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O43524 (FOXO3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 156. 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 O3
Alternative name(s):
AF6q21 protein
Forkhead in rhabdomyosarcoma-like 1
Gene names
Name:FOXO3
Synonyms:FKHRL1, FOXO3A
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length673 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Transcriptional activator which triggers apoptosis in the absence of survival factors, including neuronal cell death upon oxidative stress. Recognizes and binds to the DNA sequence 5'-[AG]TAAA[TC]A-3'. Participates in post-transcriptional regulation of MYC: following phosphorylation by MAPKAPK5, promotes induction of miR-34b and miR-34c expression, 2 post-transcriptional regulators of MYC that bind to the 3'UTR of MYC transcript and prevent its translation. Ref.6 Ref.8 Ref.16

Subunit structure

Interacts with YWHAB/14-3-3-beta and YWHAZ/14-3-3-zeta, which are required for cytosolic sequestration. Upon oxidative stress, interacts with STK4/MST1, which disrupts interaction with YWHAB/14-3-3-beta and leads to nuclear translocation. Interacts with PIM1. Interacts with DDIT3/CHOP. Ref.8 Ref.10 Ref.18

Subcellular location

Cytoplasmcytosol. Nucleus. Note: Translocates to the nucleus upon oxidative stress and in the absence of survival factors. Ref.6 Ref.8 Ref.9 Ref.16 Ref.18

Tissue specificity

Ubiquitous. Ref.1

Post-translational modification

In the presence of survival factors such as IGF-1, phosphorylated on Thr-32 and Ser-253 by AKT1/PKB. This phosphorylated form then interacts with 14-3-3 proteins and is retained in the cytoplasm. Survival factor withdrawal induces dephosphorylation and promotes translocation to the nucleus where the dephosphorylated protein induces transcription of target genes and triggers apoptosis. Although AKT1/PKB doesn't appear to phosphorylate Ser-315 directly, it may activate other kinases that trigger phosphorylation at this residue. Phosphorylated by STK4/MST1 on Ser-209 upon oxidative stress, which leads to dissociation from YWHAB/14-3-3-beta and nuclear translocation. Phosphorylated by PIM1. Phosphorylation by AMPK leads to the activation of transcriptional activity without affecting subcellular localization. Phosphorylation by MAPKAPK5 promotes nuclear localization and DNA-binding, leading to induction of miR-34b and miR-34c expression, 2 post-transcriptional regulators of MYC that bind to the 3'UTR of MYC transcript and prevent its translation. Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.16

Heavyly methylated by SET9 which decreases stability, while moderately increasing transcriptional activity. The main methylation site is Lys-271. Methylation doesn't affect subcellular location. Ref.17

Involvement in disease

A chromosomal aberration involving FOXO3 is found in secondary acute leukemias. Translocation t(6;11)(q21;q23) with KMT2A/MLL1.

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
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA damage response, signal transduction by p53 class mediator

Inferred from electronic annotation. Source: Ensembl

Fc-epsilon receptor signaling pathway

Traceable author statement. Source: Reactome

antral ovarian follicle growth

Inferred from electronic annotation. Source: Ensembl

cellular response to DNA damage stimulus

Inferred from Biological aspect of Ancestor. Source: RefGenome

epidermal growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

extrinsic apoptotic signaling pathway in absence of ligand

Inferred from electronic annotation. Source: Ensembl

fibroblast growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

glucose homeostasis

Inferred from electronic annotation. Source: Ensembl

initiation of primordial ovarian follicle growth

Inferred from electronic annotation. Source: Ensembl

innate immune response

Traceable author statement. Source: Reactome

insulin receptor signaling pathway

Inferred from Biological aspect of Ancestor. Source: RefGenome

negative regulation of transcription from RNA polymerase II promoter

Inferred from mutant phenotype PubMed 18787191. Source: BHF-UCL

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

oocyte maturation

Inferred from electronic annotation. Source: Ensembl

ovulation from ovarian follicle

Inferred from electronic annotation. Source: Ensembl

pattern specification process

Inferred from Biological aspect of Ancestor. Source: RefGenome

phosphatidylinositol-mediated signaling

Traceable author statement. Source: Reactome

positive regulation of erythrocyte differentiation

Inferred from direct assay PubMed 14734530. Source: MGI

positive regulation of neuron apoptotic process

Inferred from mutant phenotype Ref.6. Source: UniProtKB

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay Ref.6. Source: UniProtKB

positive regulation of transcription, DNA-templated

Inferred from direct assay Ref.6. Source: UniProtKB

regulation of cell proliferation

Inferred from Biological aspect of Ancestor. Source: RefGenome

regulation of translation

Inferred from direct assay Ref.16. Source: UniProtKB

tissue development

Inferred from Biological aspect of Ancestor. Source: RefGenome

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytoplasm

Inferred from direct assay Ref.6Ref.8Ref.16. Source: UniProtKB

cytosol

Inferred from Biological aspect of Ancestor. Source: RefGenome

membrane

Inferred from electronic annotation. Source: Ensembl

nucleoplasm

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay Ref.6Ref.8Ref.16Ref.18. Source: UniProtKB

   Molecular_functionDNA binding

Inferred from direct assay Ref.16. Source: UniProtKB

DNA binding, bending

Inferred from Biological aspect of Ancestor. Source: RefGenome

protein binding

Inferred from physical interaction Ref.18. Source: UniProtKB

protein kinase binding

Inferred from physical interaction Ref.8Ref.10Ref.16. Source: UniProtKB

sequence-specific DNA binding

Inferred from direct assay Ref.6. Source: UniProtKB

sequence-specific DNA binding transcription factor activity

Inferred from direct assay PubMed 14734530. Source: MGI

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 673673Forkhead box protein O3
PRO_0000091874

Regions

DNA binding157 – 25195Fork-head Ref.16
Motif242 – 25918Nuclear localization signal Ref.19

Amino acid modifications

Modified residue321Phosphothreonine; by PKB/AKT1 Ref.6
Modified residue461N6-methyllysine Ref.17
Modified residue1491N6-methyllysine Ref.17
Modified residue1791Phosphothreonine; by AMPK Ref.9
Modified residue2091Phosphoserine; by STK4/MST1 Ref.8
Modified residue2151Phosphoserine; by MAPKAPK5 Ref.16
Modified residue2301N6-methyllysine Ref.17
Modified residue2421N6-acetyllysine By similarity
Modified residue2531Phosphoserine; by PKB/AKT1 and MAPKAPK5 Ref.6 Ref.16
Modified residue2621N6-methyllysine Ref.17
Modified residue2711N6-methyllysine Ref.17
Modified residue2801Phosphoserine Ref.12 Ref.14
Modified residue2841Phosphoserine Ref.12
Modified residue2901N6-methyllysine Ref.17
Modified residue3151Phosphoserine; by SGK1 Ref.6 Ref.7
Modified residue3991Phosphoserine; by AMPK Ref.9
Modified residue4131Phosphoserine; by AMPK Ref.9
Modified residue4191N6-methyllysine Ref.17
Modified residue4211Phosphoserine Ref.11
Modified residue5511Phosphoserine; by MAPKAPK5 Ref.16
Modified residue5551Phosphoserine; by AMPK and MAPKAPK5 Ref.9 Ref.16
Modified residue5881Phosphoserine; by AMPK Ref.9
Modified residue6261Phosphoserine; by AMPK Ref.9

Experimental info

Mutagenesis321T → A: Abolishes YWHAZ-binding; when associated with A-253. Exclusively nuclear, induces transcription and promotes apoptosis; when associated with A-253 and A-315. Ref.6
Mutagenesis1791T → A: Decreased phosphorylation by AMPK and impaired ability to transactivate a reporter gene; when associated with A-399; A-413; A-555; A-588 and A-626. Ref.9
Mutagenesis2091S → A: Impairs nuclear translocation upon oxidative stress. Ref.8
Mutagenesis2421K → A: Slightly decreases DNA affinity. Ref.19
Mutagenesis2451K → A: Decreases DNA affinity. Ref.19
Mutagenesis2531S → A: Abolishes YWHAZ-binding; when associated with A-32. Exclusively nuclear, induces transcription and promotes apoptosis; when associated with A-32 and A-315. Ref.6
Mutagenesis2691K → R: Methylation levels similar to wild-type; when associated with ARG-270. Ref.17
Mutagenesis2701K → R: Methylation levels similar to wild-type; when associated with ARG-269. Ref.17
Mutagenesis2711K → R: Methylation levels strongly reduced. Ref.17
Mutagenesis3151S → A: No effect on YWHAZ-binding. Promotes nuclear translocation. Exclusively nuclear, induces transcription and promotes apoptosis; when associated with A-32 and A-253. Ref.6
Mutagenesis3991S → A: Decreased phosphorylation by AMPK and impaired ability to transactivate a reporter gene; when associated with A-179; A-413; A-555; A-588 and A-626. Ref.9
Mutagenesis4131S → A: Decreased phosphorylation by AMPK and impaired ability to transactivate a reporter gene; when associated with A-179; A-399; A-555; A-588 and A-626. Ref.9
Mutagenesis5551S → A: Decreased phosphorylation by AMPK and impaired ability to transactivate a reporter gene; when associated with A-179; A-399; A-413; A-588 and A-626. Ref.9
Mutagenesis5881S → A: Decreased phosphorylation by AMPK and impaired ability to transactivate a reporter gene; when associated with A-179; A-399; A-413; A-555 and A-626. Ref.9
Mutagenesis6261S → A: Decreased phosphorylation by AMPK and impaired ability to transactivate a reporter gene; when associated with A-179; A-399; A-413; A-555 and A-588. Ref.9
Sequence conflict156 – 1638AWGNLSYA → WGKPVYS in CAA04860. Ref.5
Sequence conflict238 – 2469PDGGKSGKA → LMGEERKT in CAA04860. Ref.5
Sequence conflict2531S → T in CAA04860. Ref.5
Sequence conflict2711Missing in CAA04860. Ref.5
Sequence conflict292 – 33039PGSPT…PIMAS → AWQPHVNAAVMSWMRGRTSV HAPILTPAQSVAACRPSWQV in CAA04860. Ref.5
Sequence conflict345 – 36117PMLYS…SVSKP → AHALQHVSQPVTFSKQA in CAA04860. Ref.5
Sequence conflict3671P → R in CAA04860. Ref.5
Sequence conflict3711D → E in CAA04860. Ref.5
Sequence conflict382 – 3832LT → AD in CAA04860. Ref.5

Secondary structure

.......................... 673
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O43524 [UniParc].

Last modified June 1, 1998. Version 1.
Checksum: E5B4E830665A9982

FASTA67371,277
        10         20         30         40         50         60 
MAEAPASPAP LSPLEVELDP EFEPQSRPRS CTWPLQRPEL QASPAKPSGE TAADSMIPEE 

        70         80         90        100        110        120 
EDDEDDEDGG GRAGSAMAIG GGGGSGTLGS GLLLEDSARV LAPGGQDPGS GPATAAGGLS 

       130        140        150        160        170        180 
GGTQALLQPQ QPLPPPQPGA AGGSGQPRKC SSRRNAWGNL SYADLITRAI ESSPDKRLTL 

       190        200        210        220        230        240 
SQIYEWMVRC VPYFKDKGDS NSSAGWKNSI RHNLSLHSRF MRVQNEGTGK SSWWIINPDG 

       250        260        270        280        290        300 
GKSGKAPRRR AVSMDNSNKY TKSRGRAAKK KAALQTAPES ADDSPSQLSK WPGSPTSRSS 

       310        320        330        340        350        360 
DELDAWTDFR SRTNSNASTV SGRLSPIMAS TELDEVQDDD APLSPMLYSS SASLSPSVSK 

       370        380        390        400        410        420 
PCTVELPRLT DMAGTMNLND GLTENLMDDL LDNITLPPSQ PSPTGGLMQR SSSFPYTTKG 

       430        440        450        460        470        480 
SGLGSPTSSF NSTVFGPSSL NSLRQSPMQT IQENKPATFS SMSHYGNQTL QDLLTSDSLS 

       490        500        510        520        530        540 
HSDVMMTQSD PLMSQASTAV SAQNSRRNVM LRNDPMMSFA AQPNQGSLVN QNLLHHQHQT 

       550        560        570        580        590        600 
QGALGGSRAL SNSVSNMGLS ESSSLGSAKH QQQSPVSQSM QTLSDSLSGS SLYSTSANLP 

       610        620        630        640        650        660 
VMGHEKFPSD LDLDMFNGSL ECDMESIIRS ELMDADGLDF NFDSLISTQN VVGLNVGNFT 

       670 
GAKQASSQSW VPG 

« Hide

References

« Hide 'large scale' references
[1]"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.
[2]"The DNA sequence and analysis of human chromosome 6."
Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. expand/collapse author list , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"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: Muscle and Placenta.
[5]"AF6q21, a novel partner of the MLL gene in t(6;11)(q21;q23), defines a forkhead transcriptional factor subfamily."
Hillion J., Le Coniat M., Jonveaux P., Berger R., Bernard O.A.
Blood 90:3714-3719(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 1-383, INVOLVEMENT IN SECONDARY ACUTE LEUKEMIAS.
[6]"Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor."
Brunet A., Bonni A., Zigmond M.J., Lin M.Z., Juo P., Hu L.S., Anderson M.J., Arden K.C., Blenis J., Greenberg M.E.
Cell 96:857-868(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT THR-32; SER-253 AND SER-315, MUTAGENESIS OF THR-32; SER-253 AND SER-315.
[7]"Protein kinase SGK mediates survival signals by phosphorylating the forkhead transcription factor FKHRL1 (FOXO3a)."
Brunet A., Park J., Tran H., Hu L.S., Hemmings B.A., Greenberg M.E.
Mol. Cell. Biol. 21:952-965(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-315.
[8]"A conserved MST-FOXO signaling pathway mediates oxidative-stress responses and extends life span."
Lehtinen M.K., Yuan Z., Boag P.R., Yang Y., Villen J., Becker E.B.E., DiBacco S., de la Iglesia N., Gygi S.P., Blackwell T.K., Bonni A.
Cell 125:987-1001(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, PHOSPHORYLATION AT SER-209, INTERACTION WITH STK4/MST1 AND YWHAB, SUBCELLULAR LOCATION, MUTAGENESIS OF SER-209.
[9]"The energy sensor AMP-activated protein kinase directly regulates the mammalian FOXO3 transcription factor."
Greer E.L., Oskoui P.R., Banko M.R., Maniar J.M., Gygi M.P., Gygi S.P., Brunet A.
J. Biol. Chem. 282:30107-30119(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-179; SER-399; SER-413; SER-555; SER-588 AND SER-626, MUTAGENESIS OF THR-179; SER-399; SER-413; SER-555; SER-588 AND SER-626, SUBCELLULAR LOCATION.
[10]"Pim kinases promote cell cycle progression by phosphorylating and down-regulating p27Kip1 at the transcriptional and posttranscriptional levels."
Morishita D., Katayama R., Sekimizu K., Tsuruo T., Fujita N.
Cancer Res. 68:5076-5085(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH PIM1, PHOSPHORYLATION.
[11]"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis."
Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III
J. Proteome Res. 7:1346-1351(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-421, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[12]"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-280 AND SER-284, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[13]"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].
[14]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-280, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[15]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[16]"The MK5/PRAK kinase and Myc form a negative feedback loop that is disrupted during colorectal tumorigenesis."
Kress T.R., Cannell I.G., Brenkman A.B., Samans B., Gaestel M., Roepman P., Burgering B.M., Bushell M., Rosenwald A., Eilers M.
Mol. Cell 41:445-457(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, DNA-BINDING, PHOSPHORYLATION AT SER-215; SER-253; SER-551 AND SER-555.
[17]"Methylation by Set9 modulates FoxO3 stability and transcriptional activity."
Calnan D.R., Webb A.E., White J.L., Stowe T.R., Goswami T., Shi X., Espejo A., Bedford M.T., Gozani O., Gygi S.P., Brunet A.
Aging (Albany NY) 4:462-479(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: METHYLATION AT LYS-46; LYS-149; LYS-230; LYS-262; LYS-271; LYS-290 AND LYS-419, MUTAGENESIS OF LYS-269; LYS-270 AND LYS-271.
[18]"CHOP potentially co-operates with FOXO3a in neuronal cells to regulate PUMA and BIM expression in response to ER stress."
Ghosh A.P., Klocke B.J., Ballestas M.E., Roth K.A.
PLoS ONE 7:E39586-E39586(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DDIT3, SUBCELLULAR LOCATION.
[19]"Crystal structure of the human FOXO3a-DBD/DNA complex suggests the effects of post-translational modification."
Tsai K.-L., Sun Y.-J., Huang C.-Y., Yang J.-Y., Hung M.-C., Hsiao C.-D.
Nucleic Acids Res. 35:6984-6994(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 158-253 IN COMPLEX WITH DNA, MUTAGENESIS OF LYS-242 AND LYS-245, NUCLEAR LOCALIZATION SIGNAL.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF032886 mRNA. Translation: AAC39592.1.
AL391646, AL365509 Genomic DNA. Translation: CAI16405.1.
AL365509, AL391646 Genomic DNA. Translation: CAI16295.1.
CH471051 Genomic DNA. Translation: EAW48373.1.
CH471051 Genomic DNA. Translation: EAW48374.1.
BC020227 mRNA. Translation: AAH20227.1.
BC021224 mRNA. Translation: AAH21224.1.
BC068552 mRNA. Translation: AAH68552.1.
AJ001589 mRNA. Translation: CAA04860.1.
AJ001590 Genomic DNA. Translation: CAA04861.1.
CCDSCCDS5068.1.
RefSeqNP_001446.1. NM_001455.3.
NP_963853.1. NM_201559.2.
UniGeneHs.220950.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2K86NMR-A151-251[»]
2LQHNMR-B461-635[»]
2LQINMR-B461-635[»]
2UZKX-ray2.70A/C158-253[»]
ProteinModelPortalO43524.
SMRO43524. Positions 158-253.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108598. 42 interactions.
DIPDIP-29723N.
IntActO43524. 22 interactions.
MINTMINT-89098.
STRING9606.ENSP00000339527.

Chemistry

ChEMBLCHEMBL5778.

PTM databases

PhosphoSiteO43524.

Proteomic databases

MaxQBO43524.
PaxDbO43524.
PRIDEO43524.

Protocols and materials databases

DNASU2309.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000343882; ENSP00000339527; ENSG00000118689.
ENST00000406360; ENSP00000385824; ENSG00000118689.
GeneID2309.
KEGGhsa:2309.
UCSCuc003psk.2. human.

Organism-specific databases

CTD2309.
GeneCardsGC06P108881.
HGNCHGNC:3821. FOXO3.
HPACAB004074.
MIM602681. gene.
neXtProtNX_O43524.
PharmGKBPA28239.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5025.
HOGENOMHOG000251635.
HOVERGENHBG057789.
InParanoidO43524.
KOK09408.
OMANLPVMGH.
OrthoDBEOG7R2BJD.
PhylomeDBO43524.
TreeFamTF315583.

Enzyme and pathway databases

ReactomeREACT_111045. Developmental Biology.
REACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_6900. Immune System.
SignaLinkO43524.

Gene expression databases

ArrayExpressO43524.
BgeeO43524.
CleanExHS_FOXO3.
GenevestigatorO43524.

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

ChiTaRSFOXO3. human.
EvolutionaryTraceO43524.
GeneWikiFOXO3.
GenomeRNAi2309.
NextBio9379.
PROO43524.
SOURCESearch...

Entry information

Entry nameFOXO3_HUMAN
AccessionPrimary (citable) accession number: O43524
Secondary accession number(s): E1P5E6 expand/collapse secondary AC list , O15171, Q5T2I7, Q9BZ04
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: June 1, 1998
Last modified: July 9, 2014
This is version 156 of the entry and version 1 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 6

Human chromosome 6: entries, gene names and cross-references to MIM