InnateDB: Systems Biology of the Innate Immune Response

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

IDBP-47296

toll-like receptor 3

IDBP-478741

toll-like receptor 3

IDBP-477976

toll-like receptor 3

Protein Structure

Useful resources

Stemformatics EHFPI ImmGen

InnateDB Annotation

Summary

PMID 19074283

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

PMID 19865078

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

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

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

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

PMID 14982987

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

PMID 20861016

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

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. (Demonstrated in murine model)

PMID 21498625

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

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.

PMID 22016778

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

PMID 22072781

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

PMID 22262694

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

PMID 22421964

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

PMID 22754655

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

PMID 22570612

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

PMID 22986631

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

PMID 23035017

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

PMID 25452586

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

PMID 25641411

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

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

PMID 26296370

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

InnateDB Annotation from Orthologs

Summary

PMID 21220319

[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.

PMID 21367858

[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.

PMID 21402738

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

PMID 21498625

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

PMID 21695051

[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)

PMID 22016778

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

PMID 22072781

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

PMID 22262694

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

PMID 22421964

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

PMID 22754655

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

PMID 22570612

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

PMID 22986631

[Mus musculus] TLR3 activation differentially regulates phagocytosis of bacteria and apoptotic neutrophils by peritoneal macrophages.

PMID 23142781

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

PMID 25736436

[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

ENSMUSG00000031639

View Gene Order

ENSBTAG00000008682

Not yet available

Pathways

NETPATH

REACTOME

REACT_118563

RIP-mediated NFkB activation via ZBP1 pathway

REACT_118764

ZBP1(DAI) mediated induction of type I IFNs pathway

REACT_25351

TRAF6 mediated induction of TAK1 complex pathway

REACT_25374

IKK complex recruitment mediated by RIP1 pathway

REACT_25148

Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon pathway

REACT_150361

TRIF-mediated programmed cell death pathway

REACT_6809

MyD88-independent cascade pathway

REACT_6783

Toll Like Receptor 3 (TLR3) Cascade pathway

REACT_6894

Toll Like Receptor 4 (TLR4) Cascade pathway

REACT_118632

Trafficking and processing of endosomal TLR pathway

REACT_6802

Innate Immune System pathway

REACT_6966

Toll-Like Receptors Cascades pathway

REACT_6900

Immune System pathway

REACT_6890

Activated TLR4 signalling pathway

REACT_25281

TRIF-mediated TLR3/TLR4 signaling pathway

REACT_118823

Cytosolic sensors of pathogen-associated DNA pathway

KEGG

hsa04620

Toll-like receptor signaling pathway pathway

hsa05160

Hepatitis C pathway

INOH

PID NCI

toll_endogenous_pathway

Endogenous TLR signaling

Cross-References

SwissProt

O15455

TrEMBL

Q1KMK2

UniProt Splice Variant

Entrez Gene

7098

UniGene

Hs.657724

RefSeq

NM_003265 XM_006714294

HUGO

HGNC:11849

OMIM

603029

CCDS

CCDS3846

HPRD

04324

IMGT

EMBL

AB445631 AC104070 AK302143 AK314208 BC094737 BC096333 BC096334 BC096335 CH471056 DQ360814 DQ360815 DQ360816 DQ445682 DQ470075 DQ470076 DQ470077 DQ470078 DQ470079 U88879

GenPept

AAC34134 AAH94737 AAH96333 AAH96334 AAH96335 ABC86908 ABC86909 ABC86910 ABE01399 ABF06633 ABF06634 ABF06635 ABF06636 ABF06637 BAG36884 BAG55028 BAH13636 EAX04628

RNA Seq Atlas

7098