Display Settings:

Format

Send to:

Choose Destination

    FOXO4 forkhead box O4 [ Homo sapiens ]

    Gene ID: 4303, updated on 19-May-2012

    Summary

    Official Symbol
    FOXO4provided by HGNC
    Official Full Name
    forkhead box O4provided by HGNC
    Primary source
    HGNC:7139
    See related
    Ensembl:ENSG00000184481; HPRD:02070; MIM:300033; Vega:OTTHUMG00000021789
    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
    AFX; AFX1; MLLT7; MGC120490
    Summary
    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]

    Genomic context

    Location :
    Xq13.1
    Sequence :
    Chromosome: X; NC_000023.10 (70315999..70323384)
    See FOXO4 in Epigenomics, MapViewer

    Chromosome X - NC_000023.10Genomic Context describing neighboring genes Neighboring gene suppressor of cytokine signaling 5-like Neighboring gene sorting nexin 12 Neighboring gene chromosome X open reading frame 65 Neighboring gene interleukin 2 receptor, gamma

    Genomic regions, transcripts, and products

    Bibliography

    Related articles in PubMed

    GeneRIFs: Gene References Into Functions What's a GeneRIF?

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description
    NP_005929.1 NP_005154.1 AKT1    BIND  PubMed AKT1 interacts with MLLT7 (FOXO4). This interaction was modelled on a demonstrated interaction between human AKT1 and FOXO4 from an unspecified species. 
    NP_005929.1 NT_035113.6 CCND1    BIND  PubMed MLLT7 (FOXO4) interacts with the CCND1 (Cyclin D1) promoter. This interaction was modelled on a demonstrated interaction between MLLT7 and CCND1 both from unspecified species. 
    NP_005929.1 NT_007592.14 CDKN1A    BIND  PubMed FoxO4 binds the distal region of the p21Cip1 promoter. This interaction was modelled on a demonstrated interaction between FoxO4 from an unspecified species and p21Cip1 promoter from an unspecified species. 
    NP_005929.1 NP_001895.1 CTNNB1    BIND  PubMed beta-catenin interacts with FOXO4. This interaction was modelled on a demonstrated interaction between human FOXO4 and beta-catenin from an unspecified species. 
    NP_005929.1 NP_005240.3 FOXG1    BIND  PubMed FoxO4 interacts with FoxG1. This interaction was modelled on a demonstrated interaction between human FoxO4 and mouse FoxG1. 
    NP_005929.1 NP_005893.1 SMAD3    BIND  PubMed FoxO4 interacts with Smad3. This interaction was modelled on a demonstrated interaction between FoxO4 from human and Smad3 from an unspecified species. 
    NP_005929.1 NP_005350.1 SMAD4    BIND  PubMed FoxO4 interacts with Smad4. 
    P98177 P31749 AKT1    HPRD  PubMed  
    P98177 P31751 AKT2    HPRD  PubMed  
    P98177 Q92793 CREBBP    HPRD  PubMed  
    P98177 P35222 CTNNB1    HPRD  PubMed  
    P98177 P03372 ESR1    HPRD  PubMed  
    P98177 P55315 FOXG1    HPRD  PubMed  
    P98177 P84022 SMAD3    HPRD  PubMed  
    P98177 Q13485 SMAD4    HPRD  PubMed  
    P98177 O14980 XPO1    HPRD  PubMed  
    P98177 P63104 YWHAZ    HPRD  PubMed  
    BioGRID:110449 BioGRID:110433 ATXN3    BioGRID  PubMed Affinity Capture-Western; Co-localization 
    BioGRID:110449 BioGRID:107777 CREBBP    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex 
    BioGRID:110449 BioGRID:107880 CTNNB1    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:110449 BioGRID:108403 ESR1    BioGRID  PubMed Reconstituted Complex 
    BioGRID:110449 BioGRID:110358 MDM2    BioGRID  PubMed Affinity Capture-Western; Biochemical Activity 
    BioGRID:110449 BioGRID:119685 NLK    BioGRID  PubMed Affinity Capture-Western; Biochemical Activity 
    BioGRID:110449 BioGRID:111317 PIN1    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex 
    BioGRID:110449 BioGRID:116983 SIRT1    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:110449 BioGRID:110263 SMAD3    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:110449 BioGRID:110264 SMAD4    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:110449 BioGRID:113164 UBC    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:110449 BioGRID:113622 USP7    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:110449 BioGRID:113264 VDR    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:110449 BioGRID:113348 XPO1    BioGRID  PubMed Reconstituted Complex 

