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Q99MB1 (TLR3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 128. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·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
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length905 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 By similarity. Ref.4

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 By similarity. Ref.5 Ref.6

Subcellular location

Endoplasmic reticulum membrane; Single-pass type I membrane protein. Endosome membrane By similarity.

Tissue specificity

Highly expressed in lung. After intraperitoneal injection of lipopolysaccharide, highly expressed in brain, heart, kidney, liver, lung and spleen.

Domain

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

Post-translational modification

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 By similarity.

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
   DomainLeucine-rich repeat
Repeat
Signal
Transmembrane
Transmembrane helix
   LigandRNA-binding
   Molecular functionReceptor
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processI-kappaB phosphorylation

Inferred from electronic annotation. Source: Ensembl

MyD88-independent toll-like receptor signaling pathway

Inferred from electronic annotation. Source: InterPro

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 electronic annotation. Source: Ensembl

defense response

Inferred from mutant phenotype Ref.1. Source: MGI

defense response to virus

Traceable author statement PubMed 15356140. Source: BHF-UCL

extrinsic apoptotic signaling pathway

Inferred from electronic annotation. Source: Ensembl

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 electronic annotation. Source: Ensembl

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 direct assay PubMed 16260493PubMed 19734906. Source: MGI

positive regulation of JNK cascade

Inferred from direct assay PubMed 16260493. Source: MGI

positive regulation of NF-kappaB import into nucleus

Inferred from electronic annotation. Source: Ensembl

positive regulation of NF-kappaB transcription factor activity

Inferred from mutant phenotype PubMed 12855817. Source: MGI

positive regulation of apoptotic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of chemokine biosynthetic process

Inferred from mutant phenotype PubMed 12855817. Source: MGI

positive regulation of chemokine production

Inferred from electronic annotation. Source: InterPro

positive regulation of inflammatory response

Inferred from electronic annotation. Source: InterPro

positive regulation of interferon-alpha biosynthetic process

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of interferon-beta biosynthetic process

Inferred from sequence or structural similarity PubMed 12054664. Source: UniProtKB

positive regulation of interferon-beta production

Inferred from direct assay PubMed 15356140. Source: BHF-UCL

positive regulation of interferon-gamma biosynthetic process

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of interleukin-12 production

Inferred from direct assay PubMed 15356140. Source: BHF-UCL

positive regulation of interleukin-6 production

Inferred from direct assay PubMed 15356140. Source: BHF-UCL

positive regulation of interleukin-8 production

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein phosphorylation

Inferred from electronic annotation. Source: Ensembl

positive regulation of toll-like receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 15356140. Source: BHF-UCL

positive regulation of tumor necrosis factor production

Inferred from direct assay PubMed 15356140. Source: BHF-UCL

positive regulation of type I interferon production

Inferred from direct assay PubMed 18207576. Source: MGI

positive regulation of type III interferon production

Inferred from direct assay PubMed 18207576. Source: MGI

response to exogenous dsRNA

Inferred from mutant phenotype PubMed 12855817. Source: MGI

response to virus

Inferred from mutant phenotype Ref.4. Source: MGI

toll-like receptor 3 signaling pathway

Inferred from electronic annotation. Source: InterPro

   Cellular_componentcell surface

Inferred from electronic annotation. Source: Ensembl

endoplasmic reticulum membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

endosome membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

lysosomal membrane

Inferred from electronic annotation. Source: Ensembl

   Molecular_functiondouble-stranded RNA binding

Inferred from sequence or structural similarity. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.5. Source: UniProtKB

transmembrane signaling receptor activity

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2525 Potential
Chain26 – 905880Toll-like receptor 3
PRO_0000034716

Regions

Topological domain26 – 705680Lumenal Potential
Transmembrane706 – 72621Helical; Potential
Topological domain727 – 905179Cytoplasmic Potential
Domain26 – 5227LRRNT
Repeat53 – 7422LRR 1
Repeat77 – 9822LRR 2
Repeat101 – 12222LRR 3
Repeat125 – 14622LRR 4
Repeat149 – 17022LRR 5
Repeat173 – 19624LRR 6
Repeat199 – 22022LRR 7
Repeat250 – 27122LRR 8
Repeat276 – 29722LRR 9
Repeat300 – 32122LRR 10
Repeat324 – 34522LRR 11
Repeat357 – 37822LRR 12
Repeat381 – 40121LRR 13
Repeat409 – 43022LRR 14
Repeat433 – 45422LRR 15
Repeat458 – 47922LRR 16
Repeat482 – 50221LRR 17
Repeat508 – 52922LRR 18
Repeat532 – 55322LRR 19
Repeat564 – 58522LRR 20
Repeat588 – 60922LRR 21
Repeat612 – 63322LRR 22
Domain646 – 69954LRRCT
Domain755 – 897143TIR

Amino acid modifications

Modified residue7601Phosphotyrosine By similarity
Modified residue8591Phosphotyrosine By similarity
Glycosylation531N-linked (GlcNAc...) Potential
Glycosylation581N-linked (GlcNAc...) Potential
Glycosylation711N-linked (GlcNAc...) Ref.6
Glycosylation1251N-linked (GlcNAc...) Potential
Glycosylation1971N-linked (GlcNAc...) Ref.6
Glycosylation2481N-linked (GlcNAc...) Potential
Glycosylation2531N-linked (GlcNAc...) Ref.6
Glycosylation2761N-linked (GlcNAc...) Ref.6
Glycosylation2921N-linked (GlcNAc...) Ref.6
Glycosylation3991N-linked (GlcNAc...) Ref.6
Glycosylation4141N-linked (GlcNAc...) Ref.6
Glycosylation4251N-linked (GlcNAc...) Ref.6
Glycosylation5081N-linked (GlcNAc...) Ref.6
Glycosylation6631N-linked (GlcNAc...) Ref.6
Glycosylation6681N-linked (GlcNAc...) Ref.6
Disulfide bond29 ↔ 38 Ref.6
Disulfide bond96 ↔ 123 Ref.6
Disulfide bond650 ↔ 678 Ref.6
Disulfide bond652 ↔ 697 Ref.6

Experimental info

Sequence conflict6701S → F in AAK26117. Ref.2

Secondary structure

.............................................................................................................................. 905
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q99MB1 [UniParc].

Last modified January 31, 2002. Version 2.
Checksum: 8EA6DBA9818E14B4

FASTA905103,671
        10         20         30         40         50         60 
MKGCSSYLMY SFGGLLSLWI LLVSSTNQCT VRYNVADCSH LKLTHIPDDL PSNITVLNLT 

        70         80         90        100        110        120 
HNQLRRLPPT NFTRYSQLAI LDAGFNSISK LEPELCQILP LLKVLNLQHN ELSQISDQTF 

       130        140        150        160        170        180 
VFCTNLTELD LMSNSIHKIK SNPFKNQKNL IKLDLSHNGL SSTKLGTGVQ LENLQELLLA 

       190        200        210        220        230        240 
KNKILALRSE ELEFLGNSSL RKLDLSSNPL KEFSPGCFQT IGKLFALLLN NAQLNPHLTE 

       250        260        270        280        290        300 
KLCWELSNTS IQNLSLANNQ LLATSESTFS GLKWTNLTQL DLSYNNLHDV GNGSFSYLPS 

       310        320        330        340        350        360 
LRYLSLEYNN IQRLSPRSFY GLSNLRYLSL KRAFTKQSVS LASHPNIDDF SFQWLKYLEY 

       370        380        390        400        410        420 
LNMDDNNIPS TKSNTFTGLV SLKYLSLSKT FTSLQTLTNE TFVSLAHSPL LTLNLTKNHI 

       430        440        450        460        470        480 
SKIANGTFSW LGQLRILDLG LNEIEQKLSG QEWRGLRNIF EIYLSYNKYL QLSTSSFALV 

       490        500        510        520        530        540 
PSLQRLMLRR VALKNVDISP SPFRPLRNLT ILDLSNNNIA NINEDLLEGL ENLEILDFQH 

       550        560        570        580        590        600 
NNLARLWKRA NPGGPVNFLK GLSHLHILNL ESNGLDEIPV GVFKNLFELK SINLGLNNLN 

       610        620        630        640        650        660 
KLEPFIFDDQ TSLRSLNLQK NLITSVEKDV FGPPFQNLNS LDMRFNPFDC TCESISWFVN 

       670        680        690        700        710        720 
WINQTHTNIS ELSTHYLCNT PHHYYGFPLK LFDTSSCKDS APFELLFIIS TSMLLVFILV 

       730        740        750        760        770        780 
VLLIHIEGWR ISFYWNVSVH RILGFKEIDT QAEQFEYTAY IIHAHKDRDW VWEHFSPMEE 

       790        800        810        820        830        840 
QDQSLKFCLE ERDFEAGVLG LEAIVNSIKR SRKIIFVITH HLLKDPLCRR FKVHHAVQQA 

       850        860        870        880        890        900 
IEQNLDSIIL IFLQNIPDYK LNHALCLRRG MFKSHCILNW PVQKERINAF HHKLQVALGS 


