BioPAX pathway converted from "Viral dsRNA binds the Toll-Like Receptor 3 (TLR3)" in the Reactome database. LEFT-TO-RIGHT 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 TLR3 Toll-like Receptor 3 Reactome DB_ID: 2000341 endosome membrane GENE ONTOLOGY GO:0010008 UniProt:O15455 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. Homo sapiens NCBI Taxonomy 9606 UniProt O15455 24 EQUAL 904 EQUAL Reactome Database ID Release 81 2000341 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=2000341 Reactome R-HSA-2000341 1 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-2000341.1 Reactome http://www.reactome.org 2 Converted from EntitySet in Reactome TLR3 ligand Reactome DB_ID: 9038432 Rotavirus dsRNA Reactome DB_ID: 8982440 endosome lumen GENE ONTOLOGY GO:0031904 Reactome Database ID Release 81 8982440 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=8982440 Reactome R-ROT-8982440 2 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-ROT-8982440.2 ChEBI 33697 additional information MI MI:0361 viral double-stranded RNA HSV1 dsRNA intermediate form HSV1 dsRNA replicative intermediate form Reactome DB_ID: 6791257 Reactome Database ID Release 81 6791257 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=6791257 Reactome R-HER-6791257 1 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-HER-6791257.1 ChEBI 67208 viral double-stranded RNA HCV dsRNA intermediate form HCV dsRNA replicative intermediate form Reactome DB_ID: 8982462 Reactome Database ID Release 81 8982462 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=8982462 Reactome R-HCV-8982462 2 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-HCV-8982462.2 ChEBI 67208 viral double-stranded RNA HBV dsRNA intermediate form HBV dsRNA replicative intermediate form Reactome DB_ID: 8982481 Reactome Database ID Release 81 8982481 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=8982481 Reactome R-HBV-8982481 2 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-HBV-8982481.2 ChEBI 67208 FLUAV dsRNA Stranded Influenza A dsRNA intermediate form Reactome DB_ID: 9028895 Reactome Database ID Release 81 9028895 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=9028895 Reactome R-FLU-9028895 3 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-FLU-9028895.3 ChEBI 67208 Reactome Database ID Release 81 9038432 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=9038432 Reactome R-NUL-9038432 1 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-NUL-9038432.1 viral dsRNA :TLR3 Reactome DB_ID: 167985 2 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