TIR domain-containing adapter molecule 1 (TICAM-1; proline-rich, vinculin & TIR domain-containing protein B; Toll-interleukin 1 receptor domain-containing adapter protein inducing interferon-beta; TIR domain-containing adapter protein inducing IFN-beta; NF-kappa-B-activating protein 502H; TICAM1; PRVTIRB; TRIF)
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Function
- role in innate immunity against invading pathogens
- adapter used by TLR3 & TLR4 (through TICAM2) to mediate NF-kappa-B & interferon-regulatory factor (IRF) activation, & to induce apoptosis
- ligand binding to these receptors results in TRIF recruitment through its TIR domain
- distinct protein-interaction motifs allow recruitment of the effector proteins TBK1, TRAF6 & RIPK1, which in turn, lead to the activation of transcription factors IRF3 & IRF7, NF-kappa-B & FADD respectively
- phosphorylated by TBK1
- interacts with the TIR domain of TLR3
- interacts with AZI2, TBK1, IRF3 & IRF7
- interacts with TRAF6
- interacts with TICAM2 in TLR4 recruitment
- interaction with PIAS4 inhibits the TICAM1-induced NF-kappa-B, IRF & IFNB1 activation
- interacts with IKBKB & IKBKE
- interaction with SARM1
- blocks TICAM1-dependent transcription factor activation
- interacts with TRAF3 (putative)
Structure
- homodimer (probable)
- N-terminal region is essential for activation of the IFNB promoter activity
- contains 1 TIR domain
Expression
- ubiquitously expressed
- higher levels in liver