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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
    Physical map
    LOC390028 11 similar to Olfactory receptor 4F3 LOC387731 11 similar to bA476I15.3 (novel protein similar to septin) LOC387732 11 LOC387732 RYD5 11p15.5 ligand binding protein RYD5 ODF3 11p15.5 outer dense fiber of sperm tails 3 BET1L 11p15.5 blocked early in transport 1 homolog (S. cerevisiae) like RIC-8 11p15.5 likely ortholog of mouse synembryn SIRT3 11p15.5 sirtuin (silent mating type information regulation 2 homolog) 3 (S. cerevisiae) PSMD13 11p15.5 proteasome (prosome, macropain) 26S subunit, non-ATPase, 13 NALP6 11p15 NACHT, leucine rich repeat and PYD containing 6 FLJ22635 11p15.5 hypothetical protein FLJ22635 LOC387733 11 similar to putative haemopoietic membrane protein MRPS24P1 11p15.4 mitochondrial ribosomal protein S24 pseudogene IFITM2 11p15.5 interferon induced transmembrane protein 2 (1-8D) IFITM1 11p15.5 interferon induced transmembrane protein 1 (9-27) IFITM3 11p15.5 interferon induced transmembrane protein 3 (1-8U) PKP3 11p15 plakophilin 3 LOC387734 11 similar to beta 1,4-N-acetylgalactosaminyltransferase-transferase-III FLJ25045 11p15.5 hypothetical protein FLJ25045 SIGIRR 11p15.5 single Ig IL-1R-related molecule PTDSS2 11p15 phosphatidylserine synthase 2 RNH 11p15.5 ribonuclease/angiogenin inhibitor LOC387735 11 similar to Collagen alpha 1(V) chain precursor HRAS 11p15.5 v-Ha-ras Harvey rat sarcoma viral oncogene homolog DKFZp761L1518 11p15.5 hypothetical protein DKFZp761L1518 MGC35138 11p15.5 hypothetical protein MGC35138 C11orf13 11p15,5 chromosome 11 open reading frame 13 KIAA1542 11p15.5 CTD-binding SR-like protein rA9 IRF7 11p15,5 interferon regulatory factor 7 MUCDHL 11p15,5 mucin and cadherin-like SCT 11p15.5 secretin DRD4 11p15.5 dopamine receptor D4 LOC387736 11 LOC387736 DEAF1 11p15,5 deformed epidermal autoregulatory factor 1 (Drosophila) LOC283232 11p15.5 hypothetical protein LOC283232 EPS8L2 11p15.5 EPS8-like 2 TALDO1 11p15.5-p15.4 transaldolase 1 FLJ34283 11p15.5 hypothetical protein FLJ34283 NS3BP 11p15.5 NS3BP BM88 11p15.5 NS3BP SLC25A22 11p15.5 solute carrier family 25 (mitochondrial carrier: glutamate), member 22 LOC387737 11 LOC387737 LRDD 11pter-p15.5 leucine-rich and death domain containing
    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