SARM binds viral dsRNA:TLR3:TICAM1

Stable Identifier
R-HSA-9014320
Type
Reaction [binding]
Species
Homo sapiens
Related Species
Influenza A virus, Rotavirus, Hepatitis B virus, Hepatitis C Virus, Human herpesvirus 1
Compartment
endosome membrane, cytosol
Synonyms
Negative regulator SARM binds to TRIF within activated TLR3 complex
ReviewStatus
5/5
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SARM binds viral dsRNA:TLR3:TICAM1
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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.

Literature References
PubMed ID Title Journal Year
16964262 The human adaptor SARM negatively regulates adaptor protein TRIF-dependent Toll-like receptor signaling

Schröder, M, Stack, J, Moynagh, PN, Carty, M, Bowie, AG, Goodbody, R

Nat. Immunol. 2006
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Output
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Event Information
Go Biological Process
negative regulation of MyD88-independent toll-like receptor signaling pathway (0034128)
Authored
Shamovsky, V  (2012-05-15)
Reviewed
Fitzgerald, KA  (2012-11-13)
Created
Shamovsky, V  (2017-07-28)
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