InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Gene: Tlr3

Summary

InnateDB Gene

IDBG-152685.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

Tlr3

Gene Name

toll-like receptor 3

Synonyms

Species

Mus musculus

Ensembl Gene

ENSMUSG00000031639

Encoded Proteins

IDBP-152687

toll-like receptor 3

IDBP-619675

toll-like receptor 3

Protein Structure

Useful resources

Stemformatics EHFPI ImmGen

InnateDB Annotation

Summary

PMID 21220319

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.

PMID 21367858

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.

PMID 21402738

Tlr3 requires proteolytic processing in endolysosome by asparagine endopeptidase and cathepsin in the endolysosome to initiate signalling in response to DNA.

PMID 21498625

Tlr3 expression is inducible by LPS via Tlr4-Myd88-Irak-Traf6-NfkB dependent signalling pathway. (Demonstrated in human)

PMID 21695051

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)

PMID 22016778

TLR3 signalling is enhanced by the presence of viral double-strand RNA-binding proteins. (Demonstrated in human)

PMID 22072781

Tlr3-Ticam1-mediated signalling pathway plays an essential role in the anti-viral response against poliovirus infection.

PMID 22262694

Tlr3 is constitutively expressed in spermatogonia and spermatocytes, and has the ability to activate anti-viral responses.

PMID 22421964

Upon engagement with its ligand, dsRNA, Tlr3 possesses the ability to recruit Casp8 and Ripk1 to induce apoptosis. (Demonstrated in human)

PMID 22754655

Activation of Tlr3 with poly(I:C) mediates antiviral immunity that diminishes coronavirus production in macrophages.

PMID 22570612

Upregulation of Tlr3 in intestinal epithelia during infancy may contribute to age-dependent susceptibility to rotavirus infection.

PMID 22986631

TLR3 activation differentially regulates phagocytosis of bacteria and apoptotic neutrophils by peritoneal macrophages.

PMID 23142781

Tlr3 contributes to the control of activated endogenous retroviruses (ERVs) and ERV-induced tumours.

PMID 25736436

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.

InnateDB Annotation from Orthologs

Summary

PMID 19074283

[Homo sapiens] TLR3-type II IFN signalling cooperates with the RIG-I/MDA5-type I IFN axes for efficient innate antiviral immune responses.

PMID 19865078

[Homo sapiens] 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.

PMID 19865078

[Homo sapiens] TLR3, TLR2, or TLR4 cooperate with proteinase-activated receptors (PARs) for activation of nuclear factor-kappaB-dependent signalling in mucosal epithelial cell lines.

PMID 20019748

[Homo sapiens] 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.

PMID 11607032

[Homo sapiens] TLR3 is activated by poly(I:C) and this induces cytokine production through a signalling pathway dependent on MyD88.

PMID 14982987

[Homo sapiens] TLR3-mediated activation of NF-kappaB and IRF3 diverges at Toll-IL-1 receptor domain-containing adapter 1 (TICAM1) inducing IFN-beta.

PMID 20861016

[Homo sapiens] 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.

PMID 21220319

[Homo sapiens] 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.

PMID 21367858

[Homo sapiens] 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.

PMID 21402738

[Homo sapiens] 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)

PMID 21498625

[Homo sapiens] TLR3 expression is inducible by LPS via TLR4-MYD88-IRAK-TRAF6-NFKB dependent signalling pathway.

PMID 21695051

[Homo sapiens] 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.

PMID 22016778

[Homo sapiens] TLR3 signalling is enhanced by the presence of viral double-strand RNA-binding proteins.

PMID 22072781

[Homo sapiens] TLR3-TICAM1-mediated signalling pathway plays an essential role in the anti-viral response against poliovirus infection. (Demonstrated in mice)

PMID 22262694

[Homo sapiens] TLR3 is constitutively expressed in spermatogonia and spermatocytes, and has the ability to activate anti-viral responses. (Demonstrated in mice)

PMID 22421964

[Homo sapiens] Upon engagement with its ligand, dsRNA, TLR3 possesses the ability to recruit CASP8 and RIPK1 to induce apoptosis.

PMID 22754655

[Homo sapiens] Activation of TLR3 with poly(I:C) mediates antiviral immunity that diminishes coronavirus production in macrophages. (Demonstrated in mice)

PMID 22570612

[Homo sapiens] Upregulation of TLR3 in intestinal epithelia during infancy may contribute to age-dependent susceptibility to rotavirus infection. (Demonstrated in mice)

PMID 22986631

[Homo sapiens] TLR3 activation differentially regulates phagocytosis of bacteria and apoptotic neutrophils by peritoneal macrophages. (Demonstrated in mice)

PMID 23035017

[Homo sapiens] TLR3 is more efficiently activated by high molecular mass than by low molecular weight poly(I:C).

PMID 25452586

[Homo sapiens] TLR3-mediated antibody response to Chikungunya virus plays a key role in its infection, replication and pathology.

PMID 25641411

[Homo sapiens] 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.

PMID 25880109

[Homo sapiens] Signalling through both DDX58 and TLR3 is important for interferon induction by influenza A virus in alveolar epithelial cells.

PMID 26296370

[Homo sapiens] Bluetongue virus activates TLR3/interferons signalling pathway resulting in the inhibition of human immunodeficiency virus in macrophages.

Entrez Gene

Summary

This gene does not have any Entrez summary - the following is the summary from its human ortholog ENSG00000164342:
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 8:45395665-45410608

Strand

Reverse strand

Band

B1.1

Transcripts

ENSMUST00000034056	ENSMUSP00000034056
ENSMUST00000167106	ENSMUSP00000126556

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 13 experimentally validated interaction(s) in this database.
They are also associated with 28 interaction(s) predicted by orthology.

Experimentally validated
Total	13 [view]
Protein-Protein	10 [view]
Protein-DNA	3 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	28 [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:0007165	signal transduction
GO:0007252	I-kappaB phosphorylation
GO:0008584	male gonad development
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:0034346	positive regulation of type III interferon production
GO:0035458	cellular response to interferon-beta
GO:0035690	cellular response to drug
GO:0042346	positive regulation of NF-kappaB import into nucleus
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: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:0052033	pathogen-associated molecular pattern dependent induction by symbiont of host innate immune response
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:0005622	intracellular
GO:0005737	cytoplasm
GO:0005765	lysosomal membrane
GO:0005789	endoplasmic reticulum membrane
GO:0009986	cell surface
GO:0010008	endosome membrane
GO:0016021	integral component of membrane