Toll-like receptor 3

TLR3
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1ZIW, 2A0Z, 3ULU, 3ULV, 2MK9, 2MKA
Identifiers
Aliases	TLR3, CD283, IIAE2, toll like receptor 3, IMD83
External IDs	OMIM: 603029; MGI: 2156367; HomoloGene: 20696; GeneCards: TLR3; OMA:TLR3 - orthologs
Gene location (Human) Chr. Chromosome 4 (human) Band 4q35.1 Start 186,069,155 bp End 186,088,073 bp
Gene location (Mouse) Chr. Chromosome 8 (mouse) Band 8|8 B1.1 Start 45,848,702 bp End 45,864,117 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in jejunal mucosa palpebral conjunctiva placenta rectum sperm duodenum gallbladder Achilles tendon epithelium of colon pancreatic epithelial cell Top expressed in conjunctival fornix gastrula stria vascularis transitional epithelium of urinary bladder vestibular membrane of cochlear duct vestibular sensory epithelium secondary oocyte lumbar subsegment of spinal cord Epithelium of choroid plexus jejunum More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding identical protein binding RNA binding double-stranded RNA binding transmembrane signaling receptor activity signaling receptor activity Cellular component cytoplasm integral component of membrane endosome endoplasmic reticulum membrane membrane Golgi membrane integral component of plasma membrane intracellular anatomical structure cell surface lysosomal membrane early endosome endoplasmic reticulum endolysosome membrane endosome membrane extracellular space extracellular matrix Biological process positive regulation of interferon-beta production response to dsRNA defense response positive regulation of toll-like receptor signaling pathway positive regulation of protein phosphorylation male gonad development positive regulation of inflammatory response positive regulation of interleukin-12 production positive regulation of type III interferon production cellular response to interferon-beta response to exogenous dsRNA negative regulation of osteoclast differentiation positive regulation of cytokine production immune system process response to virus activation of NF-kappaB-inducing kinase activity I-kappaB phosphorylation positive regulation of JNK cascade hyperosmotic response cellular response to dsRNA regulation of dendritic cell cytokine production microglial cell activation toll-like receptor signaling pathway TRIF-dependent toll-like receptor signaling pathway cellular response to mechanical stimulus microglial cell activation involved in immune response positive regulation of gene expression defense response to bacterium positive regulation of NF-kappaB transcription factor activity defense response to virus necroptotic signaling pathway positive regulation of interleukin-8 production cellular response to exogenous dsRNA positive regulation of interleukin-6 production positive regulation of tumor necrosis factor production cellular response to interferon-gamma positive regulation of chemokine production positive regulation of apoptotic process positive regulation of I-kappaB kinase/NF-kappaB signaling detection of virus inflammatory response innate immune response I-kappaB kinase/NF-kappaB signaling toll-like receptor 3 signaling pathway positive regulation of type I interferon production MyD88-independent toll-like receptor signaling pathway signal transduction positive regulation of transcription by RNA polymerase II necroptosis apoptotic signaling pathway negative regulation of MyD88-independent toll-like receptor signaling pathway extrinsic apoptotic signaling pathway positive regulation of angiogenesis positive regulation of NIK/NF-kappaB signaling Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 7098 142980 Ensembl ENSG00000164342 ENSMUSG00000031639 UniProt O15455 Q99MB1 RefSeq (mRNA) NM_003265 NM_126166 NM_001357316 NM_001357317 RefSeq (protein) NP_003256 NP_569054 NP_001344245 NP_001344246 Location (UCSC) Chr 4: 186.07 – 186.09 Mb Chr 8: 45.85 – 45.86 Mb PubMed search
Wikidata
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Toll-like receptor 3 (TLR3) also known as CD283 (cluster of differentiation 283) is a protein that in humans is encoded by the TLR3 gene. TLR3 is a member of the toll-like receptor family of pattern recognition receptors of the innate immune system. TLR3 recognizes double-stranded RNA in endosomes, which is a common feature of viral genomes internalised by macrophages and dendritic cells.

Function

TLR3 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 IRF3 and NF-κB. Unlike other TLRs, TLR3 uses TRIF as the sole adaptor. IRF3 ultimately induces the production of type I interferons. It may thus play a role in host defense against viruses.

TLR3 recognizes double-stranded RNA, a form of genetic information carried by some viruses such as reoviruses. Additionally, an ephemeral form of double-stranded RNA exists as a replicative intermediate during virus replication. Upon recognition, TLR3 induces the activation of IRF3 to increase production of type I interferons which signal other cells to increase their antiviral defenses. Double-stranded RNA is also recognised by the cytoplasmic receptors RIG-I and MDA-5.

TLR3 displays a protective role in mouse models of atherosclerosis, and activation of TLR3 signaling is associated with ischemic preconditioning-induced protection against brain ischemia and attenuation of reactive astrogliosis. Furthermore, TLR3 activation has been shown to promote hair follicle regeneration in skin wound healing. In addition, TLR3 activators show effects on human vascular cells.

Structure

The structure of TLR3 was reported in June 2005 by researchers at The Scripps Research Institute. TLR3 forms a large horseshoe shape that contacts with a neighboring horseshoe, forming a "dimer" of two horseshoes. Much of the TLR3 protein surface is covered with sugar molecules, making it a glycoprotein, but on one face (including the proposed interface between the two horseshoes), there is a large sugar-free surface. This surface also contains two distinct patches rich in positively charged amino acids, which may be a binding site for negatively charged double-stranded RNA.

Despite being a glycoprotein, TLR3 crystallises readily – a prerequisite for structural analysis by x-ray crystallography.

Ligands

Antagonists

• CU-CPT4a

Further reading

• Lien E, Ingalls RR (January 2002). "Toll-like receptors". Critical Care Medicine. 30 (1 Suppl): S1-11. doi:10.1097/00003246-200201001-00001. PMID 11782555.
• Wang PF, Fang H, Chen J, Lin S, Liu Y, Xiong XY, et al. (May 2014). "Polyinosinic-polycytidylic acid has therapeutic effects against cerebral ischemia/reperfusion injury through the downregulation of TLR4 signaling via TLR3". Journal of Immunology. 192 (10): 4783–4794. doi:10.4049/jimmunol.1303108. PMC 4009499. PMID 24729619.
• Li Y, Xu XL, Zhao D, Pan LN, Huang CW, Guo LJ, et al. (November 2015). "TLR3 ligand Poly IC Attenuates Reactive Astrogliosis and Improves Recovery of Rats after Focal Cerebral Ischemia". CNS Neuroscience & Therapeutics. 21 (11): 905–913. doi:10.1111/cns.12469. PMC 4638223. PMID 26494128.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.