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Q12778 (FOXO1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 150. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Forkhead box protein O1
Alternative name(s):
Forkhead box protein O1A
Forkhead in rhabdomyosarcoma
Gene names
Name:FOXO1
Synonyms:FKHR, FOXO1A
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length655 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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 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. Ref.8 Ref.12 Ref.13 Ref.14 Ref.18 Ref.20 Ref.23

Subunit structure

Interacts with LRPPRC. 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-256 leading to its nuclear import By similarity. 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. Binds to CDK1. 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. The interaction requires the presence of KRIT1. 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 PRMT1; the interaction methylates FOXO1, prevents PKB/AKT1 phosphorylation and retains FOXO1 in the nucleus. Interacts with EP300 and CREBBP; the interactions acetylate FOXO1. Ref.10 Ref.13 Ref.14 Ref.15 Ref.16 Ref.18

Subcellular location

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-256 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. Retained in the nucleus on methylation. Ref.9 Ref.10 Ref.12 Ref.14 Ref.20 Ref.23

Tissue specificity

Ubiquitous. Ref.2

Induction

Expression is regulated by KRIT1. Levels of expression also regulated by FOXC1 which binds to a conserved element in the FOXO1 promoter. Ref.21

Post-translational modification

Phosphorylation by NLK promotes nuclear export and inhibits the transcriptional activity. In response to growth factors, phosphorylation on Thr-24, Ser-256 and Ser-322 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-256 decreases DNA-binding activity and promotes the phosphorylation of Thr-24 and Ser-319, permitting phosphorylation of Ser-322 and Ser-325, 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-329 is independent of IGF1 and leads to reduced function. Dephosphorylated on Thr-24 and Ser-256 by PP2A in beta-cells under oxidative stress leading to nuclear retention By similarity. Phosphorylation of Ser-249 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-212, upon oxidative stress, inhibits binding to 14-3-3 proteins and nuclear export. Ref.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.14 Ref.18 Ref.20 Ref.23 Ref.25

Ubiquitinated by SRT2. Ubiquitination leads to proteasomal degradation. Ref.15

Methylation inhibits AKT1-mediated phosphorylation at Ser-256 and is increased by oxidative stress 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-256. Deacetylation by SIRT1 results in reactivation of the transcriptional activity. Oxidative stress by hydrogen peroxide treatment appears to promote deacetylation and uncoupling of insulin-induced phosphorylation. By contrast, resveratrol acts independently of acetylation. Ref.13 Ref.14 Ref.25

Involvement in disease

Rhabdomyosarcoma 2 (RMS2) [MIM:268220]: A form of rhabdomyosarcoma, a highly malignant tumor of striated muscle derived from primitive mesenchymal cells and exhibiting differentiation along rhabdomyoblastic lines. Rhabdomyosarcoma is one of the most frequently occurring soft tissue sarcomas and the most common in children. It occurs in four forms: alveolar, pleomorphic, embryonal and botryoidal rhabdomyosarcomas.
Note: The gene represented in this entry may be involved in disease pathogenesis. Chromosomal aberrations involving FOXO1 are found in rhabdomyosarcoma. Translocation (2;13)(q35;q14) with PAX3 and translocation t(1;13)(p36;q14) with PAX7. The resulting protein is a transcriptional activator.

Sequence similarities

Contains 1 fork-head DNA-binding domain.

Ontologies

Keywords
   Biological processApoptosis
Transcription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityChromosomal rearrangement
   DiseaseProto-oncogene
   LigandDNA-binding
   Molecular functionActivator
   PTMAcetylation
Methylation
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processFc-epsilon receptor signaling pathway

Traceable author statement. Source: Reactome

apoptotic process

Inferred from electronic annotation. Source: UniProtKB-KW

blood vessel development

Inferred from Biological aspect of Ancestor. Source: RefGenome

cellular glucose homeostasis

Inferred from sequence or structural similarity PubMed 22510882. Source: UniProtKB

cellular response to DNA damage stimulus

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to cold

Inferred from sequence or structural similarity PubMed 22510882. Source: UniProtKB

cellular response to nitric oxide

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to oxidative stress

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to starvation

Inferred from sequence or structural similarity PubMed 22510882. Source: UniProtKB

embryo development

Inferred from Biological aspect of Ancestor. Source: RefGenome

endocrine pancreas development

Traceable author statement. Source: Reactome

epidermal growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

fat cell differentiation

Inferred from sequence or structural similarity PubMed 22510882. Source: UniProtKB

fibroblast growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

innate immune response

Traceable author statement. Source: Reactome

insulin receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of apoptotic process

Inferred from direct assay PubMed 10871843. Source: UniProtKB

negative regulation of fat cell differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of stress-activated MAPK cascade

Inferred from direct assay PubMed 19696738. Source: BHF-UCL

negative regulation of transcription, DNA-templated

Inferred from sequence or structural similarity PubMed 22510882. Source: UniProtKB

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

pattern specification process

Inferred from Biological aspect of Ancestor. Source: RefGenome

phosphatidylinositol-mediated signaling

Traceable author statement. Source: Reactome

positive regulation of gluconeogenesis

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 10871843Ref.12. Source: UniProtKB

positive regulation of transcription, DNA-templated

Inferred from direct assay PubMed 10871843Ref.12PubMed 7862145. Source: UniProtKB

protein acetylation

Inferred from sequence or structural similarity PubMed 22510882. Source: UniProtKB

regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

regulation of energy homeostasis

Inferred from sequence or structural similarity PubMed 22510882. Source: UniProtKB

regulation of gluconeogenesis by regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

temperature homeostasis

Inferred from sequence or structural similarity PubMed 22510882. Source: UniProtKB

tissue development

Inferred from Biological aspect of Ancestor. Source: RefGenome

   Cellular_componentcytoplasm

Inferred from direct assay Ref.10Ref.9Ref.12. Source: UniProtKB

cytosol

Inferred from sequence or structural similarity PubMed 22510882. Source: UniProtKB

mitochondrion

Inferred from sequence or structural similarity PubMed 22510882. Source: UniProtKB

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay Ref.9Ref.12PubMed 18680538. Source: UniProtKB

   Molecular_functionDNA binding, bending

Inferred from Biological aspect of Ancestor. Source: RefGenome

RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in negative regulation of transcription

Inferred from electronic annotation. Source: Ensembl

chromatin binding

Inferred from sequence or structural similarity PubMed 22510882. Source: UniProtKB

protein phosphatase 2A binding

Inferred from sequence or structural similarity. Source: UniProtKB

sequence-specific DNA binding

Inferred from direct assay Ref.12. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 655655Forkhead box protein O1
PRO_0000091872

Regions

DNA binding159 – 23577Fork-head Ref.8 Ref.25
Region211 – 2188DNA-binding
Region234 – 2374DNA-binding
Region283 – 563281Sufficient for interaction with NLK By similarity
Region363 – 45997Required for interaction with RUNX2 By similarity
Motif251 – 2533Nuclear localization signal
Motif462 – 4665Required for interaction with SIRT1 By similarity
Compositional bias91 – 10212Poly-Ala
Compositional bias120 – 13011Poly-Pro
Compositional bias152 – 1554Poly-Ser

Sites

Site1581DNA-binding
Site1651DNA-binding
Site2251DNA-binding

Amino acid modifications

Modified residue241Phosphothreonine; by PKB/AKT1 or PKB/AKT2 and SGK1 Ref.7 Ref.10 Ref.11
Modified residue2121Phosphoserine; by STK4/MST1 Ref.20 Ref.23 Ref.25
Modified residue2181Phosphoserine; by STK4/MST1 Ref.25
Modified residue2341Phosphoserine; by STK4/MST1 Ref.25
Modified residue2351Phosphoserine; by STK4/MST1 Ref.25
Modified residue2451N6-acetyllysine By similarity
Modified residue2481N6-acetyllysine By similarity
Modified residue2491Phosphoserine; by CDK1 Ref.18
Modified residue2511Omega-N-methylarginine; by PRMT1 By similarity
Modified residue2531Omega-N-methylarginine; by PRMT1 By similarity
Modified residue2561Phosphoserine; by PKB/AKT1 and SGK1 Ref.7 Ref.8 Ref.10 Ref.11
Modified residue2651N6-acetyllysine By similarity
Modified residue2871Phosphoserine Ref.17 Ref.22 Ref.24
Modified residue3191Phosphoserine; by PKB/AKT1 Ref.7 Ref.10 Ref.11
Modified residue3221Phosphoserine; by CK1 and SGK1 Ref.11
Modified residue3251Phosphoserine; by CK1 Ref.11
Modified residue3291Phosphoserine; by DYRK1A Ref.9 Ref.11
Modified residue4671Phosphothreonine By similarity
Modified residue4681Phosphoserine By similarity

Experimental info

Mutagenesis241T → A: Abolishes PKB/AKT1-mediated phosphorylation but does not prevent phosphorylation of Ser-256 or Ser-319. Also inhibits binding of 14-3-3 proteins. Nuclear in unstimulated cells, and little export to cytoplasm on IGF1 stimulation. Inhibits the PKB/AKT1-mediated activity towards other substrates but does not block the IGF1-activated 'T-308' of phosphorylation of PKB/AKT1; when associated with A-256 and A-319. Targeted to the nucleus and enhances transactivation; when associated with A-319. Ref.10 Ref.12
Mutagenesis2121S → A: Abolishes STK4/MST1-mediated phosphorylation. Ref.20
Mutagenesis2451K → A: Disrupts DNA-binding; when associated with A-248.
Mutagenesis2481K → A: Disrupts DNA-binding; when associated with A-245.
Mutagenesis2491S → A: Impaired phosphorylation by CDK1. Ref.18 Ref.25
Mutagenesis2491S → E: No effect on DNA-binding. Ref.18 Ref.25
Mutagenesis251 – 2533RRR → SAS: No targeting to the nucleus and disruption of DNA-binding.
Mutagenesis2561S → A: Completely abolishes PKB/AKT1-mediated phosphorylation at all three sites, and inhibits binding of 14-3-3 proteins. Inhibits the PKB/AKT1-mediated activity towards other substrates but does not block the IGF1-activated 'T-308' of phosphorylation of PKB/AKT1; when associated with or without A-24 and A-319. Nuclear in unstimulated cells, and little export to cytoplasm on IGF1 stimulation. Abolishes the ability of IGF1 to suppress transactivation. Prevents T-24 and S-319 phosphorylation. Enhances transactivation; when associated with A-24 and A-319. Ref.10 Ref.12 Ref.15
Mutagenesis2561S → D: Reduces DNA binding, promotes nuclear exclusion and partially promotes T-24 and S-319 phosphorylation. Reduces DNA binding, does not promote nuclear exclusion but reduces transactivation; when associated with A-24 and A-319. Ref.10 Ref.12 Ref.15
Mutagenesis3191S → A: Abolishes PKB/AKT1-mediated phosphorylation but does not prevent phosphorylation of Ser-24 or Ser-256. Inhibits the PKB/AKT1-mediated activity towards other substrates but does not block the IGF1-activated 'T-308' of phosphorylation of PKB/AKT1; when associated with A-24 and A-256. Targeted to the nucleus and enhances transactivation; when associated with A-24. Ref.10 Ref.12
Mutagenesis3291S → A: Targeted to the nucleus and enhances transactivation. Ref.9
Sequence conflict1311L → V in AAA03629. Ref.1
Sequence conflict3431V → M in AAH70065. Ref.5

Secondary structure

.................. 655
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q12778 [UniParc].

