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FLASH GENE
Symbol IRF1 contributors: mct/npt/pgu - updated : 28-03-2020
HGNC name interferon regulatory factor 1
HGNC id 6116
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a tryptophan pentad repeat DNA-binding domain
  • C-terminal 70 AAs inhibits both its degradation and polyubiquitination, whereas removal of the C-terminal 25 AAs inhibits degradation of the protein but does not prevent its ubiquitination
    • HOMOLOGY
    interspecies homolog to rattus Irf1 (85.2 pc)
    homolog to murine Irf1 (85.5 pc)
    Homologene
    FAMILY
  • interferon regulatory transcription factor (IRF) family
    • CATEGORY immunity/defense , regulatory , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,chromatin/chromosome
    basic FUNCTION
  • acting as a transcriptional activator for IFNA, IFNB and IFN-stimulated genes
  • being tumor suppressor transcription factor inducing apoptosis of tumorigenic cell lines
  • playing a role of modulator of virus-induced signaling
  • exhibiting a growth inhibitory function in coronary artery smooth muscle cells (limitation of neointimal hyperplasia)
  • mediates upregulation PSMB8 by IFN-gamma and concerted expression of immunosubunits of the proteasome
  • acts as a master regulator for the concerted expression of immunoproteasome components
  • transcription factor that regulates the functions of type I and II interferons and plays a role in host protection
  • transcription factor that regulates key processes in the immune system and in tumour suppression (F
  • role for IRF1 in regulating the DNA interstrand crosslink DNA damage response
  • tumour suppressor protein that is activated in response to viral infection and cell signalling activated by double stranded DNA lesions
  • may play a potentially important role as a breast cancer tumor suppressor gene
  • plays a critical role in eliminating TP53-damaged cells, and may play a more global role in mammary gland homeostasis
  • IFNG-induced transcription factor pivotal in the regulation of infection and inflammation
  • IRF1 and IRF2 may regulate the progression of pancreatic cancer by functioning as an antioncoprotein and oncoprotein, respectively
  • plays a key role in the terminal effector pathways of human preterm labor
  • IRF1 is one of the key transcriptional factors for the prevention of neointimal formation involving AGTR1, AGTR2
  • critical role of IRF1 and BATF in forming chromatin landscape during type 1 regulatory cell differentiation
  • expression of IRF1 in adipocytes contributes to upregulation of inflammatory processes, leading to phenotypes associated with metabolic disease
  • downstream target of TNF-mediated signal transduction in endothelial cells
  • although IRF1 can trigger enhanceosome formation independently of STAT1, its ability to do so depends on local chromatin cues
  • IRF1 promotes DNA binding of STAT1, which can in turn participate in a positive feedback loop of JAK-STAT signaling
  • XAF1 forms a positive feedback loop with IRF1 to drive apoptotic stress response and suppress tumorigenesis
  • IRF1-dependent genes in neurons play a role in ischemic neuronal death
  • has a protective effect on cognitive decline in a normal conditionbut not after chronic cerebral hypoperfusion treatment
  • IRF1-mediated suppression of specific Endogenous retroviruses (ERVs) may contribute to the overall tumor suppressor activity of this host factor
  • IRF1 is involved in the activation of TRIM14 by IFNA1
    • CELLULAR PROCESS cell life, cell death/apoptosis
    nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    text
  • negative regulation of cell cycle
  • positive regulation of interleukin-12 biosynthetic process
  • positive regulation of transcription from RNA polymerase II promoter
    • PATHWAY
    metabolism
    signaling
  • IRF1-mediated proinflammatory signaling pathway that specifically regulates LPS-mediated VCAM1 expression, independent of NFKB1
    • a component
    INTERACTION
    DNA binding to upstream regulatory region of type I/FN and IFN inducible MHC class I genes (the interferon consensus sequence (ICS))
    RNA
    small molecule
    protein
  • IRF1 and IRF9 are sequentially activated and recruited to the IL27 IFN-stimulated regulatory element site
  • SMARCA4 may help IRF1 to overcome the chromatin barrier to activate TRIM22 transcription
  • IRF1 cooperates with NFKB to activate optineurin promoter
  • IRF1 and IRF2 could bind to IFP35 promoter and upregulate endogenous IFP35 protein level, and IRF1 activates IFP35 expression in an IFNG1-inducible manner
  • SMAD7 recruits IRF1 protein on the CASP8 promoter and functions as a transcriptional coactivator
  • IRF1-NOS2 axis is a crucial regulator of cardiac remodeling
  • IRF1 is critical dual regulator of DIABLO mimetic-induced apoptosis and inflammatory cytokine response
  • (IRF1) regulates downstream signals of tumor necrosis factor alpha (TNF)
  • PPARGC1A is able to suppress the induction of IRF1 mediated by Jak/Stat signaling pathway
  • interactions of IRF1, IFNB1 and IRF5 are involved in the M1 polarization of macrophages and have antitumor functions
  • IRF1 is involved in the IFN-inducible expression of NMI
  • IRF1 could induce STAT1 phosphorylation and in turn STAT1 activation
  • XAF1 functions as a transcriptional coactivator of IRF1 to suppress tumorigenesis
  • IRF1 is a transcriptional target of FOXM1c and a FOXM1c-binding site is in the IRF1 promoter region
  • IRF1 and IRF2 bind to the TRIM14 promoter and activate transcription of TRIM14
  • PARP1 is a crucial regulator of IRF1-mediated immune response
  • IRF2 was found to be a transcriptional activator of CASP4, and in its absence, induction of IRF1 could substitute to maintain CASP4 expression
  • ATG10S as a transcription factor competes with IRF1 for the same binding site to promote IFNL2 gene transcription
  • IRF1 mediates the suppressive effects of MTOR inhibition on arterial endothelium
    • cell & other
    REGULATION
    induced by viruses and IFN
    repressed by UBE2I (UBE2I functions as a transcriptional repressor of IRF1 by inducing sumoylation, and this effect may be required for the physiological activity of IRF1)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   deletion    
    in MDS, AML, differentiated gastric adenocarcinomas (see TSG5D)
    Susceptibility
  • putative susceptibility gene for rheumatoid arthritis and for asthma
  • to Beh
    • et disease with thrombotic event
    Variant & Polymorphism other frequency of the CAAA haplotype was significantly higher in BD patients that had experienced a thrombotic event
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS