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FLASH GENE
Symbol IRF5 contributors: SGE/npt - updated : 13-07-2018
HGNC name interferon regulatory factor 5
HGNC id 6120
Location 7q32.1      Physical location : 128.577.993 - 128.590.086
Synonym symbol(s) IBD14, SLEB10
DNA
TYPE functioning gene
STRUCTURE 13.01 kb     9 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
Physical map
NSG-X 7q31 brain and nasopharyngeal carcinoma susceptibility protein LRRC4 7q31 leucine rich repeat containing 4 LEP 7q31.3 leptin (obesity homolog, mouse) MGC27345 7q32.2 hypothetical protein MGC27345 FLJ10377 7q32.2 hypothetical protein FLJ10377 LOC389551 7 hypothetical gene supported by BC063892 IMPDH1 7q31.3-q32 IMP (inosine monophosphate) dehydrogenase 1 HIG2 7q32.2 hypoxia-inducible protein 2 METTL2 17q24.1 methyltransferase like 2 LOC389552 7 similar to Serine/threonine-protein kinase tousled-like 2 (Tousled-like kinase 2) (PKU-alpha) LOC389553 7 hypothetical gene supported by AL137733 LOC389554 7 hypothetical gene supported by BC062355 LOC392095 7 similar to capicua homolog LOC346653 7q32.2 hypothetical protein LOC346653 NYD-SP18 7q32.2-q32.3 testes development-related NYD-SP18 CALU 7q32 calumenin OPN1SW 7q31.3-q32 opsin 1 (cone pigments), short-wave-sensitive (color blindness, tritan) DKFZP434G156 7q33 hypothetical protein DKFZp434G156 FLNC 7q32 filamin C, gamma (actin binding protein 280) ATP6V1F 7q32 ATPase, H+ transporting, lysosomal 14kDa, V1 subunit F LOC389555 7 similar to Filamin C (Gamma-filamin) (Filamin 2) (Protein FLNc) (Actin-binding like protein) (ABP-L) (ABP-280-like protein) IRF5 7q32 interferon regulatory factor 5 TNPO3 7q32.3 transportin 3 LOC392096 7 similar to Triosephosphate isomerase (TIM) HCP20 7q32.3 cytochrome c, somatic pseudogene LOC286017 7q32.3 similar to mitogen-activated protein kinase kinase 2; mitogen-activated protein kinase kinase 2, p45; MAP kinase kinase 2; MAPK/ERK kinase 2; dual specificity mitogen-activated protein kinase kinase 2; ERK activator kinase 2 MGC50844 7q32.3 hypothetical protein MGC50844 LOC154981 7q32.3 hypothetical LOC154981 SMO 7q31 smoothened homolog (Drosophila) KIAA0828 7q32.3 KIAA0828 protein KIAA1170 7q32.3 KIAA1170 protein NRF1 7q32 nuclear respiratory factor 1 UBE2H 7q32 ubiquitin-conjugating enzyme E2H (UBC8 homolog, yeast)
regionally located mapped in a region containing a cluster of imprinted genes
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
- splicing 2870 56.7 504 - 2014 25084355
  • exon 1A
  • containing an additional 48 nt region in the CDS
  • lacking a 30 nt region in the CDS
  • 9 splicing 2771 56 498 - 2014 25084355
  • also called variant 2
  • using an alternative exon for the 5' UTR, exon 1B
  • lacking a 48 nt region in the CDS
  • containing an additional 30 nt region in the CDS
  • - - 2126 - - plasmacytoid dendritic cells 2014 25084355
    exon 1A
    9 - 2910 - 514 peripheral blood mononuclear cells 2014 25084355
  • also called variant 5
  • exon 1A
  • 9 - 2852 - 498 - 2014 25084355
  • also called variant 6
  • exon 1A
  • - - 1217 - 389 peripheral blood mononuclear cells 2014 25084355
    exon 1A
    - - 1377 - 413 only in cancers 2014 25084355
    exon 1A
    - - - - 157 only in cancer 2014 25084355
    exon 1B
    9 - 3031 - 514 - 2014 25084355
    8 - 2604 - 412 - 2014 25084355
    9 - 2955 - 498 - 2014 25084355
    9 - 2937 - 514 - 2014 25084355
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Lymphoid/Immunelymph node   highly
     spleen   highly
     thymus   highly
    Nervousbrain    
    Respiratorylung    
    Urinarykidney   highly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticmonocyte Homo sapiens
    Blood/Hematopoieticneutrophil Homo sapiens
    Lymphoid/ImmuneB cell Homo sapiens
    Lymphoid/Immunedendritic cell Homo sapiens
    Lymphoid/Immunemacrophage Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a conserved N-terminal DNA-binding domain
  • a PESTv domain
  • a protein interaction/transactivation domain
  • tryptophan (W) repeats
  • mono polymer heteromer , dimer
    HOMOLOGY
    interspecies ortholog to murine Irf5
    homolog to C.elegans Y87G2A.7
    Homologene
    FAMILY
  • interferon regulatory factor (IRF) family
  • CATEGORY regulatory , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    text nuclear translocation resulting of TLR activation
    basic FUNCTION
  • stimulating transcription of numerous inflammatory proteins in a virus-specific manner
  • involved downstream of the TLR-MYD88 signaling pathway for gene induction of proinflammatory cytokines
  • having a role in the response to kinases involved in viral infections or in Toll-like-receptor (TLR) signaling
  • acting as repressor or activator of type I interferon genes, but also as inducer of pro-inflammatory cytokines, such as interleukin-6 (IL-6), IL-12 and tumor-necrosis factor-alpha
  • playing a general role in autoimmune diseases
  • involved in the innate immune response to pathogens (hu 2009)
