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O43524

- FOXO3_HUMAN

UniProt

O43524 - FOXO3_HUMAN

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Protein

Forkhead box protein O3

Gene

FOXO3

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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.3 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi157 – 25195Fork-headPROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  1. chromatin DNA binding Source: UniProtKB
  2. core promoter binding Source: UniProtKB
  3. DNA binding Source: UniProtKB
  4. protein kinase binding Source: UniProtKB
  5. sequence-specific DNA binding Source: UniProtKB
  6. sequence-specific DNA binding transcription factor activity Source: MGI

GO - Biological processi

  1. antral ovarian follicle growth Source: Ensembl
  2. cellular response to oxidative stress Source: UniProtKB
  3. DNA damage response, signal transduction by p53 class mediator Source: Ensembl
  4. epidermal growth factor receptor signaling pathway Source: Reactome
  5. extrinsic apoptotic signaling pathway in absence of ligand Source: Ensembl
  6. Fc-epsilon receptor signaling pathway Source: Reactome
  7. fibroblast growth factor receptor signaling pathway Source: Reactome
  8. glucose homeostasis Source: Ensembl
  9. initiation of primordial ovarian follicle growth Source: Ensembl
  10. innate immune response Source: Reactome
  11. negative regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  12. neurotrophin TRK receptor signaling pathway Source: Reactome
  13. oocyte maturation Source: Ensembl
  14. ovulation from ovarian follicle Source: Ensembl
  15. phosphatidylinositol-mediated signaling Source: Reactome
  16. positive regulation of erythrocyte differentiation Source: MGI
  17. positive regulation of neuron apoptotic process Source: UniProtKB
  18. positive regulation of transcription, DNA-templated Source: UniProtKB
  19. positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  20. regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  21. regulation of translation Source: UniProtKB
  22. transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Apoptosis, Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

ReactomeiREACT_111057. Signaling by NODAL.
REACT_12442. AKT phosphorylates targets in the nucleus.
REACT_147727. Constitutive PI3K/AKT Signaling in Cancer.
SignaLinkiO43524.

Names & Taxonomyi

Protein namesi
Recommended name:
Forkhead box protein O3
Alternative name(s):
AF6q21 protein
Forkhead in rhabdomyosarcoma-like 1
Gene namesi
Name:FOXO3
Synonyms:FKHRL1, FOXO3A
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 6

Organism-specific databases

HGNCiHGNC:3821. FOXO3.

Subcellular locationi

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

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. cytosol Source: Ensembl
  3. membrane Source: Ensembl
  4. nucleoplasm Source: Reactome
  5. nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

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

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi32 – 321T → A: Abolishes YWHAZ-binding; when associated with A-253. Exclusively nuclear, induces transcription and promotes apoptosis; when associated with A-253 and A-315. 1 Publication
Mutagenesisi179 – 1791T → 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. 1 Publication
Mutagenesisi209 – 2091S → A: Impairs nuclear translocation upon oxidative stress. 1 Publication
Mutagenesisi242 – 2421K → A: Slightly decreases DNA affinity. 2 Publications
Mutagenesisi242 – 2421K → R: Reduces acetylation, increases interaction with SKP2 and inhibits FOXO3 ubiquitination and degradation; when associated with R-259; R-290 and R-569. 2 Publications
Mutagenesisi245 – 2451K → A: Decreases DNA affinity. 1 Publication
Mutagenesisi253 – 2531S → A: Abolishes YWHAZ-binding; when associated with A-32. Exclusively nuclear, induces transcription and promotes apoptosis; when associated with A-32 and A-315. 1 Publication
Mutagenesisi259 – 2591K → R: Reduces acetylation, increases interaction with SKP2 and inhibits FOXO3 ubiquitination and degradation; when associated with R-242; R-290 and R-569. 1 Publication
Mutagenesisi269 – 2691K → R: Methylation levels similar to wild-type; when associated with ARG-270. 1 Publication
Mutagenesisi270 – 2701K → R: Methylation levels similar to wild-type; when associated with ARG-269. 1 Publication
Mutagenesisi271 – 2711K → R: Methylation levels strongly reduced. 1 Publication
Mutagenesisi290 – 2901K → R: Reduces acetylation, increases interaction with SKP2 and inhibits FOXO3 ubiquitination and degradation; when associated with R-242; R-259 and R-569. 1 Publication
Mutagenesisi315 – 3151S → A: No effect on YWHAZ-binding. Promotes nuclear translocation. Exclusively nuclear, induces transcription and promotes apoptosis; when associated with A-32 and A-253. 1 Publication
Mutagenesisi399 – 3991S → 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. 1 Publication
Mutagenesisi413 – 4131S → 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. 1 Publication
Mutagenesisi555 – 5551S → 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. 1 Publication
Mutagenesisi569 – 5691K → R: Reduces acetylation, increases interaction with SKP2 and inhibits FOXO3 ubiquitination and degradation; when associated with R-242; R-259 and R-290. 1 Publication
Mutagenesisi588 – 5881S → 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. 1 Publication
Mutagenesisi626 – 6261S → 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. 1 Publication

Keywords - Diseasei

Proto-oncogene

Organism-specific databases

PharmGKBiPA28239.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 673673Forkhead box protein O3PRO_0000091874Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei32 – 321Phosphothreonine; by PKB/AKT11 Publication
Modified residuei46 – 461N6-methyllysine1 Publication
Modified residuei149 – 1491N6-methyllysine1 Publication
Modified residuei179 – 1791Phosphothreonine; by AMPK1 Publication
Modified residuei209 – 2091Phosphoserine; by STK4/MST11 Publication
Modified residuei215 – 2151Phosphoserine; by MAPKAPK51 Publication
Modified residuei230 – 2301N6-methyllysine1 Publication
Modified residuei242 – 2421N6-acetyllysineBy similarity
Modified residuei253 – 2531Phosphoserine; by PKB/AKT1 and MAPKAPK52 Publications
Modified residuei262 – 2621N6-methyllysine1 Publication
Modified residuei271 – 2711N6-methyllysine1 Publication
Modified residuei280 – 2801Phosphoserine2 Publications
Modified residuei284 – 2841Phosphoserine1 Publication
Modified residuei290 – 2901N6-methyllysine1 Publication
Modified residuei315 – 3151Phosphoserine; by SGK12 Publications
Modified residuei399 – 3991Phosphoserine; by AMPK1 Publication
Modified residuei413 – 4131Phosphoserine; by AMPK1 Publication
Modified residuei419 – 4191N6-methyllysine1 Publication
Modified residuei421 – 4211Phosphoserine1 Publication
Modified residuei551 – 5511Phosphoserine; by MAPKAPK51 Publication
Modified residuei555 – 5551Phosphoserine; by AMPK and MAPKAPK52 Publications
Modified residuei588 – 5881Phosphoserine; by AMPK1 Publication
Modified residuei626 – 6261Phosphoserine; by AMPK1 Publication

Post-translational modificationi

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.9 Publications
Deacetylation by SIRT2 stimulates FOXO3-mediated transcriptional activity in response to oxidative stress (By similarity). Deacetylation by SIRT1 or SIRT2 stimulates interaction of FOXO3 with SKP2 and facilitates SCF(SKP2)-mediated FOXO3 ubiquitination and proteasomal degradation.By similarity1 Publication
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.1 Publication
Polyubiquitinated. Ubiquitinated by a SCF complex containing SKP2, leading to proteasomal degradation.1 Publication

Keywords - PTMi

Acetylation, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiO43524.
PaxDbiO43524.
PRIDEiO43524.

PTM databases

PhosphoSiteiO43524.

Expressioni

Tissue specificityi

Ubiquitous.1 Publication

Gene expression databases

BgeeiO43524.
CleanExiHS_FOXO3.
ExpressionAtlasiO43524. baseline and differential.
GenevestigatoriO43524.

Organism-specific databases

HPAiCAB004074.

Interactioni

Subunit structurei

Interacts with SIRT2; the interaction occurs independently of SIRT2 deacetylase activity (By similarity). 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. Interacts (deacetylated form) with SKP2.By similarity5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
FOXM1Q080502EBI-1644164,EBI-866480
HCFC1P516102EBI-1644164,EBI-396176
SIRT1Q96EB65EBI-1644164,EBI-1802965
SMAD4Q134854EBI-1644164,EBI-347263
TP53P046372EBI-1644164,EBI-366083

Protein-protein interaction databases

BioGridi108598. 42 interactions.
DIPiDIP-29723N.
IntActiO43524. 24 interactions.
MINTiMINT-89098.
STRINGi9606.ENSP00000339527.

Structurei

Secondary structure

1
673
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Turni156 – 1583Combined sources
Helixi162 – 1698Combined sources
Beta strandi172 – 1765Combined sources
Helixi180 – 18910Combined sources
Beta strandi198 – 2003Combined sources
Helixi206 – 21611Combined sources
Beta strandi217 – 22913Combined sources
Beta strandi233 – 2364Combined sources
Beta strandi238 – 2403Combined sources
Beta strandi463 – 4653Combined sources
Helixi468 – 47710Combined sources
Turni478 – 4803Combined sources
Helixi621 – 6233Combined sources
Helixi624 – 63310Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2K86NMR-A151-251[»]
2LQHNMR-B461-635[»]
2LQINMR-B461-635[»]
2UZKX-ray2.70A/C158-253[»]
ProteinModelPortaliO43524.
SMRiO43524. Positions 158-253.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO43524.

Family & Domainsi

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi242 – 25918Nuclear localization signal1 PublicationAdd
BLAST

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiCOG5025.
GeneTreeiENSGT00390000000589.
HOGENOMiHOG000251635.
HOVERGENiHBG057789.
InParanoidiO43524.
KOiK09408.
OMAiNLPVMGH.
OrthoDBiEOG7R2BJD.
PhylomeDBiO43524.
TreeFamiTF315583.

Family and domain databases

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

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: O43524-1) [UniParc]FASTAAdd to Basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAEAPASPAP LSPLEVELDP EFEPQSRPRS CTWPLQRPEL QASPAKPSGE
60 70 80 90 100
TAADSMIPEE EDDEDDEDGG GRAGSAMAIG GGGGSGTLGS GLLLEDSARV
110 120 130 140 150
LAPGGQDPGS GPATAAGGLS GGTQALLQPQ QPLPPPQPGA AGGSGQPRKC
160 170 180 190 200
SSRRNAWGNL SYADLITRAI ESSPDKRLTL SQIYEWMVRC VPYFKDKGDS
210 220 230 240 250
NSSAGWKNSI RHNLSLHSRF MRVQNEGTGK SSWWIINPDG GKSGKAPRRR
260 270 280 290 300
AVSMDNSNKY TKSRGRAAKK KAALQTAPES ADDSPSQLSK WPGSPTSRSS
310 320 330 340 350
DELDAWTDFR SRTNSNASTV SGRLSPIMAS TELDEVQDDD APLSPMLYSS
360 370 380 390 400
SASLSPSVSK PCTVELPRLT DMAGTMNLND GLTENLMDDL LDNITLPPSQ
410 420 430 440 450
PSPTGGLMQR SSSFPYTTKG SGLGSPTSSF NSTVFGPSSL NSLRQSPMQT
460 470 480 490 500
IQENKPATFS SMSHYGNQTL QDLLTSDSLS HSDVMMTQSD PLMSQASTAV
510 520 530 540 550
SAQNSRRNVM LRNDPMMSFA AQPNQGSLVN QNLLHHQHQT QGALGGSRAL
560 570 580 590 600
SNSVSNMGLS ESSSLGSAKH QQQSPVSQSM QTLSDSLSGS SLYSTSANLP
610 620 630 640 650
VMGHEKFPSD LDLDMFNGSL ECDMESIIRS ELMDADGLDF NFDSLISTQN
660 670
VVGLNVGNFT GAKQASSQSW VPG
Length:673
Mass (Da):71,277
Last modified:June 1, 1998 - v1
Checksum:iE5B4E830665A9982
GO
Isoform 2 (identifier: O43524-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-220: Missing.

Note: No experimental confirmation available.

Show »
Length:453
Mass (Da):48,406
Checksum:iE093364532E78AE1
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti156 – 1638AWGNLSYA → WGKPVYS in CAA04860. (PubMed:9345057)Curated
Sequence conflicti238 – 2469PDGGKSGKA → LMGEERKT in CAA04860. (PubMed:9345057)Curated
Sequence conflicti253 – 2531S → T in CAA04860. (PubMed:9345057)Curated
Sequence conflicti271 – 2711Missing in CAA04860. (PubMed:9345057)Curated
Sequence conflicti292 – 33039PGSPT…PIMAS → AWQPHVNAAVMSWMRGRTSV HAPILTPAQSVAACRPSWQV in CAA04860. (PubMed:9345057)CuratedAdd
BLAST
Sequence conflicti345 – 36117PMLYS…SVSKP → AHALQHVSQPVTFSKQA in CAA04860. (PubMed:9345057)CuratedAdd
BLAST
Sequence conflicti367 – 3671P → R in CAA04860. (PubMed:9345057)Curated
Sequence conflicti371 – 3711D → E in CAA04860. (PubMed:9345057)Curated
Sequence conflicti382 – 3832LT → AD in CAA04860. (PubMed:9345057)Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 220220Missing in isoform 2. 1 PublicationVSP_056225Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF032886 mRNA. Translation: AAC39592.1.
AK301304 mRNA. Translation: BAG62858.1.
AL096818 Genomic DNA. No translation available.
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.
CCDSiCCDS5068.1. [O43524-1]
RefSeqiNP_001446.1. NM_001455.3. [O43524-1]
NP_963853.1. NM_201559.2. [O43524-1]
XP_005266925.1. XM_005266868.1. [O43524-2]
UniGeneiHs.220950.

Genome annotation databases

EnsembliENST00000343882; ENSP00000339527; ENSG00000118689. [O43524-1]
ENST00000406360; ENSP00000385824; ENSG00000118689. [O43524-1]
ENST00000540898; ENSP00000446316; ENSG00000118689. [O43524-2]
GeneIDi2309.
KEGGihsa:2309.
UCSCiuc003psk.2. human. [O43524-1]

Keywords - Coding sequence diversityi

Alternative splicing, Chromosomal rearrangement

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF032886 mRNA. Translation: AAC39592.1 .
AK301304 mRNA. Translation: BAG62858.1 .
AL096818 Genomic DNA. No translation available.
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 .
CCDSi CCDS5068.1. [O43524-1 ]
RefSeqi NP_001446.1. NM_001455.3. [O43524-1 ]
NP_963853.1. NM_201559.2. [O43524-1 ]
XP_005266925.1. XM_005266868.1. [O43524-2 ]
UniGenei Hs.220950.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2K86 NMR - A 151-251 [» ]
2LQH NMR - B 461-635 [» ]
2LQI NMR - B 461-635 [» ]
2UZK X-ray 2.70 A/C 158-253 [» ]
ProteinModelPortali O43524.
SMRi O43524. Positions 158-253.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 108598. 42 interactions.
DIPi DIP-29723N.
IntActi O43524. 24 interactions.
MINTi MINT-89098.
STRINGi 9606.ENSP00000339527.

Chemistry

ChEMBLi CHEMBL5778.

PTM databases

PhosphoSitei O43524.

Proteomic databases

MaxQBi O43524.
PaxDbi O43524.
PRIDEi O43524.

Protocols and materials databases

DNASUi 2309.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000343882 ; ENSP00000339527 ; ENSG00000118689 . [O43524-1 ]
ENST00000406360 ; ENSP00000385824 ; ENSG00000118689 . [O43524-1 ]
ENST00000540898 ; ENSP00000446316 ; ENSG00000118689 . [O43524-2 ]
GeneIDi 2309.
KEGGi hsa:2309.
UCSCi uc003psk.2. human. [O43524-1 ]

Organism-specific databases

CTDi 2309.
GeneCardsi GC06P108881.
HGNCi HGNC:3821. FOXO3.
HPAi CAB004074.
MIMi 602681. gene.
neXtProti NX_O43524.
PharmGKBi PA28239.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG5025.
GeneTreei ENSGT00390000000589.
HOGENOMi HOG000251635.
HOVERGENi HBG057789.
InParanoidi O43524.
KOi K09408.
OMAi NLPVMGH.
OrthoDBi EOG7R2BJD.
PhylomeDBi O43524.
TreeFami TF315583.

Enzyme and pathway databases

Reactomei REACT_111057. Signaling by NODAL.
REACT_12442. AKT phosphorylates targets in the nucleus.
REACT_147727. Constitutive PI3K/AKT Signaling in Cancer.
SignaLinki O43524.

Miscellaneous databases

ChiTaRSi FOXO3. human.
EvolutionaryTracei O43524.
GeneWikii FOXO3.
GenomeRNAii 2309.
NextBioi 35475594.
PROi O43524.
SOURCEi Search...

Gene expression databases

Bgeei O43524.
CleanExi HS_FOXO3.
ExpressionAtlasi O43524. baseline and differential.
Genevestigatori O43524.

Family and domain databases

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

Publicationsi

« Hide 'large scale' publications
  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] (ISOFORM 1), TISSUE SPECIFICITY.
    Tissue: Rhabdomyosarcoma.
  2. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
    Tissue: Stomach.
  3. "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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. 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] (ISOFORM 1).
    Tissue: Muscle and Placenta.
  6. "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 (ISOFORM 1), INVOLVEMENT IN SECONDARY ACUTE LEUKEMIAS.
  7. "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.
  8. "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.
  9. "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.
  10. "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.
  11. "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.
  12. "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.
  13. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-280 AND SER-284, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  14. "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].
  15. "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.
  16. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  17. "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.
  18. "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.
  19. "Deacetylation of FOXO3 by SIRT1 or SIRT2 leads to Skp2-mediated FOXO3 ubiquitination and degradation."
    Wang F., Chan C.H., Chen K., Guan X., Lin H.K., Tong Q.
    Oncogene 31:1546-1557(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION, DEACETYLATION BY SIRT2, INTERACTION WITH SKP2, UBIQUITINATION BY SKP2, MUTAGENESIS OF LYS-242; LYS-259; LYS-290 AND LYS-569.
  20. "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.
  21. "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.

Entry informationi

Entry nameiFOXO3_HUMAN
AccessioniPrimary (citable) accession number: O43524
Secondary accession number(s): B4DVZ6
, E1P5E6, O15171, Q5T2I7, Q9BZ04
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: June 1, 1998
Last modified: November 26, 2014
This is version 160 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3