RNSAH 

« Hide

References

« Hide 'large scale' references
[1]"Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3."
Alexopoulou L., Holt A.C., Medzhitov R., Flavell R.A.
Nature 413:732-738(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: 129/Sv.
[2]"Molecular cloning of mouse Toll-like receptor 3 cDNA."
Applequist S.E., Ljunggren H.G.
Submitted (FEB-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: BALB/c X NIH.
Tissue: Macrophage.
[3]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6J.
Tissue: Spinal ganglion.
[4]"Toll-like receptors 9 and 3 as essential components of innate immune defense against mouse cytomegalovirus infection."
Tabeta K., Georgel P., Janssen E., Du X., Hoebe K., Crozat K., Mudd S., Shamel L., Sovath S., Goode J., Alexopoulou L., Flavell R.A., Beutler B.
Proc. Natl. Acad. Sci. U.S.A. 101:3516-3521(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CYTOMEGALOVIRUS INFECTION.
[5]"The interaction between the ER membrane protein UNC93B and TLR3, 7, and 9 is crucial for TLR signaling."
Brinkmann M.M., Spooner E., Hoebe K., Beutler B., Ploegh H.L., Kim Y.M.
J. Cell Biol. 177:265-275(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY, INTERACTION WITH UNC93B1.
[6]"Structural basis of toll-like receptor 3 signaling with double-stranded RNA."
Liu L., Botos I., Wang Y., Leonard J.N., Shiloach J., Segal D.M., Davies D.R.
Science 320:379-381(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.66 ANGSTROMS) OF 28-704 IN COMPLEX WITH DS-RNA, SUBUNIT, DISULFIDE BONDS, GLYCOSYLATION AT ASN-71; ASN-197; ASN-253; ASN-276; ASN-292; ASN-399; ASN-414; ASN-425; ASN-508; ASN-663 AND ASN-668.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF420279 mRNA. Translation: AAL27007.1.
AF355152 mRNA. Translation: AAK26117.1.
AK083977 mRNA. Translation: BAC39082.1.
CCDSCCDS22278.1.
RefSeqNP_569054.2. NM_126166.4.
XP_006509341.1. XM_006509278.1.
XP_006509342.1. XM_006509279.1.
XP_006509343.1. XM_006509280.1.
XP_006509344.1. XM_006509281.1.
XP_006509345.1. XM_006509282.1.
XP_006509346.1. XM_006509283.1.
UniGeneMm.33874.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3CIGX-ray2.66A28-704[»]
3CIYX-ray3.41A/B28-704[»]
ProteinModelPortalQ99MB1.
SMRQ99MB1. Positions 28-698, 757-898.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ99MB1. 1 interaction.
MINTMINT-4138015.

Chemistry

ChEMBLCHEMBL2146340.

PTM databases

PhosphoSiteQ99MB1.

Proteomic databases

MaxQBQ99MB1.
PaxDbQ99MB1.
PRIDEQ99MB1.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000034056; ENSMUSP00000034056; ENSMUSG00000031639.
ENSMUST00000167106; ENSMUSP00000126556; ENSMUSG00000031639.
GeneID142980.
KEGGmmu:142980.
UCSCuc009loy.1. mouse.

Organism-specific databases

CTD7098.
MGIMGI:2156367. Tlr3.

Phylogenomic databases

eggNOGNOG265249.
GeneTreeENSGT00750000117512.
HOGENOMHOG000251618.
HOVERGENHBG023181.
InParanoidQ99MB1.
KOK05401.
OMAIANINDD.
OrthoDBEOG79SDZG.
PhylomeDBQ99MB1.
TreeFamTF325595.

Gene expression databases

ArrayExpressQ99MB1.
BgeeQ99MB1.
CleanExMM_TLR3.
GenevestigatorQ99MB1.

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.
PfamPF00560. LRR_1. 1 hit.
PF13855. LRR_8. 6 hits.
PF01582. TIR. 1 hit.
[Graphical view]
SMARTSM00369. LRR_TYP. 4 hits.
SM00082. LRRCT. 1 hit.
SM00013. LRRNT. 1 hit.
SM00255. TIR. 1 hit.
[Graphical view]
SUPFAMSSF52200. SSF52200. 1 hit.
PROSITEPS51450. LRR. 18 hits.
PS50104. TIR. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ99MB1.
NextBio370067.
PROQ99MB1.
SOURCESearch...

Entry information

Entry nameTLR3_MOUSE
AccessionPrimary (citable) accession number: Q99MB1
Secondary accession number(s): Q91ZM4
Entry history
Integrated into UniProtKB/Swiss-Prot: January 31, 2002
Last sequence update: January 31, 2002
Last modified: July 9, 2014
This is version 128 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot