SARM (sterile alpha-and armadillo-motif-containing protein) is a TIR-domain-containing adaptor, which functions as a negative regulator of TRIF (TICAM1)-dependent Toll-like receptor signaling in humans. A pairwise yeast two-hybrid assay demonstrated that SARM is capable of binding directly to TICAM1 (Carty M et al. 2006). GST pulldown studies suggest that protein-protein interactions occur between the TIR domains of SARM and TICAM1 (Carlsson E et al. 2016). The complex of TICAM1:SARM is thought to inhibit downstream TRIF signaling by preventing the recruitment of TRIF effector proteins (Carty M et al. 2006).
SARM expression was shown to inhibit poly(I:C)-induced TICAM1-dependent NFkappaB activaion, RANTES production and IRF activation in human embryonic kidney HEK293 cells (Carty M et al. 2006). Moreover, suppression of endogenous SARM expression by siRNA led to enhanced TLR3- and TLR4-dependent gene induction in both transformed HEK293 and primary PBMC cells (Carty M et al. 2006), Thus, SARM associates with TICAM1 via its TIR and sterile-alpha motif (SAM) domains to block the induction of proinflammatory genes downstream TLR3.