  • critical regulator of DNA damage-induced apoptosis (Hu 2009)
  • promoting apoptosis upon signaling through TRAIL death receptors (Hu 2009)
  • required for B-cell maturation and expression of PRDM1 a hallmark of plasma cells (Lien 2010)
  • having a key role in the induction of the antiviral and inflammatory response (Lien 2010)
  • critical specificity-determining residue that inhibits IRF5 binding to the interferon-stimulated response element (ISRE)-variants present in the IFN gene promoters
  • IRF5 is an important tumor suppressor that regulates multiple cellular processes involved in the conversion of normal mammary epithelial cells to tumor epithelial cells with metastatic potential
  • IRF5-IKZF1 axis is a critical modulator of IgG2a/c class switching
  • roles of IRF5 in autoimmune lupus
  • is a specific marker of inflammatory macrophages
  • likely a central role for IRF5 in the regulation of the immune response
  • is essential for the induction of inflammatory cytokines
  • new function for IRF5 in controlling the relative mass of different adipose tissue depots and thus insulin sensitivity in obesity
  • IRF5 and IRF8, two transcription factors with opposing functions, control TLR9 signaling in human plasmacytoid dendritic cells (pDCs)
  • is a key transcription factor involved in the control of the expression of proinflammatory cytokine and responses to infection
  • IRF5-expressing macrophages are a key component of the immune defense of the airways
  • CELLULAR PROCESS cell life, proliferation/growth
    nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • heterodimerizing with IRF3
  • INTERACTION
    DNA binding
    RNA
    small molecule
    protein
  • MYD88
  • TRAF6
  • interacting with CHUK (CHUK and alkaline phosphatase are negative regulators of IRF5 activity in MYD88 pathway and have role in the control of the inflammatory response by attenuation of IRF5 activity)
  • is a transcription factor activated by toll like receptor TLR7 and TLR9 during innate immune responses
  • TRIM28 is a novel protein-protein interaction partner of IRF5, and is an inhibitor of IRF5 function in inflammatory macrophages
  • IRF5 is degraded following TLR7 activation and TRIM21 is involved in this process
  • IKBKB activates two "master" transcription factors of the innate immune system, IRF5 and NFKB1
  • IKBKB is an IRF5 kinase that instigates inflammation
  • IRF8 inhibits TLR9-dependent gene expression by directly blocking the activity of IRF5
  • interactions of IRF1, IFNB1 and IRF5 are involved in the M1 polarization of macrophages and have antitumor functions
  • SP1 transcription factor is the primary determinant for activating the basal transcription of the IRF5
  • IRF5 targeted the expression of vascular cell adhesion molecule 1 (VCAM1) at the transcriptional level by binding to its promoter
  • IRAK4 kinase activity controls the activation of IRF5, a transcription factor implicated in the pathogenesis of multiple autoimmune diseases
  • IKBKB, an upstream IRF5 activator, is phosphorylated in response to the agonist-induced TLR signaling
  • IRAK4 activity regulates MAP3K7 and IKBKB activation, leading to the nuclear translocation of IRF5 and induction of inflammatory cytokines in human monocytes
  • cell & other
    REGULATION
    activated by the MyD88 signaling pathway (Lien 2010)
    TRAF6
    phosphorylation (due to a signaling cascade induced by TRAIL), resulting in transcativation of key death receptor signaling components (Hu 2009)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in peripheral blood mononuclear cells from SLE patients carrying the risk allele of the CGGGG indel
    Susceptibility
  • to lupus erythematosus
  • to inflammatory bowel diseases
  • to primary biliary cirrhosis
  • to Systemic sclerosis (SSc)
  • Variant & Polymorphism SNP , repeat , other
  • IRF5 exon 1B isoforms strongly linked to elevated expression of IRF5 and to risk of lupus erythematosus
  • exceptionally strong association signal for a 5 bp insertion
  • deletion polymorphism (CGGGG indel) in the promoter region in inflammatory bowel diseases patients
  • polymorphisms in the IRF5 gene are associated with a predisposition to autoimmune diseases (Lien 2010)
  • rs10488631 at the locus IRF5-TNPO3, strongly assocated to primary biliary cirrhosis
  • polymorphisms of IRF5 may play an important role in susceptibility to SSc
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    immunologyinflammatory 
    IRF5 blockade would ameliorate more acute forms of inflammation, including lung injury
    ANIMAL & CELL MODELS
  • Irf5&
  • 8722;/&
    8722; mice show higher susceptibility to viral infection and decreased serum levels of type I IFN and the inflammatory cytokines IL-6 and TNF-alpha (Lien 2010)
  • mice lacking Irf5 accumulate far fewer neutrophils at the site of inflammation due to the reduced levels of chemokines important for neutrophil recruitment, such as the chemokine (C-X-C motif) ligand 1