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Protein

Toll-like receptor 3

Gene

Tlr3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: 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 (By similarity).By similarity1 Publication

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Receptor

Keywords - Biological processi

Immunity, Inflammatory response, Innate immunity

Keywords - Ligandi

RNA-binding

Enzyme and pathway databases

ReactomeiR-MMU-1679131. Trafficking and processing of endosomal TLR.

Names & Taxonomyi

Protein namesi
Recommended name:
Toll-like receptor 3
Alternative name(s):
CD_antigen: CD283
Gene namesi
Name:Tlr3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 8

Organism-specific databases

MGIiMGI:2156367. Tlr3.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini26 – 705LumenalSequence analysisAdd BLAST680
Transmembranei706 – 726HelicalSequence analysisAdd BLAST21
Topological domaini727 – 905CytoplasmicSequence analysisAdd BLAST179

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Endosome, Membrane

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL2146340.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 25Sequence analysisAdd BLAST25
ChainiPRO_000003471626 – 905Toll-like receptor 3Add BLAST880

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi29 ↔ 381 Publication
Glycosylationi53N-linked (GlcNAc...)Sequence analysis1
Glycosylationi58N-linked (GlcNAc...)Sequence analysis1
Glycosylationi71N-linked (GlcNAc...)1 Publication1
Disulfide bondi96 ↔ 1231 Publication
Glycosylationi125N-linked (GlcNAc...)Sequence analysis1
Glycosylationi197N-linked (GlcNAc...)1 Publication1
Glycosylationi248N-linked (GlcNAc...)Sequence analysis1
Glycosylationi253N-linked (GlcNAc...)1 Publication1
Glycosylationi276N-linked (GlcNAc...)1 Publication1
Glycosylationi292N-linked (GlcNAc...)1 Publication1
Glycosylationi399N-linked (GlcNAc...)1 Publication1
Glycosylationi414N-linked (GlcNAc...)1 Publication1
Glycosylationi425N-linked (GlcNAc...)1 Publication1
Glycosylationi508N-linked (GlcNAc...)1 Publication1
Disulfide bondi650 ↔ 6781 Publication
Disulfide bondi652 ↔ 6971 Publication
Glycosylationi663N-linked (GlcNAc...)1 Publication1
Glycosylationi668N-linked (GlcNAc...)1 Publication1
Modified residuei760PhosphotyrosineBy similarity1
Modified residuei859PhosphotyrosineBy similarity1

Post-translational modificationi

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).By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

MaxQBiQ99MB1.
PaxDbiQ99MB1.
PRIDEiQ99MB1.

PTM databases

iPTMnetiQ99MB1.
PhosphoSitePlusiQ99MB1.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSMUSG00000031639.
CleanExiMM_TLR3.
GenevisibleiQ99MB1. MM.

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 SRC; upon binding of double-stranded RNA (By similarity). Interacts with TICAM1 (via the TIR domain) in response to poly(I:C) and this interaction is enhanced in the presence of WDFY1 (PubMed:25736436). The tyrosine-phosphorylated form (via TIR domain) interacts with WDFY1 (via WD repeat 2) in response to poly(I:C) (PubMed:25736436).By similarity1 Publication

Protein-protein interaction databases

BioGridi228338. 8 interactors.
IntActiQ99MB1. 1 interactor.
MINTiMINT-4138015.
STRINGi10090.ENSMUSP00000034056.

Structurei

Secondary structure

1905
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi33 – 37Combined sources5
Beta strandi55 – 58Combined sources4
Turni69 – 72Combined sources4
Turni74 – 77Combined sources4
Beta strandi79 – 82Combined sources4
Helixi94 – 98Combined sources5
Beta strandi104 – 106Combined sources3
Helixi117 – 120Combined sources4
Beta strandi128 – 130Combined sources3
Turni143 – 146Combined sources4
Beta strandi152 – 154Combined sources3
Beta strandi167 – 169Combined sources3
Beta strandi176 – 178Combined sources3
Helixi190 – 195Combined sources6
Beta strandi199 – 204Combined sources6
Turni215 – 220Combined sources6
Beta strandi221 – 224Combined sources4
Beta strandi226 – 228Combined sources3
Helixi236 – 246Combined sources11
Beta strandi247 – 249Combined sources3
Beta strandi253 – 255Combined sources3
Beta strandi262 – 264Combined sources3
Turni266 – 269Combined sources4
Helixi270 – 272Combined sources3
Beta strandi279 – 281Combined sources3
Turni292 – 297Combined sources6
Beta strandi303 – 305Combined sources3
Turni316 – 321Combined sources6
Beta strandi327 – 329Combined sources3
Beta strandi339 – 341Combined sources3
Turni349 – 354Combined sources6
Beta strandi360 – 362Combined sources3
Turni373 – 378Combined sources6
Beta strandi384 – 386Combined sources3
Beta strandi391 – 393Combined sources3
Turni399 – 402Combined sources4
Helixi403 – 405Combined sources3
Beta strandi412 – 414Combined sources3
Turni425 – 430Combined sources6
Beta strandi436 – 438Combined sources3
Beta strandi445 – 447Combined sources3
Helixi451 – 453Combined sources3
Beta strandi461 – 463Combined sources3
Beta strandi468 – 471Combined sources4
Turni474 – 479Combined sources6
Beta strandi485 – 487Combined sources3
Beta strandi493 – 495Combined sources3
Beta strandi497 – 500Combined sources4
Turni502 – 505Combined sources4
Beta strandi511 – 513Combined sources3
Turni524 – 529Combined sources6
Beta strandi535 – 537Combined sources3
Beta strandi567 – 569Combined sources3
Turni580 – 585Combined sources6
Beta strandi591 – 593Combined sources3
Turni604 – 609Combined sources6
Beta strandi615 – 617Combined sources3
Helixi628 – 635Combined sources8
Beta strandi639 – 642Combined sources4
Helixi652 – 664Combined sources13
Helixi672 – 675Combined sources4
Beta strandi677 – 681Combined sources5
Helixi682 – 684Combined sources3
Helixi689 – 691Combined sources3
Helixi694 – 696Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3CIGX-ray2.66A28-704[»]
3CIYX-ray3.41A/B28-704[»]
ProteinModelPortaliQ99MB1.
SMRiQ99MB1.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ99MB1.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini26 – 52LRRNTAdd BLAST27
Repeati53 – 74LRR 1Add BLAST22
Repeati77 – 98LRR 2Add BLAST22
Repeati101 – 122LRR 3Add BLAST22
Repeati125 – 146LRR 4Add BLAST22
Repeati149 – 170LRR 5Add BLAST22
Repeati173 – 196LRR 6Add BLAST24
Repeati199 – 220LRR 7Add BLAST22
Repeati250 – 271LRR 8Add BLAST22
Repeati276 – 297LRR 9Add BLAST22
Repeati300 – 321LRR 10Add BLAST22
Repeati324 – 345LRR 11Add BLAST22
Repeati357 – 378LRR 12Add BLAST22
Repeati381 – 401LRR 13Add BLAST21
Repeati409 – 430LRR 14Add BLAST22
Repeati433 – 454LRR 15Add BLAST22
Repeati458 – 479LRR 16Add BLAST22
Repeati482 – 502LRR 17Add BLAST21
Repeati508 – 529LRR 18Add BLAST22
Repeati532 – 553LRR 19Add BLAST22
Repeati564 – 585LRR 20Add BLAST22
Repeati588 – 609LRR 21Add BLAST22
Repeati612 – 633LRR 22Add BLAST22
Domaini646 – 699LRRCTAdd BLAST54
Domaini755 – 897TIRPROSITE-ProRule annotationAdd BLAST143

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

eggNOGiKOG4641. Eukaryota.
COG4886. LUCA.
GeneTreeiENSGT00760000119006.
HOGENOMiHOG000251618.
HOVERGENiHBG023181.
InParanoidiQ99MB1.
KOiK05401.
OMAiLNMDDNN.
OrthoDBiEOG091G02Q2.
PhylomeDBiQ99MB1.
TreeFamiTF325595.

