FOXO4
Forkhead box protein O4
Also known as: AFX1, FOXO4_HUMAN, MLLT7
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P98177
- Gene
- FOXO4
- Ensembl
- ENSG00000184481
- Chromosome
- X
- Canonical length
- 505 aa
- Protein class
- Cancer-related genes, Disease related genes, Predicted intracellular proteins, RAS pathway related proteins, Transcription factors
- Subcellular location
- Nuclear speckles,Cytosol
OverviewNCBI Gene
This gene encodes a member of the O class of winged helix/forkhead transcription factor family. Proteins encoded by this class are regulated by factors involved in growth and differentiation indicating they play a role in these processes. A translocation involving this gene on chromosome X and the homolog of the Drosophila trithorax gene, encoding a DNA binding protein, located on chromosome 11 is associated with leukemia. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2010]
Canonical amino-acid sequenceUniProt
505 residues, UniProt reviewed canonical sequence.
>P98177|FOXO4
1 MDPGNENSAT EAAAIIDLDP DFEPQSRPRS CTWPLPRPEI ANQPSEPPEV EPDLGEKVHT
61 EGRSEPILLP SRLPEPAGGP QPGILGAVTG PRKGGSRRNA WGNQSYAELI SQAIESAPEK
121 RLTLAQIYEW MVRTVPYFKD KGDSNSSAGW KNSIRHNLSL HSKFIKVHNE ATGKSSWWML
181 NPEGGKSGKA PRRRAASMDS SSKLLRGRSK APKKKPSVLP APPEGATPTS PVGHFAKWSG
241 SPCSRNREEA DMWTTFRPRS SSNASSVSTR LSPLRPESEV LAEEIPASVS SYAGGVPPTL
301 NEGLELLDGL NLTSSHSLLS RSGLSGFSLQ HPGVTGPLHT YSSSLFSPAE GPLSAGEGCF
361 SSSQALEALL TSDTPPPPAD VLMTQVDPIL SQAPTLLLLG GLPSSSKLAT GVGLCPKPLE
421 APGPSSLVPT LSMIAPPPVM ASAPIPKALG TPVLTPPTEA ASQDRMPQDL DLDMYMENLE
481 CDMDNIISDL MDEGEGLDFN FEPDPLocalizationUniProt · AlphaFold · HPA
Whether an antibody against FOXO4 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
- Intracellular
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.66
- Highest tissue expression
- 110 nTPM
Expression across tissuesHPA
Tissue
- placenta: 110 nTPM
- skeletal muscle: 63 nTPM
- midbrain: 61 nTPM
- basal ganglia: 56 nTPM
- amygdala: 54 nTPM
- hippocampal formation: 53 nTPM
Single-cell type
- cytotrophoblasts: 317 nCPM
- syncytiotrophoblasts: 314 nCPM
- migrating cytotrophoblasts: 202 nCPM
- platelets: 21 nCPM
- esophageal apical cells: 20 nCPM
- neutrophils: 18 nCPM
Immune cell
- eosinophil: 1 nTPM
- neutrophil: 0.9 nTPM
- naive CD8 T-cell: 0.4 nTPM
- T-reg: 0.3 nTPM
- total PBMC: 0.3 nTPM
- gdT-cell: 0.2 nTPM
Brain region
- white matter: 98 nTPM
- basal ganglia: 96 nTPM
- amygdala: 83 nTPM
- medulla oblongata: 79 nTPM
- midbrain: 76 nTPM
- thalamus: 73 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)
- 0.48
- gnomAD pLI
- 0.81
- gnomAD missense Z
- 1.65
- DepMap mean gene effect
- 0.07
- DepMap dependency class
- none
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
- insulin receptor signaling pathway
- mitotic G2 DNA damage checkpoint signaling
- muscle organ development
- negative regulation of angiogenesis
- negative regulation of cell population proliferation
- negative regulation of G0 to G1 transition
- negative regulation of smooth muscle cell differentiation
- positive regulation of smooth muscle cell migration
- positive regulation of transcription by RNA polymerase II
- regulation of DNA-templated transcription
- regulation of transcription by RNA polymerase II
- response to nutrient levels
- response to oxidative stress
- response to water-immersion restraint stress
- stem cell differentiation
Molecular functions
- beta-catenin 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 factor binding
- enzyme binding
- identical protein binding
- nucleic acid binding
- promoter-specific chromatin binding
- RNA polymerase II cis-regulatory region sequence-specific DNA binding
- sequence-specific DNA binding
- sequence-specific double-stranded DNA binding
Cellular components
Protein domainsUniProt · Pfam · InterPro
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of FOXO4 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 FOXO4 as an antibody target. Whether an autoantibody or antibody against FOXO4 could matter depends on whether native FOXO4 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
FOXO4 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 FOXO4 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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