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O15455

- TLR3_HUMAN

UniProt

O15455 - TLR3_HUMAN

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Protein

Toll-like receptor 3

Gene

TLR3

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

Key component of innate and adaptive immunity. TLRs (Toll-like receptors) control host immune response against pathogens through recognition of molecular patterns specific to microorganisms. TLR3 is a nucleotide-sensing TLR which is activated by double-stranded RNA, a sign of viral infection. Acts via the adapter TRIF/TICAM1, leading to NF-kappa-B activation, IRF3 nuclear translocation, cytokine secretion and the inflammatory response.9 Publications

GO - Molecular functioni

  1. double-stranded RNA binding Source: UniProtKB
  2. receptor activity Source: ProtInc
  3. transmembrane signaling receptor activity Source: UniProtKB

GO - Biological processi

  1. activation of NF-kappaB-inducing kinase activity Source: UniProtKB
  2. cellular response to drug Source: Ensembl
  3. cellular response to exogenous dsRNA Source: Ensembl
  4. cellular response to interferon-beta Source: Ensembl
  5. cellular response to interferon-gamma Source: Ensembl
  6. cellular response to mechanical stimulus Source: UniProtKB
  7. defense response to bacterium Source: ProtInc
  8. defense response to virus Source: BHF-UCL
  9. detection of virus Source: UniProtKB
  10. extrinsic apoptotic signaling pathway Source: UniProtKB
  11. hyperosmotic response Source: UniProtKB
  12. I-kappaB kinase/NF-kappaB signaling Source: Reactome
  13. I-kappaB phosphorylation Source: BHF-UCL
  14. inflammatory response Source: UniProtKB-KW
  15. innate immune response Source: BHF-UCL
  16. male gonad development Source: Ensembl
  17. microglial cell activation involved in immune response Source: Ensembl
  18. MyD88-independent toll-like receptor signaling pathway Source: Reactome
  19. necroptotic signaling pathway Source: UniProtKB
  20. negative regulation of osteoclast differentiation Source: UniProtKB
  21. pathogen-associated molecular pattern dependent induction by symbiont of host innate immune response Source: Ensembl
  22. positive regulation of apoptotic process Source: Ensembl
  23. positive regulation of chemokine biosynthetic process Source: Ensembl
  24. positive regulation of chemokine production Source: BHF-UCL
  25. positive regulation of I-kappaB kinase/NF-kappaB signaling Source: Ensembl
  26. positive regulation of inflammatory response Source: BHF-UCL
  27. positive regulation of interferon-alpha biosynthetic process Source: UniProtKB
  28. positive regulation of interferon-beta biosynthetic process Source: UniProtKB
  29. positive regulation of interferon-beta production Source: BHF-UCL
  30. positive regulation of interferon-gamma biosynthetic process Source: UniProtKB
  31. positive regulation of interleukin-12 production Source: BHF-UCL
  32. positive regulation of interleukin-6 production Source: BHF-UCL
  33. positive regulation of interleukin-8 production Source: BHF-UCL
  34. positive regulation of JNK cascade Source: Ensembl
  35. positive regulation of NF-kappaB import into nucleus Source: BHF-UCL
  36. positive regulation of NF-kappaB transcription factor activity Source: Ensembl
  37. positive regulation of toll-like receptor signaling pathway Source: BHF-UCL
  38. positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  39. positive regulation of tumor necrosis factor production Source: BHF-UCL
  40. positive regulation of type III interferon production Source: Ensembl
  41. response to exogenous dsRNA Source: MGI
  42. signal transduction Source: ProtInc
  43. toll-like receptor 3 signaling pathway Source: Reactome
  44. toll-like receptor 4 signaling pathway Source: Reactome
  45. toll-like receptor signaling pathway Source: Reactome
  46. TRIF-dependent toll-like receptor signaling pathway Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Receptor

Keywords - Biological processi

Immunity, Inflammatory response, Innate immunity

Keywords - Ligandi

RNA-binding

Enzyme and pathway databases

ReactomeiREACT_118563. RIP-mediated NFkB activation via ZBP1.
REACT_118632. Trafficking and processing of endosomal TLR.
REACT_150361. TRIF-mediated programmed cell death.
REACT_25148. Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon.
REACT_25351. TRAF6 mediated induction of TAK1 complex.
REACT_25374. IKK complex recruitment mediated by RIP1.
REACT_6783. Toll Like Receptor 3 (TLR3) Cascade.
SignaLinkiO15455.

Names & Taxonomyi

Protein namesi
Recommended name:
Toll-like receptor 3
Alternative name(s):
CD_antigen: CD283
Gene namesi
Name:TLR3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 4

Organism-specific databases

HGNCiHGNC:11849. TLR3.

Subcellular locationi

GO - Cellular componenti

  1. cytoplasm Source: BHF-UCL
  2. endolysosome membrane Source: Reactome
  3. endoplasmic reticulum membrane Source: Reactome
  4. endosome membrane Source: Reactome
  5. Golgi membrane Source: Reactome
  6. integral component of plasma membrane Source: ProtInc
  7. lysosomal membrane Source: UniProtKB
  8. membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Endosome, Membrane

Pathology & Biotechi

Involvement in diseasei

Herpes simplex encephalitis 2 (HSE2) [MIM:613002]: A rare complication of human herpesvirus 1 (HHV-1) infection, occurring in only a small minority of HHV-1 infected individuals. HSE is characterized by hemorrhagic necrosis of parts of the temporal and frontal lobes. Onset is over several days and involves fever, headache, seizures, stupor, and often coma, frequently with a fatal outcome.1 Publication
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. TLR3 mutations predispose otherwise healthy individuals to isolated herpes simplex encephalitis through a mechanism that involves impaired IFNs production and reduced immune defense against viral infection in the central nervous system.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti554 – 5541P → S in HSE2; causes TLR3 deficiency and predisposition to herpes simplex encephalitis. 1 Publication
VAR_054887

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi95 – 951C → A: Reduced response to ds-RNA. 1 Publication
Mutagenesisi122 – 1221C → A: Reduced response to ds-RNA. 1 Publication
Mutagenesisi196 – 1961N → G: Reduced expression levels; when associated with R-247. 1 Publication
Mutagenesisi247 – 2471N → R: Reduced response to ds-RNA. Reduced expression levels; when associated with G-196. 1 Publication
Mutagenesisi539 – 5391H → A: No effect. 1 Publication
Mutagenesisi539 – 5391H → E: Loss of RNA binding. Constitutive activation of NF-kappa-B. 1 Publication
Mutagenesisi541 – 5411N → A: Loss of RNA binding. Abolishes activation of NF-kappa-B. 1 Publication
Mutagenesisi759 – 7591Y → F: Reduced activation of NF-kappa-B in response to ds-RNA. Reduced induction of IL-8 in response to ds-RNA. 1 Publication

Keywords - Diseasei

Disease mutation

Organism-specific databases

MIMi613002. phenotype.
Orphaneti1930. Herpetic encephalitis.
PharmGKBiPA36551.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 23231 PublicationAdd
BLAST
Chaini24 – 904881Toll-like receptor 3PRO_0000034715Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi28 ↔ 37
Glycosylationi52 – 521N-linked (GlcNAc...)3 Publications
Glycosylationi57 – 571N-linked (GlcNAc...)1 Publication
Glycosylationi70 – 701N-linked (GlcNAc...)2 Publications
Disulfide bondi95 ↔ 122
Glycosylationi124 – 1241N-linked (GlcNAc...)2 Publications
Glycosylationi196 – 1961N-linked (GlcNAc...)1 Publication
Glycosylationi247 – 2471N-linked (GlcNAc...)1 Publication
Glycosylationi252 – 2521N-linked (GlcNAc...)3 Publications
Glycosylationi265 – 2651N-linked (GlcNAc...)2 Publications
Glycosylationi275 – 2751N-linked (GlcNAc...)3 Publications
Glycosylationi291 – 2911N-linked (GlcNAc...)3 Publications
Glycosylationi398 – 3981N-linked (GlcNAc...)3 Publications
Glycosylationi413 – 4131N-linked (GlcNAc...)3 Publications
Glycosylationi507 – 5071N-linked (GlcNAc...)3 Publications
Glycosylationi636 – 6361N-linked (GlcNAc...)1 Publication
Disulfide bondi649 ↔ 677
Disulfide bondi651 ↔ 696
Glycosylationi662 – 6621N-linked (GlcNAc...)Sequence Analysis
Modified residuei759 – 7591Phosphotyrosine1 Publication
Modified residuei858 – 8581Phosphotyrosine1 Publication

