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FLASH GENE
Symbol IFITM3 contributors: mct - updated : 04-10-2017
HGNC name interferon induced transmembrane protein 3 (1-8U)
HGNC id 5414
Location 11p15.5      Physical location : 319.672 - 320.914
Synonym name
  • interferon-inducible
  • interferon inducible genes I-8U and I-8D in the MHC1 cluster
  • dispanin subfamily A member 2b
  • Synonym symbol(s) 1-8U, IP15, IFI8R, DSPA2b
    DNA
    TYPE functioning gene
    STRUCTURE 1.24 kb     2 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Binding site   HRE
    text structure
  • two ISRE (interferon-stimulable respnsive element)
  • two KLF4-binding sites in the IFITM3 promoter bound specifically to KLF4 protein
  • MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    2 - 678 14 133 - 2008 18177740
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    cell lineage
    cell lines colon and prostate cancer
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • two transmembrane domains
  • a N-terminal signal sequence
  • three potential phosphorylation sites
  • a DNA-binding domain, which interacts with SPP1
  • a C-terminal leucine zipper
  • HOMOLOGY
    interspecies homolog to C.elegans C14A6.8
    Homologene
    FAMILY
  • IFN-induced transmembrane protein family
  • CD225 family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endosome
    intracellular,cytoplasm,organelle,lysosome
    text
  • localizes to late endosomes, where reoviruses undergo proteolytic disassembly
  • localizes to endolysosomes where it prevents virus fusion
  • basic FUNCTION
  • involved in antiviral response
  • IFITM1, IFITM2, IFITM3 mediate cellular resistance to influenza A H1N1 virus, West Nile virus, and dengue virus
  • IFITM1, IFITM2, IFITM3 are important components of the innate immune system to restrict HIV-1 infection
  • act as antiviral restriction factor
  • suppress cellular and HCV IRES-mediated translation
  • IFITM1, IFITM2, IFITM3 are potentially involved in the differentiation and cell proliferation during heart development
  • is essential for defending the host against influenza A virus
  • acts as an essential barrier to influenza A virus infection, and plays a pivotal role in defence against influenza virus infections
  • can inhibit viruses that enter cells via different routes and its N-terminal region is specifically required for controlling pH-dependent viruses
  • restricts infection by a nonenveloped virus and suggest that IFITM3 targets an increasing number of viruses through a shared requirement for endosomes during cell entry
  • essential for innate defense against influenza virus in humans
  • role of IFITM3 in the pathogenesis of neurodevelopmental diseases associated with immune activation
  • is a cellular endosome- and lysosome-localized protein that restricts numerous virus infections
  • IFITM3 can play an important role in regulating inflammation balance
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS immunity/defense , inflammation
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • IFITM3 and SPP1 interact and IFITM3 reduces osteopontin (SPP1) mRNA expression, possibly by affecting SPP1 mRNA stability
  • direct transcriptional target of KLF4 and dysregulated KLF4 expression leads to aberrant IFITM3 expression, thus contributing to colon cancer progression and metastasis
  • ZDHHC20 uniquely increased IFITM3 antiviral activity when both proteins were overexpressed
  • IFITM3 interacts with ABHD16A, following which it can better inhibit the replication of influenza virus and the inflammatory response caused by the disease process
  • cell & other
    REGULATION
    activated by palmitoylation, a lipid posttranslational modification
    induced by interferon alpha/beta(IFNA/IFNB),interferon gamma(IFNG),angiotensine 2(A-II),IL-1
    Phosphorylated by by FYN and mutagenesis of Tyr(20) both resulted in decreased IFITM3 ubiquitination
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in human colorectal cancer
    tumoral     --over  
    in gastric cancer (
    Susceptibility to influenza virus infection
    Variant & Polymorphism SNP SNP rs12252-C alters a splice acceptor site, and the minor CC genotype IFITM3 has reduced influenza virus restriction
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerdigestivestomach
    is a potential therapeutic target for gastric cancer
    ANIMAL & CELL MODELS