Ticam1

Domain

The pLxIS motif constitutes an IRF3-binding motif: following phosphorylation by TBK1, the phosphorylated pLxIS motif of TICAM1 recruits IRF3. IRF3 is then phosphorylated and activated by TBK1 to induce type-I interferons and other cytokines.

The N-terminal region is essential for activation of the IFNB promoter activity.

The N-terminal domain (TRIF-NTD) is globular and consists of two alpha-helical subdomains connected by a 14-residue linker. It shares structural similarity with IFIT family members N-terminal regions.

Function

Involved in innate immunity against invading pathogens. Adapter used by TLR3, TLR4 (through TICAM2) and TLR5 to mediate NF-kappa-B and interferon-regulatory factor (IRF) activation, and to induce apoptosis (PubMed:12855817, PubMed:16002681, PubMed:21703541). Ligand binding to these receptors results in TRIF recruitment through its TIR domain (PubMed:12855817, PubMed:16002681, PubMed:21703541). Distinct protein-interaction motifs allow recruitment of the effector proteins TBK1, TRAF6 and RIPK1, which in turn, lead to the activation of transcription factors IRF3 and IRF7, NF-kappa-B and FADD respectively (PubMed:12855817, PubMed:16002681, PubMed:21703541). Phosphorylation by TBK1 on the pLxIS motif leads to recruitment and subsequent activation of the transcription factor IRF3 to induce expression of type I interferon and exert a potent immunity against invading pathogens (By similarity). Component of a multi-helicase-TICAM1 complex that acts as a cytoplasmic sensor of viral double-stranded RNA (dsRNA) and plays a role in the activation of a cascade of antiviral responses including the induction of pro-inflammatory cytokines (PubMed:21703541).

Post-translational modifications

Phosphorylated by TBK1. Following activation, phosphorylated by TBK1 at Ser-209 in the pLxIS motif. The phosphorylated pLxIS motif constitutes an IRF3-binding motif, leading to recruitment of the transcription factor IRF3 to induce type-I interferons and other cytokines.

Polyubiquitinated at Lys-228 by TRIM38 with 'Lys-48'-linked chains, leading to proteasomal degradation (PubMed:26392463). Polyubiquitinated with 'Lys-6'- and 'Lys-33'-linked chains in a TRIM8-dependent manner; ubiquitination disrupts the interaction with TBK1 and subsequent interferon production (By similarity).

Cellular localization

• Cytoplasm
• Cytosol
• Cytoplasmic vesicle
• Autophagosome
• Mitochondrion
• Colocalizes with UBQLN1 in the autophagosome. Colocalizes in the cytosol with DDX1, DDX21 and DHX36 (PubMed:21703541). Colocalizes in the mitochondria with DDX1 and poly(I:C) RNA ligand (PubMed:21703541). The multi-helicase-TICAM1 complex may translocate to the mitochondria upon poly(I:C) RNA ligand stimulation (PubMed:21703541).

Alternative names

Trif, Ticam1, TIR domain-containing adapter molecule 1, TICAM-1, Toll-interleukin-1 receptor domain-containing adapter protein inducing interferon beta, TIR domain-containing adapter protein inducing IFN-beta

Database links

swissprot:Q80UF7 entrezGene:106759

Other research areas

• Oncology