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Immunol.17865-874FUNCTIONUBIQUITINATION BY RNF170MUTAGENESIS OF LYS-766Structural basis of toll-like receptor 3 signaling with double-stranded RNA.Liu L.Botos I.Wang Y.Leonard J.N.Shiloach J.Segal D.M.Davies D.R.doi:10.1126/science.11554062008Science320379-381X-RAY CRYSTALLOGRAPHY (2.66 ANGSTROMS) OF 28-704 IN COMPLEX WITH DS-RNASUBUNITDISULFIDE BONDSGLYCOSYLATION AT ASN-71; ASN-197; ASN-253; ASN-276; ASN-292; ASN-399; ASN-414; ASN-425; ASN-508; ASN-663 AND ASN-668Cryo-EM structures of Toll-like receptors in complex with UNC93B1.Ishida H.Asami J.Zhang Z.Nishizawa T.Shigematsu H.Ohto U.Shimizu T.doi:10.1038/s41594-020-00542-w2021Nat. Struct. Mol. Biol.28173-180STRUCTURE BY ELECTRON MICROSCOPY (3.30 ANGSTROMS) IN COMPLEX WITH UNC93B1INTERACTION WITH UNC93B12.66A=28-7043.41A/B=28-7043.30A=1-9053.47A/B=28-6983.64A/B=28-6983.20C/D/E/F=26-70513115 sites, No reported glycans15 sites10 sequenced antibodies1231 antibodies from 48 providersmouseTlr3Eukaryota4 hits in 76 CRISPR screensmouseProteinExpressed in conjunctival fornix and 212 other cell types or tissuesbaseline and differentialRibonuclease InhibitorToll/interleukin-1 receptor homology (TIR) domainCys-rich_flank_reg_CLeu-rich_rptLeu-rich_rpt_typical-subtypLRR_dom_sfTIR_domTLR3_TMDToll-like_receptorToll_tir_struct_dom_sfTOLL-LIKE RECEPTORTOLL-LIKE RECEPTOR 3LRR_1LRR_8TIRTlr3_TMDLEURICHRPTLRR_SD22LRR_TYPLRRCTTIRL domain-likeToll/Interleukin receptor TIR domainLRRTIRMMToll-like receptor 3CD283Tlr3Key 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 (By similarity).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 (By similarity). 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). Ubiquitinated by RNF170 at Lys-766 via 'Lys-48'-linked ubiquitin chains; leading to TLR3 proteasomal degradation (PubMed:31076723).Highly expressed in lung. After intraperitoneal injection of lipopolysaccharide, highly expressed in brain, heart, kidney, liver, lung and spleen.ds-RNA binding is mediated by LRR 1 to 3, and LRR 17 to 18.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 (By similarity).Ubiquitinated by TRIM3; leading to recognition and sorting of polyubiquitinated TLR3 by the ESCRT complexes. Ubiquitinated by ZNRF1 via 'Lys-63'-linked ubiquitin chains; leading to TLR3 lysosomal trafficking and degradation.Belongs to the Toll-like receptor family.125Toll-like receptor 310093326905Lumenal705Helical706726Cytoplasmic727LRRNT52LRR 15374LRR 27798LRR 3101122LRR 4125146LRR 5149170LRR 6173196LRR 7199220LRR 8250271LRR 9276297LRR 10300321LRR 11324345LRR 12357378LRR 13381401LRR 14409430LRR 15433454LRR 16458479LRR 17482502LRR 18508529LRR 19532553LRR 20564585LRR 21588609LRR 22612633LRRCT646699TIR755898Phosphotyrosine760Phosphotyrosine859N-linked (GlcNAc...) asparagineN-linked (GlcNAc...) asparagine58N-linked (GlcNAc...) asparagine71N-linked (GlcNAc...) asparagineN-linked (GlcNAc...) asparagine197N-linked (GlcNAc...) asparagine248N-linked (GlcNAc...) asparagine253N-linked (GlcNAc...) asparagineN-linked (GlcNAc...) asparagine292N-linked (GlcNAc...) asparagine399N-linked (GlcNAc...) asparagine414N-linked (GlcNAc...) asparagine425N-linked (GlcNAc...) asparagineN-linked (GlcNAc...) asparagine663N-linked (GlcNAc...) asparagine668293896123650678652697Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)766Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)813Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)832F67033355569727982941041061171201281301431521541671691761781901952042152212242262282362462472492552622642662692702722792813033053163273293393413493543603623733843863913933953974024034054124364384454474514534614634684714744854874934954985005055115135245355375445475515545675695805915936046156176286356396426646716726756776816826846896916956987007032002-01-312true1036710ef6489ee67097f9ac346381c3d5af88MKGCSSYLMYSFGGLLSLWILLVSSTNQCTVRYNVADCSHLKLTHIPDDLPSNITVLNLTHNQLRRLPPTNFTRYSQLAILDAGFNSISKLEPELCQILPLLKVLNLQHNELSQISDQTFVFCTNLTELDLMSNSIHKIKSNPFKNQKNLIKLDLSHNGLSSTKLGTGVQLENLQELLLAKNKILALRSEELEFLGNSSLRKLDLSSNPLKEFSPGCFQTIGKLFALLLNNAQLNPHLTEKLCWELSNTSIQNLSLANNQLLATSESTFSGLKWTNLTQLDLSYNNLHDVGNGSFSYLPSLRYLSLEYNNIQRLSPRSFYGLSNLRYLSLKRAFTKQSVSLASHPNIDDFSFQWLKYLEYLNMDDNNIPSTKSNTFTGLVSLKYLSLSKTFTSLQTLTNETFVSLAHSPLLTLNLTKNHISKIANGTFSWLGQLRILDLGLNEIEQKLSGQEWRGLRNIFEIYLSYNKYLQLSTSSFALVPSLQRLMLRRVALKNVDISPSPFRPLRNLTILDLSNNNIANINEDLLEGLENLEILDFQHNNLARLWKRANPGGPVNFLKGLSHLHILNLESNGLDEIPVGVFKNLFELKSINLGLNNLNKLEPFIFDDQTSLRSLNLQKNLITSVEKDVFGPPFQNLNSLDMRFNPFDCTCESISWFVNWINQTHTNISELSTHYLCNTPHHYYGFPLKLFDTSSCKDSAPFELLFIISTSMLLVFILVVLLIHIEGWRISFYWNVSVHRILGFKEIDTQAEQFEYTAYIIHAHKDRDWVWEHFSPMEEQDQSLKFCLEERDFEAGVLGLEAIVNSIKRSRKIIFVITHHLLKDPLCRRFKVHHAVQQAIEQNLDSIILIFLQNIPDYKLNHALCLRRGMFKSHCILNWPVQKERINAFHHKLQVALGSRNSAHtruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetruetrue