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FLASH GENE
Symbol TICAM1 contributors: mct/npt/shn - updated : 17-05-2017
HGNC name toll-like receptor adaptor molecule 1
HGNC id 18348
Location 19p13.3      Physical location : 4.815.938 - 4.831.737
Synonym name
  • TIR domain containing adaptor inducing interferon-beta
  • TIR domain-containing adapter molecule 1
  • TIR domain-containing adapter protein inducing IFN-beta
  • TIR domain-containing adaptor molecule 1
  • proline-rich, vinculin and TIR domain-containing protein B
  • putative NF-kappa-B-activating protein 502H
  • toll-interleukin-1 receptor domain-containing adapter protein inducing interferon beta
  • Synonym symbol(s) TRIF, PRVTIRB, TICAM-1, MGC35334, IIAE6, MyD88-3
    DNA
    TYPE functioning gene
    STRUCTURE 2.46 kb     1 Exon(s)
    regulatory sequence Binding site
    text structure
  • regulated primarily by NF-kappaB
  • induced by multiple stimuli, such as the ligands for TLR2, TLR3 and TLR4, and by the pro-inflammatory cytokines tumour necrosis factor alpha and interleukin-1alpha
  • MAPPING cloned Y linked N status confirmed
    Map pter - D19S209 - D19S894 - TICAM1 - D19S216 - D19S1034 - cen
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    1 - 2720 - 712 - Takaki (2009)
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinelarge intestinecolon moderately
     liver   highly
     pancreas exocrine   highly
    Lymphoid/Immunelymph node   highly
    Reproductivefemale systemuteruscervix highly
     female systemovary  highly
    Respiratorylung   moderately
    Visualeye   moderately
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectivebone  highly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/Immunedendritic cell
    cell lineage
    cell lines
    fluid/secretion predominantly in lymph
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a TIR domain
  • a protease-resistant N-terminal region is believed to be involved in self-regulation of TRIF by interacting with its TIR domain
  • HOMOLOGY
    interspecies ortholog to Ticam1, Mus musculus
    ortholog to ticam1, Danio rerio
    ortholog to TICAM1, Pan troglodytes
    Homologene
    FAMILY
    CATEGORY adaptor , immunity/defense
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endosome
    intracellular,cytoplasm,cytosolic
    basic FUNCTION
  • involved in the TLR signaling, particularly in the MyD88-independent pathway
  • functions in LPS-TLR4 signaling to regulate the MyD88-independent pathway during the innate immune response to endotoxin lipopolysaccharide (LPS)
  • critically involved in Toll-like receptor-3-mediated IFN-beta production through activation of IFN regulatory factor (IRF)-3 and IRF-7 5
  • activating NF-kappa B
  • inducing interferon-beta
  • inducing apoptosis in a dependent manner on the presence of an intact homotypic interaction motif (RHIM)
  • adaptor protein that couples with TLR3 around the endosome (Takaki 2009)
  • in the cytoplasm recruits nuclear ZMYND11 to enhance NF-kappaB activation and type I IFN induction (Takaki 2009)
  • with cytoplasmic MAVS, converge at the IRF3-activating kinase in human cells (Seya 2009)
  • involved in mediating TLR5-induced nuclear factor kappaB and mitogen-activated protein kinases, specifically JNK1/2 and ERK1/2, activation in intestinal epithelial cells
  • in human dendritic cell (DCs) the TICAM1 pathway is important for overall pro-inflammatory DC differentiation via TLR4 by mediating co-stimulation and playing a non-redundant role in pro-inflammatory cytokine induction
  • is the adaptor protein in the Toll-like receptor (TLR) 3 and 4 signalling pathway that leads to the production of type 1 interferons and cytokines
  • may be a crucial factor promoting the interaction between atrial fibroblasts and macrophages, leading to atrial fibrosis
  • adaptor signaling is important in abdominal aortic aneurysm formation
  • CELLULAR PROCESS cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling signal transduction
  • TLR3-TICAM1 pathway (Takaki 2009)
  • TICAM1 signaling is essential for TLR4-driven IgE class switching
  • a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • toll-like receptor adaptor molecule 2, TICAM2
  • TNF receptor-associated factor 6 and TANK-binding kinase 1, and activates NF-kappa B and IFN-regulatory factor-3
  • IRF-7 and IRF-3
  • NAK-associated protein 1, NAP1
  • TNF receptor-associated factor, TRAF1
  • TICAM1-signaling pathway promotes TNF-alpha mRNA translation through activation of the protein kinase MAPKAPK2
  • toll-like receptor 5, TLR5
  • UBQLN1 is a novel inhibitor of the TLR3-TICAM1 antiviral pathway by reducing the abundance of TICAM1
  • DEFB103B affects the activity of pro-inflammatory pathways associated with MYD88 and TICAM1
  • regulatory impact of IRAK1/4 and PELI3 on the TICAM1-dependent TLR4-signaling cascade, which might be of general importance for disease conditions associated with macrophage pathologies such as atherosclerosis
  • ADAM15 is a novel TCAM1-interacting partner
  • is an adapter protein required for TLR3-mediated signaling
  • WWP2 is a TICAM1-associated protein by biochemical purification (WWP2 mediated K48-linked ubiquitination and degradation of TICAM1 upon TLR3 activation)
  • physical association of TLR9, ICAM1 and TRAF6 leads to activation of noncanonical NFKB1 signalling
  • critical role for ARF6 in regulating TICAM2/TICAM1-dependent TLR4 signaling
  • WDFY1 recruits the signaling adaptor TICAM1 to TLR3 and TLR4, thereby potentiating signaling from these pattern recognition receptors (PRRs)
  • TLR4 recruits TICAM2 as a sorting adaptor to facilitate the interaction between TLR4 and TICAM1 and then initiate TICAM1-dependent IRF3 activation
  • TICAM2 bridges TLR4 and TICAM1 for LPS signaling in the endosome
  • important distinction between the TICAM1-mediated signaling pathways of TLR4 and TLR3
  • ANXA2 directly exerted negative regulation of inflammatory responses through TLR4-initiated TICAM2-TICAM1 pathway occurring on endosomes
  • is required for optimal activation of innate immune responses in mesothelial cells against microbial infections
  • regulated foam cell formation via regulation of the expression levels of CCL2, F3, OLR1
  • TRIM32 negatively regulates TLR3/4-mediated immune responses by targeting TICAM1 to TAX1BP1-mediated selective autophagic degradation
  • cell & other
    REGULATION
    inhibited by PIASy is an inhibitor of TRIF-induced ISRE
    Other downregulated by Triad3A
    SARM a negative regulator of TRIF
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • germline mutation Lps2 abolishing cytokine responses to double-stranded mRNA and severely impairing responses to the endotoxin lipopolysaccharide (LPS)
  • mice genetically deficient in both MyD88 and TRIF have a complete lack of known TLR signaling
  • Trif-deficient mice by target disruption are defective in both TLR3- and TLR4-mediated expression of IFN-beta and activation of IRF-3
  • mice deficient in both MyD88 and TRIF show complete loss of nuclear factor kappa B activation in response to TLR4 stimulation
  • TRIF-KO intestinal epithelial cells exhibited substantially reduced inflammatory cytokine and TRIF-KO mice are resistant to in vivo intestinal inflammatory responses