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O15455 (TLR3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 143. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Toll-like receptor 3
Alternative name(s):
CD_antigen=CD283
Gene names
Name:TLR3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length904 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.18 Ref.19

Subunit structure

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. Ref.10 Ref.11 Ref.12 Ref.13 Ref.16 Ref.18 Ref.19 Ref.21

Subcellular location

Endoplasmic reticulum membrane; Single-pass type I membrane protein. Endosome membrane Ref.13 Ref.18.

Tissue specificity

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. Ref.2

Domain

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

Post-translational modification

Heavily N-glycosylated, except on that part of the surface of the ectodomain that is involved in ligand binding. Ref.19 Ref.20 Ref.21

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. Ref.18

Polymorphism

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.

Involvement in disease

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.
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. Ref.22

Sequence similarities

Belongs to the Toll-like receptor family.

Contains 22 LRR (leucine-rich) repeats.

Contains 1 LRRCT domain.

Contains 1 LRRNT domain.

Contains 1 TIR domain.

Ontologies

Keywords
   Biological processImmunity
Inflammatory response
Innate immunity
   Cellular componentEndoplasmic reticulum
Endosome
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
   DomainLeucine-rich repeat
Repeat
Signal
Transmembrane
Transmembrane helix
   LigandRNA-binding
   Molecular functionReceptor
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processI-kappaB kinase/NF-kappaB signaling

Traceable author statement. Source: Reactome

I-kappaB phosphorylation

Inferred from direct assay PubMed 19740627. Source: BHF-UCL

MyD88-independent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

TRIF-dependent toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

activation of NF-kappaB-inducing kinase activity

Non-traceable author statement PubMed 12054664. Source: UniProtKB

cellular response to drug

Inferred from electronic annotation. Source: Ensembl

cellular response to exogenous dsRNA

Inferred from electronic annotation. Source: Ensembl

cellular response to interferon-beta

Inferred from electronic annotation. Source: Ensembl

cellular response to interferon-gamma

Inferred from electronic annotation. Source: Ensembl

cellular response to mechanical stimulus

Inferred from expression pattern PubMed 19593445. Source: UniProtKB

defense response to bacterium

Traceable author statement PubMed 10426995. Source: ProtInc

defense response to virus

Traceable author statement PubMed 15356140. Source: BHF-UCL

detection of virus

Non-traceable author statement PubMed 12054664. Source: UniProtKB

extrinsic apoptotic signaling pathway

Inferred from direct assay PubMed 21737330. Source: UniProtKB

hyperosmotic response

Non-traceable author statement PubMed 12054664. Source: UniProtKB

inflammatory response

Inferred from electronic annotation. Source: UniProtKB-KW

innate immune response

Traceable author statement PubMed 15356140. Source: BHF-UCL

male gonad development

Inferred from electronic annotation. Source: Ensembl

microglial cell activation involved in immune response

Inferred from electronic annotation. Source: Ensembl

necroptotic signaling pathway

Inferred from direct assay PubMed 21737330. Source: UniProtKB

negative regulation of osteoclast differentiation

Non-traceable author statement PubMed 12133979. Source: UniProtKB

pathogen-associated molecular pattern dependent induction by symbiont of host innate immune response

Inferred from electronic annotation. Source: Ensembl

positive regulation of I-kappaB kinase/NF-kappaB signaling

Inferred from electronic annotation. Source: Ensembl

positive regulation of JNK cascade

Inferred from electronic annotation. Source: Ensembl

positive regulation of NF-kappaB import into nucleus

Inferred from direct assay PubMed 19740627. Source: BHF-UCL

positive regulation of NF-kappaB transcription factor activity

Inferred from electronic annotation. Source: Ensembl

positive regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of chemokine biosynthetic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of chemokine production

Inferred from direct assay PubMed 19740627. Source: BHF-UCL

positive regulation of inflammatory response

Inferred by curator PubMed 19740627. Source: BHF-UCL

positive regulation of interferon-alpha biosynthetic process

Inferred from direct assay PubMed 16286015. Source: UniProtKB

positive regulation of interferon-beta biosynthetic process

Inferred from direct assay PubMed 16286015. Source: UniProtKB

positive regulation of interferon-beta production

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of interferon-gamma biosynthetic process

Inferred from direct assay PubMed 16286015. Source: UniProtKB

positive regulation of interleukin-12 production

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of interleukin-6 production

Inferred from direct assay PubMed 19740627. Source: BHF-UCL

positive regulation of interleukin-8 production

Inferred from direct assay PubMed 17128265. Source: BHF-UCL

positive regulation of toll-like receptor signaling pathway

Inferred from direct assay PubMed 17128265. Source: BHF-UCL

positive regulation of transcription from RNA polymerase II promoter

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of tumor necrosis factor production

Inferred from sequence or structural similarity. Source: BHF-UCL

positive regulation of type III interferon production

Inferred from electronic annotation. Source: Ensembl

response to exogenous dsRNA

Inferred from direct assay PubMed 21266579. Source: MGI

signal transduction

Traceable author statement PubMed 10426995Ref.1. Source: ProtInc

toll-like receptor 3 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor 4 signaling pathway

Traceable author statement. Source: Reactome

toll-like receptor signaling pathway

Traceable author statement. Source: Reactome

   Cellular_componentGolgi membrane

Traceable author statement. Source: Reactome

cytoplasm

Inferred from direct assay PubMed 19740627. Source: BHF-UCL

endolysosome membrane

Traceable author statement. Source: Reactome

endoplasmic reticulum membrane

Traceable author statement. Source: Reactome

endosome membrane

Traceable author statement. Source: Reactome

integral component of plasma membrane

Traceable author statement Ref.1. Source: ProtInc

lysosomal membrane

Inferred from direct assay PubMed 17897319. Source: UniProtKB

membrane

Non-traceable author statement PubMed 12054664. Source: UniProtKB

   Molecular_functiondouble-stranded RNA binding

Inferred from direct assay PubMed 16111635. Source: UniProtKB

receptor activity

Traceable author statement PubMed 10426995. Source: ProtInc

transmembrane signaling receptor activity

Non-traceable author statement PubMed 12054664. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

PIK3R1P279862EBI-6289595,EBI-79464

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O15455-1)

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.
Isoform 2 (identifier: O15455-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-277: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2323 Ref.9
Chain24 – 904881Toll-like receptor 3
PRO_0000034715

Regions

Topological domain24 – 704681Lumenal Potential
Transmembrane705 – 72521Helical; Potential
Topological domain726 – 904179Cytoplasmic Potential
Domain24 – 5128LRRNT
Repeat52 – 7322LRR 1
Repeat76 – 9722LRR 2
Repeat100 – 12122LRR 3
Repeat124 – 14522LRR 4
Repeat148 – 16821LRR 5
Repeat172 – 19322LRR 6
Repeat198 – 21922LRR 7
Repeat222 – 24423LRR 8
Repeat249 – 27022LRR 9
Repeat275 – 29622LRR 10
Repeat299 – 32022LRR 11
Repeat323 – 34422LRR 12
Repeat356 – 37722LRR 13
Repeat380 – 40021LRR 14
Repeat408 – 42922LRR 15
Repeat432 – 45423LRR 16
Repeat465 – 48622LRR 17
Repeat507 – 52822LRR 18
Repeat531 – 55222LRR 19
Repeat563 – 58422LRR 20
Repeat587 – 60822LRR 21
Repeat611 – 63222LRR 22
Domain645 – 69854LRRCT
Domain754 – 896143TIR

Amino acid modifications

Modified residue7591Phosphotyrosine Ref.15
Modified residue8581Phosphotyrosine Ref.15
Glycosylation521N-linked (GlcNAc...) Ref.17 Ref.19 Ref.21
Glycosylation571N-linked (GlcNAc...) Ref.17
Glycosylation701N-linked (GlcNAc...) Ref.19 Ref.21
Glycosylation1241N-linked (GlcNAc...) Ref.20 Ref.21
Glycosylation1961N-linked (GlcNAc...) Ref.19
Glycosylation2471N-linked (GlcNAc...) Ref.21
Glycosylation2521N-linked (GlcNAc...) Ref.19 Ref.20 Ref.21
Glycosylation2651N-linked (GlcNAc...) Ref.19 Ref.21
Glycosylation2751N-linked (GlcNAc...) Ref.19 Ref.20 Ref.21
Glycosylation2911N-linked (GlcNAc...) Ref.19 Ref.20 Ref.21
Glycosylation3981N-linked (GlcNAc...) Ref.19 Ref.20 Ref.21
Glycosylation4131N-linked (GlcNAc...) Ref.19 Ref.20 Ref.21
Glycosylation5071N-linked (GlcNAc...) Ref.19 Ref.20 Ref.21
Glycosylation6361N-linked (GlcNAc...) Ref.19
Glycosylation6621N-linked (GlcNAc...) Potential
Disulfide bond28 ↔ 37 Ref.19 Ref.20 Ref.21
Disulfide bond95 ↔ 122 Ref.19 Ref.20 Ref.21
Disulfide bond649 ↔ 677 Ref.19 Ref.20 Ref.21
Disulfide bond651 ↔ 696 Ref.19 Ref.20 Ref.21

Natural variations

Alternative sequence1 – 277277Missing in isoform 2.
VSP_054188
Natural variant2841N → I.
Corresponds to variant rs5743316 [ dbSNP | Ensembl ].
VAR_052361
Natural variant3071Y → D.
Corresponds to variant rs5743317 [ dbSNP | Ensembl ].
VAR_052362
Natural variant4121L → F. Ref.4 Ref.5 Ref.23 Ref.25
Corresponds to variant rs3775291 [ dbSNP | Ensembl ].
VAR_021976
Natural variant5541P → S in HSE2; causes TLR3 deficiency and predisposition to herpes simplex encephalitis. Ref.22
VAR_054887
Natural variant7371S → T.
Corresponds to variant rs5743318 [ dbSNP | Ensembl ].
VAR_024664

Experimental info

Mutagenesis951C → A: Reduced response to ds-RNA. Ref.12
Mutagenesis1221C → A: Reduced response to ds-RNA. Ref.12
Mutagenesis1961N → G: Reduced expression levels; when associated with R-247. Ref.12
Mutagenesis2471N → R: Reduced response to ds-RNA. Reduced expression levels; when associated with G-196. Ref.12
Mutagenesis5391H → A: No effect. Ref.14
Mutagenesis5391H → E: Loss of RNA binding. Constitutive activation of NF-kappa-B. Ref.14
Mutagenesis5411N → A: Loss of RNA binding. Abolishes activation of NF-kappa-B. Ref.14
Mutagenesis7591Y → F: Reduced activation of NF-kappa-B in response to ds-RNA. Reduced induction of IL-8 in response to ds-RNA. Ref.15
Sequence conflict2901G → R in BAG36884. Ref.5
Sequence conflict5751D → N in AAH94737. Ref.8
Sequence conflict6051V → A in BAG36884. Ref.5
Sequence conflict6631E → G in BAG36884. Ref.5

Secondary structure

......................................................................................................................... 904
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified January 1, 1998. Version 1.
Checksum: 034E05ECA7A4D2F7

FASTA904103,829
        10         20         30         40         50         60 
MRQTLPCIYF WGGLLPFGML CASSTTKCTV SHEVADCSHL KLTQVPDDLP TNITVLNLTH 

        70         80         90        100        110        120 
NQLRRLPAAN FTRYSQLTSL DVGFNTISKL EPELCQKLPM LKVLNLQHNE LSQLSDKTFA 

       130        140        150        160        170        180 
FCTNLTELHL MSNSIQKIKN NPFVKQKNLI TLDLSHNGLS STKLGTQVQL ENLQELLLSN 

       190        200        210        220        230        240 
NKIQALKSEE LDIFANSSLK KLELSSNQIK EFSPGCFHAI GRLFGLFLNN VQLGPSLTEK 

       250        260        270        280        290        300 
LCLELANTSI RNLSLSNSQL STTSNTTFLG LKWTNLTMLD LSYNNLNVVG NDSFAWLPQL 

       310        320        330        340        350        360 
EYFFLEYNNI QHLFSHSLHG LFNVRYLNLK RSFTKQSISL ASLPKIDDFS FQWLKCLEHL 

       370        380        390        400        410        420 
NMEDNDIPGI KSNMFTGLIN LKYLSLSNSF TSLRTLTNET FVSLAHSPLH ILNLTKNKIS 

       430        440        450        460        470        480 
KIESDAFSWL GHLEVLDLGL NEIGQELTGQ EWRGLENIFE IYLSYNKYLQ LTRNSFALVP 

       490        500        510        520        530        540 
SLQRLMLRRV ALKNVDSSPS PFQPLRNLTI LDLSNNNIAN INDDMLEGLE KLEILDLQHN 

       550        560        570        580        590        600 
NLARLWKHAN PGGPIYFLKG LSHLHILNLE SNGFDEIPVE VFKDLFELKI IDLGLNNLNT 

       610        620        630        640        650        660 
LPASVFNNQV SLKSLNLQKN LITSVEKKVF GPAFRNLTEL DMRFNPFDCT CESIAWFVNW 

       670        680        690        700        710        720 
INETHTNIPE LSSHYLCNTP PHYHGFPVRL FDTSSCKDSA PFELFFMINT SILLIFIFIV 

       730        740        750        760        770        780 
LLIHFEGWRI SFYWNVSVHR VLGFKEIDRQ TEQFEYAAYI IHAYKDKDWV WEHFSSMEKE 

       790        800        810        820        830        840 
DQSLKFCLEE RDFEAGVFEL EAIVNSIKRS RKIIFVITHH LLKDPLCKRF KVHHAVQQAI 

       850        860        870        880        890        900 
EQNLDSIILV FLEEIPDYKL NHALCLRRGM FKSHCILNWP VQKERIGAFR HKLQVALGSK 


NSVH 

« Hide

Isoform 2 [UniParc].

Checksum: 0D376D88306EBEFC
Show »

FASTA62772,937

References

« Hide 'large scale' references
[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. expand/collapse author list , 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. expand/collapse author list , 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]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
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]"The dsRNA binding site of human Toll-like receptor 3."
Bell J.K., Askins J., Hall P.R., Davies D.R., Segal D.M.
Proc. Natl. Acad. Sci. U.S.A. 103:8792-8797(2006) [PubMed] [Europe PMC] [Abstract]
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]"The TLR3 signaling complex forms by cooperative receptor dimerization."
Leonard J.N., Ghirlando R., Askins J., Bell J.K., Margulies D.H., Davies D.R., Segal D.M.
Proc. Natl. Acad. Sci. U.S.A. 105:258-263(2008) [PubMed] [Europe PMC] [Abstract]
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]"Cleavage of Toll-like receptor 3 by cathepsins B and H is essential for signaling."
Garcia-Cattaneo A., Gobert F.X., Muller M., Toscano F., Flores M., Lescure A., Del Nery E., Benaroch P.
Proc. Natl. Acad. Sci. U.S.A. 109:9053-9058(2012) [PubMed] [Europe PMC] [Abstract]
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]"Lateral clustering of TLR3:dsRNA signaling units revealed by TLR3ecd:3Fabs quaternary structure."
Luo J., Obmolova G., Malia T.J., Wu S.J., Duffy K.E., Marion J.D., Bell J.K., Ge P., Zhou Z.H., Teplyakov A., Zhao Y., Lamb R.J., Jordan J.L., San Mateo L.R., Sweet R.W., Gilliland G.L.
J. Mol. Biol. 421:112-124(2012) [PubMed] [Europe PMC] [Abstract]
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]"TLR3 deficiency in patients with herpes simplex encephalitis."
Zhang S.-Y., Jouanguy E., Ugolini S., Smahi A., Elain G., Romero P., Segal D., Sancho-Shimizu V., Lorenzo L., Puel A., Picard C., Chapgier A., Plancoulaine S., Titeux M., Cognet C., von Bernuth H., Ku C.-L., Casrouge A. expand/collapse author list , Zhang X.-X., Barreiro L., Leonard J., Hamilton C., Lebon P., Heron B., Vallee L., Quintana-Murci L., Hovnanian A., Rozenberg F., Vivier E., Geissmann F., Tardieu M., Abel L., Casanova J.-L.
Science 317:1522-1527(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HSE2 SER-554.
[23]"Toll-like receptor 3 and geographic atrophy in age-related macular degeneration."
Yang Z., Stratton C., Francis P.J., Kleinman M.E., Tan P.L., Gibbs D., Tong Z., Chen H., Constantine R., Yang X., Chen Y., Zeng J., Davey L., Ma X., Hau V.S., Wang C., Harmon J., Buehler J. expand/collapse author list , Pearson E., Patel S., Kaminoh Y., Watkins S., Luo L., Zabriskie N.A., Bernstein P.S., Cho W., Schwager A., Hinton D.R., Klein M.L., Hamon S.C., Simmons E., Yu B., Campochiaro B., Sunness J.S., Campochiaro P., Jorde L., Parmigiani G., Zack D.J., Katsanis N., Ambati J., Zhang K.
N. Engl. J. Med. 359:1456-1463(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PHE-412.
[24]Erratum
Yang Z., Stratton C., Francis P.J., Kleinman M.E., Tan P.L., Gibbs D., Tong Z., Chen H., Constantine R., Yang X., Chen Y., Zeng J., Davey L., Ma X., Hau V.S., Wang C., Harmon J., Buehler J. expand/collapse author list , Pearson E., Patel S., Kaminoh Y., Watkins S., Luo L., Zabriskie N.A., Bernstein P.S., Cho W., Schwager A., Hinton D.R., Klein M.L., Hamon S.C., Simmons E., Yu B., Campochiaro B., Sunness J.S., Campochiaro P., Jorde L., Parmigiani G., Zack D.J., Katsanis N., Ambati J., Zhang K.
N. Engl. J. Med. 359:1859-1859(2008)
[25]"A common polymorphism in TLR3 confers natural resistance to HIV-1 infection."
Sironi M., Biasin M., Cagliani R., Forni D., De Luca M., Saulle I., Lo Caputo S., Mazzotta F., Macias J., Pineda J.A., Caruz A., Clerici M.
J. Immunol. 188:818-823(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PHE-412.
+Additional computationally mapped references.

Web resources

TLR3base

TLR3 mutation db

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_003256.1. NM_003265.2.
UniGeneHs.657724.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1ZIWX-ray2.10A27-700[»]
2A0ZX-ray2.40A22-703[»]
3ULUX-ray3.52A22-702[»]
3ULVX-ray3.52A22-702[»]
ProteinModelPortalO15455.
SMRO15455. Positions 26-903.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112953. 15 interactions.
DIPDIP-29660N.
IntActO15455. 6 interactions.
MINTMINT-2840066.
STRING9606.ENSP00000296795.

Chemistry

ChEMBLCHEMBL1075113.
GuidetoPHARMACOLOGY1753.

PTM databases

PhosphoSiteO15455.

Proteomic databases

PaxDbO15455.
PRIDEO15455.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000296795; ENSP00000296795; ENSG00000164342.
ENST00000504367; ENSP00000423684; ENSG00000164342.
GeneID7098.
KEGGhsa:7098.
UCSCuc003iyq.3. human.

Organism-specific databases

CTD7098.
GeneCardsGC04P186990.
HGNCHGNC:11849. TLR3.
HPACAB025658.
MIM603029. gene.
613002. phenotype.
neXtProtNX_O15455.
Orphanet1930. Herpetic encephalitis.
PharmGKBPA36551.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG4886.
HOGENOMHOG000251618.
HOVERGENHBG023181.
InParanoidO15455.
KOK05401.
OMAIANINDD.
OrthoDBEOG79SDZG.
PhylomeDBO15455.
TreeFamTF325595.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.
SignaLinkO15455.

Gene expression databases

ArrayExpressO15455.
BgeeO15455.
CleanExHS_TLR3.
GenevestigatorO15455.

Family and domain databases

Gene3D3.40.50.10140. 1 hit.
InterProIPR000483. 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]
PANTHERPTHR24365:SF5. PTHR24365:SF5. 1 hit.
PfamPF01582. TIR. 1 hit.
[Graphical view]
SMARTSM00369. LRR_TYP. 2 hits.
SM00082. LRRCT. 1 hit.
SM00013. LRRNT. 1 hit.
SM00255. TIR. 1 hit.
[Graphical view]
SUPFAMSSF52200. SSF52200. 1 hit.
PROSITEPS51450. LRR. 19 hits.
PS50104. TIR. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceO15455.
GeneWikiTLR_3.
GenomeRNAi7098.
NextBio27769.
PROO15455.
SOURCESearch...

Entry information

Entry nameTLR3_HUMAN
AccessionPrimary (citable) accession number: O15455
Secondary accession number(s): B2RAI7 expand/collapse secondary AC list , B7Z7K0, E6Y0F0, E6Y0F1, E9PGH4, Q4VAL2, Q504W0
Entry history
Integrated into UniProtKB/Swiss-Prot: January 31, 2002
Last sequence update: January 1, 1998
Last modified: April 16, 2014
This is version 143 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM

Human cell differentiation molecules

CD nomenclature of surface proteins of human leucocytes and list of entries