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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
SGMS2 Singleton-Merten syndrome 2
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
    Cardiovascularheart   highly Homo sapiens
    Lymphoid/Immunespleen   highly
    Reproductivefemale systemuterus  highly
    Skin/Tegumentskin   highly Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialbarrier liningepidermis   Homo sapiens
    Muscularstriatumcardiac   Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Digestiveameloblast Mus musculus
    Digestiveodontoblast Mus musculus
    Muscularmyocyte Homo sapiens
    not specificchondrocyte Homo sapiens
    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
  • forms filaments upon viral dsRNA recognition and this filament formation is essential for interferon signal activation
  • 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)
  • RAD23A inhibits DDX58/IFIH1 signaling by interacting with TRAF2 and down-regulates its protein level (PMUID: 23357418)
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) AGS7 , SGMS2
    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