BioPAX pathway converted from "Viral dsRNA binds the Toll-Like Receptor 3 (TLR3)" in the Reactome database. Viral dsRNA binds the Toll-Like Receptor 3 (TLR3) Viral dsRNA binds the Toll-Like Receptor 3 (TLR3) Viral dsRNA triggers an antiviral pathway mediated by toll like receptor 3. TLR3 dimerization occurs upon ligand binding to positivly charged residues on the ectodomain termini of TLR3 wich are responsible for the interaction with sugar-phosphate groups of dsRNA. Authored: Luo, F, 2005-11-10 11:23:18 Reviewed: Gay, NJ, 2006-04-24 16:48:17 Edited: Shamovsky, V, 2012-02-19 Reactome DB_ID: 2000341 2 endosome membrane GO 0010008 UniProt:O15455 TLR3 TLR3 TLR3 FUNCTION Key component of innate and adaptive immunity. TLRs (Toll-like receptors) control host immune response against pathogens through recognition of molecular patterns specific to microorganisms. TLR3 is a nucleotide-sensing TLR which is activated by double-stranded RNA, a sign of viral infection. Acts via the adapter TRIF/TICAM1, leading to NF-kappa-B activation, IRF3 nuclear translocation, cytokine secretion and the inflammatory response.SUBUNIT Monomer and homodimer; dimerization is triggered by ligand-binding, the signaling unit is composed of one ds-RNA of around 40 bp and two TLR3 molecules, and lateral clustering of signaling units along the length of the ds-RNA ligand is required for TLR3 signal transduction. Interacts (via transmembrane domain) with UNC93B1; the interaction is required for transport from the ER to the endosomes (PubMed:33432245). Interacts with SRC; upon binding of double-stranded RNA. Interacts with TICAM1 (via the TIR domain) in response to poly(I:C) and this interaction is enhanced in the presence of WDFY1 (PubMed:25736436). The tyrosine-phosphorylated form (via TIR domain) interacts with WDFY1 (via WD repeat 2) in response to poly(I:C) (PubMed:25736436).TISSUE SPECIFICITY Expressed at high level in placenta and pancreas. Also detected in CD11c+ immature dendritic cells. Only expressed in dendritic cells and not in other leukocytes, including monocyte precursors. TLR3 is the TLR that is expressed most strongly in the brain, especially in astrocytes, glia, and neurons.DOMAIN ds-RNA binding is mediated by LRR 1 to 3, and LRR 17 to 18.PTM Heavily N-glycosylated, except on that part of the surface of the ectodomain that is involved in ligand binding.PTM TLR3 signaling requires a proteolytic cleavage mediated by cathepsins CTSB and CTSH, the cleavage occurs between amino acids 252 and 346. The cleaved form of TLR3 is the predominant form found in endosomes.POLYMORPHISM The Phe-412 allele (dbSNP:rs3775291) occurs with a frequency of 30% in populations with European and Asian ancestry, and confers some natural resistance to HIV-1 infection.SIMILARITY Belongs to the Toll-like receptor family. Reactome http://www.reactome.org Homo sapiens NCBI Taxonomy 9606 UniProt O15455 Chain Coordinates 24 EQUAL 904 EQUAL Converted from EntitySet in Reactome Reactome DB_ID: 9038432 1 endosome lumen GO 0031904 TLR3 ligand [endosome lumen] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity Reactome DB_ID: 167985 1 viral dsRNA :TLR3 [endosome membrane] viral dsRNA :TLR3 Reactome DB_ID: 2000341 2 24 EQUAL 904 EQUAL Converted from EntitySet in Reactome Reactome DB_ID: 9038432 1 Reactome Database ID Release 81 167985 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=167985 Reactome R-HSA-167985 4 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-167985.4 Reactome Database ID Release 81 168092 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=168092 Reactome R-HSA-168092 4 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-168092.4 11607032 Pubmed 2001 Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3 Alexopoulou, L Holt, AC Medzhitov, R Flavell, RA Nature 413:732-8 18420935 Pubmed 2008 Structural basis of toll-like receptor 3 signaling with double-stranded RNA Liu, L Botos, I Wang, Y Leonard, JN Shiloach, J Segal, DM Davies, DR Science 320:379-81