TICAM1

Description

The TICAM1 (TIR domain containing adaptor molecule 1) is a protein-coding gene located on chromosome 19.

TICAM1 (formerly known as TRIF) is an adapter protein involved in responding to toll-like receptor (TLR) activation. It mediates the delayed signaling cascade associated with TLRs, distinct from the MyD88-dependent pathway. TLRs recognize microbial components and initiate immune responses. Upon recognition of conserved pathogen patterns, TLRs trigger downstream signaling cascades, leading to the release of inflammatory cytokines and chemokines and the upregulation of immune cells. All TLRs possess a TIR domain that initiates signaling through TIR adapters. Adapters organize downstream signaling cascades, resulting in specific cellular responses to pathogens. TICAM1 is primarily active in the spleen and its regulation is often influenced by MyD88 deficiency in the liver, suggesting organ-specific control of signaling pathways. Notably, mutations within the TLR4 signaling pathway can lead to microbial evasion of immune responses due to a lack of redundancy. TICAM1 contains three TRAF-binding motifs in its amino terminal region, essential for its association with TRAF6. Disruption of these motifs reduces the activation of NF-κB, a transcription factor also activated by the carboxy-terminal domain of TICAM1, which promotes the upregulation of cytokines and co-stimulatory immune molecules.

TICAM1 is involved in innate immunity against invading pathogens. It acts as an adapter for TLR3, TLR4 (via TICAM2), and TLR5, mediating activation of NF-kappa-B and interferon-regulatory factors (IRF), and inducing apoptosis. Ligand binding to these receptors recruits TICAM1 through its TIR domain. TICAM1 then interacts with effector proteins like TBK1, TRAF6, and RIPK1, activating transcription factors IRF3, IRF7, NF-kappa-B, and FADD. Phosphorylation by TBK1 on the pLxIS motif recruits and activates IRF3, leading to type I interferon expression and potent immunity against pathogens. TICAM1 is part of a multi-helicase complex that acts as a cytoplasmic sensor for viral double-stranded RNA (dsRNA), activating antiviral responses and pro-inflammatory cytokine production.

TICAM1 is also known as IIAE6, MyD88-3, PRVTIRB, TICAM-1, TRIF.

Associated Diseases

• Herpes simplex virus encephalitis
• Encephalopathy, acute, infection-induced (herpes-specific), susceptibility to, 6