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FLASH GENE
Symbol SIGIRR contributors: mct - updated : 19-08-2011
HGNC name single immunoglobulin and toll-interleukin 1 receptor (TIR) domain
HGNC id 30575
Location 11p15.5      Physical location : 405.715 - 417.397
Synonym name
  • single Ig IL-1R-related molecule
  • Toll/interleukin-1 receptor 8
  • Synonym symbol(s) TIR8, MGC110992, UNQ301/PRO342
    DNA
    TYPE functioning gene
    STRUCTURE 11.68 kb     10 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    10 - 1657 - 410 - 2011 21187075
    10 - 1688 - 410 - 2011 21187075
    10 - 1761 - 410 - 2011 21187075
    EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinelarge intestinecolon highly Homo sapiens
     liver    
    Respiratorylung    
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Digestiveepithelial cell Homo sapiens
    cell lineage
    cell lines highly in epithelial cell lines, moderatly in splenocytes, lowly in fibroblasts and endothelial cell lines
    fluid/secretion blood
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a single Ig extracellular domain
  • four potential N-glycosylation sites
  • four IL1R-like signaling motifs which are unable to mediate activation of the IL8 promoter or of NFKB
  • TIR domain
  • mono polymer homomer , heteromer , dimer
    HOMOLOGY
    interspecies ortholog to murine AI256711
    Homologene
    FAMILY
  • interleukin-1 receptor family
  • subtype of IL1R superfamily
  • CATEGORY receptor membrane
    SUBCELLULAR LOCALIZATION     plasma membrane
    text SIGIRR and PALM3 localize in cell membrane
    basic FUNCTION
  • acting as a negative regulator of TLR-IL1R signaling
  • role of SIGIRR as an inhibitor of inflammation (
  • Ig-like membrane protein critical for negative regulation of Toll-like receptor (TLR)-4-mediated signalling (
  • serves as a negative regulator to maintain gut innate immunity, which is down-regulated during inflammation by inhibition of an SP1-mediated pathway
  • important negatively regulatory molecular in the TIR signaling and can block the TIR signal transduction by trapping the crucial components of this signaling pathway
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS inflammation
    PATHWAY
    metabolism
    signaling
    negative regulation of lipopolysaccharide-mediated signaling pathway
    a component heterodimerizing with TLR4, TLR5, TLR9, IL1R, TRAF6 and IRAK
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interaction with IL36RN (mediates anti-inflammatory activity in the brain through induction of IL4 following interaction with SIGIRR)
  • PALM3 is a novel binding protein of SIGIRR (interaction between SIGIRR and PALM3 may partly account for the mechanism of the negatively regulatory effect of SIGIRR)
  • cell & other
    REGULATION
    repressed by LPS exposure
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    immunologyautoimmunearticular
    potential therapeutic target for rheumatoid arthritis
    ANIMAL & CELL MODELS
  • Sigirr -/- mice (Wald 2003) had an increased inflammatory response after injection of LPS and were hyperresponsive to IL1
  • Sigirr-deficient mice (Garlanda 2004) had normal susceptibility to systemic LPS toxicity and to intraperitoneal or subcutaneous inflammation, but were more susceptible than normal controls to intestinal inflammation