TLR3 toll-like receptor 3 [Homo sapiens (human)] - Gene

Summary

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Official Symbol: TLR3provided by HGNC
Official Full Name: toll-like receptor 3provided by HGNC
Primary source: HGNC:11849
See related: Ensembl:ENSG00000164342; HPRD:04324; MIM:603029; Vega:OTTHUMG00000160345
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: CD283; IIAE2
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]

Genomic context

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Location :: 4q35

Sequence :: Chromosome: 4; NC_000004.11 (186990309..187006252)

See TLR3 in Epigenomics, MapViewer

Chromosome 4 - NC_000004.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

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Go to reference sequence details

Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

Liver expression of TLR2, TLR3 and TLR7, which are more involved in the immune-pathogenesis of chronic hepatitis C, was investigated.
Title: In vivo liver expression of TLR2, TLR3 and TLR7 in chronic hepatitis C.
TLR3 expression was not associated with prognosis in cutaneous malignant melanoma.
Title: Expression of TLR3, 4, 7 and 9 in cutaneous malignant melanoma: relationship with clinicopathological characteristics and prognosis.
The expression of TLR3 in decidual natural killer cells is abnormally higher in unexplained recurrent spontaneous miscarriage patients.
Title: Increased expression of Toll-like receptor 3 in decidual natural killer cells of patients with unexplained recurrent spontaneous miscarriage.
Negative regulation of the IRAK1 kinase TLR3-interferon (IFN)-beta and proinflammatory cytokine response includes roles for IRAK1 and IKKepsilon in limiting the intensity of the TLR3-NF-kappaB-signaling pathway as well as IRAK1-IKKepsilon-TAK1-directed regulatory mechanism.
Title: A novel IRAK1-IKKε signaling axis limits the activation of TAK1-IKKβ downstream of TLR3.
A single nucleotide polymorphism in the promoter region of TLR-3 is associated with elevated TLR-3 gene expression and susceptibility to knee osteoarthritis in a Chinese Han population.
Title: Association of a functional polymorphism in the promoter region of TLR-3 with osteoarthritis: a two-stage case-control study.
TRIM38 may act as a novel negative regulator for TLR3-mediated type I interferon signaling by targeting TRIF for degradation
Title: TRIM38 negatively regulates TLR3-mediated IFN-β signaling by targeting TRIF for degradation.
There is a close relationship between the presence of TLR3 rs5743313/CT and an increased risk of pneumonia in children infected by the pandemic A/H1N1/2009 influenza virus.
Title: Toll-like receptor 3 gene polymorphisms and severity of pandemic A/H1N1/2009 influenza in otherwise healthy children.
TNFA significantly enhanced the TLR3-dependent induction of MMP-9 in human mesangial cells.
Title: TNFα enhances TLR3-dependent effects on MMP-9 expression in human mesangial cells.
Data suggest that adrenocortical cells express functional TLR3; stimulation through TLR3 may serve to synergistically enhance production of proinflammatory chemokine CXCL10 in such cells.
Title: Induction of CXCL10 chemokine in adrenocortical cells by stimulation through toll-like receptor 3.
these analyses revealed that although IL-8 and MCP-1 gene inductions depended on TLR3 the downstream signalling pathways were distinct.
Title: Double-stranded RNA induces IL-8 and MCP-1 gene expression via TLR3 in HaCaT-keratinocytes.

Submit: New GeneRIF Correction See all (285)

Phenotypes

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Review eQTL and phenotype association data in this region using PheGenI

Congenital human immunodeficiency virus

MIM: 609423

Genetic Testing Registry

Interactions

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Products	Interactant	Other Gene	Source	Pubs	Description
O15455	P08571	CD14	HPRD	PubMed
O15455	P41240	CSK	HPRD	PubMed
O15455	Q99836	MYD88	HPRD	PubMed
O15455	TRIAD3	RNF216	HPRD	PubMed
O15455	Toll-like receptor adaptor molecule 1	TICAM1	HPRD	PubMed
O15455	Toll like receptor adaptor molecule 2	TICAM2	HPRD	PubMed
O15455	O15455	TLR3	HPRD	PubMed
O15455	Q9Y4K3	TRAF6	HPRD	PubMed
BioGRID:112953	BioGRID:109865	IRAK2	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112953	BioGRID:111594	MAP2K6	BioGRID	PubMed	Biochemical Activity
BioGRID:112953	BioGRID:112748	MAP3K7	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112953	BioGRID:110700	MYD88	BioGRID	PubMed	Reconstituted Complex
BioGRID:112953	BioGRID:114274	RIPK1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112953	BioGRID:119981	RNF216	BioGRID	PubMed	Two-hybrid
BioGRID:112953	BioGRID:116740	TAB2	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112953	BioGRID:118878	TBK1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112953	BioGRID:127114	TICAM1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112953	BioGRID:119978	TOLLIP	BioGRID	PubMed	Affinity Capture-MS
BioGRID:112953	BioGRID:113039	TRAF3	BioGRID	PubMed	Affinity Capture-MS
BioGRID:112953	BioGRID:113041	TRAF6	BioGRID	PubMed	Affinity Capture-Western
BioGRID:112953	BioGRID:126654	TRIM69	BioGRID	PubMed	Affinity Capture-Western

