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Q9WVH4 (FOXO3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 124. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Forkhead box protein O3
Gene names
Name:Foxo3
Synonyms:Fkhr2, Foxo3a
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length672 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 By similarity.

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 By similarity. Interacts with DDIT3/CHOP By similarity.

Subcellular location

Cytoplasmcytosol By similarity. Nucleus By similarity. Note: Translocates to the nucleus upon oxidative stress and in the absence of survival factors By similarity.

Tissue specificity

Expressed in white and brown adipose tissues (at protein level). Ref.6

Post-translational modification

In the presence of survival factors such as IGF-1, phosphorylated on Thr-32 and Ser-252 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-314 directly, it may activate other kinases that trigger phosphorylation at this residue. Phosphorylated by STK4/MST1 on Ser-208 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 By similarity.

Heavyly methylated by SET9 which decreases stability, while moderately increasing transcriptional activity. The main methylation site is Lys-270. Methylation doesn't affect subcellular location By similarity.

Sequence similarities

Contains 1 fork-head DNA-binding domain.

Sequence caution

The sequence AAH19532.1 differs from that shown. Reason: Contaminating sequence. Potential poly-A sequence.

Ontologies

Keywords
   Biological processApoptosis
Transcription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   DiseaseProto-oncogene
   LigandDNA-binding
   Molecular functionActivator
   PTMAcetylation
Methylation
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA damage response, signal transduction by p53 class mediator

Inferred from direct assay PubMed 15383658. Source: MGI

antral ovarian follicle growth

Inferred from mutant phenotype PubMed 14978268. Source: MGI

extrinsic apoptotic signaling pathway in absence of ligand

Inferred from genetic interaction PubMed 12431371. Source: MGI

glucose homeostasis

Inferred from mutant phenotype PubMed 12855809. Source: MGI

initiation of primordial ovarian follicle growth

Inferred from mutant phenotype PubMed 12855809. Source: MGI

insulin receptor signaling pathway

Inferred from Biological aspect of Ancestor. Source: RefGenome

negative regulation of transcription from RNA polymerase II promoter

Inferred from electronic annotation. Source: Ensembl

oocyte maturation

Inferred from mutant phenotype PubMed 12855809. Source: MGI

ovulation from ovarian follicle

Inferred from mutant phenotype PubMed 12855809. Source: MGI

pattern specification process

Inferred from Biological aspect of Ancestor. Source: RefGenome

positive regulation of erythrocyte differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of neuron apoptotic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from Biological aspect of Ancestor. Source: RefGenome

positive regulation of transcription, DNA-templated

Inferred from direct assay PubMed 12048180. Source: MGI

regulation of cell proliferation

Inferred from Biological aspect of Ancestor. Source: RefGenome

regulation of transcription, DNA-templated

Inferred from direct assay PubMed 12930811. Source: MGI

regulation of translation

Inferred from sequence or structural similarity. 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 PubMed 12857750PubMed 14966295PubMed 15383658. Source: MGI

cytosol

Inferred from Biological aspect of Ancestor. Source: RefGenome

membrane

Inferred from direct assay PubMed 15383658. Source: MGI

nucleus

Inferred from direct assay PubMed 12857750PubMed 14966295. Source: MGI

   Molecular_functionDNA binding

Inferred from direct assay PubMed 14966295PubMed 15383658. Source: MGI

DNA binding, bending

Inferred from Biological aspect of Ancestor. Source: RefGenome

protein binding

Inferred from physical interaction PubMed 17521387Ref.6. Source: UniProtKB

protein kinase binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

sequence-specific DNA binding

Inferred from direct assay Ref.1. Source: MGI

sequence-specific DNA binding transcription factor activity

Inferred from direct assay PubMed 14966295PubMed 15322035. Source: MGI

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

FcorP0DJI62EBI-6127038,EBI-6126630
SETD7Q8WTS65EBI-6127038,EBI-1268586From a different organism.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 672672Forkhead box protein O3
PRO_0000415334

Regions

DNA binding156 – 25095Fork-head
Motif241 – 25818Nuclear localization signal By similarity
Compositional bias546 – 59550Ser-rich

Amino acid modifications

Modified residue321Phosphothreonine; by PKB/AKT1 By similarity
Modified residue461N6-methyllysine By similarity
Modified residue1481N6-methyllysine By similarity
Modified residue1781Phosphothreonine; by AMPK By similarity
Modified residue2081Phosphoserine; by STK4/MST1 By similarity
Modified residue2141Phosphoserine; by MAPKAPK5 By similarity
Modified residue2291N6-methyllysine By similarity
Modified residue2411N6-acetyllysine Ref.7
Modified residue2521Phosphoserine; by PKB/AKT1 and MAPKAPK5 By similarity
Modified residue2611N6-methyllysine By similarity
Modified residue2701N6-methyllysine By similarity
Modified residue2791Phosphoserine By similarity
Modified residue2831Phosphoserine By similarity
Modified residue2891N6-methyllysine By similarity
Modified residue3141Phosphoserine; by SGK1 By similarity
Modified residue3981Phosphoserine; by AMPK By similarity
Modified residue4121Phosphoserine; by AMPK By similarity
Modified residue4181N6-methyllysine By similarity
Modified residue4201Phosphoserine By similarity
Modified residue5501Phosphoserine; by MAPKAPK5 By similarity
Modified residue5541Phosphoserine; by AMPK and MAPKAPK5 By similarity
Modified residue5871Phosphoserine; by AMPK By similarity
Modified residue6251Phosphoserine; by AMPK By similarity

Sequences

Sequence LengthMass (Da)Tools
Q9WVH4 [UniParc].

Last modified November 1, 1999. Version 1.
Checksum: EC218D9BA0C1DAC5

FASTA67271,064
        10         20         30         40         50         60 
MAEAPASPVP LSPLEVELDP EFEPQSRPRS CTWPLQRPEL QASPAKPSGE TAADSMIPEE 

        70         80         90        100        110        120 
DDDEDDEDGG GRASSAMVIG GGVSSTLGSG LLLEDSAMLL APGGQDLGSG PASAAGALSG 

       130        140        150        160        170        180 
GTPTQLQPQQ PLPQPQPGAA GGSGQPRKCS SRRNAWGNLS YADLITRAIE SSPDKRLTLS 

       190        200        210        220        230        240 
QIYEWMVRCV PYFKDKGDSN SSAGWKNSIR HNLSLHSRFM RVQNEGTGKS SWWIINPDGG 

       250        260        270        280        290        300 
KSGKAPRRRA VSMDNSNKYT KSRGRAAKKK AALQAAPESA DDSPSQLSKW PGSPTSRSSD 

       310        320        330        340        350        360 
ELDAWTDFRS RTNSNASTVS GRLSPILAST ELDDVQDDDG PLSPMLYSSS ASLSPSVSKP 

       370        380        390        400        410        420 
CTVELPRLTD MAGTMNLNDG LAENLMDDLL DNIALPPSQP SPPGGLMQRG SSFPYTAKSS 

       430        440        450        460        470        480 
GLGSPTGSFN STVFGPSSLN SLRQSPMQTI QENRPATFSS VSHYGNQTLQ DLLASDSLSH 

       490        500        510        520        530        540 
SDVMMTQSDP LMSQASTAVS AQNARRNVML RNDPMMSFAA QPTQGSLVNQ NLLHHQHQTQ 

       550        560        570        580        590        600 
GALGGSRALS NSVSNMGLSD SSSLGSAKHQ QQSPASQSMQ TLSDSLSGSS LYSASANLPV 

       610        620        630        640        650        660 
MGHDKFPSDL DLDMFNGSLE CDMESIIRSE LMDADGLDFN FDSLISTQNV VGLNVGNFTG 

       670 
AKQASSQSWV PG 

« Hide

References

« Hide 'large scale' references
[1]"Identification and characterization of members of the FKHR (FOX O) subclass of winged-helix transcription factors in the mouse."
Biggs W.H. III, Cavenee W.K., Arden K.C.
Mamm. Genome 12:416-425(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"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. expand/collapse author list , 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.
Tissue: Cerebellum.
[3]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[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]"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] OF 1-255.
[6]"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: TISSUE SPECIFICITY.
[7]"SIRT5-mediated lysine desuccinylation impacts diverse metabolic pathways."
Park J., Chen Y., Tishkoff D.X., Peng C., Tan M., Dai L., Xie Z., Zhang Y., Zwaans B.M., Skinner M.E., Lombard D.B., Zhao Y.
Mol. Cell 50:919-930(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-241, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic fibroblast.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF114259 mRNA. Translation: AAD42107.1.
AK047413 mRNA. Translation: BAC33049.1.
AC116179 Genomic DNA. No translation available.
AC140402 Genomic DNA. No translation available.
CH466540 Genomic DNA. Translation: EDL04998.1.
BC019532 mRNA. Translation: AAH19532.1. Sequence problems.
CCDSCCDS23810.1.
RefSeqNP_062714.1. NM_019740.2.
XP_006512869.1. XM_006512806.1.
UniGeneMm.338613.
Mm.391700.
Mm.417859.
Mm.466459.

3D structure databases

ProteinModelPortalQ9WVH4.
SMRQ9WVH4. Positions 157-252.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ9WVH4. 2 interactions.
STRING10090.ENSMUSP00000101141.

PTM databases

PhosphoSiteQ9WVH4.

Proteomic databases

PRIDEQ9WVH4.

Protocols and materials databases

DNASU56484.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000056974; ENSMUSP00000050683; ENSMUSG00000048756.
ENSMUST00000105502; ENSMUSP00000101141; ENSMUSG00000048756.
ENSMUST00000175881; ENSMUSP00000135380; ENSMUSG00000048756.
GeneID56484.
KEGGmmu:56484.
UCSCuc007eyl.1. mouse.

Organism-specific databases

CTD2309.
MGIMGI:1890081. Foxo3.

Phylogenomic databases

eggNOGCOG5025.
GeneTreeENSGT00390000000589.
HOGENOMHOG000251635.
HOVERGENHBG078744.
InParanoidQ9WVH4.
KOK09408.
OMANLPVMGH.
OrthoDBEOG7R2BJD.
PhylomeDBQ9WVH4.
TreeFamTF315583.

Gene expression databases

ArrayExpressQ9WVH4.
BgeeQ9WVH4.
GenevestigatorQ9WVH4.

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. mouse.
NextBio312750.
PROQ9WVH4.
SOURCESearch...

Entry information

Entry nameFOXO3_MOUSE
AccessionPrimary (citable) accession number: Q9WVH4
Secondary accession number(s): D3Z6Y6, Q05CZ4
Entry history
Integrated into UniProtKB/Swiss-Prot: January 25, 2012
Last sequence update: November 1, 1999
Last modified: July 9, 2014
This is version 124 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot