O43524 (FOXO3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Forkhead box protein O3

Alternative name(s):
AF6q21 protein
Forkhead in rhabdomyosarcoma-like 1

Gene names

Name:	FOXO3
Synonyms:	FKHRL1, FOXO3A

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	673 AA.
Sequence status	Complete.
Protein existence	Evidence 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
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. Ref.8 Ref.10
Subcellular location	Cytoplasm › cytosol. Nucleus. Note: Translocates to the nucleus upon oxidative stress and in the absence of survival factors. Ref.6 Ref.8 Ref.9
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.11 Ref.12 Ref.13 Ref.14
Involvement in disease	Note=A chromosomal aberration involving FOXO3 is found in secondary acute leukemias. Translocation t(6;11)(q21;q23) with MLL/HRX.
Sequence similarities	Contains 1 fork-head DNA-binding domain.

Ontologies

Keywords
Biological process	Apoptosis Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Chromosomal rearrangement
Disease	Proto-oncogene
Ligand	DNA-binding
Molecular function	Activator
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Uncategorized	promoter binding Inferred from Biological aspect of Ancestor. Source: RefGenome specific RNA polymerase II transcription factor activity Inferred from Biological aspect of Ancestor. Source: RefGenome specific transcriptional repressor activity Inferred from Biological aspect of Ancestor. Source: RefGenome
Biological process	antral ovarian follicle growth Inferred from Biological aspect of Ancestor. Source: RefGenome apoptotic process Inferred from direct assay Ref.6. Source: UniProtKB embryo development Inferred from Biological aspect of Ancestor. Source: RefGenome fibroblast growth factor receptor signaling pathway Traceable author statement. Source: Reactome glucose homeostasis Inferred from Biological aspect of Ancestor. Source: RefGenome induction of apoptosis Inferred from Biological aspect of Ancestor. Source: RefGenome initiation of primordial ovarian follicle growth Inferred from Biological aspect of Ancestor. Source: RefGenome 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. Source: BHF-UCL nerve growth factor receptor signaling pathway Traceable author statement. Source: Reactome oocyte maturation Inferred from Biological aspect of Ancestor. Source: RefGenome ovulation from ovarian follicle Inferred from Biological aspect of Ancestor. Source: RefGenome 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. Source: MGI positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay Ref.6. Source: UniProtKB regulation of cell proliferation Inferred from Biological aspect of Ancestor. Source: RefGenome regulation of sequence-specific DNA binding transcription factor activity Inferred from Biological aspect of Ancestor. Source: RefGenome tissue development Inferred from Biological aspect of Ancestor. Source: RefGenome
Cellular component	cytosol Inferred from Biological aspect of Ancestor. Source: RefGenome transcription factor complex Inferred from Biological aspect of Ancestor. Source: RefGenome
Molecular function	DNA binding, bending Inferred from Biological aspect of Ancestor. Source: RefGenome double-stranded DNA binding Inferred from Biological aspect of Ancestor. Source: RefGenome 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 distal enhancer binding RNA polymerase II transcription factor activity Inferred from Biological aspect of Ancestor. Source: RefGenome transcription factor binding Inferred from Biological aspect of Ancestor. Source: RefGenome
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
FOXM1	Q08050	2	EBI-1644164,EBI-866480
HCFC1	P51610	2	EBI-1644164,EBI-396176
SIRT1	Q96EB6	5	EBI-1644164,EBI-1802965
SMAD4	Q13485	4	EBI-1644164,EBI-347263

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 673

673

Forkhead box protein O3

PRO_0000091874

Regions

DNA binding

157 – 251

95

Fork-head

Motif

242 – 259

18

Nuclear localization signal Ref.17

Amino acid modifications

Modified residue

7

1

Phosphoserine Ref.14

Modified residue

12

1

Phosphoserine Ref.14

Modified residue

32

1

Phosphothreonine; by PKB/AKT1 Ref.6

Modified residue

179

1

Phosphothreonine; by AMPK Ref.9

Modified residue

209

1

Phosphoserine; by STK4/MST1 Ref.8

Modified residue

215

1

Phosphoserine; by MAPKAPK5

Modified residue

253

1

Phosphoserine; by PKB/AKT1 and MAPKAPK5

Modified residue

280

1

Phosphoserine Ref.12 Ref.13 Ref.14

Modified residue

284

1

Phosphoserine Ref.12 Ref.13

Modified residue

286

1

Phosphoserine Ref.13

Modified residue

315

1

Phosphoserine; by SGK1 Ref.6 Ref.7

Modified residue

399

1

Phosphoserine; by AMPK Ref.9

Modified residue

413

1

Phosphoserine; by AMPK Ref.9

Modified residue

421

1

Phosphoserine Ref.11

Modified residue

427

1

Phosphothreonine Ref.11

Modified residue

551

1

Phosphoserine; by MAPKAPK5

Modified residue

555

1

Phosphoserine; by AMPK and MAPKAPK5

Modified residue

588

1

Phosphoserine; by AMPK Ref.9

Modified residue

626

1

Phosphoserine; by AMPK Ref.9

Experimental info

Mutagenesis

32

1

T → 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

Mutagenesis

179

1

T → 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

Mutagenesis

209

1

S → A: Impairs nuclear translocation upon oxidative stress. Ref.8

Mutagenesis

242

1

K → A: Slightly decreases DNA affinity. Ref.17

Mutagenesis

245

1

K → A: Decreases DNA affinity. Ref.17

Mutagenesis

253

1

S → 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

Mutagenesis

315

1

S → 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

Mutagenesis

399

1

S → 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

Mutagenesis

413

1

S → 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

Mutagenesis

555

1

S → 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

Mutagenesis

588

1

S → 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

Mutagenesis

626

1

S → 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 conflict

156 – 163

8

AWGNLSYA → WGKPVYS in CAA04860. Ref.5

Sequence conflict

238 – 246

9

PDGGKSGKA → LMGEERKT in CAA04860. Ref.5

Sequence conflict

253

1

S → T in CAA04860. Ref.5

Sequence conflict

271

1

Missing in CAA04860. Ref.5

Sequence conflict

292 – 330

39

PGSPT…PIMAS → AWQPHVNAAVMSWMRGRTSV HAPILTPAQSVAACRPSWQV in CAA04860. Ref.5

Sequence conflict

345 – 361

17

PMLYS…SVSKP → AHALQHVSQPVTFSKQA in CAA04860. Ref.5

Sequence conflict

367

1

P → R in CAA04860. Ref.5

Sequence conflict

371

1

D → E in CAA04860. Ref.5

Sequence conflict

382 – 383

2

LT → AD in CAA04860. Ref.5

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

673

Helix Strand Turn

Details...

Helix

162 – 169

8

Beta strand

172 – 176

5

Helix

180 – 189

10

Beta strand

198 – 200

3

Helix

206 – 216

11

Beta strand

217 – 223

7

Beta strand

226 – 229

4

Beta strand

233 – 236

4

Sequences

	Sequence		Length	Mass (Da)
	O43524 [UniParc]. Last modified June 1, 1998. Version 1. Checksum: E5B4E830665A9982	FASTA	673	71,277
	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

References

	« Hide 'large scale' referencesShow '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: 9479491] [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. , 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: 14574404] [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. , 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: 15489334] [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: 9345057] [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: 10102273] [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: 11154281] [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: 16751106] [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: 17711846] [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: 18593906] [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: 18220336] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-421 AND THR-427, MASS SPECTROMETRY. 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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-280 AND SER-284, MASS SPECTROMETRY. 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: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-280; SER-284 AND SER-286, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[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: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-7; SER-12 AND SER-280, MASS SPECTROMETRY. 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: 21269460] [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: 21329882] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, DNA-BINDING, PHOSPHORYLATION AT SER-215; SER-253; SER-551 AND SER-555.
[17]	"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: 17940099] [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.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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.

IPI

IPI00012856.

RefSeq

NP_001446.1. NM_001455.3.
NP_963853.1. NM_201559.2.

UniGene

Hs.220950.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2K86	NMR	-	A	151-251	[»]
2UZK	X-ray	2.70	A/C	158-253	[»]

ProteinModelPortal

O43524.

SMR

O43524. Positions 151-251.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29723N.

IntAct

O43524. 18 interactions.

MINT

MINT-89098.

STRING

O43524.

PTM databases

PhosphoSite

O43524.

Proteomic databases

PRIDE

O43524.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000343882; ENSP00000339527; ENSG00000118689.
ENST00000406360; ENSP00000385824; ENSG00000118689.

GeneID

2309.

KEGG

hsa:2309.

UCSC

uc003psk.2. human.

Organism-specific databases

CTD

2309.

GeneCards

GC06P108881.

H-InvDB

HIX0006119.

HGNC

HGNC:3821. FOXO3.

HPA

CAB004074.

MIM

602681. gene.

neXtProt

NX_O43524.

PharmGKB

PA162388869.
PA28239.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG19446.

HOGENOM

HBG714085.

HOVERGEN

HBG057789.

InParanoid

O43524.

OMA

MGHEKFP.

OrthoDB

EOG4N8R4G.

PhylomeDB

O43524.

Enzyme and pathway databases

Pathway_Interaction_DB

pi3kcipathway. Class I PI3K signaling events.
pi3kciaktpathway. Class I PI3K signaling events mediated by Akt.
foxopathway. FoxO family signaling.
il2_pi3kpathway. IL2 signaling events mediated by PI3K.
insulin_pathway. Insulin Pathway.
smad2_3nuclearpathway. Regulation of nuclear SMAD2/3 signaling.
hdac_classiii_pathway. Signaling events mediated by HDAC Class III.
kitpathway. Signaling events mediated by Stem cell factor receptor (c-Kit).
pi3kplctrkpathway. Trk receptor signaling mediated by PI3K and PLC-gamma.

Reactome

REACT_111045. Developmental Biology.
REACT_111102. Signal Transduction.

Gene expression databases

ArrayExpress

O43524.

Bgee

O43524.

CleanEx

HS_FOXO3.

Genevestigator

O43524.

GermOnline

ENSG00000118689. Homo sapiens.

Family and domain databases

InterPro

IPR001766. TF_fork_head.
IPR018122. TF_fork_head_CS.
IPR011991. WHTH_trsnscrt_rep_DNA-bd.
[Graphical view]

Gene3D

G3DSA:1.10.10.10. Wing_hlx_DNA_bd. 1 hit.

KO

K09408.

Pfam

PF00250. Fork_head. 1 hit.
[Graphical view]

PRINTS

PR00053. FORKHEAD.

SMART

SM00339. FH. 1 hit.
[Graphical view]

PROSITE

PS00657. FORK_HEAD_1. False negative.
PS00658. FORK_HEAD_2. 1 hit.
PS50039. FORK_HEAD_3. 1 hit.
[Graphical view]

ProtoNet

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Other

NextBio

9379.

SOURCE

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Entry information

Entry name

FOXO3_HUMAN

Accession

Primary (citable) accession number: O43524
Secondary accession number(s): E1P5E6 , O15171, Q5T2I7, Q9BZ04

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	June 1, 1998
Last modified:	January 25, 2012
This is version 129 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.