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

Summary

Official Symbol: TLR3provided by HGNC
Official Full Name: toll like receptor 3provided by HGNC
Primary source: HGNC:HGNC:11849
See related: Ensembl:ENSG00000164342 MIM:603029; AllianceGenome:HGNC:11849
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; IMD83
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 thus plays a role in host defense against multiple viruses. [provided by RefSeq, Jul 2021]
Annotation information: Note: This gene has been reviewed for its involvement in coronavirus biology, and is involved in immune response or antiviral activity.
Expression: Ubiquitous expression in duodenum (RPKM 5.4), small intestine (RPKM 5.0) and 24 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 4q35.1

Exon count:: 5

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	4	NC_000004.12 (186069156..186088073)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	4	NC_060928.1 (189409568..189428483)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	4	NC_000004.11 (186990310..187009227)

Chromosome 4 - NC_000004.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Sterile inflammation via TRPM8 RNA-dependent TLR3-NF-kB/IRF3 activation promotes antitumor immunity in prostate cancer.
Title: Sterile inflammation via TRPM8 RNA-dependent TLR3-NF-kB/IRF3 activation promotes antitumor immunity in prostate cancer.
Analysis of associations between the TLR3 SNPs rs3775291 and rs3775290 and COVID-19 in a cohort of professionals of Belem-PA, Brazil.
Title: Analysis of associations between the TLR3 SNPs rs3775291 and rs3775290 and COVID-19 in a cohort of professionals of Belém-PA, Brazil.
Glioma-derived ANXA1 suppresses the immune response to TLR3 ligands by promoting an anti-inflammatory tumor microenvironment.
Title: Glioma-derived ANXA1 suppresses the immune response to TLR3 ligands by promoting an anti-inflammatory tumor microenvironment.
The Functional Mechanisms of Toll-Like Receptor 3 and Its Implications in Digestive System Tumors.
Title: The Functional Mechanisms of Toll-Like Receptor 3 and Its Implications in Digestive System Tumors.
The effect of TLR3 priming conditions on MSC immunosuppressive properties.
Title: The effect of TLR3 priming conditions on MSC immunosuppressive properties.
TLR3 Gene Polymorphism in HCV Infection in the Kazakh Population of Western Kazakhstan.
Title: TLR3 Gene Polymorphism in HCV Infection in the Kazakh Population of Western Kazakhstan.
Activation of Toll-like receptor 3 inhibits HIV infection of human iPSC-derived microglia.
Title: Activation of Toll-like receptor 3 inhibits HIV infection of human iPSC-derived microglia.
Necrotic Cells from Head and Neck Carcinomas Release Biomolecules That Are Activating Toll-like Receptor 3.
Title: Necrotic Cells from Head and Neck Carcinomas Release Biomolecules That Are Activating Toll-like Receptor 3.
Investigation of the impact of AXL, TLR3, and STAT2 in congenital Zika syndrome through genetic polymorphisms and protein-protein interaction network analyses.
Title: Investigation of the impact of AXL, TLR3, and STAT2 in congenital Zika syndrome through genetic polymorphisms and protein-protein interaction network analyses.
Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19.
Title: Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19.

Submit: New GeneRIF Correction See all GeneRIFs (650)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Immunodeficiency 83, susceptibility to viral infections MedGen: C2751803 OMIM: 613002 GeneReviews: Not available	Compare labs
Susceptibility to HIV infection MedGen: C1836230 OMIM: 609423 GeneReviews: Not available	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
HIV-1 replication is restricted by TLR3 stimulation in Langerhans cells	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

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

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables double-stranded RNA binding	IBA Inferred from Biological aspect of Ancestor more info
enables double-stranded RNA binding	IDA Inferred from Direct Assay more info	PubMed
enables double-stranded RNA binding	NAS Non-traceable Author Statement more info	PubMed
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables pattern recognition receptor activity	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables signaling receptor activity	IBA Inferred from Biological aspect of Ancestor more info
enables transmembrane signaling receptor activity	NAS Non-traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
involved_in I-kappaB phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in JNK cascade	IEA Inferred from Electronic Annotation more info
involved_in activation of NF-kappaB-inducing kinase activity	NAS Non-traceable Author Statement more info	PubMed
involved_in cellular response to exogenous dsRNA	IEA Inferred from Electronic Annotation more info
involved_in cellular response to interferon-beta	IEA Inferred from Electronic Annotation more info
involved_in cellular response to mechanical stimulus	IEP Inferred from Expression Pattern more info	PubMed
involved_in cellular response to type II interferon	IEA Inferred from Electronic Annotation more info
involved_in cellular response to virus	IEA Inferred from Electronic Annotation more info
involved_in cellular response to xenobiotic stimulus	IEA Inferred from Electronic Annotation more info
involved_in defense response to bacterium	TAS Traceable Author Statement more info	PubMed
involved_in defense response to virus	IEP Inferred from Expression Pattern more info	PubMed
involved_in defense response to virus	TAS Traceable Author Statement more info	PubMed
involved_in detection of virus	NAS Non-traceable Author Statement more info	PubMed
involved_in extrinsic apoptotic signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in hyperosmotic response	NAS Non-traceable Author Statement more info	PubMed
involved_in inflammatory response to wounding	IDA Inferred from Direct Assay more info	PubMed
involved_in innate immune response	TAS Traceable Author Statement more info	PubMed
involved_in male gonad development	IEA Inferred from Electronic Annotation more info
involved_in microglial cell activation	IEA Inferred from Electronic Annotation more info
involved_in necroptotic signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of osteoclast differentiation	NAS Non-traceable Author Statement more info	PubMed
involved_in positive regulation of JNK cascade	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of angiogenesis	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of canonical NF-kappaB signal transduction	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of chemokine production	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of cytokine production involved in inflammatory response	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of gene expression	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of inflammatory response	IC Inferred by Curator more info	PubMed
involved_in positive regulation of interferon-alpha production	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of interferon-beta production	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of interferon-beta production	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of interferon-beta production	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of interleukin-12 production	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of interleukin-6 production	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of positive regulation of interleukin-8 production	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of macrophage cytokine production	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of non-canonical NF-kappaB signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of tumor necrosis factor production	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of type II interferon production	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of type III interferon production	IEA Inferred from Electronic Annotation more info
involved_in regulation of dendritic cell cytokine production	IEA Inferred from Electronic Annotation more info
involved_in response to dsRNA	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within response to exogenous dsRNA	IDA Inferred from Direct Assay more info	PubMed
involved_in signal transduction	TAS Traceable Author Statement more info	PubMed
involved_in toll-like receptor 3 signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in toll-like receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in type III interferon production	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in Golgi membrane	TAS Traceable Author Statement more info
NOT located_in cell surface	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
is_active_in early endosome	IDA Inferred from Direct Assay more info	PubMed
located_in endolysosome membrane	TAS Traceable Author Statement more info
located_in endoplasmic reticulum membrane	TAS Traceable Author Statement more info
is_active_in endosome membrane	ISS Inferred from Sequence or Structural Similarity more info	PubMed
located_in endosome membrane	TAS Traceable Author Statement more info
is_active_in extracellular matrix	IBA Inferred from Biological aspect of Ancestor more info
is_active_in extracellular space	IBA Inferred from Biological aspect of Ancestor more info
located_in lysosomal membrane	HDA more info	PubMed
located_in membrane	NAS Non-traceable Author Statement more info	PubMed
located_in plasma membrane	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred 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_003265.3 → NP_003256.1 toll-like receptor 3 precursor

See identical proteins and their annotated locations for NP_003256.1

Status: REVIEWED

Source sequence(s)

AC104070, BC096333, BU624267, DA374150, U88879

Consensus CDS

CCDS3846.1

UniProtKB/Swiss-Prot

B2RAI7, B7Z7K0, E6Y0F0, E6Y0F1, E9PGH4, O15455, Q4VAL2, Q504W0

UniProtKB/TrEMBL

Q6PCD4

Related

ENSP00000296795.3, ENST00000296795.8

Conserved Domains (7) summary

smart00082
Location:645 → 697

LRRCT; Leucine rich repeat C-terminal domain

smart00255
Location:755 → 900

TIR; Toll - interleukin 1 - resistance

PLN00113
Location:72 → 542

PLN00113; leucine-rich repeat receptor-like protein kinase; Provisional

sd00033
Location:33 → 52

LRR_RI; leucine-rich repeat [structural motif]

pfam01462
Location:28 → 50

LRRNT; Leucine rich repeat N-terminal domain

pfam13855
Location:562 → 622

LRR_8; Leucine rich repeat

pfam17968
Location:698 → 730

Tlr3_TMD; Toll-like receptor 3 trans-membrane domain