. "The forkhead FKHR is involved in thymocyte proliferation."
      Leenders H., Benoist C., Mathis D.
      Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    3. "The transcriptional landscape of the mammalian genome."
      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.
      Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: C57BL/6J and NOD.
      Tissue: Thymus and Vagina.
    4. Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
      Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    5. "Insulin-regulated hepatic gluconeogenesis through FOXO1-PGC-1alpha interaction."
      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.
      Nature 423:550-555(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH PPARGC1A, FUNCTION, PHOSPHORYLATION.
    6. Cited for: DISRUPTION PHENOTYPE, FUNCTION.
    7. "Silent information regulator 2 potentiates Foxo1-mediated transcription through its deacetylase activity."
      Daitoku H., Hatta M., Matsuzaki H., Aratani S., Ohshima T., Miyagishi M., Nakajima T., Fukamizu A.
      Proc. Natl. Acad. Sci. U.S.A. 101:10042-10047(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACETYLATION AT LYS-242; LYS-245 AND LYS-262, INTERACTION WITH SIRT1, DEACETYLATION, FUNCTION, MUTAGENESIS OF LYS-242; LYS-245 AND LYS-262.
    8. "Acetylation of Foxo1 alters its DNA-binding ability and sensitivity to phosphorylation."
      Matsuzaki H., Daitoku H., Hatta M., Aoyama H., Yoshimochi K., Fukamizu A.
      Proc. Natl. Acad. Sci. U.S.A. 102:11278-11283(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACETYLATION AT LYS-242; LYS-245 AND LYS-262, PHOSPHORYLATION AT SER-253, DNA-BINDING, MUTAGENESIS OF LYS-242; LYS-245; SER-253 AND LYS-262.
    9. "Defects in energy homeostasis in Leigh syndrome French Canadian variant through PGC-1alpha/LRP130 complex."
      Cooper M.P., Qu L., Rohas L.M., Lin J., Yang W., Erdjument-Bromage H., Tempst P., Spiegelman B.M.
      Genes Dev. 20:2996-3009(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH LRPPRC.
    10. "The LXXLL motif of murine forkhead transcription factor FoxO1 mediates Sirt1-dependent transcriptional activity."
      Nakae J., Cao Y., Daitoku H., Fukamizu A., Ogawa W., Yano Y., Hayashi Y.
      J. Clin. Invest. 116:2473-2483(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH SIRT1, PHOSPHORYLATION, SUBCELLULAR LOCATION, FUNCTION, MUTAGENESIS OF THR-24; SER-253; SER-316; LEU-462 AND LEU-463.
    11. "SIRT2 regulates adipocyte differentiation through FoxO1 acetylation/deacetylation."
      Jing E., Gesta S., Kahn C.R.
      Cell Metab. 6:105-114(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACETYLATION, DEACETYLATION BY SIRT2, FUNCTION IN INHIBITION OF ADIPOCYTE DIFFERENTIATION, INTERACTION WITH SIRT2.
    12. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Liver.
    13. "Arginine methylation of FOXO transcription factors inhibits their phosphorylation by Akt."
      Yamagata K., Daitoku H., Takahashi Y., Namiki K., Hisatake K., Kako K., Mukai H., Kasuya Y., Fukamizu A.
      Mol. Cell 32:221-231(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION, SUBCELLULAR LOCATION, METHYLATION AT ARG-248 AND ARG-250, MUTAGENESIS OF ARG-29; ARG-147; ARG-154; ARG-248; ARG-250; ARG-311 AND ARG-313.
    14. "SIRT2 suppresses adipocyte differentiation by deacetylating FOXO1 and enhancing FOXO1's repressive interaction with PPARgamma."
      Wang F., Tong Q.
      Mol. Biol. Cell 20:801-808(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACETYLATION, DEACETYLATION BY SIRT2, INTERACTION WITH PPARG AND SIRT2, SUBCELLULAR LOCATION.
    15. "Regulation of FOXO1 by TAK1-Nemo-like kinase pathway."
      Kim S., Kim Y., Lee J., Chung J.
      J. Biol. Chem. 285:8122-8129(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH NLK, SUBCELLULAR LOCATION, PHOSPHORYLATION BY NLK, MUTAGENESIS OF SER-284; SER-295; SER-326; SER-380; SER-391; THR-399; SER-413 AND SER-415.
    16. "Uncoupling of acetylation from phosphorylation regulates FoxO1 function independent of its subcellular localization."
      Qiang L., Banks A.S., Accili D.
      J. Biol. Chem. 285:27396-27401(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT THR-24 AND SER-253, ACETYLATION, SUBCELLULAR LOCATION, FUNCTION, MUTAGENESIS OF THR-24; LYS-219; LYS-242; LYS-245; SER-253; LYS-259; LYS-262; LYS-271 AND LYS-291.
    17. "Serum- and glucocorticoid-inducible kinase 1 (SGK1) regulates adipocyte differentiation via forkhead box O1."
      Di Pietro N., Panel V., Hayes S., Bagattin A., Meruvu S., Pandolfi A., Hugendubler L., Fejes-Toth G., Naray-Fejes-Toth A., Mueller E.
      Mol. Endocrinol. 24:370-380(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT THR-24; SER-253 AND SER-319 BY SGK1, SUBCELLULAR LOCATION.
    18. "KRIT1 regulates the homeostasis of intracellular reactive oxygen species."
      Goitre L., Balzac F., Degani S., Degan P., Marchi S., Pinton P., Retta S.F.
      PLoS ONE 5:E11786-E11786(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, PHOSPHORYLATION, INTERACTION WITH SIRT1, INDUCTION.
    19. "FoxO1 and SIRT1 regulate beta-cell responses to nitric oxide."
      Hughes K.J., Meares G.P., Hansen P.A., Corbett J.A.
      J. Biol. Chem. 286:8338-8348(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, ACETYLATION, RESPONSE TO NITRIC OXIDE.
    20. "Nucleo-cytosolic shuttling of FoxO1 directly regulates mouse Ins2 but not Ins1 gene expression in pancreatic beta cells (MIN6)."
      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.
      J. Biol. Chem. 286:13647-13656(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, FUNCTION, DNA-BINDING.
    21. "Foxo1 mediates insulin-like growth factor 1 (IGF1)/insulin regulation of osteocalcin expression by antagonizing Runx2 in osteoblasts."
      Yang S., Xu H., Yu S., Cao H., Fan J., Ge C., Fransceschi R.T., Dong H.H., Xiao G.
      J. Biol. Chem. 286:19149-19158(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH RUNX2, FUNCTION.
    22. "The B55alpha-containing PP2A holoenzyme dephosphorylates FOXO1 in islet beta-cells under oxidative stress."
      Yan L., Guo S., Brault M., Harmon J., Robertson R.P., Hamid R., Stein R., Yang E.
      Biochem. J. 444:239-247(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: CHARACTERISTICS OF AN ANIMAL MODEL OF DIABETES MELLITUS TYPE 2, FUNCTION, DEPHOSPHORYLATION AT THR-24 AND SER-253, INTERACTION WITH PPP2R1A.
    23. "Novel repressor regulates insulin sensitivity through interaction with Foxo1."
      Nakae J., Cao Y., Hakuno F., Takemori H., Kawano Y., Sekioka R., Abe T., Kiyonari H., Tanaka T., Sakai J., Takahashi S., Itoh H.
      EMBO J. 31:2275-2295(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION AS A TRANSCRIPTIONAL ACTIVATOR, INTERACTION WITH FCOR AND SIRT1, TISSUE SPECIFICITY, MUTAGENESIS OF LYS-242; LYS-245; LYS-259; LYS-262; LYS-271 AND LYS-291.
    24. "FoxO1 protein cooperates with ATF4 protein in osteoblasts to control glucose homeostasis."
      Kode A., Mosialou I., Silva B.C., Joshi S., Ferron M., Rached M.T., Kousteni S.
      J. Biol. Chem. 287:8757-8768(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, INTERACTION WITH ATF4, FUNCTION.

    Entry informationi

    Entry nameiFOXO1_MOUSE
    AccessioniPrimary (citable) accession number: Q9R1E0
    Secondary accession number(s): Q9JJW4
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 30, 2000
    Last sequence update: July 27, 2011
    Last modified: October 1, 2014
    This is version 131 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    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.

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3