Toll-like receptor 3

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.

Classification

Family (Pfam)

PF13516 LRR_6, PF13855 LRR_8, PF01582 TIR, PF17968 Tlr3_TMD

InterPro

Cys-rich_flank_reg_C, Leu-rich_rpt, Leu-rich_rpt_typical-subtyp, LRR_dom_sf, TIR_dom, TLR3_TMD, Toll_tir_struct_dom_sf

Functional cluster

Immunoglobulin-Domain Cell Adhesion Proteins

Experimental structures · PDB · 20

• 1ZIW X-ray 2.10A
• 2A0Z X-ray 2.40A
• 2MK9 NMR
• 2MKA NMR
• 3ULU X-ray 3.52A
• 3ULV X-ray 3.52A
• 5GS0 X-ray 3.27A
• 7C76 EM 3.40A
• 7WV3 EM 2.26A
• 7WV4 EM 3.35A
• 7WV5 EM 3.10A
• 7WVE EM 3.11A
• … and 8 more

A predicted model is available from AlphaFold.

Gene Ontology · 48

• GO:0005737 cytoplasm
• GO:0005769 early endosome
• GO:0036020 endolysosome membrane
• GO:0005789 endoplasmic reticulum membrane
• GO:0010008 endosome membrane
• GO:0000139 Golgi membrane
• GO:0005765 lysosomal membrane
• GO:0016020 membrane
• GO:0005886 plasma membrane
• GO:0003725 double-stranded RNA binding
• GO:0042802 identical protein binding
• GO:0038187 pattern recognition receptor activity
• GO:0038023 signaling receptor activity
• GO:0004888 transmembrane signaling receptor activity
• GO:0044389 ubiquitin-like protein ligase binding
• GO:0007250 activation of NF-kappaB-inducing kinase activity
• GO:0071260 cellular response to mechanical stimulus
• GO:0098586 cellular response to virus
• GO:0042742 defense response to bacterium
• GO:0051607 defense response to virus
• GO:0009597 detection of virus
• GO:0097191 extrinsic apoptotic signaling pathway
• GO:0006972 hyperosmotic response
• GO:0090594 inflammatory response to wounding
• GO:0045087 innate immune response
• GO:0007254 JNK cascade
• GO:0097527 necroptotic signaling pathway
• GO:0045671 negative regulation of osteoclast differentiation
• GO:0045766 positive regulation of angiogenesis
• GO:0043123 positive regulation of canonical NF-kappaB signal transduction
• GO:0032722 positive regulation of chemokine production
• GO:1900017 positive regulation of cytokine production involved in inflammatory response
• GO:0010628 positive regulation of gene expression
• GO:0050729 positive regulation of inflammatory response
• GO:0032727 positive regulation of interferon-alpha production
• GO:0032728 positive regulation of interferon-beta production
• GO:0032735 positive regulation of interleukin-12 production
• GO:0032755 positive regulation of interleukin-6 production
• GO:0032757 positive regulation of interleukin-8 production
• GO:0046330 positive regulation of JNK cascade
• GO:0045944 positive regulation of transcription by RNA polymerase II
• GO:0032760 positive regulation of tumor necrosis factor production
• GO:0032729 positive regulation of type II interferon production
• GO:0043331 response to dsRNA
• GO:0043330 response to exogenous dsRNA
• GO:0007165 signal transduction
• GO:0034138 toll-like receptor 3 signaling pathway
• GO:0002224 toll-like receptor signaling pathway

Disease associations

• immunodeficiency 83, susceptibility to viral infections MONDO:0800187

Drugs targeting this protein · 2

• BEVASIRANIB SODIUM activator
• BEVASIRANIB activator

Related proteins · sequence + function similarity

• Toll-like receptor 3 0.98
• Toll-like receptor 3 0.98
• Toll-like receptor 3 0.98
• Toll-like receptor 13 0.93
• Toll-like receptor 4 0.92
• Toll-like receptor 4 0.92
• Toll-like receptor 4 0.92
• Toll-like receptor 4 0.91
• Toll-like receptor 4 0.91
• Toll-like receptor 4 0.91
• Toll-like receptor 4 0.91
• Toll-like receptor 4 0.90

Co-cited proteins · studied together in the literature

• Toll-like receptor 3 3 shared papers
• Tripartite motif-containing protein 3 1 shared papers
• E3 ubiquitin-protein ligase RNF170 1 shared papers
• TIR domain-containing adapter molecule 1 2 shared papers
• Tripartite motif-containing protein 3 1 shared papers
• TIR domain-containing adapter molecule 1 5 shared papers
• E3 ubiquitin-protein ligase ZNRF1 1 shared papers
• E3 ubiquitin-protein ligase ZNRF1 1 shared papers
• E3 ubiquitin-protein ligase RNF170 1 shared papers
• Protein unc-93 homolog B1 1 shared papers
• Toll-like receptor 2 3 shared papers
• Toll-like receptor 5 2 shared papers

Literature · 28 cited papers

• The Src-ZNRF1 axis controls TLR3 trafficking and interferon responses to limit lung barrier damage. J. Exp. Med. · 2023
• Cryo-EM structures of Toll-like receptors in complex with UNC93B1. Nat. Struct. Mol. Biol. · 2021
• Inborn errors of type I IFN immunity in patients with life-threatening COVID-19. Science · 2020
• Ubiquitination of TLR3 by TRIM3 signals its ESCRT-mediated trafficking to the endolysosomes for innate antiviral response. Proc. Natl. Acad. Sci. U.S.A. · 2020
• E3 ubiquitin ligase RNF170 inhibits innate immune responses by targeting and degrading TLR3 in murine cells. Cell. Mol. Immunol. · 2020
• WDFY1 mediates TLR3/4 signaling by recruiting TRIF. EMBO Rep. · 2015
• Cleavage of Toll-like receptor 3 by cathepsins B and H is essential for signaling. Proc. Natl. Acad. Sci. U.S.A. · 2012
• Lateral clustering of TLR3:dsRNA signaling units revealed by TLR3ecd:3Fabs quaternary structure. J. Mol. Biol. · 2012
• A common polymorphism in TLR3 confers natural resistance to HIV-1 infection. J. Immunol. · 2012
• Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry. J. Proteome Res. · 2009
• Natural selection in the TLR-related genes in the course of primate evolution. Immunogenetics · 2008
• Toll-like receptor 3 and geographic atrophy in age-related macular degeneration. N. Engl. J. Med. · 2008
• … and 16 more in the literature graph