TLR3

The protein encoded by this gene is a member of the Toll-like receptor (TLR) family which plays a fundamental role in pathogen recognition and activation of innate immunity. TLRs are highly conserved from Drosophila to humans and share structural and functional similarities. They recognize pathogen-associated molecular patterns (PAMPs) that are expressed on infectious agents, and mediate the production of cytokines necessary for the development of effective immunity. The various TLRs exhibit different patterns of expression. This receptor is most abundantly expressed in placenta and pancreas, and is restricted to the dendritic subpopulation of the leukocytes. It recognizes dsRNA associated with viral infection, and induces the activation of NF-kappaB and the production of type I interferons. It may thus play a role in host defense against viruses. Use of alternative polyadenylation sites to generate different length transcripts has been noted for this gene. [provided by RefSeq, Jul 2008]

TLR3 Gene(Protein Coding) Toll Like Receptor 3

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.

Biological Process activation of NF-kappaB-inducing kinase activitySource:UniProtKB1 Publication
Biological Process cellular response to exogenous dsRNASource:Ensembl
Biological Process cellular response to interferon-betaSource:Ensembl
Biological Process cellular response to interferon-gammaSource:Ensembl
Biological Process cellular response to mechanical stimulusSource:UniProtKB1 Publication
Biological Process cellular response to virusSource:Ensembl
Biological Process cellular response to xenobiotic stimulusSource:Ensembl
Biological Process defense response to bacteriumSource:ProtInc1 Publication
Biological Process defense response to virusSource:ARUK-UCL1 Publication
Biological Process detection of virusSource:UniProtKB1 Publication
Biological Process extrinsic apoptotic signaling pathwaySource:UniProtKB1 Publication
Biological Process hyperosmotic responseSource:UniProtKB1 Publication
Biological Process I-kappaB phosphorylationSource:BHF-UCL1 Publication
Biological Process innate immune responseSource:BHF-UCL1 Publication
Biological Process JNK cascadeSource:Ensembl
Biological Process male gonad developmentSource:Ensembl
Biological Process microglial cell activationSource:Ensembl
Biological Process MyD88-independent toll-like receptor signaling pathwaySource:InterPro
Biological Process necroptotic signaling pathwaySource:UniProtKB1 Publication
Biological Process negative regulation of osteoclast differentiationSource:UniProtKB1 Publication
Biological Process positive regulation of angiogenesisSource:Ensembl
Biological Process positive regulation of apoptotic processSource:Ensembl
Biological Process positive regulation of chemokine productionSource:BHF-UCL1 Publication
Biological Process positive regulation of gene expressionSource:UniProtKB2 Publications
Biological Process positive regulation of I-kappaB kinase/NF-kappaB signalingSource:Ensembl
Biological Process positive regulation of inflammatory responseSource:BHF-UCL1 Publication
Biological Process positive regulation of interferon-alpha productionSource:UniProtKB1 Publication
Biological Process positive regulation of interferon-beta productionSource:UniProtKB1 Publication
Biological Process positive regulation of interferon-gamma productionSource:UniProtKB1 Publication
Biological Process positive regulation of interleukin-12 productionSource:BHF-UCL
Biological Process positive regulation of interleukin-6 productionSource:BHF-UCL1 Publication
Biological Process positive regulation of interleukin-8 productionSource:BHF-UCL1 Publication
Biological Process positive regulation of JNK cascadeSource:Ensembl
Biological Process positive regulation of macrophage cytokine productionSource:Ensembl
Biological Process positive regulation of NF-kappaB transcription factor activitySource:Ensembl
Biological Process positive regulation of NIK/NF-kappaB signalingSource:BHF-UCL1 Publication
Biological Process positive regulation of toll-like receptor signaling pathwaySource:BHF-UCL1 Publication
Biological Process positive regulation of transcription by RNA polymerase IISource:BHF-UCL
Biological Process positive regulation of tumor necrosis factor productionSource:BHF-UCL
Biological Process positive regulation of type III interferon productionSource:Ensembl
Biological Process regulation of dendritic cell cytokine productionSource:Ensembl
Biological Process response to dsRNASource:GO_Central1 Publication
Biological Process response to exogenous dsRNASource:MGI1 Publication
Biological Process signal transductionSource:ProtInc2 Publications
Biological Process toll-like receptor 3 signaling pathwaySource:InterPro
Biological Process type III interferon productionSource:Ensembl

Endoplasmic reticulum membrane
Endosome membrane
Early endosome

Immunodeficiency 83, susceptibility to viral infections (IMD83):
An immunologic disorder characterized by increased susceptibility to severe viral infections, including herpes simplex virus (HSV), varicella zoster virus (VZV), influenza A virus (IAV), hantavirus, and possibly respiratory syncytial virus (RSV). IMD83 clinical manifestations include acute infection-induced encephalitis and pneumonitis. The susceptibility to encephalitis or pneumonitis appears to result from impaired TLR3-dependent interferon production by nonhematopoietic cells that reside within the central nervous system or lung epithelial cells. IMD83 transmission pattern is consistent with autosomal dominant or autosomal recessive inheritance with incomplete penetrance.

Lumenal: 24-704
Helical: 705-725
Cytoplasmic: 726-904

Heavily N-glycosylated, except on that part of the surface of the ectodomain that is involved in ligand binding.
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.