Homo sapiens Gene: TLR3
Summary
InnateDB Gene IDBG-47294.6
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol TLR3
Gene Name toll-like receptor 3
Synonyms CD283; IIAE2;
Species Homo sapiens
Ensembl Gene ENSG00000164342
Encoded Proteins
toll-like receptor 3
toll-like receptor 3
toll-like receptor 3
Protein Structure
Useful resources Stemformatics EHFPI ImmGen
InnateDB Annotation
Summary
TLR3-type II IFN signalling cooperates with the RIG-I/MDA5-type I IFN axes for efficient innate antiviral immune responses.
TLR3-dependent antiviral pathway is negatively regulated by activated F2RL1 leading to blunted expression of TLR3/IRF3 driven genes, as well as activation of IRF3 and STAT1.
TLR3, TLR2, or TLR4 cooperate with proteinase-activated receptors (PARs) for activation of nuclear factor-kappaB-dependent signalling in mucosal epithelial cell lines.
TLR3-induced proapoptotic signalling involves TICAM1 (TRIF)-dependent activation of CASP8 and is under the control of inhibitor of apoptosis proteins (IAPs) in melanoma cells.
TLR3 is activated by poly(I:C) and this induces cytokine production through a signalling pathway dependent on MyD88.
TLR3-mediated activation of NF-kappaB and IRF3 diverges at Toll-IL-1 receptor domain-containing adapter 1 (TICAM1) inducing IFN-beta.
TLR3 dimerizes when it binds dsRNA and this is essential for ligand binding. Although the three TLR3 contact sites individually interact weakly with their binding partners, together they form a high affinity ligand-receptor complex.
TLR3 deletion dramatically enhanced the development of elastic lamina damage after collar-induced injury, indicating that TLR3 signalling plays a protective role in arterial vessel wall.
TLR3 activation by Poly(I:C) in the endothelial cells induces Poly(I:C) dose- and time-dependent cell apoptosis. Specifically, TLR3 stimulation triggered the signalling of both extrinsic and intrinsic apoptotic pathways.
TLR3 requires proteolytic processing in endolysosome by asparagine endopeptidase and cathepsin in the endolysosome to initiate signalling in response to DNA. (Demonstrated in murine model)
TLR3 expression is inducible by LPS via TLR4-MYD88-IRAK-TRAF6-NFKB dependent signalling pathway.
TLR3 is necessary to establish an antiviral state in hepatocytes infected with hepatitis C Virus. HCV envelope proteins counteract the antiviral host defence by inhibiting the expression of TLR3.
TLR3 signalling is enhanced by the presence of viral double-strand RNA-binding proteins.
TLR3-TICAM1-mediated signalling pathway plays an essential role in the anti-viral response against poliovirus infection. (Demonstrated in mice)
TLR3 is constitutively expressed in spermatogonia and spermatocytes, and has the ability to activate anti-viral responses. (Demonstrated in mice)
Upon engagement with its ligand, dsRNA, TLR3 possesses the ability to recruit CASP8 and RIPK1 to induce apoptosis.
Activation of TLR3 with poly(I:C) mediates antiviral immunity that diminishes coronavirus production in macrophages. (Demonstrated in mice)
Upregulation of TLR3 in intestinal epithelia during infancy may contribute to age-dependent susceptibility to rotavirus infection. (Demonstrated in mice)
TLR3 activation differentially regulates phagocytosis of bacteria and apoptotic neutrophils by peritoneal macrophages. (Demonstrated in mice)
TLR3 is more efficiently activated by high molecular mass than by low molecular weight poly(I:C).
TLR3-mediated antibody response to Chikungunya virus plays a key role in its infection, replication and pathology.
Intracellular/endocytic TLR3 interacts with SCARF 1 in the presence of Poly I:C to boost TLR3-mediated inflammatory signalling and stimulate cytokine production in macrophages.
Signalling through both DDX58 and TLR3 is important for interferon induction by influenza A virus in alveolar epithelial cells.
Bluetongue virus activates TLR3/interferons signalling pathway resulting in the inhibition of human immunodeficiency virus in macrophages.
InnateDB Annotation from Orthologs
Summary
[Mus musculus] Tlr3 deletion dramatically enhanced the development of elastic lamina damage after collar-induced injury, indicating that Tlr3 signalling plays a protective role in arterial vessel wall.
[Mus musculus] Tlr3 activation by Poly(I:C) in the endothelial cells induces Poly(I:C) dose- and time-dependent cell apoptosis. Specifically, Tlr3 stimulation triggered the signalling of both extrinsic and intrinsic apoptotic pathways.
[Mus musculus] Tlr3 requires proteolytic processing in endolysosome by asparagine endopeptidase and cathepsin in the endolysosome to initiate signalling in response to DNA.
[Mus musculus] Tlr3 expression is inducible by LPS via Tlr4-Myd88-Irak-Traf6-NfkB dependent signalling pathway. (Demonstrated in human)
[Mus musculus] Tlr3 is necessary to establish an antiviral state in hepatocytes infected with hepatitis C Virus. HCV envelope proteins counteract the antiviral host defence by inhibiting the expression of Tlr3. (Demonstrated in human)
[Mus musculus] TLR3 signalling is enhanced by the presence of viral double-strand RNA-binding proteins. (Demonstrated in human)
[Mus musculus] Tlr3-Ticam1-mediated signalling pathway plays an essential role in the anti-viral response against poliovirus infection.
[Mus musculus] Tlr3 is constitutively expressed in spermatogonia and spermatocytes, and has the ability to activate anti-viral responses.
[Mus musculus] Upon engagement with its ligand, dsRNA, Tlr3 possesses the ability to recruit Casp8 and Ripk1 to induce apoptosis. (Demonstrated in human)
[Mus musculus] Activation of Tlr3 with poly(I:C) mediates antiviral immunity that diminishes coronavirus production in macrophages.
[Mus musculus] Upregulation of Tlr3 in intestinal epithelia during infancy may contribute to age-dependent susceptibility to rotavirus infection.
[Mus musculus] TLR3 activation differentially regulates phagocytosis of bacteria and apoptotic neutrophils by peritoneal macrophages.
[Mus musculus] Tlr3 contributes to the control of activated endogenous retroviruses (ERVs) and ERV-induced tumours.
[Mus musculus] Wdfy1 is a crucial adaptor protein in the Tlr3/4 signalling pathway. Wdfy1 interacts with Tlr3 and Tlr4 and mediates the recruitment of Ticam1 to these receptors.
Entrez Gene
Summary 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]
Gene Information
Type Protein coding
Genomic Location Chromosome 4:186069152-186088069
Strand Forward strand
Band q35.1
Transcripts
ENST00000296795 ENSP00000296795
ENST00000513189 ENSP00000423386
ENST00000512264
ENST00000504367 ENSP00000423684
ENST00000508051
Interactions
Number of Interactions This gene and/or its encoded proteins are associated with 42 experimentally validated interaction(s) in this database.
They are also associated with 7 interaction(s) predicted by orthology.
Experimentally validated
Total 42 [view]
Protein-Protein 38 [view]
Protein-DNA 4 [view]
Protein-RNA 0
DNA-DNA 0
RNA-RNA 0
DNA-RNA 0
Predicted by orthology
Total 7 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0003725 double-stranded RNA binding
GO:0004872 receptor activity
GO:0004888 transmembrane signaling receptor activity
GO:0005515 protein binding
Biological Process
GO:0001774 microglial cell activation
GO:0001934 positive regulation of protein phosphorylation
GO:0002224 toll-like receptor signaling pathway
GO:0002282 microglial cell activation involved in immune response
GO:0002756 MyD88-independent toll-like receptor signaling pathway
GO:0006952 defense response
GO:0006954 inflammatory response
GO:0006972 hyperosmotic response
GO:0007165 signal transduction
GO:0007249 I-kappaB kinase/NF-kappaB signaling
GO:0007250 activation of NF-kappaB-inducing kinase activity
GO:0007252 I-kappaB phosphorylation
GO:0008584 male gonad development
GO:0009597 detection of virus
GO:0009615 response to virus
GO:0032481 positive regulation of type I interferon production
GO:0032722 positive regulation of chemokine 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:0032760 positive regulation of tumor necrosis factor production
GO:0034123 positive regulation of toll-like receptor signaling pathway
GO:0034138 toll-like receptor 3 signaling pathway
GO:0034142 toll-like receptor 4 signaling pathway
GO:0034346 positive regulation of type III interferon production
GO:0035458 cellular response to interferon-beta
GO:0035666 TRIF-dependent toll-like receptor signaling pathway
GO:0035690 cellular response to drug
GO:0042346 positive regulation of NF-kappaB import into nucleus
GO:0042742 defense response to bacterium
GO:0043065 positive regulation of apoptotic process
GO:0043123 positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0043330 response to exogenous dsRNA
GO:0043331 response to dsRNA
GO:0045078 positive regulation of interferon-gamma biosynthetic process
GO:0045080 positive regulation of chemokine biosynthetic process
GO:0045087 innate immune response (InnateDB)
GO:0045356 positive regulation of interferon-alpha biosynthetic process
GO:0045359 positive regulation of interferon-beta biosynthetic process
GO:0045671 negative regulation of osteoclast differentiation
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0046330 positive regulation of JNK cascade
GO:0050729 positive regulation of inflammatory response
GO:0051092 positive regulation of NF-kappaB transcription factor activity
GO:0051607 defense response to virus
GO:0071260 cellular response to mechanical stimulus
GO:0071346 cellular response to interferon-gamma
GO:0071359 cellular response to dsRNA
GO:0071360 cellular response to exogenous dsRNA
GO:0097191 extrinsic apoptotic signaling pathway
GO:0097527 necroptotic signaling pathway
Cellular Component
GO:0000139 Golgi membrane
GO:0005622 intracellular
GO:0005737 cytoplasm
GO:0005765 lysosomal membrane
GO:0005789 endoplasmic reticulum membrane
GO:0005887 integral component of plasma membrane
GO:0009986 cell surface
GO:0010008 endosome membrane
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0036020 endolysosome membrane
Orthologs
Species
Mus musculus
Bos taurus
Gene ID
Gene Order
Method
Confidence
Comments
SSD Ortholog
Ortholog supports species divergence
Not yet available
SSD Ortholog
Ortholog supports species divergence
Pathways
NETPATH
REACTOME
RIP-mediated NFkB activation via ZBP1 pathway
Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon pathway
TRIF-mediated programmed cell death pathway
ZBP1(DAI) mediated induction of type I IFNs pathway
Innate Immune System pathway
IKK complex recruitment mediated by RIP1 pathway
Toll Like Receptor 3 (TLR3) Cascade pathway
Toll-Like Receptors Cascades pathway
TRAF6 mediated induction of TAK1 complex pathway
Immune System pathway
Trafficking and processing of endosomal TLR pathway
MyD88-independent cascade pathway
Toll Like Receptor 4 (TLR4) Cascade pathway
Activated TLR4 signalling pathway
TRIF-mediated TLR3/TLR4 signaling pathway
Cytosolic sensors of pathogen-associated DNA pathway
KEGG
Toll-like receptor signaling pathway pathway
Hepatitis C pathway
INOH
PID BIOCARTA
Toll-like receptor pathway [Biocarta view]
PID NCI
Endogenous TLR signaling
Cross-References
SwissProt
TrEMBL
UniProt Splice Variant
Entrez Gene
UniGene Hs.657724
RefSeq NM_003265 XM_006714294
HUGO
OMIM
CCDS CCDS3846
HPRD 04324
IMGT
EMBL
GenPept
RNA Seq Atlas