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FLASH GENE
Symbol IRF7 contributors: mct/ - updated : 30-01-2018
HGNC name interferon regulatory factor 7
HGNC id 6122
DNA
TYPE functioning gene
STRUCTURE 3.45 kb     11 Exon(s)
10 Kb 5' upstream gene genomic sequence study
regulatory sequence Promoter (TATA box)
cytosine-phosphate-guanine/HTF
text structure
  • two IFN responsive elements, an IRF-binding element (IRFE) in the promoter region and an ISRE in the first intron
  • VAF binds to the IRF7 ISRE and IRFE and can directly activate IRF7 transcription
  • an NFkappaB site located next to the TATA box
    • MAPPING cloned Y linked N status confirmed
    Map see MUCDHL
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    11 - 1972 - 503 - 1997 9315633
  • IRF7A
  • has oncogenic potential and is associated with EBV transformation processes
    • 10 - 1885 51.4 474 - 1997 9315633
    IRF7B
    9 - 2051 55.5 516 lymphoid cells 1997 9315633
    IRF7D
    - - - - - - 2010 20209099
  • alternative splicing variant with only the DNA-binding domain of IRF7
  • inhibits the function of IRF7 in transcriptional regulation of IFN genes
    		•
    EXPRESSION
    Type restricted
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Lymphoid/Immunespleen   predominantly
     thymus    
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticleukocyte
    cell lineage
    cell lines
    fluid/secretion blood
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • the last three C-terminal lysine sites (positions 444, 446, and 452) of IRF7 variant A are essential for activation of IRF7
    • conjugated PhosphoP
    mono polymer complex
    HOMOLOGY
    Homologene
    FAMILY
  • interferon regulatory transcription factor (IRF) family
    • CATEGORY regulatory , transcription factor
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endosome
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    text activation leads to nuclear retention, DNA binding, and repression of transactivation ability
    basic FUNCTION
  • essential regulator of IFNA, via the virus-activated, MYD88-independent pathway and the toll-like receptor (TLR)-activated, MYD88-dependent pathway
  • IFN-stimulated genes and Epstein-Barr virus
  • transcriptional activation of virus-inducible cellular genes
  • involved in translational control of the innate immune response
  • master regulator of type I IFN responses and has been shown to be critical for innate antiviral immunity
  • plays important roles in innate immunity and immune cell differentiation
  • is a novel modulator of neointima formation and VSMC proliferation
  • master transcription factor that plays a pivotal role in the transcriptional activation of type I interferon genes in the inflammatory response
  • IRF7-dependent amplification of type I and III IFNs is required for protection against primary infection by influenza virus in humans
  • is a key regulator of type I interferon and plays essential roles in restricting virus infection and spread
  • represents a novel regulator of Granulocytic- myeloid-derived suppressor cells (MDSCs)development in cancer, which may have predictive value for tumor progression
    • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS immunity/defense
    PATHWAY
    metabolism
    signaling
    a component
  • component of VAF (virus-activated factor) which is composed of IRF7, IRF3, and the transcriptional coactivator proteins p300 and CBP
  • forming a complex with MYD88
  • forms a complex with TLR9 and promotes association of TRAF3 and AP3B1
    • INTERACTION
    DNA binding to interferon stimulated response element (ISRE) in IFN promoter and in the Q promoter of EBV nuclear antigen-1 (EBNA1)
    RNA
    small molecule
    protein
  • interacting with IRF3 in a biologically active complex
  • substrate for TRAF6 E3 ligase and IRF7 is ubiquitinated by TRAF6 at multiple sites
  • its expression induces multiple IFNA genes
  • GBP4 is a negative regulator of virus-triggered IFNI production, and it is identified as a novel protein targeting IRF7 and inhibiting its function
  • IRF7 gene is a critical target of FOXO3 (FOXO3 was identified as a negative regulator of IRF7 transcription)
  • PELI3 targets the IRF7 pathway and facilitates autoregulation of TLR3- and viral-induced expression of type I interferons
  • NMI is a negative regulator of the virus-triggered induction of type I IFNs that targets IRF7
  • IRF7 promotes glioma cell invasion and both chemoresistance and radioresistance through AGO2 inhibition
  • TRIM35 is a negative feedback regulator of TLR7/9-mediated type I IFN production due to its ability to suppress the stability of IRF7
  • AIP (aryl hydrocarbon receptor interacting protein) is a new binding partner of IRF7
  • AIP is a novel inhibitor of IRF7 and a negative regulator of innate antiviral signaling
  • BCL6 specifically binds to the interferon-regulatory factor IRF7 loci and restrains its transcription, thereby functioning as a negative regulator for interferon IFNB1 production and antiviral responses
  • IRF7 directly binds to the two conserved IRF binding sites on the USP25 promoter to drive transcription of USP25, and mutation of these two sites abolished Sendai virus-induced IRF7-mediated activation of the USP25 promoter
  • adaptor molecule CRADD coordinates IKBKE and IRF7 interaction to ensure efficient expression of type I interferon
  • NFATC3 specifically binds to IRF7 and enhances IRF7-mediated IFN production
  • S100A9, a negative regulator of myeloid cell differentiation, was transrepressed by the IRF7 protein
  • IRF3 and IRF7 bind to many interferon-stimulated response element (ISRE)-type sites in the virus-response elements (VREs) of IFN promoters
  • TRIM8 emerged as an essential regulator of IFN regulatory factor 7 (IRF7) function (PMID
    • cell & other
    REGULATION
    activated by TRAF6
    TRAF3 (TRF3 activates IRF7 through K63-linked ubiquitination which requires RIP1 and TRAF6)
    induced by lipopolysaccharide, virus infection, and IFNA but not by IFNG
    the IFN-triggered Jak-STAT pathway
    repressed by TNFAIP3 (negatively regulates IRF7 transcriptional activity induced by TRAF3)
    Other phosphorylated and activated by IKKE or TBK1
    is targeted for degradation by binding to the RTA immediate-early nuclear transcription factor encoded by KSHV
    ubiquitination is required for phosphorylation and activation of IRF7
    ASSOCIATED DISORDERS
    corresponding disease(s) IMD39
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    most lung cells from stable Chronic Obstructive Pulmonary Disease (COPD) patients show a constitutive decreased expression of IFNB1, IRF7, DDX58 and IFIH1, suggesting that this deficiency is the main cause of their acute viral exacerbations
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    miscelleaneousvascular 
    may represent a promising target for vascular disease therapy
    ANIMAL & CELL MODELS
    Irf7-null mice are consistently more vulnerable than Myd88-null mice to viral infection, and this correlated with marked decrease in serum interferon levels, indicating the importance of the IRF7-dependent induction of systemic interferon responses for innate antiviral immunity