TICAM1 gene

The TICAM1 gene (TICAM1 stands for: TIR Domain Containing Adaptor Molecule 1) is a protein-coding gene located on chromosome 19p13.3. Associated signaling pathways include the MyD88-dependent endosome-initiated immunological cascade.

The TICAM1 gene encodes an adaptor protein that contains a Toll/interleukin-1 receptor (TIR) homology domain, an intracellular signaling domain that mediates protein-protein interactions between Toll-like receptors (TLRs) and components of signal transduction. This protein is involved in native immunity against invading pathogens. It interacts specifically with Toll-like receptor 3, but not with other TLRs, and this association mediates dsRNA induction of interferon-beta through activation of nuclear factor kappa-B during an antiviral immune response.

Mutations in this gene are associated with acute infection-induced encephalopathy and herpes simplex virus encephalitis.

The encoded protein TICAM1 is involved in innate immunity against invading pathogens. Here, the protein acts as an adaptor that is used by Toll-like receptor (TLR3), TLR4 (via TICAM2) and TLR5 to mediate the activation of NF-kappa-B and interferon-regulatory factor (IRF) and induce apoptosis (Yamamoto M et al.2002; Ye W et al. 2017). Ligand binding to these receptors leads to the recruitment of TICAM-1 via its TIR domain Han KJ et al. 2004).

Different protein interaction motifs enable the recruitment of the effector proteins TBK1, TRAF6 and RIPK1, which in turn lead to the activation of the transcription factors IRF3 and IRF7, NF-kappa-B and FADD respectively (Yamamoto M et al.2002). Phosphorylation by TBK1 at the pLxIS motif leads to the recruitment and subsequent activation of the transcription factor IRF3 to induce the expression of type I interferon and exert effective immunity against invading pathogens (Liu S et al. 2015). The adapter molecule TICAM1 is part of a multi-helicase TICAM1 complex that acts as a cytoplasmic sensor for viral double-stranded RNA (dsRNA) and plays a role in activating a cascade of antiviral responses, including the induction of pro-inflammatory cytokines.

1. Han KJ et al. (2004) Mechanisms of the TRIF-induced interferon-stimulated response element and NF-kappaB activation and apoptosis pathways. J Biol Chem 279:15652-15661.
2. Liu S et al. (2015) Phosphorylation of innate immune adaptor proteins MAVS, STING, and TRIF induces IRF3 activation. Science 347(6227):aaa2630.
3. Yamamoto M et al.(2002) Cutting edge: a novel Toll/IL-1 receptor domain-containing adapter that preferentially activates the IFN-beta promoter in the Toll-like receptor signaling. J Immunol 169:6668-6672.
4. Ye W et al. (2017) TRIM8 Negatively Regulates TLR3/4-Mediated Innate Immune Response by Blocking TRIF-TBK1 Interaction. J Immunol 199:1856-1864.