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FOXO3 forkhead box O3 [ Homo sapiens (human) ]

Gene ID: 2309, updated on 1-Jun-2020

Summary

Official Symbol
FOXO3provided by HGNC
Official Full Name
forkhead box O3provided by HGNC
Primary source
HGNC:HGNC:3821
See related
Ensembl:ENSG00000118689 MIM:602681
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
FOXO2; AF6q21; FKHRL1; FOXO3A; FKHRL1P2
Summary
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]
Expression
Ubiquitous expression in fat (RPKM 14.1), bone marrow (RPKM 13.9) and 25 other tissues See more
Orthologs

Genomic context

See FOXO3 in Genome Data Viewer
Location:
6q21
Exon count:
9
Annotation release Status Assembly Chr Location
109.20200522 current GRCh38.p13 (GCF_000001405.39) 6 NC_000006.12 (108559825..108684774)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (108881026..109005972)

Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene AFG1 like ATPase Neighboring gene uncharacterized LOC105377932 Neighboring gene translocase of outer mitochondrial membrane 5 homolog (yeast) pseudogene Neighboring gene RNA, U6 small nuclear 770, pseudogene Neighboring gene Sharpr-MPRA regulatory region 14072 Neighboring gene SUMO2 pseudogene 8 Neighboring gene uncharacterized LOC107986629 Neighboring gene long intergenic non-protein coding RNA 222

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Phenotypes

NHGRI GWAS Catalog

Description
A genome-wide association study identifies novel loci associated with circulating IGF-I and IGFBP-3.
NHGRI GWA Catalog
Genome-wide association analysis of susceptibility and clinical phenotype in multiple sclerosis.
NHGRI GWA Catalog
Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array.
NHGRI GWA Catalog

HIV-1 interactions

Replication interactions

Interaction Pubs
Knockdown of forkhead box O3 (FOXO3) by shRNA library screening inhibits HIV-1 replication in cultured Jurkat T-cells PubMed

Protein interactions

Protein Gene Interaction Pubs
Tat tat HIV-1 Tat expression in Jurkat T cells increases the amount and the translocation of FOXO3a from the cytoplasm to the nucleus, indicating that FOXO3a is no longer phosphorylated PubMed
Vpr vpr HIV-1 Vpr inhibits insulin-induced association of 14-3-3 and Foxo3a in HeLa cells PubMed
vpr HIV-1 Vpr inhibits insulin- and Akt-induced cytoplasmic translocation of Foxo3a, a subtype of the forkhead transcription factors PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Clone Names

  • MGC12739, MGC31925, DKFZp781A0677

Gene Ontology Provided by GOA

Function Evidence Code Pubs
DNA binding IDA
Inferred from Direct Assay
more info
PubMed 
DNA-binding transcription activator activity, RNA polymerase II-specific ISS
Inferred from Sequence or Structural Similarity
more info
 
DNA-binding transcription factor activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
DNA-binding transcription factor activity IDA
Inferred from Direct Assay
more info
PubMed 
DNA-binding transcription factor activity, RNA polymerase II-specific IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
DNA-binding transcription factor activity, RNA polymerase II-specific ISA
Inferred from Sequence Alignment
more info
 
DNA-binding transcription factor activity, RNA polymerase II-specific ISM
Inferred from Sequence Model
more info
PubMed 
DNA-binding transcription repressor activity, RNA polymerase II-specific IDA
Inferred from Direct Assay
more info
PubMed 
RNA polymerase II proximal promoter sequence-specific DNA binding ISS
Inferred from Sequence or Structural Similarity
more info
 
beta-catenin binding IPI
Inferred from Physical Interaction
more info
PubMed 
chromatin DNA binding ISS
Inferred from Sequence or Structural Similarity
more info
 
mitochondrial sequence-specific DNA-binding transcription factor activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein kinase binding IPI
Inferred from Physical Interaction
more info
PubMed 
sequence-specific DNA binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
sequence-specific DNA binding IDA
Inferred from Direct Assay
more info
PubMed 
transcription cofactor binding IEA
Inferred from Electronic Annotation
more info
 
transcription factor binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
transcription regulatory region sequence-specific DNA binding ISS
Inferred from Sequence or Structural Similarity
more info
 
Process Evidence Code Pubs
DNA damage response, signal transduction by p53 class mediator IEA
Inferred from Electronic Annotation
more info
 
aging IEA
Inferred from Electronic Annotation
more info
 
antral ovarian follicle growth IEA
Inferred from Electronic Annotation
more info
 
brain morphogenesis IEA
Inferred from Electronic Annotation
more info
 
cellular response to amyloid-beta IEA
Inferred from Electronic Annotation
more info
 
cellular response to corticosterone stimulus IEA
Inferred from Electronic Annotation
more info
 
cellular response to glucose starvation IDA
Inferred from Direct Assay
more info
PubMed 
cellular response to glucose stimulus IEA
Inferred from Electronic Annotation
more info
 
cellular response to hypoxia IEA
Inferred from Electronic Annotation
more info
 
cellular response to nerve growth factor stimulus IEA
Inferred from Electronic Annotation
more info
 
cellular response to oxidative stress ISS
Inferred from Sequence or Structural Similarity
more info
 
cytokine-mediated signaling pathway TAS
Traceable Author Statement
more info
 
extrinsic apoptotic signaling pathway in absence of ligand IEA
Inferred from Electronic Annotation
more info
 
glucose homeostasis IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
initiation of primordial ovarian follicle growth IEA
Inferred from Electronic Annotation
more info
 
insulin receptor signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
mitochondrial transcription IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of canonical Wnt signaling pathway IEA
Inferred from Electronic Annotation
more info
 
negative regulation of cell migration IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of neuron differentiation IEA
Inferred from Electronic Annotation
more info
 
negative regulation of transcription by RNA polymerase II IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
negative regulation of transcription by RNA polymerase II IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of transcription by RNA polymerase II IMP
Inferred from Mutant Phenotype
more info
PubMed 
neuronal stem cell population maintenance IEA
Inferred from Electronic Annotation
more info
 
oocyte maturation IEA
Inferred from Electronic Annotation
more info
 
ovulation from ovarian follicle IEA
Inferred from Electronic Annotation
more info
 
positive regulation of apoptotic process IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of autophagy ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of endothelial cell apoptotic process IEA
Inferred from Electronic Annotation
more info
 
positive regulation of erythrocyte differentiation IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of hydrogen peroxide-mediated programmed cell death IEA
Inferred from Electronic Annotation
more info
 
positive regulation of muscle atrophy ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of neuron apoptotic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of pri-miRNA transcription by RNA polymerase II ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of reactive oxygen species biosynthetic process IEA
Inferred from Electronic Annotation
more info
 
positive regulation of transcription by RNA polymerase II IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
positive regulation of transcription by RNA polymerase II IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of transcription, DNA-templated IDA
Inferred from Direct Assay
more info
PubMed 
regulation of neural precursor cell proliferation IEA
Inferred from Electronic Annotation
more info
 
regulation of transcription by RNA polymerase II ISS
Inferred from Sequence or Structural Similarity
more info
 
regulation of translation IDA
Inferred from Direct Assay
more info
PubMed 
response to dexamethasone IEA
Inferred from Electronic Annotation
more info
 
response to starvation ISS
Inferred from Sequence or Structural Similarity
more info
 
response to water-immersion restraint stress IEA
Inferred from Electronic Annotation
more info
 
tumor necrosis factor-mediated signaling pathway IMP
Inferred from Mutant Phenotype
more info
PubMed 
Component Evidence Code Pubs
cell IEA
Inferred from Electronic Annotation
more info
 
cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
cytoplasm IDA
Inferred from Direct Assay
more info
PubMed 
cytosol IDA
Inferred from Direct Assay
more info
PubMed 
cytosol TAS
Traceable Author Statement
more info
 
colocalizes_with mitochondrial matrix IDA
Inferred from Direct Assay
more info
PubMed 
mitochondrial outer membrane IDA
Inferred from Direct Assay
more info
PubMed 
colocalizes_with mitochondrion IDA
Inferred from Direct Assay
more info
PubMed 
nuclear chromatin ISA
Inferred from Sequence Alignment
more info
 
nucleoplasm IDA
Inferred from Direct Assay
more info
 
nucleoplasm TAS
Traceable Author Statement
more info
 
nucleus IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
nucleus IDA
Inferred from Direct Assay
more info
PubMed 
nucleus IMP
Inferred from Mutant Phenotype
more info
PubMed 
protein-containing complex IDA
Inferred from Direct Assay
more info
PubMed 

General protein information

Preferred Names
forkhead box protein O3
Names
forkhead box O3A
forkhead homolog (rhabdomyosarcoma) like 1
forkhead in rhabdomyosarcoma-like 1
forkhead, Drosophila, homolog of, in rhabdomyosarcoma-like 1

NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

  1. NM_001455.4NP_001446.1  forkhead box protein O3

    See identical proteins and their annotated locations for NP_001446.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) differs in the 5' end and represents the longer transcript compared to variant 2. Both variants encode the same protein.
    Source sequence(s)
    AF032886, AK024103, AL096818, AL365509, CA389775
    Consensus CDS
    CCDS5068.1
    UniProtKB/Swiss-Prot
    O43524
    Related
    ENSP00000385824.1, ENST00000406360.2
    Conserved Domains (3) summary
    cd00059
    Location:157237
    FH; Forkhead (FH), also known as a "winged helix". FH is named for the Drosophila fork head protein, a transcription factor which promotes terminal rather than segmental development. This family of transcription factor domains, which bind to B-DNA as ...
    pfam16675
    Location:433508
    FOXO_KIX_bdg; KIX-binding domain of forkhead box O, CR2
    pfam16676
    Location:606644
    FOXO-TAD; Transactivation domain of FOXO protein family
  2. NM_201559.3NP_963853.1  forkhead box protein O3

    See identical proteins and their annotated locations for NP_963853.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in the 5' end compared to variant 1. Both variants encode the same protein.
    Source sequence(s)
    AK024103, AL096818, AL365509, BC020227, CD101760
    Consensus CDS
    CCDS5068.1
    UniProtKB/Swiss-Prot
    O43524
    Related
    ENSP00000339527.6, ENST00000343882.10
    Conserved Domains (3) summary
    cd00059
    Location:157237
    FH; Forkhead (FH), also known as a "winged helix". FH is named for the Drosophila fork head protein, a transcription factor which promotes terminal rather than segmental development. This family of transcription factor domains, which bind to B-DNA as ...
    pfam16675
    Location:433508
    FOXO_KIX_bdg; KIX-binding domain of forkhead box O, CR2
    pfam16676
    Location:606644
    FOXO-TAD; Transactivation domain of FOXO protein family

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000006.12 Reference GRCh38.p13 Primary Assembly

    Range
    108559825..108684774
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_005266867.4XP_005266924.1  forkhead box protein O3 isoform X2

    Conserved Domains (3) summary
    pfam16675
    Location:244319
    FOXO_KIX_bdg; KIX-binding domain of forkhead box O, CR2
    pfam16676
    Location:417455
    FOXO-TAD; Transactivation domain of FOXO protein family
    cl00061
    Location:1750
    FH; Forkhead (FH), also known as a "winged helix". FH is named for the Drosophila fork head protein, a transcription factor which promotes terminal rather than segmental development. This family of transcription factor domains, which bind to B-DNA as ...
  2. XM_011535626.2XP_011533928.1  forkhead box protein O3 isoform X1

    Conserved Domains (3) summary
    pfam16675
    Location:266341
    FOXO_KIX_bdg; KIX-binding domain of forkhead box O, CR2
    pfam16676
    Location:439477
    FOXO-TAD; Transactivation domain of FOXO protein family
    cl00061
    Location:4072
    FH; Forkhead (FH), also known as a "winged helix". FH is named for the Drosophila fork head protein, a transcription factor which promotes terminal rather than segmental development. This family of transcription factor domains, which bind to B-DNA as ...
  3. XM_017010585.1XP_016866074.1  forkhead box protein O3 isoform X2

    Conserved Domains (3) summary
    pfam16675
    Location:244319
    FOXO_KIX_bdg; KIX-binding domain of forkhead box O, CR2
    pfam16676
    Location:417455
    FOXO-TAD; Transactivation domain of FOXO protein family
    cl00061
    Location:1750
    FH; Forkhead (FH), also known as a "winged helix". FH is named for the Drosophila fork head protein, a transcription factor which promotes terminal rather than segmental development. This family of transcription factor domains, which bind to B-DNA as ...
  4. XM_017010586.1XP_016866075.1  forkhead box protein O3 isoform X3

    UniProtKB/Swiss-Prot
    O43524
    Conserved Domains (2) summary
    pfam16675
    Location:213288
    FOXO_KIX_bdg; KIX-binding domain of forkhead box O, CR2
    pfam16676
    Location:386424
    FOXO-TAD; Transactivation domain of FOXO protein family
  5. XM_011535628.3XP_011533930.1  forkhead box protein O3 isoform X3

    See identical proteins and their annotated locations for XP_011533930.1

    UniProtKB/Swiss-Prot
    O43524
    Conserved Domains (2) summary
    pfam16675
    Location:213288
    FOXO_KIX_bdg; KIX-binding domain of forkhead box O, CR2
    pfam16676
    Location:386424
    FOXO-TAD; Transactivation domain of FOXO protein family
  6. XM_011535629.2XP_011533931.1  forkhead box protein O3 isoform X3

    See identical proteins and their annotated locations for XP_011533931.1

    UniProtKB/Swiss-Prot
    O43524
    Conserved Domains (2) summary
    pfam16675
    Location:213288
    FOXO_KIX_bdg; KIX-binding domain of forkhead box O, CR2
    pfam16676
    Location:386424
    FOXO-TAD; Transactivation domain of FOXO protein family
  7. XM_005266868.3XP_005266925.1  forkhead box protein O3 isoform X3

    See identical proteins and their annotated locations for XP_005266925.1

    UniProtKB/Swiss-Prot
    O43524
    Related
    ENSP00000446316.1, ENST00000540898.1
    Conserved Domains (2) summary
    pfam16675
    Location:213288
    FOXO_KIX_bdg; KIX-binding domain of forkhead box O, CR2
    pfam16676
    Location:386424
    FOXO-TAD; Transactivation domain of FOXO protein family
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