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wikipedia jump to content main menu main menu move to sidebar hide navigation main page contents current events random article about wikipedia contact us contribute help learn to edit community portal recent changes upload file special pages search search appearance donate create account log in personal tools donate create account log in contents move to sidebar hide top 1 structure 2 function 3 ligands 4 references 5 further reading toggle the table of contents toll like receptor 3 10 languages čeština cymraeg فارسی français galego 日本語 polski русский türkçe українська edit links article talk english read edit view history tools tools move to sidebar hide actions read edit view history general what links here related changes upload file permanent link page information cite this page get shortened url switch to legacy parser print export download as pdf printable version in other projects wikidata item appearance move to sidebar hide from wikipedia the free encyclopedia protein found in humans tlr3 identifiers aliases tlr3 cd283 iiae2 toll like receptor 3 imd83 external ids omim 603029 mgi 2156367 genecards tlr3 available structures pdb ortholog search pdbe rcsb list of pdb id codes 1ziw 2a0z 3ulu 3ulv 2mk9 2mka gene location human chr chromosome 4 human 1 band 4q35 1 start 186 069 155 bp 1 end 186 088 073 bp 1 gene location mouse chr chromosome 8 mouse 2 band 8 8 b1 1 start 45 848 702 bp 2 end 45 864 117 bp 2 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 databases ncbi entry oma entry 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 3 4 wikidata view edit human view edit mouse 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 5 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 structure edit toll like receptor 3 tlr3 is a type i transmembrane receptor consisting of an extracellular ectodomain pf13855 pf13516 a single transmembrane helix pf17968 and a cytoplasmic toll interleukin 1 receptor tir signaling domain pf01582 its ectodomain forms a large horseshoe shaped solenoid built from 23 leucine rich repeats lrrs each stabilized by conserved asparagine residues that create extensive hydrogen bonding networks along the coil with specialized n and c terminal cap domains closing off the horseshoe s ends 6 7 function edit 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 8 unlike other tlrs tlr3 uses trif as the sole adaptor 8 irf3 ultimately induces the production of type i interferons it may thus play a role in host defense against viruses 9 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 10 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 11 tlr3 displays a protective role in mouse models of atherosclerosis 12 and activation of tlr3 signaling is associated with ischemic preconditioning induced protection against brain ischemia and attenuation of reactive astrogliosis 13 14 furthermore tlr3 activation has been shown to promote hair follicle regeneration in skin wound healing 15 in addition tlr3 activators show effects on human vascular cells 12 ligands edit agonists natural dsrna from viruses and some dead cells synthetic dsrna such as poly i c poly a u rgc100 nexavant endogenous mrna presumably due to secondary structure stems resemble dsrna 16 pvp 057 small molecule 17 various minibinder proteins allosteric antagonists cu cpt4a competitive there is a minimum dsrna size required to effectively trigger tlr3 this size is lower than the activation threshold for mda5 another dsrna sensor with higher inflammatory and cytotoxic potential as a result synthetic dsrna can be made to avoid mda5 activation by controlling the size of the molecule 18 references edit 1 2 3 grch38 ensembl release 89 ensg00000164342 ensembl may 2017 1 2 3 grcm38 ensembl release 89 ensmusg00000031639 ensembl may 2017 human pubmed reference national center for biotechnology information u s national library of medicine mouse pubmed reference national center for biotechnology information u s national library of medicine rock fl hardiman g timans jc kastelein ra bazan jf january 1998 a family of human receptors structurally related to drosophila toll proceedings of the national academy of sciences of the united states of america 95 2 588 593 bibcode 1998pnas 95 588r doi 10 1073 pnas 95 2 588 pmc 18464 pmid 9435236 botos i liu l wang y segal dm davies dr 2009 the toll like receptor 3 dsrna signaling complex biochimica et biophysica acta 1789 9 10 667 74 doi 10 1016 j bbagrm 2009 06 005 pmc 2784288 pmid 19595807 choe j kelker ms wilson ia july 2005 crystal structure of human toll like receptor 3 tlr3 ectodomain science 309 5734 new york n y 581 585 bibcode 2005sci 309 581c doi 10 1126 science 1115253 pmid 15961631 s2cid 4962727 1 2 kawai t akira s november 2007 signaling to nf kappab by toll like receptors trends in molecular medicine 13 11 460 469 doi 10 1016 j molmed 2007 09 002 pmid 18029230 entrez gene toll like receptor 3 ncbi nlm nih gov norval m 2012 virus cell interactions in greenwood d slack rc barer mr irving wl eds medical microbiology 18th ed edinburgh churchill livingstone p 88 isbn 978 0 7020 4089 4 alexopoulou l holt ac medzhitov r flavell ra october 2001 recognition of double stranded rna and activation of nf kappab by toll like receptor 3 nature 413 6857 732 738 bibcode 2001natur 413 732a doi 10 1038 35099560 pmid 11607032 s2cid 4346537 1 2 cole je navin tj cross aj goddard me alexopoulou l mitra at et al february 2011 unexpected protective role for toll like receptor 3 in the arterial wall proceedings of the national academy of sciences of the united states of america 108 6 2372 2377 doi 10 1073 pnas 1018515108 pmc 3038746 pmid 21220319 pan ln zhu w li y xu xl guo lj lu q et al 2014 astrocytic toll like receptor 3 is associated with ischemic preconditioning induced protection against brain ischemia in rodents plos one 9 6 e99526 bibcode 2014ploso 999526p doi 10 1371 journal pone 0099526 pmc 4051824 pmid 24914679 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 nelson am reddy sk ratliff ts hossain mz katseff as zhu as et al august 2015 dsrna released by tissue damage activates tlr3 to drive skin regeneration cell stem cell 17 2 139 151 doi 10 1016 j stem 2015 07 008 pmc 4529957 pmid 26253200 karikó k ni h capodici j lamphier m weissman d march 2004 mrna is an endogenous ligand for toll like receptor 3 the journal of biological chemistry 279 13 12542 12550 doi 10 1074 jbc m310175200 pmid 14729660 lee b dong d nanishi e awad jm abedi kz saito y et al december 2025 discovery of a small molecule tlr3 agonist adjuvant nature communications 17 1 364 doi 10 1038 s41467 025 66878 3 pmc 12796313 pmid 41339634 lee sh choi yh kang sm lee mg debin a perouzel e et al december 2023 the defined tlr3 agonist nexavant exhibits anti cancer efficacy and potentiates anti pd 1 antibody therapy by enhancing immune cell infiltration cancers 15 24 basel 5752 doi 10 3390 cancers15245752 pmc 10741573 pmid 38136298 further reading edit 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 baltimore 4783 4794 doi 10 4049 jimmunol 1303108 pmc 4009499 pmid 24729619 this article incorporates text from the united states national library of medicine which is in the public domain v t e pdb gallery 1ziw human toll like receptor 3 extracellular domain structure 2a0z the molecular structure of toll like receptor 3 ligand binding domain v t e proteins clusters of differentiation see also list of human clusters of differentiation 1 50 1 a c 1a 1b 1d 1e 2 3 γ δ ε 4 5 6 7 8 a 9 10 11 a b c d 13 14 15 16 a b 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 a b 33 34 35 36 37 38 39 40 41 42 a b c d 43 44 45 46 47 48 49 a b c d e f 50 51 100 51 52 53 54 55 56 57 58 59 61 62 e l p 63 64 a b c 66 a b c d e f 68 69 70 71 72 73 74 78 79 a b 80 81 82 83 84 85 a d e h j k 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 150 101 102 103 104 105 106 107 a b 108 109 110 111 112 113 114 115 116 117 118 119 120 a b 121 a b 122 123 124 125 126 127 129 130 131 132 133 134 135 136 137 138 140b 141 142 143 144 146 147 148 150 151 200 151 152 153 154 155 156 a b c 157 158 a d e i k 159 a c 160 161 162 163 164 166 167 a b 168 169 170 171 172 a b g 174 177 178 179 a b 180 181 182 183 184 185 186 191 192 193 194 195 196 197 w198 w199 200 201 250 201 202b 204 205 206 207 208 209 w210 a b 212 213a 1 2 217 218 a b 220 221 222 223 224 225 226 227 228 229 230 233 234 235 a b 236 238 239 240ce 240d 241 243 244 246 247 248 249 251 300 252 253 254 256 257 258 261 262 263 264 265 266 267 268 269 271 272 273 274 275 276 278 279 280 281 282 283 284 286 288 289 290 292 w293 294 295 297 298 299 301 350 300a 301 302 303 304 305 306 307 309 312 314 315 316 317 318 320 321 322 324 325 326 327 328 329 331 332 333 334 335 336 337 338 339 340 344 349 350 351 371 351 352 353 354 355 357 358 360 361 362 363 364 365 366 367 368 369 370 371 category commons v t e signaling pathway tlr signaling pathway tlrs tlr1 tlr2 tlr3 tlr4 tlr5 tlr6 tlr7 tlr8 tlr9 tlr10 tlr11 tlr12 tlr13 other receptors cd14 lbp md2 downstream signalling irak1 irak2 irak3 irak4 irf3 map3k7 myd88 tab1 ticam1 tirap tollip traf6 retrieved from https en wikipedia org w index php title toll like_receptor_3 oldid 1378641739 categories genes on human chromosome 4 clusters of differentiation toll like receptors hidden categories articles with short description short description is different from wikidata wikipedia articles incorporating text from the united states national library of medicine this page was last edited on 5 october 2026 at 11 39 utc page was rendered with parsoid text is available under the creative commons attribution sharealike 4 0 license additional terms may apply by using this site you agree to the terms 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