Post-translational modificationi

Heavily N-glycosylated, except on that part of the surface of the ectodomain that is involved in ligand binding.4 Publications
TLR3 signaling requires a proteolytic cleavage mediated by cathepsins CTSB and CTSH, the cleavage occurs between amino acids 252 and 346. The cleaved form of TLR3 is the predominant form found in endosomes.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiO15455.
PaxDbiO15455.
PRIDEiO15455.

PTM databases

PhosphoSiteiO15455.

Expressioni

Tissue specificityi

Expressed at high level in placenta and pancreas. Also detected in CD11c+ immature dendritic cells. Only expressed in dendritic cells and not in other leukocytes, including monocyte precursors. TLR3 is the TLR that is expressed most strongly in the brain, especially in astrocytes, glia, and neurons.1 Publication

Gene expression databases

BgeeiO15455.
CleanExiHS_TLR3.
ExpressionAtlasiO15455. baseline and differential.
GenevestigatoriO15455.

Organism-specific databases

HPAiCAB025658.

Interactioni

Subunit structurei

Monomer and homodimer; dimerization is triggered by ligand-binding, the signaling unit is composed of one ds-RNA of around 40 bp and two TLR3 molecules, and lateral clustering of signaling units along the length of the ds-RNA ligand is required for TLR3 signal transduction. Interacts (via transmembrane domain) with UNC93B1; the interaction is required for transport from the ER to the endosomes. Interacts with TICAM1 (via the TIR domain); mediates TLR3 signaling. Interacts with SRC; upon binding of double-stranded RNA.7 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
PIK3R1P279862EBI-6116630,EBI-79464

Protein-protein interaction databases

BioGridi112953. 15 interactions.
DIPiDIP-29660N.
IntActiO15455. 6 interactions.
MINTiMINT-2840066.
STRINGi9606.ENSP00000296795.

Structurei

Secondary structure

1
904
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi31 – 366Combined sources
Beta strandi47 – 493Combined sources
Beta strandi54 – 574Combined sources
Helixi68 – 747Combined sources
Beta strandi78 – 814Combined sources
Helixi94 – 974Combined sources
Beta strandi103 – 1053Combined sources
Turni118 – 1214Combined sources
Beta strandi126 – 1294Combined sources
Turni142 – 1454Combined sources
Beta strandi151 – 1533Combined sources
Beta strandi166 – 1683Combined sources
Beta strandi175 – 1773Combined sources
Helixi188 – 1914Combined sources
Helixi192 – 1943Combined sources
Beta strandi198 – 2036Combined sources
Helixi216 – 2194Combined sources
Beta strandi220 – 2234Combined sources
Beta strandi225 – 2273Combined sources
Helixi234 – 24512Combined sources
Beta strandi252 – 2543Combined sources
Turni265 – 2684Combined sources
Helixi269 – 2735Combined sources
Beta strandi278 – 2803Combined sources
Turni291 – 2966Combined sources
Beta strandi302 – 3043Combined sources
Beta strandi310 – 3134Combined sources
Turni315 – 3206Combined sources
Beta strandi326 – 3283Combined sources
Beta strandi338 – 3403Combined sources
Turni348 – 3536Combined sources
Beta strandi359 – 3613Combined sources
Turni372 – 3776Combined sources
Beta strandi383 – 3853Combined sources
Turni398 – 4014Combined sources
Helixi402 – 4043Combined sources
Beta strandi411 – 4133Combined sources
Turni424 – 4296Combined sources
Beta strandi435 – 4373Combined sources
Beta strandi444 – 4463Combined sources
Helixi450 – 4523Combined sources
Beta strandi460 – 4623Combined sources
Beta strandi467 – 4704Combined sources
Turni473 – 4786Combined sources
Beta strandi484 – 4863Combined sources
Turni501 – 5044Combined sources
Beta strandi510 – 5123Combined sources
Turni523 – 5286Combined sources
Beta strandi534 – 5363Combined sources
Helixi543 – 5464Combined sources
Turni557 – 5604Combined sources
Beta strandi566 – 5683Combined sources
Turni579 – 5846Combined sources
Beta strandi590 – 5923Combined sources
Turni603 – 6086Combined sources
Beta strandi614 – 6163Combined sources
Helixi627 – 6348Combined sources
Beta strandi638 – 6414Combined sources
Beta strandi655 – 6584Combined sources
Helixi671 – 6744Combined sources
Beta strandi676 – 6805Combined sources
Helixi688 – 6903Combined sources

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1ZIWX-ray2.10A27-700[»]
2A0ZX-ray2.40A22-703[»]
2MK9NMR-A/B698-730[»]
2MKANMR-A/B/C698-730[»]
3ULUX-ray3.52A22-702[»]
3ULVX-ray3.52A22-702[»]
ProteinModelPortaliO15455.
SMRiO15455. Positions 26-897.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO15455.

Topological domain

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini24 – 704681LumenalSequence AnalysisAdd
BLAST
Topological domaini726 – 904179CytoplasmicSequence AnalysisAdd
BLAST

Transmembrane

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei705 – 72521HelicalSequence AnalysisAdd
BLAST

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini24 – 5128LRRNTAdd
BLAST
Repeati52 – 7322LRR 1Add
BLAST
Repeati76 – 9722LRR 2Add
BLAST
Repeati100 – 12122LRR 3Add
BLAST
Repeati124 – 14522LRR 4Add
BLAST
Repeati148 – 16821LRR 5Add
BLAST
Repeati172 – 19322LRR 6Add
BLAST
Repeati198 – 21922LRR 7Add
BLAST
Repeati222 – 24423LRR 8Add
BLAST
Repeati249 – 27022LRR 9Add
BLAST
Repeati275 – 29622LRR 10Add
BLAST
Repeati299 – 32022LRR 11Add
BLAST
Repeati323 – 34422LRR 12Add
BLAST
Repeati356 – 37722LRR 13Add
BLAST
Repeati380 – 40021LRR 14Add
BLAST
Repeati408 – 42922LRR 15Add
BLAST
Repeati432 – 45423LRR 16Add
BLAST
Repeati465 – 48622LRR 17Add
BLAST
Repeati507 – 52822LRR 18Add
BLAST
Repeati531 – 55222LRR 19Add
BLAST
Repeati563 – 58422LRR 20Add
BLAST
Repeati587 – 60822LRR 21Add
BLAST
Repeati611 – 63222LRR 22Add
BLAST
Domaini645 – 69854LRRCTAdd
BLAST
Domaini754 – 896143TIRPROSITE-ProRule annotationAdd
BLAST

Domaini

ds-RNA binding is mediated by LRR 1 to 3, and LRR 17 to 18.

Sequence similaritiesi

Belongs to the Toll-like receptor family.Curated
Contains 22 LRR (leucine-rich) repeats.Curated
Contains 1 LRRCT domain.Curated
Contains 1 LRRNT domain.Curated
Contains 1 TIR domain.PROSITE-ProRule annotation

Keywords - Domaini

Leucine-rich repeat, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG4886.
GeneTreeiENSGT00760000119006.
HOGENOMiHOG000251618.
HOVERGENiHBG023181.
InParanoidiO15455.
KOiK05401.
OMAiIANINDD.
OrthoDBiEOG79SDZG.
PhylomeDBiO15455.
TreeFamiTF325595.