Pathways from BioSystems

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Activated TLR4 signalling, organism-specific biosystem (from REACTOME)
Activated TLR4 signalling, organism-specific biosystemTLR4 is unique among the TLR family in its ability to recruit four adapters to activate two distinct signaling pathways. One pathway is activated by the pair of the adapters Mal or TIRAP (Toll/inter...
Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon, organism-specific biosystem (from REACTOME)
Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon, organism-specific biosystemCell stimulation with viral ds RNA leads to the activation of two IKK-related serine/threonine kinases, TBK1 and IKK-i which directly phosphorylate IRF3 and IRF7 promoting their dimerization and tran...
Cytosolic sensors of pathogen-associated DNA, organism-specific biosystem (from REACTOME)
Cytosolic sensors of pathogen-associated DNA, organism-specific biosystemPresence of pathogen-associated DNA in cytosol induces type I IFN production. Several intracellular receptors have been implicated to some degree. These include DNA-dependent activator of interferon ...
DAI mediated induction of type I IFNs, organism-specific biosystem (from REACTOME)
DAI mediated induction of type I IFNs, organism-specific biosystemDNA-dependent activator of IFN-regulatory factors (DAI), also known as Z-DNA-binding protein-1 (ZBP-1), was reported to initiate innate immune responses in murine L929 cells upon stimulation by multi...
Hepatitis B, organism-specific biosystem (from KEGG)
Hepatitis B, organism-specific biosystemHepatitis B virus (HBV) is an enveloped virus and contains a partially double-stranded relaxed circular DNA (RC-DNA) genome. After entry into hepatocytes, HBV RC-DNA is transported to the nucleus and...
Hepatitis C, organism-specific biosystem (from KEGG)
Hepatitis C, organism-specific biosystemHepatitis C virus (HCV) is a major cause of chronic liver disease. The HCV employ several strategies to perturb host cell immunity. After invasion, HCV RNA genome functions directly as an mRNA in the...
Hepatitis C, conserved biosystem (from KEGG)
Hepatitis C, conserved biosystemHepatitis C virus (HCV) is a major cause of chronic liver disease. The HCV employ several strategies to perturb host cell immunity. After invasion, HCV RNA genome functions directly as an mRNA in the...
Herpes simplex infection, organism-specific biosystem (from KEGG)
Herpes simplex infection, organism-specific biosystemHerpes simplex virus (HSV) infections are very common worldwide, with the prevalence of HSV-1 reaching up to 80%-90%. Primary infection with HSV takes place in the mucosa, followed by the establishme...
Herpes simplex infection, conserved biosystem (from KEGG)
Herpes simplex infection, conserved biosystemHerpes simplex virus (HSV) infections are very common worldwide, with the prevalence of HSV-1 reaching up to 80%-90%. Primary infection with HSV takes place in the mucosa, followed by the establishme...
IKK complex recruitment mediated by RIP1, organism-specific biosystem (from REACTOME)
IKK complex recruitment mediated by RIP1, organism-specific biosystemReceptor-interacting protein 1 (RIP1) mediates the activation of proinflammatory cytokines via intermediate induction of IKK complex in NFkB pathways [Ea et al. 2006]. Poly(I-C) treatment stimulated ...
Immune System, organism-specific biosystem (from REACTOME)
Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
Influenza A, organism-specific biosystem (from KEGG)
Influenza A, organism-specific biosystemInfluenza is a contagious respiratory disease caused by influenza virus infection. Influenza A virus is responsible for both annual seasonal epidemics and periodic worldwide pandemics. Novel strains ...
Influenza A, conserved biosystem (from KEGG)
Influenza A, conserved biosystemInfluenza is a contagious respiratory disease caused by influenza virus infection. Influenza A virus is responsible for both annual seasonal epidemics and periodic worldwide pandemics. Novel strains ...
Innate Immune System, organism-specific biosystem (from REACTOME)
Innate Immune System, organism-specific biosystemInnate immunity encompases the nonspecific part of immunity tha are part of an individual's natural biologic makeup
MyD88-independent cascade, organism-specific biosystem (from REACTOME)
MyD88-independent cascade, organism-specific biosystemMyD88-independent signaling route utilizes TRAM and TRIF adapters, that are essential for production of both type 1 interferons(IFNs) and pro-inflammatory cytokines. TRAM is thought to bridge between...
RIP-mediated NFkB activation via DAI, organism-specific biosystem (from REACTOME)
RIP-mediated NFkB activation via DAI, organism-specific biosystemOverexpression of human or murine DAI in human embryonic kidney 293T cells (HEK293T) activated NF-kB-dependent promoter in a dose-dependent manner. Two RHIM-contaning kinases RIP1 and RIP3 are implic...
TRAF6 mediated induction of TAK1 complex, organism-specific biosystem (from REACTOME)
TRAF6 mediated induction of TAK1 complex, organism-specific biosystemIn human, together with ubiquitin-conjugating E2-type enzymes UBC13 and UEV1A (also known as UBE2V1), TRAF6 catalyses Lys63-linked ubiquitination. It is believed that auto polyubiquitination and oli...
TRIF-mediated TLR3/TLR4 signaling, organism-specific biosystem (from REACTOME)
TRIF-mediated TLR3/TLR4 signaling, organism-specific biosystemTRIF was shown to induce IRF3/7 and NF-?B activation and apoptosis through distinct intracellular signaling pathways [Han KJ et al 2004; Kaiser WJ and Offermann MK et al 2005]. TRIF consists of an N...
TRIF-mediated programmed cell death, organism-specific biosystem (from REACTOME)
TRIF-mediated programmed cell death, organism-specific biosystemTLR3 and -4 trigger TRIF-dependent programmed cell death in various human and mouse cells [Kalai M et al 2002; Han KJ et al 2004; Kaiser WJ and Offermann MK 2005; Estornes Y et al 2012; He S et al 20...
Toll Like Receptor 3 (TLR3) Cascade, organism-specific biosystem (from REACTOME)
Toll Like Receptor 3 (TLR3) Cascade, organism-specific biosystemToll-like receptor 3 (TLR3) as was shown for mammals is expressed on myeloid dendritic cells, respiratory epithelium, macrophages, and appears to play a central role in mediating the antiviral and in...
Toll Like Receptor 4 (TLR4) Cascade, organism-specific biosystem (from REACTOME)
Toll Like Receptor 4 (TLR4) Cascade, organism-specific biosystemToll-like Receptor 4 is a Microbe Associated Molecular Pattern receptor well known for it's sensitivity to Bacterial Lipopolysaccharides (LPS). LPS is assembled within diverse Gram-negative bacteria,...
Toll-Like Receptors Cascades, organism-specific biosystem (from REACTOME)
Toll-Like Receptors Cascades, organism-specific biosystemIn human, ten members of the Toll-like receptor (TLR) family (TLR1-TLR10) have been identified (TLR11 has been found in mouse, but not in human). All TLRs have a similar Toll/IL-1 receptor (TIR) doma...
Toll-like receptor signaling pathway, organism-specific biosystem (from KEGG)
Toll-like receptor signaling pathway, organism-specific biosystemSpecific families of pattern recognition receptors are responsible for detecting microbial pathogens and generating innate immune responses. Toll-like receptors (TLRs) are membrane-bound receptors id...
Toll-like receptor signaling pathway, organism-specific biosystem (from WikiPathways)
Toll-like receptor signaling pathway, organism-specific biosystemSpecific families of pattern recognition receptors are responsible for detecting microbial pathogens and generating innate immune responses. Toll-like receptors (TLRs) are membrane-bound receptors id...
Toll-like receptor signaling pathway, conserved biosystem (from KEGG)
Toll-like receptor signaling pathway, conserved biosystemSpecific families of pattern recognition receptors are responsible for detecting microbial pathogens and generating innate immune responses. Toll-like receptors (TLRs) are membrane-bound receptors id...
Trafficking and processing of endosomal TLR, organism-specific biosystem (from REACTOME)
Trafficking and processing of endosomal TLR, organism-specific biosystemMammalian TLR3, TLR7, TLR8, TLR9 are endosomal receptors that sense nucleic acids that have been released from endocytosed/phagocytosed bacteria, viruses or parasites. These TLRs have a ligand-recogn...

