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    FOXO4 forkhead box O4 [ Homo sapiens (human) ]

    Gene ID: 4303, updated on 12-Aug-2018

    Summary

    Official Symbol
    FOXO4provided by HGNC
    Official Full Name
    forkhead box O4provided by HGNC
    Primary source
    HGNC:HGNC:7139
    See related
    Ensembl:ENSG00000184481 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
    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]
    Expression
    Broad expression in placenta (RPKM 74.9), testis (RPKM 15.0) and 21 other tissues See more
    Orthologs

    Genomic context

    See FOXO4 in Genome Data Viewer
    Location:
    Xq13.1
    Exon count:
    4
    Annotation release Status Assembly Chr Location
    109 current GRCh38.p12 (GCF_000001405.38) X NC_000023.11 (71096149..71103534)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) X NC_000023.10 (70315999..70323384)

    Chromosome X - NC_000023.11Genomic Context describing neighboring genes Neighboring gene suppressor of cytokine signaling 5 pseudogene 4 Neighboring gene sorting nexin 12 Neighboring gene chromosome X open reading frame 65 Neighboring gene interleukin 2 receptor subunit gamma Neighboring gene mediator complex subunit 12

    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 Jun 15 11:32:44 2016

    Bibliography

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    Pathways from BioSystems

    • AGE/RAGE pathway, organism-specific biosystem (from WikiPathways)
      AGE/RAGE pathway, organism-specific biosystemAdvanced glycation end products (AGEs) are heterogeneous group of non-enzymatic malliard reaction products of aldose sugar with proteins and lipids. Formation of AGEs is an indicator of one of the ma...
    • 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
    • Constitutive Signaling by AKT1 E17K in Cancer, organism-specific biosystem (from REACTOME)
      Constitutive Signaling by AKT1 E17K in Cancer, organism-specific biosystemWhile AKT1 gene copy number, expression level and phosphorylation are often increased in cancer, only one low frequency point mutation has been repeatedly reported in cancer and functionally studied....
    • DAP12 interactions, organism-specific biosystem (from REACTOME)
      DAP12 interactions, organism-specific biosystemDNAX activation protein of 12kDa (DAP12) is an immunoreceptor tyrosine-based activation motif (ITAM)-bearing adapter molecule that transduces activating signals in natural killer (NK) and myeloid cel...
    • DAP12 signaling, organism-specific biosystem (from REACTOME)
      DAP12 signaling, organism-specific biosystemIn response to receptor ligation, the tyrosine residues in DAP12's immunoreceptor tyrosine-based activation motif (ITAM) are phosphorylated by Src family kinases. These phosphotyrosines form the dock...
    • Deubiquitination, organism-specific biosystem (from REACTOME)
      Deubiquitination, organism-specific biosystemUbiquitination, the modification of proteins by the covalent attachment of ubiquitin (Ub), is a key regulatory mechanism for many many cellular processes, including protein degradation by the 26S pro...
    • 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 ...
    • Diseases of signal transduction, organism-specific biosystem (from REACTOME)
      Diseases of signal transduction, organism-specific biosystemSignaling processes are central to human physiology (e.g., Pires-da Silva & Sommer 2003), and their disruption by either germ-line and somatic mutation can lead to serious disease. Here, the molecula...
    • 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 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...
    • EGF/EGFR Signaling Pathway, organism-specific biosystem (from WikiPathways)
      EGF/EGFR Signaling Pathway, organism-specific biosystemEpidermal growth factor receptor (EGFR) also known as ErbB1/HER1 is a member of the ErbB family of receptor tyrosine kinases which also includes ErbB2 (Neu, HER2), ErbB3 (HER3) and ErbB4 (HER4). Sev...
    • Fc epsilon receptor (FCERI) signaling, organism-specific biosystem (from REACTOME)
      Fc epsilon receptor (FCERI) signaling, organism-specific biosystemMast cells (MC) are distributed in tissues throughout the human body and have long been recognized as key cells of type I hypersensitivity reactions. They also play important roles in inflammatory an...
    • FoxO family signaling, organism-specific biosystem (from Pathway Interaction Database)
      FoxO family signaling, organism-specific biosystem
      FoxO family signaling
    • FoxO signaling pathway, organism-specific biosystem (from KEGG)
      FoxO signaling pathway, organism-specific biosystemThe forkhead box O (FOXO) family of transcription factors regulates the expression of genes in cellular physiological events including apoptosis, cell-cycle control, glucose metabolism, oxidative str...
    • 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...
    • 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...
    • Innate Immune System, organism-specific biosystem (from REACTOME)
      Innate Immune System, organism-specific biosystemInnate immunity encompases the nonspecific part of immunity tha are part of an individual's natural biologic makeup
    • Metabolism of proteins, organism-specific biosystem (from REACTOME)
      Metabolism of proteins, organism-specific biosystemProtein metabolism comprises the pathways of translation, post-translational modification and protein folding.
    • 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...
    • PI3K-AKT-mTOR signaling pathway and therapeutic opportunities, organism-specific biosystem (from WikiPathways)
      PI3K-AKT-mTOR signaling pathway and therapeutic opportunities, organism-specific biosystemThis pathway is based on figure 1 from Merritt et al. (See Bibliography). The PI3K-AKT-mTOR signaling pathway has been shown to have a significant correlation with the development of castration-resis...
    • PI3K/AKT Signaling in Cancer, organism-specific biosystem (from REACTOME)
      PI3K/AKT Signaling in Cancer, organism-specific biosystemClass IA PI3K is a heterodimer of a p85 regulatory subunit (encoded by PIK3R1, PIK3R2 or PIK3R3) and a p110 catalytic subunit (encoded by PIK3CA, PIK3CB or PIK3CD). In the absence of activating signa...
    • 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 receptor tyrosine kinase (RTK) activation. AKT is activated by the cellular second messenger PIP3, a phospholipid that is generated by PI3K. In ustimula...
    • Post-translational protein modification, organism-specific biosystem (from REACTOME)
      Post-translational protein modification, organism-specific biosystemAfter translation, many newly formed proteins undergo further covalent modifications that alter their functional properties and that are essentially irreversible under physiological conditions in the...
    • Ras signaling pathway, organism-specific biosystem (from KEGG)
      Ras signaling pathway, organism-specific biosystemThe Ras proteins are GTPases that function as molecular switches for signaling pathways regulating cell proliferation, survival, growth, migration, differentiation or cytoskeletal dynamism. Ras prote...
    • 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
    • Role of LAT2/NTAL/LAB on calcium mobilization, organism-specific biosystem (from REACTOME)
      Role of LAT2/NTAL/LAB on calcium mobilization, organism-specific biosystemThe lipid raft resident adaptor molecules LAT1 and Non-T cell activation linker (NTAL), also known as linker for activation of B cells (LAB)/LAT2 are known participants in the regulation of mast cell...
    • 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 Pathways in Glioblastoma, organism-specific biosystem (from WikiPathways)
      Signaling Pathways in Glioblastoma, organism-specific biosystemThe most frequently altered genes in glioblastoma. This pathway originally accompanied the 2008 Nature publication on the comprehensive genomic characterization of human glioblastoma genes and core p...
    • 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 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...
    • Ub-specific processing proteases, organism-specific biosystem (from REACTOME)
      Ub-specific processing proteases, organism-specific biosystemUb-specific processing proteases (USPs) are the largest of the DUB families with more than 50 members in humans. The USP catalytic domain varies considerably in size and consists of six conserved mo...

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Homology

    Clone Names

    • MGC120490

    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 IC
    Inferred by Curator
    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 factor activity, RNA polymerase II-specific NAS
    Non-traceable Author Statement
    more info
    PubMed 
    beta-catenin binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enzyme binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    identical protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    promoter-specific chromatin binding IEA
    Inferred from Electronic Annotation
    more info
     
    protein 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 
    sequence-specific DNA binding IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    transcription factor binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    transcription factor binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    Process Evidence Code Pubs
    aging IEA
    Inferred from Electronic Annotation
    more info
     
    cell cycle arrest IDA
    Inferred from Direct Assay
    more info
    PubMed 
    glucose homeostasis IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    insulin receptor signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    insulin receptor signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    mitotic G2 DNA damage checkpoint IEA
    Inferred from Electronic Annotation
    more info
     
    muscle organ development IEA
    Inferred from Electronic Annotation
    more info
     
    negative regulation of G0 to G1 transition IDA
    Inferred from Direct Assay
    more info
    PubMed 
    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 
    negative regulation of transcription by RNA polymerase II IBA
    Inferred from Biological aspect of Ancestor
    more info
    PubMed 
    positive regulation of cell cycle arrest IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of smooth muscle cell migration 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 
    protein deubiquitination TAS
    Traceable Author Statement
    more info
     
    regulation of transcription, DNA-templated IDA
    Inferred from Direct Assay
    more info
    PubMed 
    response to nutrient levels IEA
    Inferred from Electronic Annotation
    more info
     
    response to water-immersion restraint stress IEA
    Inferred from Electronic Annotation
    more info
     
    stem cell differentiation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    transcription by RNA polymerase II TAS
    Traceable Author Statement
    more info
    PubMed 
    Component Evidence Code Pubs
    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
    PubMed 
    nuclear speck 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 TAS
    Traceable Author Statement
    more info
    PubMed 

    General protein information

    Preferred Names
    forkhead box protein O4
    Names
    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

      See identical proteins and their annotated locations for NP_001164402.1

      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
      ENSP00000342209.3, OTTHUMP00000023497, ENST00000341558.3, OTTHUMT00000057116
      Conserved Domains (3) summary
      cd00059
      Location:58126
      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:303340
      FOXO_KIX_bdg; KIX-binding domain of forkhead box O, CR2
      pfam16676
      Location:410448
      FOXO-TAD; Transactivation domain of FOXO protein family
    2. NM_005938.3NP_005929.2  forkhead box protein O4 isoform 1

      See identical proteins and their annotated locations for NP_005929.2

      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
      ENSP00000363377.3, OTTHUMP00000023496, ENST00000374259.7, OTTHUMT00000057115
      Conserved Domains (4) summary
      pfam05887
      Location:483
      Trypan_PARP; Procyclic acidic repetitive protein (PARP)
      cd00059
      Location:101181
      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:358395
      FOXO_KIX_bdg; KIX-binding domain of forkhead box O, CR2
      pfam16676
      Location:465503
      FOXO-TAD; Transactivation domain of FOXO protein family

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...Open this link in a new tab

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

    Reference GRCh38.p12 Primary Assembly

    Genomic

    1. NC_000023.11 Reference GRCh38.p12 Primary Assembly

      Range
      71096149..71103534
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011530957.3XP_011529259.1  forkhead box protein O4 isoform X1

      Conserved Domains (2) summary
      pfam16675
      Location:180217
      FOXO_KIX_bdg; KIX-binding domain of forkhead box O, CR2
      pfam16676
      Location:287325
      FOXO-TAD; Transactivation domain of FOXO protein family
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