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Aliases for FOXO3 Gene

Aliases for FOXO3 Gene

  • Forkhead Box O3 2 3 5
  • Forkhead In Rhabdomyosarcoma-Like 1 3 4
  • FKHRL1 3 4
  • FOXO3A 3 4
  • Forkhead, Drosophila, Homolog Of, In Rhabdomyosarcoma-Like 1 3
  • Forkhead Homolog (Rhabdomyosarcoma) Like 1 3
  • Forkhead Box O3A 3
  • AF6q21 Protein 4
  • FKHRL1P2 3
  • AF6q21 3
  • FOXO2 3

External Ids for FOXO3 Gene

Previous HGNC Symbols for FOXO3 Gene

  • FKHRL1
  • FOXO3A

Previous GeneCards Identifiers for FOXO3 Gene

  • GC06P108988
  • GC06P108881
  • GC06P106448

Summaries for FOXO3 Gene

Entrez Gene Summary for FOXO3 Gene

  • This gene belongs to the forkhead family of transcription factors which are characterized by a distinct forkhead domain. This gene likely functions as a trigger for apoptosis through expression of genes necessary for cell death. Translocation of this gene with the MLL gene is associated with secondary acute leukemia. Alternatively spliced transcript variants encoding the same protein have been observed. [provided by RefSeq, Jul 2008]

GeneCards Summary for FOXO3 Gene

FOXO3 (Forkhead Box O3) is a Protein Coding gene. Diseases associated with FOXO3 include rhabdomyosarcoma and lung cancer. Among its related pathways are Signaling by GPCR and Immune System. GO annotations related to this gene include transcription factor activity, sequence-specific DNA binding and protein kinase binding. An important paralog of this gene is FOXO4.

UniProtKB/Swiss-Prot for FOXO3 Gene

  • 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 3UTR of MYC transcript and prevent its translation.

Gene Wiki entry for FOXO3 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for FOXO3 Gene

Genomics for FOXO3 Gene

Regulatory Elements for FOXO3 Gene

Promoters for FOXO3 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around FOXO3 on UCSC Golden Path with GeneCards custom track

Transcription factor binding sites by QIAGEN in the FOXO3 gene promoter:

Genomic Location for FOXO3 Gene

Chromosome:
6
Start:
108,559,823 bp from pter
End:
108,684,774 bp from pter
Size:
124,952 bases
Orientation:
Plus strand

Genomic View for FOXO3 Gene

Genes around FOXO3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
FOXO3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for FOXO3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for FOXO3 Gene

Proteins for FOXO3 Gene

  • Protein details for FOXO3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O43524-FOXO3_HUMAN
    Recommended name:
    Forkhead box protein O3
    Protein Accession:
    O43524
    Secondary Accessions:
    • B4DVZ6
    • E1P5E6
    • O15171
    • Q5T2I7
    • Q9BZ04

    Protein attributes for FOXO3 Gene

    Size:
    673 amino acids
    Molecular mass:
    71277 Da
    Quaternary structure:
    • 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 (PubMed:16751106). Upon oxidative stress, interacts with STK4/MST1, which disrupts interaction with YWHAB/14-3-3-beta and leads to nuclear translocation (PubMed:16751106). Interacts with PIM1 (PubMed:18593906). Interacts with DDIT3/CHOP (PubMed:22761832). Interacts (deacetylated form) with SKP2 (PubMed:21841822). Interacts with CHUK and IKBKB (PubMed:15084260, PubMed:22313691).

    Three dimensional structures from OCA and Proteopedia for FOXO3 Gene

    Alternative splice isoforms for FOXO3 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for FOXO3 Gene

Proteomics data for FOXO3 Gene at MOPED

Post-translational modifications for FOXO3 Gene

  • Deacetylation by SIRT1 or SIRT2 stimulates interaction of FOXO3 with SKP2 and facilitates SCF(SKP2)-mediated FOXO3 ubiquitination and proteasomal degradation (PubMed:21841822). Deacetylation by SIRT2 stimulates FOXO3-mediated transcriptional activity in response to oxidative stress (By similarity).
  • Heavily methylated by SET9 which decreases stability, while moderately increasing transcriptional activity. The main methylation site is Lys-271. Methylation doesnt affect subcellular location.
  • 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 doesnt 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 3UTR of MYC transcript and prevent its translation (PubMed:10102273, PubMed:11154281, PubMed:16751106, PubMed:17711846, PubMed:18593906, PubMed:21329882). Phosphorylated by CHUK/IKKA and IKBKB/IKKB. TNF-induced inactivation of FOXO3 requires its phosphorylation at Ser-644 by IKBKB/IKKB which promotes FOXO3 retention in the cytoplasm, polyubiquitination and ubiquitin-mediated proteasomal degradation (PubMed:15084260).
  • Polyubiquitinated. Ubiquitinated by a SCF complex containing SKP2, leading to proteasomal degradation.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for FOXO3 Gene

Antibody Products

  • Cell Signaling Technology (CST) Antibodies for FOXO3 (FOXO3A)

No data available for DME Specific Peptides for FOXO3 Gene

Domains & Families for FOXO3 Gene

Gene Families for FOXO3 Gene

Protein Domains for FOXO3 Gene

Graphical View of Domain Structure for InterPro Entry

O43524

UniProtKB/Swiss-Prot:

FOXO3_HUMAN :
  • Contains 1 fork-head DNA-binding domain.
Domain:
  • Contains 1 fork-head DNA-binding domain.
genes like me logo Genes that share domains with FOXO3: view

Function for FOXO3 Gene

Molecular function for FOXO3 Gene

UniProtKB/Swiss-Prot 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 3UTR of MYC transcript and prevent its translation.

Gene Ontology (GO) - Molecular Function for FOXO3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001221 transcription cofactor binding IEA --
GO:0003700 transcription factor activity, sequence-specific DNA binding IDA 14734530
GO:0008013 beta-catenin binding IPI 15905404
genes like me logo Genes that share ontologies with FOXO3: view
genes like me logo Genes that share phenotypes with FOXO3: view

Animal Models for FOXO3 Gene

MGI Knock Outs for FOXO3:

Animal Model Products

miRNA for FOXO3 Gene

miRTarBase miRNAs that target FOXO3

Transcription Factor Targets for FOXO3 Gene

Selected GeneGlobe predicted Target genes for FOXO3
Targeted motifs for FOXO3 Gene
HOMER Transcription Factor Regulatory Elements motif FOXO3
  • Consensus sequence: DGTAAACA Submotif: canonical Cell Type: U2OS

No data available for Enzyme Numbers (IUBMB) and Human Phenotype Ontology for FOXO3 Gene

Localization for FOXO3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for FOXO3 Gene

Cytoplasm, cytosol. Nucleus. Note=Retention in the cytoplasm contributes to its inactivation. Translocates to the nucleus upon oxidative stress and in the absence of survival factors. {ECO:0000269 PubMed:10102273, ECO:0000269 PubMed:15084260, ECO:0000269 PubMed:16751106}.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for FOXO3 Gene COMPARTMENTS Subcellular localization image for FOXO3 gene
Compartment Confidence
cytosol 5
nucleus 5
lysosome 2
mitochondrion 2
vacuole 2
extracellular 1
plasma membrane 1

Gene Ontology (GO) - Cellular Components for FOXO3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005829 cytosol TAS --
genes like me logo Genes that share ontologies with FOXO3: view

Pathways & Interactions for FOXO3 Gene

SuperPathways for FOXO3 Gene

Superpath Contained pathways
1 Interleukin-3, 5 and GM-CSF signaling
2 PI3K events in ERBB4 signaling
3 IL-7 Signaling Pathways
4 Immune System
5 Downstream signaling events of B Cell Receptor (BCR)
genes like me logo Genes that share pathways with FOXO3: view

SIGNOR curated interactions for FOXO3 Gene

Gene Ontology (GO) - Biological Process for FOXO3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription from RNA polymerase II promoter IMP 18787191
GO:0001542 ovulation from ovarian follicle IEA --
GO:0001556 oocyte maturation IEA --
GO:0006355 regulation of transcription, DNA-templated IEA --
GO:0006357 regulation of transcription from RNA polymerase II promoter ISS --
genes like me logo Genes that share ontologies with FOXO3: view

Drugs & Compounds for FOXO3 Gene

(13) Drugs for FOXO3 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(7) Additional Compounds for FOXO3 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with FOXO3: view

Transcripts for FOXO3 Gene

Unigene Clusters for FOXO3 Gene

Forkhead box O3:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for FOXO3 Gene

No ASD Table

Relevant External Links for FOXO3 Gene

GeneLoc Exon Structure for
FOXO3
ECgene alternative splicing isoforms for
FOXO3

Expression for FOXO3 Gene

mRNA expression in normal human tissues for FOXO3 Gene

Protein differential expression in normal tissues from HIPED for FOXO3 Gene

This gene is overexpressed in Bone marrow mesenchymal stem cell (27.6) and Cervix (21.2).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MOPED, and MaxQB for FOXO3 Gene



SOURCE GeneReport for Unigene cluster for FOXO3 Gene Hs.220950

mRNA Expression by UniProt/SwissProt for FOXO3 Gene

O43524-FOXO3_HUMAN
Tissue specificity: Ubiquitous.
genes like me logo Genes that share expression patterns with FOXO3: view

Primer Products

In Situ Assay Products

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues and Protein tissue co-expression partners for FOXO3 Gene

Orthologs for FOXO3 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for FOXO3 Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
Mammalia FOXO3 35
  • 91.17 (n)
  • 95.68 (a)
FOXO3 36
  • 96 (a)
OneToOne
dog
(Canis familiaris)
Mammalia FOXO3 35
  • 90.81 (n)
  • 94.04 (a)
FOXO3 36
  • 96 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Foxo3 35
  • 89.68 (n)
  • 93.9 (a)
Foxo3 16
Foxo3 36
  • 95 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia FOXO3 35
  • 99.75 (n)
  • 99.85 (a)
FOXO3 36
  • 100 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Foxo3 35
  • 89.38 (n)
  • 93.9 (a)
oppossum
(Monodelphis domestica)
Mammalia FOXO3 36
  • 83 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia FOXO3 36
  • 79 (a)
OneToOne
chicken
(Gallus gallus)
Aves FOXO3 35
  • 79.24 (n)
  • 87.62 (a)
FOXO3 36
  • 88 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia foxo3 35
  • 70.79 (n)
  • 74.19 (a)
Str.14701 35
African clawed frog
(Xenopus laevis)
Amphibia Xl.2074 35
zebrafish
(Danio rerio)
Actinopterygii -- 35
foxo3b 35
  • 62.34 (n)
  • 62.12 (a)
foxo3a 36
  • 58 (a)
OneToMany
foxo3b 36
  • 58 (a)
OneToMany
fruit fly
(Drosophila melanogaster)
Insecta foxo 36
  • 32 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea daf-16 36
  • 28 (a)
OneToMany
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes HCM1 36
  • 15 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea CSA.3143 36
  • 25 (a)
OneToMany
Species with no ortholog for FOXO3:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • lizard (Anolis carolinensis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for FOXO3 Gene

ENSEMBL:
Gene Tree for FOXO3 (if available)
TreeFam:
Gene Tree for FOXO3 (if available)

Paralogs for FOXO3 Gene

Paralogs for FOXO3 Gene

(4) SIMAP similar genes for FOXO3 Gene using alignment to 2 proteins:

Pseudogenes.org Pseudogenes for FOXO3 Gene

genes like me logo Genes that share paralogs with FOXO3: view

Variants for FOXO3 Gene

Sequence variations from dbSNP and Humsavar for FOXO3 Gene

SNP ID Clin Chr 06 pos Sequence Context AA Info Type
rs719807 -- 108,564,783(+) GTTTT(A/G)TGTTT intron-variant
rs719808 -- 108,564,907(+) TAATG(A/C)CTTTC intron-variant
rs1062034 -- 108,684,385(-) TAAGA(C/T)AGTTT utr-variant-3-prime
rs1044947 -- 108,680,457(+) CTATG(C/T)GCACC utr-variant-3-prime
rs1044951 -- 108,680,473(+) AGGAC(A/T)GAACC utr-variant-3-prime

Structural Variations from Database of Genomic Variants (DGV) for FOXO3 Gene

Variant ID Type Subtype PubMed ID
nsv830767 CNV Gain 17160897
nsv823817 CNV Gain 20364138
esv22566 CNV Loss 19812545
esv2651848 CNV Deletion 19546169
nsv5433 CNV Insertion 18451855

Variation tolerance for FOXO3 Gene

Residual Variation Intolerance Score: 45.9% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 3.51; 55.40% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for FOXO3 Gene

HapMap Linkage Disequilibrium report
FOXO3
Human Gene Mutation Database (HGMD)
FOXO3

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for FOXO3 Gene

Disorders for FOXO3 Gene

MalaCards: The human disease database

(2) MalaCards diseases for FOXO3 Gene - From: DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
rhabdomyosarcoma
lung cancer
  • lung cancer, protection against
- elite association - COSMIC cancer census association via MalaCards
Search FOXO3 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

FOXO3_HUMAN
  • Note=A chromosomal aberration involving FOXO3 is found in secondary acute leukemias. Translocation t(6;11)(q21;q23) with KMT2A/MLL1.

Relevant External Links for FOXO3

Genetic Association Database (GAD)
FOXO3
Human Genome Epidemiology (HuGE) Navigator
FOXO3
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
FOXO3
genes like me logo Genes that share disorders with FOXO3: view

No data available for Genatlas for FOXO3 Gene

Publications for FOXO3 Gene

  1. Cloning and characterization of three human forkhead genes that comprise an FKHR-like gene subfamily. (PMID: 9479491) Anderson M.J. … Arden K.C. (Genomics 1998) 2 3 4 23 67
  2. FOXO3a elicits a pro-apoptotic transcription program and cellular response to human lung carcinogen nicotine-derived nitrosaminoketone (NNK). (PMID: 19380174) Blake D.C. … Herzog C.R. (Lung Cancer 2010) 3 23
  3. Clinical and biological significance of forkhead class box O 3a expression in glioma: mediation of glioma malignancy by transcriptional regulation of p27kip1. (PMID: 19911116) Shi J. … Shi G. (J. Neurooncol. 2010) 3 23
  4. Oxidative stress-specific interaction between FANCD2 and FOXO3a. (PMID: 20040763) Li J. … Pang Q. (Blood 2010) 3 23
  5. Protein phosphatase 2A reactivates FOXO3a through a dynamic interplay with 14-3-3 and AKT. (PMID: 20110348) Singh A. … Khosravi-Far R. (Mol. Biol. Cell 2010) 3 23

Products for FOXO3 Gene

Sources for FOXO3 Gene

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