General gene information

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Markers

A009J16 (e-PCR)
- UniSTS:66831

D8S2279 (e-PCR)
- UniSTS:473907

D15S1477 (e-PCR)
- UniSTS:474482

G32577 (e-PCR)
- UniSTS:117160

PMC128073P4 (e-PCR)
- UniSTS:270566

Genotypes

See TLR3 SNP Geneview Report
See TLR3 SNP Genotype Report
See TLR3 SNP Variation Viewer Report

Homology

Homologs of the TLR3 gene: The TLR3 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, and zebrafish.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
double-stranded RNA binding	IDA Inferred from Direct Assay more info	PubMed
double-stranded RNA binding	NAS Non-traceable Author Statement more info	PubMed
receptor activity	TAS Traceable Author Statement more info	PubMed
transmembrane signaling receptor activity	NAS Non-traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
I-kappaB kinase/NF-kappaB cascade	TAS Traceable Author Statement more info
I-kappaB phosphorylation	IDA Inferred from Direct Assay more info	PubMed
MyD88-independent toll-like receptor signaling pathway	TAS Traceable Author Statement more info
TRIF-dependent toll-like receptor signaling pathway	TAS Traceable Author Statement more info
activation of NF-kappaB-inducing kinase activity	NAS Non-traceable Author Statement more info	PubMed
cellular response to mechanical stimulus	IEP Inferred from Expression Pattern more info	PubMed
defense response to bacterium	TAS Traceable Author Statement more info	PubMed
defense response to virus	TAS Traceable Author Statement more info	PubMed
detection of virus	NAS Non-traceable Author Statement more info	PubMed
hyperosmotic response	NAS Non-traceable Author Statement more info	PubMed
inflammatory response	IEA Inferred from Electronic Annotation more info
innate immune response	TAS Traceable Author Statement more info	PubMed
negative regulation of osteoclast differentiation	NAS Non-traceable Author Statement more info	PubMed
positive regulation of I-kappaB kinase/NF-kappaB cascade	IEA Inferred from Electronic Annotation more info
positive regulation of JNK cascade	IEA Inferred from Electronic Annotation more info
positive regulation of NF-kappaB import into nucleus	IDA Inferred from Direct Assay more info	PubMed
positive regulation of NF-kappaB transcription factor activity	IEA Inferred from Electronic Annotation more info
positive regulation of chemokine biosynthetic process	IEA Inferred from Electronic Annotation more info
positive regulation of chemokine production	IDA Inferred from Direct Assay more info	PubMed
positive regulation of inflammatory response	IC Inferred by Curator more info	PubMed
positive regulation of interferon-alpha biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
positive regulation of interferon-beta biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
positive regulation of interferon-beta biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of interferon-beta production	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of interferon-gamma biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
positive regulation of interleukin-12 production	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of interleukin-6 production	IDA Inferred from Direct Assay more info	PubMed
positive regulation of interleukin-8 production	IDA Inferred from Direct Assay more info	PubMed
positive regulation of toll-like receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
positive regulation of transcription from RNA polymerase II promoter	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of tumor necrosis factor production	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of type III interferon production	IEA Inferred from Electronic Annotation more info
response to exogenous dsRNA	IEA Inferred from Electronic Annotation more info
signal transduction	TAS Traceable Author Statement more info	PubMed
toll-like receptor 3 signaling pathway	TAS Traceable Author Statement more info
toll-like receptor 4 signaling pathway	TAS Traceable Author Statement more info
toll-like receptor signaling pathway	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
Golgi membrane	TAS Traceable Author Statement more info
NOT cell surface	IDA Inferred from Direct Assay more info	PubMed
cytoplasm	IDA Inferred from Direct Assay more info	PubMed
endolysosome membrane	TAS Traceable Author Statement more info
endoplasmic reticulum membrane	TAS Traceable Author Statement more info
endosome membrane	TAS Traceable Author Statement more info
integral to plasma membrane	TAS Traceable Author Statement more info	PubMed
membrane	NAS Non-traceable Author Statement more info	PubMed

General protein information

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Preferred Names: toll-like receptor 3

Names: toll-like receptor 3

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_007278.1 RefSeqGene

Range

5001..20944

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_117

mRNA and Protein(s)

NM_003265.2 → NP_003256.1 toll-like receptor 3 precursor

Status: REVIEWED

Source sequence(s)

BC096333, BU624267, DA374150, U88879

Consensus CDS

CCDS3846.1

UniProtKB/TrEMBL

E6Y0F1

UniProtKB/Swiss-Prot

O15455

Related

ENSP00000296795, OTTHUMP00000218073, ENST00000296795, OTTHUMT00000360313

Conserved Domains (4) summary

smart00082
Location:645 – 697
Blast Score: 110

LRRCT; Leucine rich repeat C-terminal domain

cl15309
Location:433 – 647
Blast Score: 130

LRR_RI; Leucine-rich repeats (LRRs), ribonuclease inhibitor (RI)-like subfamily. LRRs are 20-29 residue sequence motifs present in many proteins that participate in protein-protein interactions and have different functions and cellular locations. LRRs correspond ...

pfam01582
Location:758 – 895
Blast Score: 260

TIR; TIR domain

pfam13855
Location:481 – 542
Blast Score: 127

LRR_8; Leucine rich repeat

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000004.11 Reference GRCh37.p10 Primary Assembly

Range

186990309..187006252

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000136.1 Alternate HuRef

Range

182742451..182758393

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018915.1 Alternate CHM1_1.0

Range

186749120..186765056

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01070544.1 (11217..27159)	None
genomic	AC104070.3 (57277..73220)	None
genomic	AMYH01014779.1 (7890..23826)	None
genomic	CH471056.2	EAX04628.1
		EAX04629.1
genomic	CS441680.1	CAL68868.1
genomic	DQ360814.1	ABC86908.1
genomic	DQ360815.1	ABC86909.1
genomic	DQ360816.1	ABC86910.1
genomic	GM869032.1	CAT16976.1
mRNA	AB445631.1	BAG55028.1
mRNA	AK302143.1	BAH13636.1
mRNA	AK314208.1	BAG36884.1
mRNA	BC017954.1	None
mRNA	BC043204.2	None
mRNA	BC059372.1	AAH59372.1
mRNA	BC068487.1	None
mRNA	BC094737.1	AAH94737.1
mRNA	BC096333.1	AAH96333.1
mRNA	BC096334.3	AAH96334.1
mRNA	BC096335.1	AAH96335.1
mRNA	BU624267.1	None
mRNA	DA374150.1	None
mRNA	DQ445682.1	ABE01399.1
mRNA	DQ470075.1	ABF06633.1
mRNA	DQ470076.1	ABF06634.1
mRNA	DQ470077.1	ABF06635.1
mRNA	DQ470078.1	ABF06636.1
mRNA	DQ470079.1	ABF06637.1
mRNA	U88879.1	AAC34134.1