Family and domain databases

Gene3Di3.40.50.10140. 1 hit.
3.80.10.10. 4 hits.
InterProiIPR000483. Cys-rich_flank_reg_C.
IPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR003591. Leu-rich_rpt_typical-subtyp.
IPR000157. TIR_dom.
IPR027173. TLR3.
[Graphical view]
PANTHERiPTHR24365:SF5. PTHR24365:SF5. 2 hits.
PfamiPF00560. LRR_1. 1 hit.
PF13855. LRR_8. 5 hits.
PF01582. TIR. 1 hit.
[Graphical view]
SMARTiSM00369. LRR_TYP. 16 hits.
SM00082. LRRCT. 1 hit.
SM00255. TIR. 1 hit.
[Graphical view]
SUPFAMiSSF52058. SSF52058. 2 hits.
SSF52200. SSF52200. 1 hit.
PROSITEiPS51450. LRR. 18 hits.
PS50104. TIR. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

Q99MB1-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKGCSSYLMY SFGGLLSLWI LLVSSTNQCT VRYNVADCSH LKLTHIPDDL
60 70 80 90 100
PSNITVLNLT HNQLRRLPPT NFTRYSQLAI LDAGFNSISK LEPELCQILP
110 120 130 140 150
LLKVLNLQHN ELSQISDQTF VFCTNLTELD LMSNSIHKIK SNPFKNQKNL
160 170 180 190 200
IKLDLSHNGL SSTKLGTGVQ LENLQELLLA KNKILALRSE ELEFLGNSSL
210 220 230 240 250
RKLDLSSNPL KEFSPGCFQT IGKLFALLLN NAQLNPHLTE KLCWELSNTS
260 270 280 290 300
IQNLSLANNQ LLATSESTFS GLKWTNLTQL DLSYNNLHDV GNGSFSYLPS
310 320 330 340 350
LRYLSLEYNN IQRLSPRSFY GLSNLRYLSL KRAFTKQSVS LASHPNIDDF
360 370 380 390 400
SFQWLKYLEY LNMDDNNIPS TKSNTFTGLV SLKYLSLSKT FTSLQTLTNE
410 420 430 440 450
TFVSLAHSPL LTLNLTKNHI SKIANGTFSW LGQLRILDLG LNEIEQKLSG
460 470 480 490 500
QEWRGLRNIF EIYLSYNKYL QLSTSSFALV PSLQRLMLRR VALKNVDISP
510 520 530 540 550
SPFRPLRNLT ILDLSNNNIA NINEDLLEGL ENLEILDFQH NNLARLWKRA
560 570 580 590 600
NPGGPVNFLK GLSHLHILNL ESNGLDEIPV GVFKNLFELK SINLGLNNLN
610 620 630 640 650
KLEPFIFDDQ TSLRSLNLQK NLITSVEKDV FGPPFQNLNS LDMRFNPFDC
660 670 680 690 700
TCESISWFVN WINQTHTNIS ELSTHYLCNT PHHYYGFPLK LFDTSSCKDS
710 720 730 740 750
APFELLFIIS TSMLLVFILV VLLIHIEGWR ISFYWNVSVH RILGFKEIDT
760 770 780 790 800
QAEQFEYTAY IIHAHKDRDW VWEHFSPMEE QDQSLKFCLE ERDFEAGVLG
810 820 830 840 850
LEAIVNSIKR SRKIIFVITH HLLKDPLCRR FKVHHAVQQA IEQNLDSIIL
860 870 880 890 900
IFLQNIPDYK LNHALCLRRG MFKSHCILNW PVQKERINAF HHKLQVALGS

RNSAH
Length:905
Mass (Da):103,671
Last modified:January 31, 2002 - v2
Checksum:i8EA6DBA9818E14B4
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti670S → F in AAK26117 (Ref. 2) Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF420279 mRNA. Translation: AAL27007.1.
AF355152 mRNA. Translation: AAK26117.1.
AK083977 mRNA. Translation: BAC39082.1.
CCDSiCCDS22278.1.
RefSeqiNP_569054.2. NM_126166.4.
XP_006509341.1. XM_006509278.3.
XP_006509342.1. XM_006509279.2.
XP_006509343.1. XM_006509280.2.
XP_006509344.1. XM_006509281.3.
XP_006509345.1. XM_006509282.3.
XP_006509346.1. XM_006509283.3.
UniGeneiMm.33874.

Genome annotation databases

EnsembliENSMUST00000034056; ENSMUSP00000034056; ENSMUSG00000031639.
ENSMUST00000167106; ENSMUSP00000126556; ENSMUSG00000031639.
ENSMUST00000209772; ENSMUSP00000147738; ENSMUSG00000031639.
GeneIDi142980.
KEGGimmu:142980.
UCSCiuc009loy.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF420279 mRNA. Translation: AAL27007.1.
AF355152 mRNA. Translation: AAK26117.1.
AK083977 mRNA. Translation: BAC39082.1.
CCDSiCCDS22278.1.
RefSeqiNP_569054.2. NM_126166.4.
XP_006509341.1. XM_006509278.3.
XP_006509342.1. XM_006509279.2.
XP_006509343.1. XM_006509280.2.
XP_006509344.1. XM_006509281.3.
XP_006509345.1. XM_006509282.3.
XP_006509346.1. XM_006509283.3.
UniGeneiMm.33874.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3CIGX-ray2.66A28-704[»]
3CIYX-ray3.41A/B28-704[»]
ProteinModelPortaliQ99MB1.
SMRiQ99MB1.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi228338. 8 interactors.
IntActiQ99MB1. 1 interactor.
MINTiMINT-4138015.
STRINGi10090.ENSMUSP00000034056.

Chemistry databases

ChEMBLiCHEMBL2146340.

PTM databases

iPTMnetiQ99MB1.
PhosphoSitePlusiQ99MB1.

Proteomic databases

MaxQBiQ99MB1.
PaxDbiQ99MB1.
PRIDEiQ99MB1.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000034056; ENSMUSP00000034056; ENSMUSG00000031639.
ENSMUST00000167106; ENSMUSP00000126556; ENSMUSG00000031639.
ENSMUST00000209772; ENSMUSP00000147738; ENSMUSG00000031639.
GeneIDi142980.
KEGGimmu:142980.
UCSCiuc009loy.1. mouse.

Organism-specific databases

CTDi7098.
MGIiMGI:2156367. Tlr3.

Phylogenomic databases

eggNOGiKOG4641. Eukaryota.
COG4886. LUCA.
GeneTreeiENSGT00760000119006.
HOGENOMiHOG000251618.
HOVERGENiHBG023181.
InParanoidiQ99MB1.
KOiK05401.
OMAiLNMDDNN.
OrthoDBiEOG091G02Q2.
PhylomeDBiQ99MB1.
TreeFamiTF325595.

Enzyme and pathway databases

ReactomeiR-MMU-1679131. Trafficking and processing of endosomal TLR.

Miscellaneous databases

EvolutionaryTraceiQ99MB1.
PROiQ99MB1.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000031639.
CleanExiMM_TLR3.
GenevisibleiQ99MB1. MM.

Family and domain databases

Gene3Di3.40.50.10140. 1 hit.
3.80.10.10. 4 hits.
InterProiIPR000483. Cys-rich_flank_reg_C.
IPR032675. L_dom-like.
IPR001611. Leu-rich_rpt.
IPR003591. Leu-rich_rpt_typical-subtyp.
IPR000157. TIR_dom.
IPR027173. TLR3.
[Graphical view]
PANTHERiPTHR24365:SF5. PTHR24365:SF5. 2 hits.
PfamiPF00560. LRR_1. 1 hit.
PF13855. LRR_8. 5 hits.
PF01582. TIR. 1 hit.
[Graphical view]
SMARTiSM00369. LRR_TYP. 16 hits.
SM00082. LRRCT. 1 hit.
SM00255. TIR. 1 hit.
[Graphical view]
SUPFAMiSSF52058. SSF52058. 2 hits.
SSF52200. SSF52200. 1 hit.
PROSITEiPS51450. LRR. 18 hits.
PS50104. TIR. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTLR3_MOUSE
AccessioniPrimary (citable) accession number: Q99MB1
Secondary accession number(s): Q91ZM4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 31, 2002
Last sequence update: January 31, 2002
Last modified: November 30, 2016
This is version 152 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.