FOXO3
Forkhead box protein O3
Also known as: AF6q21, FKHRL1, FOXO2, FOXO3_HUMAN, FOXO3A
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- O43524
- Gene
- FOXO3
- Ensembl
- ENSG00000118689
- Chromosome
- 6
- Canonical length
- 673 aa
- Protein class
- Cancer-related genes, Disease related genes, Predicted intracellular proteins, Transcription factors
- Subcellular location
- Nucleoplasm
OverviewNCBI 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]
Canonical amino-acid sequenceUniProt
673 residues, UniProt reviewed canonical sequence.
>O43524|FOXO3
1 MAEAPASPAP LSPLEVELDP EFEPQSRPRS CTWPLQRPEL QASPAKPSGE TAADSMIPEE
61 EDDEDDEDGG GRAGSAMAIG GGGGSGTLGS GLLLEDSARV LAPGGQDPGS GPATAAGGLS
121 GGTQALLQPQ QPLPPPQPGA AGGSGQPRKC SSRRNAWGNL SYADLITRAI ESSPDKRLTL
181 SQIYEWMVRC VPYFKDKGDS NSSAGWKNSI RHNLSLHSRF MRVQNEGTGK SSWWIINPDG
241 GKSGKAPRRR AVSMDNSNKY TKSRGRAAKK KAALQTAPES ADDSPSQLSK WPGSPTSRSS
301 DELDAWTDFR SRTNSNASTV SGRLSPIMAS TELDEVQDDD APLSPMLYSS SASLSPSVSK
361 PCTVELPRLT DMAGTMNLND GLTENLMDDL LDNITLPPSQ PSPTGGLMQR SSSFPYTTKG
421 SGLGSPTSSF NSTVFGPSSL NSLRQSPMQT IQENKPATFS SMSHYGNQTL QDLLTSDSLS
481 HSDVMMTQSD PLMSQASTAV SAQNSRRNVM LRNDPMMSFA AQPNQGSLVN QNLLHHQHQT
541 QGALGGSRAL SNSVSNMGLS ESSSLGSAKH QQQSPVSQSM QTLSDSLSGS SLYSTSANLP
601 VMGHEKFPSD LDLDMFNGSL ECDMESIIRS ELMDADGLDF NFDSLISTQN VVGLNVGNFT
661 GAKQASSQSW VPGLocalizationUniProt · AlphaFold · HPA
Whether an antibody against FOXO3 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Other membrane
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.67
- Highest tissue expression
- 82 nTPM
Expression across tissuesHPA
Tissue
- pancreas: 82 nTPM
- skeletal muscle: 79 nTPM
- bone marrow: 65 nTPM
- tongue: 48 nTPM
- adipose tissue: 44 nTPM
- blood vessel: 42 nTPM
Single-cell type
- neutrophils: 3,967 nCPM
- monocytes: 1,186 nCPM
- thymic myoid cells: 1,065 nCPM
- neutrophil progenitors: 895 nCPM
- myonuclei: 721 nCPM
- epicardial cells: 666 nCPM
Immune cell
- neutrophil: 16 nTPM
- basophil: 7.8 nTPM
- eosinophil: 6.1 nTPM
- non-classical monocyte: 5.3 nTPM
- MAIT T-cell: 3.8 nTPM
- NK-cell: 3.7 nTPM
Brain region
- cerebellum: 96 nTPM
- choroid plexus: 67 nTPM
- cerebral cortex: 67 nTPM
- medulla oblongata: 64 nTPM
- thalamus: 63 nTPM
- white matter: 61 nTPM
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.27
- gnomAD pLI
- 0.99
- gnomAD missense Z
- 1.68
- DepMap mean gene effect
- -0.35
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- antral ovarian follicle growth
- brain morphogenesis
- canonical Wnt signaling pathway
- cellular response to amyloid-beta
- cellular response to corticosterone stimulus
- cellular response to glucose starvation
- cellular response to glucose stimulus
- cellular response to hypoxia
- cellular response to nerve growth factor stimulus
- cellular response to oxidative stress
- DNA damage response, signal transduction by p53 class mediator
- extrinsic apoptotic signaling pathway in absence of ligand
- initiation of primordial ovarian follicle growth
- mitochondrial transcription
- negative regulation of canonical Wnt signaling pathway
- negative regulation of cell migration
- negative regulation of neuron differentiation
- negative regulation of transcription by RNA polymerase II
- neuronal stem cell population maintenance
- oocyte maturation
- ovulation from ovarian follicle
- positive regulation of apoptotic process
- positive regulation of autophagy
- positive regulation of DNA-templated transcription
- positive regulation of endothelial cell apoptotic process
- positive regulation of erythrocyte differentiation
- positive regulation of hydrogen peroxide-mediated programmed cell death
- positive regulation of miRNA transcription
- positive regulation of muscle atrophy
- positive regulation of neuron apoptotic process
- positive regulation of reactive oxygen species biosynthetic process
- positive regulation of regulatory T cell differentiation
- positive regulation of transcription by RNA polymerase II
- regulation of neural precursor cell proliferation
- regulation of transcription by RNA polymerase II
- regulation of translation
- response to dexamethasone
- response to fatty acid
- response to starvation
- response to water-immersion restraint stress
- response to xenobiotic stimulus
- tumor necrosis factor-mediated signaling pathway
Molecular functions
- beta-catenin binding
- chromatin DNA binding
- DNA binding
- DNA-binding transcription activator activity, RNA polymerase II-specific
- DNA-binding transcription factor activity
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA-binding transcription repressor activity, RNA polymerase II-specific
- mitochondrial transcription factor activity
- protein kinase binding
- RNA polymerase II cis-regulatory region sequence-specific DNA binding
- sequence-specific DNA binding
- sequence-specific double-stranded DNA binding
- transcription cis-regulatory region binding
- transcription coregulator binding
Cellular components
Protein domainsUniProt · Pfam · InterPro
- Fork head domain
- Fork head domain conserved site 2
- FOXO protein, transactivation domain
- FOXO protein, KIX-binding domain
- Winged helix-like DNA-binding domain superfamily
- Winged helix DNA-binding domain superfamily
- Forkhead domain
- KIX-binding domain of forkhead box O, CR2
- Transactivation domain of FOXO protein family
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of FOXO3 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads FOXO3 as an antibody target. Whether an autoantibody or antibody against FOXO3 could matter depends on whether native FOXO3 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
FOXO3 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label FOXO3 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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