Last modified October 17, 2006. Version 2.
Checksum: 6DEF6C994BDFDBAB

FASTA65569,662
        10         20         30         40         50         60 
MAEAPQVVEI DPDFEPLPRP RSCTWPLPRP EFSQSNSATS SPAPSGSAAA NPDAAAGLPS 

        70         80         90        100        110        120 
ASAAAVSADF MSNLSLLEES EDFPQAPGSV AAAVAAAAAA AATGGLCGDF QGPEAGCLHP 

       130        140        150        160        170        180 
APPQPPPPGP LSQHPPVPPA AAGPLAGQPR KSSSSRRNAW GNLSYADLIT KAIESSAEKR 

       190        200        210        220        230        240 
LTLSQIYEWM VKSVPYFKDK GDSNSSAGWK NSIRHNLSLH SKFIRVQNEG TGKSSWWMLN 

       250        260        270        280        290        300 
PEGGKSGKSP RRRAASMDNN SKFAKSRSRA AKKKASLQSG QEGAGDSPGS QFSKWPASPG 

       310        320        330        340        350        360 
SHSNDDFDNW STFRPRTSSN ASTISGRLSP IMTEQDDLGE GDVHSMVYPP SAAKMASTLP 

       370        380        390        400        410        420 
SLSEISNPEN MENLLDNLNL LSSPTSLTVS TQSSPGTMMQ QTPCYSFAPP NTSLNSPSPN 

       430        440        450        460        470        480 
YQKYTYGQSS MSPLPQMPIQ TLQDNKSSYG GMSQYNCAPG LLKELLTSDS PPHNDIMTPV 

       490        500        510        520        530        540 
DPGVAQPNSR VLGQNVMMGP NSVMSTYGSQ ASHNKMMNPS SHTHPGHAQQ TSAVNGRPLP 

       550        560        570        580        590        600 
HTVSTMPHTS GMNRLTQVKT PVQVPLPHPM QMSALGGYSS VSSCNGYGRM GLLHQEKLPS 

       610        620        630        640        650 
DLDGMFIERL DCDMESIIRN DLMDGDTLDF NFDNVLPNQS FPHSVKTTTH SWVSG 

« Hide

References

« Hide 'large scale' references
[1]"Fusion of a fork head domain gene to PAX3 in the solid tumour alveolar rhabdomyosarcoma."
Galili N., Davis R.J., Fredericks W.J., Mukhopadhyay S., Rauscher F.J. III, Emanuel B.S., Rovera G., Barr F.G.
Nat. Genet. 5:230-235(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHROMOSOMAL TRANSLOCATION WITH PAX3.
[2]"Cloning and characterization of three human forkhead genes that comprise an FKHR-like gene subfamily."
Anderson M.J., Viars C.S., Czekay S., Cavenee W.K., Arden K.C.
Genomics 47:187-199(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
Tissue: Rhabdomyosarcoma.
[3]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]"The DNA sequence and analysis of human chromosome 13."
Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L., Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S., Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P., Ambrose K.D., Andrews D.T. expand/collapse author list , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P., Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C., Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P., Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L., Frankish A.G., Frankland J., French L., Garner P., Garnett J., Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M., Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D., Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D., Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S., Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S., Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R., Rogers J., Ross M.T.
Nature 428:522-528(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Lymph and Placenta.
[6]"Fusion of PAX7 to FKHR by the variant t(1;13)(p36;q14) translocation in alveolar rhabdomyosarcoma."
Davis R.J., D'Cruz C.M., Lovell M.A., Biegel J.A., Barr F.G.
Cancer Res. 54:2869-2872(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: CHROMOSOMAL TRANSLOCATION WITH PAX7.
[7]"Phosphorylation of the transcription factor forkhead family member FKHR by protein kinase B."
Rena G., Guo S., Cichy S.C., Unterman T.G., Cohen P.
J. Biol. Chem. 274:17179-17183(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-24; SER-256 AND SER-319.
[8]"Phosphorylation of serine 256 by protein kinase B disrupts transactivation by FKHR and mediates effects of insulin on insulin-like growth factor-binding protein-1 promoter activity through a conserved insulin response sequence."
Guo S., Rena G., Cichy S., He X., Cohen P., Unterman T.
J. Biol. Chem. 274:17184-17192(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: DNA-BINDING, PHOSPHORYLATION AT SER-256, FUNCTION.
[9]"The kinase DYRK1A phosphorylates the transcription factor FKHR at Ser329 in vitro, a novel in vivo phosphorylation site."
Woods Y.L., Rena G., Morrice N., Barthel A., Becker W., Guo S., Unterman T.G., Cohen P.
Biochem. J. 355:597-607(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-329, MUTAGENESIS OF SER-329.
[10]"Roles of the forkhead in rhabdomyosarcoma (FKHR) phosphorylation sites in regulating 14-3-3 binding, transactivation and nuclear targetting."
Rena G., Prescott A.R., Guo S., Cohen P., Unterman T.G.
Biochem. J. 354:605-612(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH YWHAG AND YWHAZ, PHOSPHORYLATION AT THR-24; SER-256 AND SER-319, SUBCELLULAR LOCATION, MUTAGENESIS OF THR-24; SER-256 AND SER-319.
[11]"Two novel phosphorylation sites on FKHR that are critical for its nuclear exclusion."
Rena G., Woods Y.L., Prescott A.R., Peggie M., Unterman T.G., Williams M.R., Cohen P.
EMBO J. 21:2263-2271(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-24; SER-256; SER-319; SER-322; SER-325 AND SER-329.
[12]"Phosphorylation of serine 256 suppresses transactivation by FKHR (FOXO1) by multiple mechanisms. Direct and indirect effects on nuclear/cytoplasmic shuttling and DNA binding."
Zhang X., Gan L., Pan H., Guo S., He X., Olson S.T., Mesecar A., Adam S., Unterman T.G.
J. Biol. Chem. 277:45276-45284(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF THR-24; SER-256 AND SER-319.
[13]"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: INTERACTION WITH CREBBP AND SIRT1, ACETYLATION, DEACETYLATION, FUNCTION.
[14]"The coactivator p300 directly acetylates the forkhead transcription factor Foxo1 and stimulates Foxo1-induced transcription."
Perrot V., Rechler M.M.
Mol. Endocrinol. 19:2283-2298(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH EP300, ACETYLATION, SUBCELLULAR LOCATION, PHOSPHORYLATION, FUNCTION.
[15]"Skp2 inhibits FOXO1 in tumor suppression through ubiquitin-mediated degradation."
Huang H., Regan K.M., Wang F., Wang D., Smith D.I., van Deursen J.M., Tindall D.J.
Proc. Natl. Acad. Sci. U.S.A. 102:1649-1654(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SKP2, UBIQUITINATION, MUTAGENESIS OF SER-256.
[16]"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: INTERACTION WITH PRMT1.
[17]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-287, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[18]"Activation of FOXO1 by Cdk1 in cycling cells and postmitotic neurons."
Yuan Z., Becker E.B.E., Merlo P., Yamada T., DiBacco S., Konishi Y., Schaefer E.M., Bonni A.
Science 319:1665-1668(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, PHOSPHORYLATION AT SER-249 BY CDK1, INTERACTION WITH CDK1 AND 14-3-3 PROTEINS, MUTAGENESIS OF SER-249.
[19]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[20]"Regulation of neuronal cell death by MST1-FOXO1 signaling."
Yuan Z., Lehtinen M.K., Merlo P., Villen J., Gygi S., Bonni A.
J. Biol. Chem. 284:11285-11292(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-212, SUBCELLULAR LOCATION, FUNCTION, MUTAGENESIS OF SER-212.
[21]"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: INDUCTION.
[22]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-287, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[23]"Hippo/Mst1 stimulates transcription of the proapoptotic mediator NOXA in a FoxO1-dependent manner."
Valis K., Prochazka L., Boura E., Chladova J., Obsil T., Rohlena J., Truksa J., Dong L.F., Ralph S.J., Neuzil J.
Cancer Res. 71:946-954(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-212.
[24]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-287, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[25]"Structural basis for DNA recognition by FoxO1 and its regulation by posttranslational modification."
Brent M.M., Anand R., Marmorstein R.
Structure 16:1407-1416(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 151-266, DNA-BINDING, PHOSPHORYLATION AT SER-212; SER-218; SER-234 AND SER-235, ACETYLATION, IDENTIFICATION BY MASS SPECTROMETRY, MUTAGENESIS OF SER-249.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U02310 mRNA. Translation: AAA03629.1.
AF032885 mRNA. Translation: AAC39591.1.
BT007455 mRNA. Translation: AAP36123.1.
AL355132, AL133318 Genomic DNA. Translation: CAH70978.1.
AL133318, AL355132 Genomic DNA. Translation: CAI16970.1.
BC021981 mRNA. Translation: AAH21981.1.
BC070065 mRNA. Translation: AAH70065.3.
PIRS40521.
RefSeqNP_002006.2. NM_002015.3.
UniGeneHs.370666.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3CO6X-ray2.10C151-249[»]
3CO7X-ray2.91C/F151-266[»]
3COAX-ray2.20C/F151-266[»]
ProteinModelPortalQ12778.
SMRQ12778. Positions 154-269.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108597. 31 interactions.
DIPDIP-35654N.
IntActQ12778. 9 interactions.
STRING9606.ENSP00000368880.

Chemistry

BindingDBQ12778.
ChEMBLCHEMBL5294.

PTM databases

PhosphoSiteQ12778.

Polymorphism databases

DMDM116241368.

Proteomic databases

PaxDbQ12778.
PRIDEQ12778.

Protocols and materials databases

DNASU2308.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000379561; ENSP00000368880; ENSG00000150907.
GeneID2308.
KEGGhsa:2308.
UCSCuc001uxl.4. human.

Organism-specific databases

CTD2308.
GeneCardsGC13M041129.
HGNCHGNC:3819. FOXO1.
HPACAB022326.
HPA001252.
MIM136533. gene.
268220. phenotype.
neXtProtNX_Q12778.
Orphanet99756. Alveolar rhabdomyosarcoma.
PharmGKBPA28237.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5025.
HOGENOMHOG000251635.
HOVERGENHBG057789.
InParanoidQ12778.
KOK07201.
OMAGVKTTTH.
OrthoDBEOG7SJD45.
PhylomeDBQ12778.
TreeFamTF315583.

Enzyme and pathway databases

ReactomeREACT_111045. Developmental Biology.
REACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_6900. Immune System.
SignaLinkQ12778.

Gene expression databases

BgeeQ12778.
CleanExHS_FOXO1.
GenevestigatorQ12778.

Family and domain databases

Gene3D1.10.10.10. 1 hit.
InterProIPR001766. TF_fork_head.
IPR018122. TF_fork_head_CS.
IPR011991. WHTH_DNA-bd_dom.
[Graphical view]
PfamPF00250. Fork_head. 1 hit.
[Graphical view]
PRINTSPR00053. FORKHEAD.
SMARTSM00339. FH. 1 hit.
[Graphical view]
PROSITEPS00658. FORK_HEAD_2. 1 hit.
PS50039. FORK_HEAD_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSFOXO1. human.
EvolutionaryTraceQ12778.
GeneWikiFOXO1.
GenomeRNAi2308.
NextBio9375.
PROQ12778.
SOURCESearch...

Entry information

Entry nameFOXO1_HUMAN
AccessionPrimary (citable) accession number: Q12778
Secondary accession number(s): O43523, Q5VYC7, Q6NSK6
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: October 17, 2006
Last modified: April 16, 2014
This is version 150 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 13

Human chromosome 13: entries, gene names and cross-references to MIM