    General gene information

    Markers

    Homology

    Pathways from BioSystems

    • AKT phosphorylates targets in the nucleus, organism-specific biosystem (from REACTOME)
      AKT phosphorylates targets in the nucleus, organism-specific biosystemAfter translocation into the nucleus, AKT can phosphorylate a number of targets there such as CREB, forkhead transcription factors, SRK and NUR77.
    • Adaptive Immune System, organism-specific biosystem (from REACTOME)
      Adaptive Immune System, organism-specific biosystemAdaptive immunity refers to antigen-specific immune response efficiently involved in clearing the pathogens. The adaptive immune system is comprised of B and T lymphocytes that express receptors with...
    • Class I PI3K signaling events mediated by Akt, organism-specific biosystem (from Pathway Interaction Database)
      Class I PI3K signaling events mediated by Akt, organism-specific biosystem
      Class I PI3K signaling events mediated by Akt
    • Disease, organism-specific biosystem (from REACTOME)
      Disease, organism-specific biosystemBiological processes are captured in Reactome by identifying the molecules (DNA, RNA, protein, small molecules) involved in them and describing the details of their interactions. From this molecular ...
    • Downstream Signaling Events Of B Cell Receptor (BCR), organism-specific biosystem (from REACTOME)
      Downstream Signaling Events Of B Cell Receptor (BCR), organism-specific biosystemSecond messengers (calcium, diacylglycerol, inositol 1,4,5-trisphosphate, and phosphatidyinositol 3,4,5-trisphosphate) trigger signaling pathways: NF-kappaB is activated via protein kinase C beta, RA...
    • Downstream signal transduction, organism-specific biosystem (from REACTOME)
      Downstream signal transduction, organism-specific biosystemThe role of autophosphorylation sites on PDGF receptors are to provide docking sites for downstream signal transduction molecules which contain SH2 domains. The SH2 domain is a conserved motif of aro...
    • Downstream signaling of activated FGFR, organism-specific biosystem (from REACTOME)
      Downstream signaling of activated FGFR, organism-specific biosystemSignaling via FGFRs is mediated via direct recruitment of signaling proteins that bind to tyrosine auto-phosphorylation sites on the activated receptor and via closely linked docking proteins that be...
    • FoxO family signaling, organism-specific biosystem (from Pathway Interaction Database)
      FoxO family signaling, organism-specific biosystem
      FoxO family signaling
    • GAB1 signalosome, organism-specific biosystem (from REACTOME)
      GAB1 signalosome, organism-specific biosystemGAB1 is recruited to the activated EGFR indirectly, through GRB2. GAB1 acts as an adaptor protein that enables formation of an active PIK3, through recruitment of PIK3 regulatory subunit PIK3R1 (also...
    • IL-6 Signaling Pathway, organism-specific biosystem (from WikiPathways)
      IL-6 Signaling Pathway, organism-specific biosystemInterleukin-6 belongs to a family of cytokines which includes IL-11, ciliary neurotrophic factor (CNTF), cardiotropin-1, cardiotrophin-like cytokine, leukemia inhibitory factor (LIF) and Oncostatin M...
    • Immune System, organism-specific biosystem (from REACTOME)
      Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
    • NGF signalling via TRKA from the plasma membrane, organism-specific biosystem (from REACTOME)
      NGF signalling via TRKA from the plasma membrane, organism-specific biosystemTrk receptors signal from the plasma membrane and from intracellular membranes, particularly from early endosomes. Signalling from the plasma membrane is fast but transient; signalling from endosomes...
    • PI-3K cascade, organism-specific biosystem (from REACTOME)
      PI-3K cascade, organism-specific biosystemThe ability of growth factors to protect from apoptosis is primarily due to the activation of the AKT survival pathway. P-I-3-kinase dependent activation of PDK leads to the activation of AKT which i...
    • PI3K events in ERBB2 signaling, organism-specific biosystem (from REACTOME)
      PI3K events in ERBB2 signaling, organism-specific biosystemERBB2:ERBB3 and ERBB2:ERBB4cyt1 heterodimers activate PI3K signaling by direct binding of PI3K regulatory subunit p85 (Yang et al. 2007, Cohen et al. 1996, Kaushansky et al. 2008) to phosphorylated t...
    • PI3K events in ERBB4 signaling, organism-specific biosystem (from REACTOME)
      PI3K events in ERBB4 signaling, organism-specific biosystemThe CYT1 isoforms of ERBB4 possess a C-tail tyrosine residue that, upon trans-autophosphorylation, serves as a docking site for the p85 alpha subunit of PI3K - PIK3R1 (Kaushansky et al. 2008, Cohen e...
    • PI3K/AKT activation, organism-specific biosystem (from REACTOME)
      PI3K/AKT activation, organism-specific biosystemPI3K/AKT signalling is a major regulator of neuron survival. It blocks cell death by both impinging on the cytoplasmic cell death machinery and by regulating the expression of genes involved in cell...
    • PIP3 activates AKT signaling, organism-specific biosystem (from REACTOME)
      PIP3 activates AKT signaling, organism-specific biosystemSignaling by AKT is one of the key outcomes of activation of receptor tyrosine kinases (RTKs). Following ligand binding and autophosphorylation, RTKs recruit the 85 kDa regulatory subunit of PI3K (PI...
    • Regulation of nuclear SMAD2/3 signaling, organism-specific biosystem (from Pathway Interaction Database)
      Regulation of nuclear SMAD2/3 signaling, organism-specific biosystem
      Regulation of nuclear SMAD2/3 signaling
    • Signal Transduction, organism-specific biosystem (from REACTOME)
      Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
    • Signaling by EGFR, organism-specific biosystem (from REACTOME)
      Signaling by EGFR, organism-specific biosystemThe epidermal growth factor receptor (EGFR) is one member of the ERBB family of transmembrane glycoprotein tyrosine receptor kinases (RTK). Binding of EGFR to its ligands induces conformational chang...
    • Signaling by EGFR in Cancer, organism-specific biosystem (from REACTOME)
      Signaling by EGFR in Cancer, organism-specific biosystemThe pathway "Signaling by EGFR in Cancer" shows "Signaling by constitutively active EGFR" in parallel with "Signaling by EGFR". This allows users to compare signaling by constitutively active EGFR ca...
    • Signaling by ERBB2, organism-specific biosystem (from REACTOME)
      Signaling by ERBB2, organism-specific biosystemERBB2, also known as HER2 or NEU, is a receptor tyrosine kinase (RTK) belonging to the EGFR family. ERBB2 possesses an extracellular domain that does not bind any known ligand, contrary to other EGFR...
    • Signaling by ERBB4, organism-specific biosystem (from REACTOME)
      Signaling by ERBB4, organism-specific biosystemERBB4, also known as HER4, belongs to the ERBB family of receptors, which also includes ERBB1 (EGFR i.e. HER1), ERBB2 (HER2 i.e. NEU) and ERBB3 (HER3). Similar to EGFR, ERBB4 has an extracellular lig...
    • Signaling by FGFR, organism-specific biosystem (from REACTOME)
      Signaling by FGFR, organism-specific biosystemThe 22 members of the fibroblast growth factor (FGF) family of growth factors mediate their cellular responses by binding to and activating the different isoforms encoded by the four receptor tyrosin...
    • Signaling by PDGF, organism-specific biosystem (from REACTOME)
      Signaling by PDGF, organism-specific biosystemPlatelet-derived Growth Factor (PDGF) is a potent stimulator of growth and motility of connective tissue cells such as fibroblasts and smooth muscle cells as well as other cells such as capillary end...
    • Signaling by SCF-KIT, organism-specific biosystem (from REACTOME)
      Signaling by SCF-KIT, organism-specific biosystemStem cell factor (SCF) is a growth factor with membrane bound and soluble forms. It is expressed by fibroblasts and endothelial cells throughout the body, promoting proliferation, migration, survival...
    • Signaling by the B Cell Receptor (BCR), organism-specific biosystem (from REACTOME)
      Signaling by the B Cell Receptor (BCR), organism-specific biosystemMature B cells express IgM and IgD immunoglobulins which are complexed at the plasma membrane with Ig-alpha (CD79A, MB-1) and Ig-beta (CD79B, B29) to form the B cell receptor (BCR) (Fu et al. 1974, F...
    • Signaling events mediated by HDAC Class III, organism-specific biosystem (from Pathway Interaction Database)
      Signaling events mediated by HDAC Class III, organism-specific biosystem
      Signaling events mediated by HDAC Class III
    • Signalling by NGF, organism-specific biosystem (from REACTOME)
      Signalling by NGF, organism-specific biosystemNeurotrophins (NGF, BDNF, NT-3, NT-4/5) play pivotal roles in survival, differentiation, and plasticity of neurons in the peripheral and central nervous system. They are produced, and secreted in mi...
    • TGF-beta Receptor Signaling Pathway, organism-specific biosystem (from WikiPathways)
      TGF-beta Receptor Signaling Pathway, organism-specific biosystem"The TGF beta receptors TGFBR1 and TGFBR2 belong to a subfamily of membrane-bound serine/threonine kinases which are designated as Type I or II based on their structural and functional properties. Th...

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    DNA binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    DNA binding, bending IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    double-stranded DNA binding IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    enzyme binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    protein kinase binding IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    sequence-specific DNA binding IEA
    Inferred from Electronic Annotation
    more info
     
    sequence-specific DNA binding transcription factor activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    sequence-specific distal enhancer binding RNA polymerase II transcription factor activity IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    transcription factor binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    Process Evidence Code Pubs
    G1 phase of mitotic cell cycle IDA
    Inferred from Direct Assay
    more info
    PubMed 
    cell cycle IEA
    Inferred from Electronic Annotation
    more info
     
    cell cycle arrest IDA
    Inferred from Direct Assay
    more info
    PubMed 
    cell differentiation IEA
    Inferred from Electronic Annotation
    more info
     
    embryo development IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    epidermal growth factor receptor signaling pathway TAS
    Traceable Author Statement
    more info
     
    fibroblast growth factor receptor signaling pathway TAS
    Traceable Author Statement
    more info
     
    insulin receptor signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    mitotic cell cycle G2/M transition DNA damage checkpoint IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    muscle organ development IEA
    Inferred from Electronic Annotation
    more info
     
    negative regulation of angiogenesis IDA
    Inferred from Direct Assay
    more info
    PubMed 
    negative regulation of cell proliferation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    negative regulation of smooth muscle cell differentiation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    nerve growth factor receptor signaling pathway TAS
    Traceable Author Statement
    more info
     
    organ development IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    pattern specification process IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    phosphatidylinositol-mediated signaling TAS
    Traceable Author Statement
    more info
     
    positive regulation of transcription from RNA polymerase II promoter IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    regulation of sequence-specific DNA binding transcription factor activity IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    regulation of transcription, DNA-dependent IDA
    Inferred from Direct Assay
    more info
    PubMed 
    tissue development IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    transcription from RNA polymerase II promoter TAS
    Traceable Author Statement
    more info
    PubMed 
    Component Evidence Code Pubs
    cytoplasm IDA
    Inferred from Direct Assay
    more info
    PubMed 
    cytosol IDA
    Inferred from Direct Assay
    more info
    PubMed 
    nucleoplasm TAS
    Traceable Author Statement
    more info
     
    nucleus IDA
    Inferred from Direct Assay
    more info
    PubMed 
    transcription factor complex IBA
    Inferred from Biological aspect of Ancestor
    more info
     

    General protein information

    Preferred Names
    forkhead box protein O4
    Names
    forkhead box protein O4
    fork head domain transcription factor AFX1
    myeloid/lymphoid or mixed-lineage leukemia (trithorax homolog, Drosophila); translocated to, 7

    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.

    Genomic

    1. NG_016418.1 RefSeqGene

      Range
      5001..12386
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001170931.1NP_001164402.1  forkhead box protein O4 isoform 2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate in-frame splice site in the 5' coding region compared to variant 1. This results in a shorter protein (isoform 2 also known as isoform zeta) compared to isoform 1.
      Source sequence(s)
      AF384029, AL590764, AW292413
      Consensus CDS
      CCDS55440.1
      UniProtKB/Swiss-Prot
      P98177
      Related
      ENSP00000342209, OTTHUMP00000023497, ENST00000341558, OTTHUMT00000057116
      Conserved Domains (1) summary
      cd00059
      Location:47126
      Blast Score: 258
      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. NM_005938.3NP_005929.2  forkhead box protein O4 isoform 1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longer transcript and encodes the longer protein (isoform 1 also known as AFX alpha).
      Source sequence(s)
      AL590764, AW292413, BC106761
      Consensus CDS
      CCDS43969.1
      UniProtKB/Swiss-Prot
      P98177
      Related
      ENSP00000363377, OTTHUMP00000023496, ENST00000374259, OTTHUMT00000057115
      Conserved Domains (1) summary
      cd00059
      Location:101181
      Blast Score: 291
      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 ...

    RefSeqs of Annotated Genomes: Build 37.3

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

    Reference GRCh37.p5 Primary Assembly

    Genomic

    1. NC_000023.10 Reference GRCh37.p5 Primary Assembly

      Range
      70315999..70323384
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000155.1 Alternate HuRef

      Range
      64135718..64143103
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Related Sequences

    Nucleotide Protein
    Heading Accession and Version
    genomic AL590764.3 (101914..109298) None
    genomic CH471132.2 EAX05321.1
      EAX05322.1
    genomic Y11284.1 CAA72156.1
    genomic Y11285.1 None
    genomic Y11286.1 None
    mRNA AF384029.1 AAL85197.1
    mRNA AW292413.1 None
    mRNA BC026735.1 None
    mRNA BC106761.2 AAI06762.1
    mRNA BP349083.1 None
    mRNA U10072.1 AAA82171.1
    mRNA X93996.1 CAA63819.1
    Protein Accession Links
    GenPept Link UniProtKB Link
    P98177.5 GenPept UniProtKB/Swiss-Prot:P98177

      Supplemental Content

      Recent activity

      Your browsing activity is empty.

      Activity recording is turned off.

      Turn recording back on

      See more...