Protein / target
Forkhead box protein O3
Protein at a glance
Biological role
Sequence-specific double-stranded DNA binding
Strongest disease association
Intelligence
Research activity
Emerging research
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function overview
Transcriptional activator that recognizes and binds to the DNA sequence 5'-[AG]TAAA[TC]A-3' and regulates different processes, such as apoptosis and autophagy.
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Transcriptional activator that recognizes and binds to the DNA sequence 5'-[AG]TAAA[TC]A-3' and regulates different processes, such as apoptosis and autophagy (PubMed:10102273, PubMed:16751106, PubMed:21329882, PubMed:30513302). Acts as a positive regulator of autophagy in skeletal muscle: in starved cells, enters the nucleus following dephosphorylation and binds the promoters of autophagy genes, such as GABARAP1L, MAP1LC3B and ATG12, thereby activating their expression, resulting in proteolysis of skeletal muscle proteins (By similarity). Triggers apoptosis in the absence of survival factors, including neuronal cell death upon oxidative stress (PubMed:10102273, PubMed:16751106). 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 (PubMed:21329882). In response to metabolic stress, translocates into the mitochondria where it promotes mtDNA transcription (PubMed:23283301). In response to metabolic stress, translocates into the mitochondria where it promotes mtDNA transcription. Also acts as a key regulator of chondrogenic commitment of skeletal progenitor cells in response to lipid availability: when lipids levels are low, translocates to the nucleus and promotes expression of SOX9, which induces chondrogenic commitment and suppresses fatty acid oxidation (By similarity). Also acts as a key regulator of regulatory T-cells (Treg) differentiation by activating expression of FOXP3 (PubMed:30513302)
Subcellular location
Domains and Gene Ontology detail (54)Hide
Gene Ontology
- Cchromatin
- Ccytoplasm
- Ccytosol
- Cmitochondrial matrix
- Cmitochondrial outer membrane
- Cnucleoplasm
- Cnucleus
- Cprotein-containing complex
- Fbeta-catenin binding
- Fchromatin DNA binding
- FDNA binding
- FDNA-binding transcription activator activity, RNA polymerase II-specific
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
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Lipid & lipoprotein metabolism
- ·Transcriptional activator that recognizes and binds to the DNA sequence 5'-[AG]TAAA[TC]A…
- ·response to fatty acid
Cell migration
- ·negative regulation of cell migration
Transcriptional regulation
- ·Transcriptional activator that recognizes and binds to the DNA sequence 5'-[AG]TAAA[TC]A…
- ·DNA-binding transcription activator activity, RNA polymerase II-specific
- ·DNA-binding transcription factor activity
- ·DNA-binding transcription factor activity, RNA polymerase II-specific
Apoptosis & cell death
- ·apoptotic process
- ·positive regulation of apoptotic process
- ·positive regulation of endothelial cell apoptotic process
- ·positive regulation of hydrogen peroxide-mediated programmed cell death
Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.
Translational evidence
Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.
Strongest disease associations · via encoding gene FOXO3
Gene-level evidence surfaced through the gene FOXO3that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.
View evidence synthesis (5)Hide
This ranking differs from Open Targets' own: re-weighting moves genetically-evidenced diseases above more heavily co-mentioned ones. The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the per-type scores above show the calculation.
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Tractability
Small molecules — Emerging
Antibodies — Emerging
Protein degraders — Emerging
View underlying tractability evidence (4)Hide
Raw Open Targets tractability assessment buckets, by modality.
Safety-related annotations
Terms indexed against this target in Open Targets' safety data, with their datasource. These are annotations, not causal claims: the direction of effect (whether activation or inhibition is implicated), species and evidence strength are not captured here, so an entry does not mean that modulating this target is known to cause that condition.
Research activity
Papers linked directly to this protein. This is the protein's own literature — descriptor-derived papers are kept separate below.
Most cited
Recent
Europe PMC papers linked directly to this protein.