Family and domain databases

Gene3Di3.40.50.10140. 1 hit.
InterProiIPR000483. Cys-rich_flank_reg_C.
IPR001611. Leu-rich_rpt.
IPR003591. Leu-rich_rpt_typical-subtyp.
IPR000372. LRR-contain_N.
IPR000157. TIR_dom.
IPR027173. TLR3.
[Graphical view]
PANTHERiPTHR24365:SF5. PTHR24365:SF5. 1 hit.
PfamiPF13855. LRR_8. 6 hits.
PF01582. TIR. 1 hit.
[Graphical view]
SMARTiSM00369. LRR_TYP. 2 hits.
SM00082. LRRCT. 1 hit.
SM00013. LRRNT. 1 hit.
SM00255. TIR. 1 hit.
[Graphical view]
SUPFAMiSSF52200. SSF52200. 1 hit.
PROSITEiPS51450. LRR. 19 hits.
PS50104. TIR. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: O15455-1) [UniParc]FASTAAdd to Basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MRQTLPCIYF WGGLLPFGML CASSTTKCTV SHEVADCSHL KLTQVPDDLP
60 70 80 90 100
TNITVLNLTH NQLRRLPAAN FTRYSQLTSL DVGFNTISKL EPELCQKLPM
110 120 130 140 150
LKVLNLQHNE LSQLSDKTFA FCTNLTELHL MSNSIQKIKN NPFVKQKNLI
160 170 180 190 200
TLDLSHNGLS STKLGTQVQL ENLQELLLSN NKIQALKSEE LDIFANSSLK
210 220 230 240 250
KLELSSNQIK EFSPGCFHAI GRLFGLFLNN VQLGPSLTEK LCLELANTSI
260 270 280 290 300
RNLSLSNSQL STTSNTTFLG LKWTNLTMLD LSYNNLNVVG NDSFAWLPQL
310 320 330 340 350
EYFFLEYNNI QHLFSHSLHG LFNVRYLNLK RSFTKQSISL ASLPKIDDFS
360 370 380 390 400
FQWLKCLEHL NMEDNDIPGI KSNMFTGLIN LKYLSLSNSF TSLRTLTNET
410 420 430 440 450
FVSLAHSPLH ILNLTKNKIS KIESDAFSWL GHLEVLDLGL NEIGQELTGQ
460 470 480 490 500
EWRGLENIFE IYLSYNKYLQ LTRNSFALVP SLQRLMLRRV ALKNVDSSPS
510 520 530 540 550
PFQPLRNLTI LDLSNNNIAN INDDMLEGLE KLEILDLQHN NLARLWKHAN
560 570 580 590 600
PGGPIYFLKG LSHLHILNLE SNGFDEIPVE VFKDLFELKI IDLGLNNLNT
610 620 630 640 650
LPASVFNNQV SLKSLNLQKN LITSVEKKVF GPAFRNLTEL DMRFNPFDCT
660 670 680 690 700
CESIAWFVNW INETHTNIPE LSSHYLCNTP PHYHGFPVRL FDTSSCKDSA
710 720 730 740 750
PFELFFMINT SILLIFIFIV LLIHFEGWRI SFYWNVSVHR VLGFKEIDRQ
760 770 780 790 800
TEQFEYAAYI IHAYKDKDWV WEHFSSMEKE DQSLKFCLEE RDFEAGVFEL
810 820 830 840 850
EAIVNSIKRS RKIIFVITHH LLKDPLCKRF KVHHAVQQAI EQNLDSIILV
860 870 880 890 900
FLEEIPDYKL NHALCLRRGM FKSHCILNWP VQKERIGAFR HKLQVALGSK

NSVH
Length:904
Mass (Da):103,829
Last modified:January 1, 1998 - v1
Checksum:i034E05ECA7A4D2F7
GO
Isoform 2 (identifier: O15455-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-277: Missing.

Note: No experimental confirmation available.

Show »
Length:627
Mass (Da):72,937
Checksum:i0D376D88306EBEFC
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti290 – 2901G → R in BAG36884. (PubMed:14702039)Curated
Sequence conflicti575 – 5751D → N in AAH94737. (PubMed:15489334)Curated
Sequence conflicti605 – 6051V → A in BAG36884. (PubMed:14702039)Curated
Sequence conflicti663 – 6631E → G in BAG36884. (PubMed:14702039)Curated

Polymorphismi

The Phe-412 allele (dbSNP:rs3775291) occurs with a frequency of 30% in populations with European and Asian ancestry, and confers some natural resistance to HIV-1 infection.

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti284 – 2841N → I.
Corresponds to variant rs5743316 [ dbSNP | Ensembl ].
VAR_052361
Natural varianti307 – 3071Y → D.
Corresponds to variant rs5743317 [ dbSNP | Ensembl ].
VAR_052362
Natural varianti412 – 4121L → F.4 Publications
Corresponds to variant rs3775291 [ dbSNP | Ensembl ].
VAR_021976
Natural varianti554 – 5541P → S in HSE2; causes TLR3 deficiency and predisposition to herpes simplex encephalitis. 1 Publication
VAR_054887
Natural varianti737 – 7371S → T.
Corresponds to variant rs5743318 [ dbSNP | Ensembl ].
VAR_024664

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 277277Missing in isoform 2. 1 PublicationVSP_054188Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U88879 mRNA. Translation: AAC34134.1.
DQ445682 mRNA. Translation: ABE01399.1.
AB445631 mRNA. Translation: BAG55028.1.
DQ360814 Genomic DNA. Translation: ABC86908.1.
DQ360815 Genomic DNA. Translation: ABC86909.1.
DQ360816 Genomic DNA. Translation: ABC86910.1.
AK302143 mRNA. Translation: BAH13636.1.
AK314208 mRNA. Translation: BAG36884.1.
AC104070 Genomic DNA. No translation available.
CH471056 Genomic DNA. Translation: EAX04628.1.
BC094737 mRNA. Translation: AAH94737.1.
BC096333 mRNA. Translation: AAH96333.1.
BC096334 mRNA. Translation: AAH96334.1.
BC096335 mRNA. Translation: AAH96335.1.
CCDSiCCDS3846.1. [O15455-1]
RefSeqiNP_003256.1. NM_003265.2. [O15455-1]
XP_006714357.1. XM_006714294.1. [O15455-1]
UniGeneiHs.657724.

Genome annotation databases

EnsembliENST00000296795; ENSP00000296795; ENSG00000164342. [O15455-1]
ENST00000504367; ENSP00000423684; ENSG00000164342. [O15455-2]
GeneIDi7098.
KEGGihsa:7098.
UCSCiuc003iyq.3. human. [O15455-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

TLR3base

TLR3 mutation db

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U88879 mRNA. Translation: AAC34134.1 .
DQ445682 mRNA. Translation: ABE01399.1 .
AB445631 mRNA. Translation: BAG55028.1 .
DQ360814 Genomic DNA. Translation: ABC86908.1 .
DQ360815 Genomic DNA. Translation: ABC86909.1 .
DQ360816 Genomic DNA. Translation: ABC86910.1 .
AK302143 mRNA. Translation: BAH13636.1 .
AK314208 mRNA. Translation: BAG36884.1 .
AC104070 Genomic DNA. No translation available.
CH471056 Genomic DNA. Translation: EAX04628.1 .
BC094737 mRNA. Translation: AAH94737.1 .
BC096333 mRNA. Translation: AAH96333.1 .
BC096334 mRNA. Translation: AAH96334.1 .
BC096335 mRNA. Translation: AAH96335.1 .
CCDSi CCDS3846.1. [O15455-1 ]
RefSeqi NP_003256.1. NM_003265.2. [O15455-1 ]
XP_006714357.1. XM_006714294.1. [O15455-1 ]
UniGenei Hs.657724.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1ZIW X-ray 2.10 A 27-700 [» ]
2A0Z X-ray 2.40 A 22-703 [» ]
2MK9 NMR - A/B 698-730 [» ]
2MKA NMR - A/B/C 698-730 [» ]
3ULU X-ray 3.52 A 22-702 [» ]
3ULV X-ray 3.52 A 22-702 [» ]
ProteinModelPortali O15455.
SMRi O15455. Positions 26-897.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 112953. 15 interactions.
DIPi DIP-29660N.
IntActi O15455. 6 interactions.
MINTi MINT-2840066.
STRINGi 9606.ENSP00000296795.

Chemistry

ChEMBLi CHEMBL1075113.
GuidetoPHARMACOLOGYi 1753.

PTM databases

PhosphoSitei O15455.

Proteomic databases

MaxQBi O15455.
PaxDbi O15455.
PRIDEi O15455.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000296795 ; ENSP00000296795 ; ENSG00000164342 . [O15455-1 ]
ENST00000504367 ; ENSP00000423684 ; ENSG00000164342 . [O15455-2 ]
GeneIDi 7098.
KEGGi hsa:7098.
UCSCi uc003iyq.3. human. [O15455-1 ]

Organism-specific databases

CTDi 7098.
GeneCardsi GC04P186990.
HGNCi HGNC:11849. TLR3.
HPAi CAB025658.
MIMi 603029. gene.
613002. phenotype.
neXtProti NX_O15455.
Orphaneti 1930. Herpetic encephalitis.
PharmGKBi PA36551.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG4886.
GeneTreei ENSGT00760000119006.
HOGENOMi HOG000251618.
HOVERGENi HBG023181.
InParanoidi O15455.
KOi K05401.
OMAi IANINDD.
OrthoDBi EOG79SDZG.
PhylomeDBi O15455.
TreeFami TF325595.

Enzyme and pathway databases

Reactomei REACT_118563. RIP-mediated NFkB activation via ZBP1.
REACT_118632. Trafficking and processing of endosomal TLR.
REACT_150361. TRIF-mediated programmed cell death.
REACT_25148. Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon.
REACT_25351. TRAF6 mediated induction of TAK1 complex.
REACT_25374. IKK complex recruitment mediated by RIP1.
REACT_6783. Toll Like Receptor 3 (TLR3) Cascade.
SignaLinki O15455.

Miscellaneous databases

EvolutionaryTracei O15455.
GeneWikii TLR_3.
GenomeRNAii 7098.
NextBioi 27769.
PROi O15455.
SOURCEi Search...

Gene expression databases

Bgeei O15455.
CleanExi HS_TLR3.
ExpressionAtlasi O15455. baseline and differential.
Genevestigatori O15455.

Family and domain databases

Gene3Di 3.40.50.10140. 1 hit.
InterProi IPR000483. Cys-rich_flank_reg_C.
IPR001611. Leu-rich_rpt.
IPR003591. Leu-rich_rpt_typical-subtyp.
IPR000372. LRR-contain_N.
IPR000157. TIR_dom.
IPR027173. TLR3.
[Graphical view ]
PANTHERi PTHR24365:SF5. PTHR24365:SF5. 1 hit.
Pfami PF13855. LRR_8. 6 hits.
PF01582. TIR. 1 hit.
[Graphical view ]
SMARTi SM00369. LRR_TYP. 2 hits.
SM00082. LRRCT. 1 hit.
SM00013. LRRNT. 1 hit.
SM00255. TIR. 1 hit.
[Graphical view ]
SUPFAMi SSF52200. SSF52200. 1 hit.
PROSITEi PS51450. LRR. 19 hits.
PS50104. TIR. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "A family of human receptors structurally related to Drosophila Toll."
    Rock F.L., Hardiman G., Timans J.C., Kastelein R.A., Bazan J.F.
    Proc. Natl. Acad. Sci. U.S.A. 95:588-593(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  2. "The innate immune facet of brain: human neurons express TLR-3 and sense viral dsRNA."
    Lafon M., Megret F., Lafage M., Prehaud C.
    J. Mol. Neurosci. 29:185-194(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
    Tissue: Neuron.
  3. "Natural selection in the TLR-related genes in the course of primate evolution."
    Nakajima T., Ohtani H., Satta Y., Uno Y., Akari H., Ishida T., Kimura A.
    Immunogenetics 60:727-735(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  4. "TLR polymorphism."
    Macquin C., Bahram S.
    Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT PHE-412.
  5. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANT PHE-412.
    Tissue: Testis and Thymus.
  6. "Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
    Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H.
    , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
    Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  7. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  8. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Placenta.
  9. "Signal peptide prediction based on analysis of experimentally verified cleavage sites."
    Zhang Z., Henzel W.J.
    Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 24-38.
  10. "A novel Toll/IL-1 receptor domain-containing adapter that preferentially activates the IFN-beta promoter in the Toll-like receptor signaling."
    Yamamoto M., Sato S., Mori K., Hoshino K., Takeuchi O., Takeda K., Akira S.
    J. Immunol. 169:6668-6672(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH TICAM1.
  11. "TICAM-1, an adapter molecule that participates in Toll-like receptor 3 mediated interferon-beta induction."
    Oshiumi H., Matsumoto M., Funami K., Akazawa T., Seya T.
    Nat. Immunol. 4:161-167(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH TICAM1.
    Tissue: Lung.
  12. "Recognition of double-stranded RNA by human toll-like receptor 3 and downstream receptor signaling requires multimerization and an acidic pH."
    de Bouteiller O., Merck E., Hasan U.A., Hubac S., Benguigui B., Trinchieri G., Bates E.E., Caux C.
    J. Biol. Chem. 280:38133-38145(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBUNIT, MUTAGENESIS OF CYS-95; CYS-122; ASN-196 AND ASN-247.
  13. "Toll-like receptor 3 associates with c-Src tyrosine kinase on endosomes to initiate antiviral signaling."
    Johnsen I.B., Nguyen T.T., Ringdal M., Tryggestad A.M., Bakke O., Lien E., Espevik T., Anthonsen M.W.
    EMBO J. 25:3335-3346(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH SRC.
  14. Cited for: FUNCTION, MUTAGENESIS OF HIS-539 AND ASN-541.
  15. "Two tyrosine residues of Toll-like receptor 3 trigger different steps of NF-kappa B activation."
    Sarkar S.N., Elco C.P., Peters K.L., Chattopadhyay S., Sen G.C.
    J. Biol. Chem. 282:3423-3427(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT TYR-759 AND TYR-858, FUNCTION, MUTAGENESIS OF TYR-759.
  16. Cited for: FUNCTION, DOUBLE-STRANDED RNA-BINDING, HOMODIMERIZATION.
  17. "Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
    Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
    J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-52 AND ASN-57.
    Tissue: Liver.
  18. Cited for: FUNCTION, PROTEOLYTIC PROCESSING, SUBCELLULAR LOCATION, INTERACTION WITH UNC93B1.
  19. "The molecular structure of the Toll-like receptor 3 ligand-binding domain."
    Bell J.K., Botos I., Hall P.R., Askins J., Shiloach J., Segal D.M., Davies D.R.
    Proc. Natl. Acad. Sci. U.S.A. 102:10976-10980(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 22-703, FUNCTION, DISULFIDE BONDS, SUBUNIT, GLYCOSYLATION AT ASN-52; ASN-70; ASN-196; ASN-252; ASN-265; ASN-275; ASN-291; ASN-398; ASN-413; ASN-507 AND ASN-636, IDENTIFICATION BY MASS SPECTROMETRY.
  20. "Crystal structure of human toll-like receptor 3 (TLR3) ectodomain."
    Choe J., Kelker M.S., Wilson I.A.
    Science 309:581-585(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 27-700, DISULFIDE BONDS, GLYCOSYLATION AT ASN-124; ASN-252; ASN-275; ASN-291; ASN-398; ASN-413 AND ASN-507.
  21. Cited for: X-RAY CRYSTALLOGRAPHY (3.52 ANGSTROMS) OF 22-702 IN COMPLEX WITH ANTIBODY, DISULFIDE BONDS, SUBUNIT, DS-RNA BINDING REGIONS, GLYCOSYLATION AT ASN-52; ASN-70; ASN-124; ASN-247; ASN-252; ASN-265; ASN-275; ASN-291; ASN-398; ASN-413 AND ASN-507.
  22. Cited for: VARIANT HSE2 SER-554.
  23. Cited for: VARIANT PHE-412.
  24. Cited for: VARIANT PHE-412.

Entry informationi

Entry nameiTLR3_HUMAN
AccessioniPrimary (citable) accession number: O15455
Secondary accession number(s): B2RAI7
, B7Z7K0, E6Y0F0, E6Y0F1, E9PGH4, Q4VAL2, Q504W0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 31, 2002
Last sequence update: January 1, 1998
Last modified: October 29, 2014
This is version 149 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  2. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3