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FLASH GENE
Symbol IFIH1 contributors: mct/npt - updated : 27-08-2014
HGNC name interferon induced with helicase C domain 1
HGNC id 18873
Corresponding disease
AGS7 Aicardi-Goutières syndrome 7
Location 2q24.2      Physical location : 163.123.589 - 163.175.039
Synonym name
  • melanoma differentiation associated protein-5
  • helicard
  • DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide
  • helicase with 2 CARD domains
  • murabutide down-regulated protein
  • interferon induced with helicase C domain 1
  • Synonym symbol(s) MDA5, MDA-5, MGC133047, Hlcd, RH116, IDDM19
    EC.number 3.6.4.13
    DNA
    TYPE functioning gene
    STRUCTURE 51.63 kb     16 Exon(s)
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    16 - 3617 116.55 1025 - 2004 14676839
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinesmall intestine  highly
    Endocrinepancreas    
    Lymphoid/Immunespleen   highly
    Reproductivefemale systembreastmammary gland  
     female systemuterus  highly
    Respiratoryrespiratory tracttrachea  highly
    cell lineage
    cell lines melanoma cell lines
    fluid/secretion
    at STAGE
    physiological period pregnancy
    Text placenta
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-terminal tandem CARD domains
  • a zinc-binding domain structurally related to GDP/GTP exchange factors of Rab-like GTPases (Cui 2008)
  • a central helicase domain,
  • a C-terminal DExH/D RNA helicase domain, CTD/dsRNA complex that may recognize the first turn of blunt-ended dsRNA in a similar manner as DHX58 (Li 2009)
  • HOMOLOGY
    interspecies homolog to DHX58, DDX58
    Homologene
    FAMILY
  • pattern-recognition receptors (PRRs) family
  • CATEGORY RNA associated
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic,granule
    intracellular,nucleus
    text
  • localizes to stress granules, but this localization is not required for the induction of type I interferon
  • basic FUNCTION
  • RNA-dependent ATPase, playing a central role in an intracellular signal transduction pathway that can lead to the activation of the IFN-beta promoter
  • may contribute to apoptosis induction during terminal differentiation and during IFN treatment
  • may be having a role in protecting the host from viral infection by sensing viral nucleic acid in the cytoplasm and triggering a cellular antiviral and apoptotic response
  • cytoplasmic DEX(D/H) helicase protein that can induce signaling in response to RNA ligands, including those from viral infections (Murali 2008)
  • cytoplasmic helicase that mediates induction of interferon response to viral RNA (Nejentsev 2009)
  • cytosolic pattern recognition receptor detecting single-stranded or double-stranded RNA in virally infected cells (Li 2009)
  • recognize single-stranded RNA with 5prime triphosphates and double-stranded RNA (dsRNA) to initiate innate antiviral immune responses (Li 2009)
  • controls the local expression of cytokines and chemokines during a viral infection (Colli 2010)
  • may contribute to the pathogenesis of diabetes by modifying the beta-cell responses to a viral infection (Colli 2010)
  • may thus modulate beta-cell apoptosis and/or local release of inflammatory mediators in the course of a viral infection by acting, at least in part, at the pancreatic beta-cell level (Colli 2010)
  • cooperatively assembles into a filamentous oligomer composed of a repeating segmental arrangement of IFIH1 dimers along the length of dsRNA
  • detects viral double-stranded RNA in the cytoplasm
  • is a polymerization-dependent signaling platform that uses the amyloid-like self-propagating properties of mitochondrial antiviral-signaling protein (MAVS) to amplify signaling
  • DDX58 and IFIH1 have emerged as key cytosolic sensors for the detection of RNA viruses and lead to antiviral interferon (IFN) production
  • PPP1CA and PPP1CC are the primary phosphatases that are responsible for IFIH1 and DDX58 dephosphorylation
  • that lead to their activation
  • IFIH1 and DDX58 sense viral RNA in the cytoplasm of infected cells and activate signal transduction pathways that trigger the production of type I interferons (IFNs)
  • cytoplasmic receptor that recognizes dsRNA, playing a role in the innate immune response triggered by viral infection
  • play a major role in the development of some autoimmune diseases
  • CELLULAR PROCESS cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with DHX58 (facilitates viral RNA recognition by DDX58 and IFIH1 through its ATPase domain (Satoh 2010)
  • RAVER1 is a specific IFIH1-interacting protein (RAVER1 was associated with IFIH1 upon viral infection)
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) AGS7
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    in the blood cells of T1D subjects, especially subjects under 10 years old
    Susceptibility
  • to insulin-dependent diabetes mellitus (T1D)
  • to Graves disease
  • Variant & Polymorphism SNP
  • A946T increasing the risk of insulin-dependent diabetes mellitus, and of Graves disease
  • association between T1D and multiple SNPs in IFIH1 (Liu 2009)
  • variants protecting against type 1 diabetes (Nejentsev 2009)
  • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS