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Protein

Toll-like receptor 3

Gene

Tlr3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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

Keywordsi

Molecular functionReceptor, RNA-binding
Biological processImmunity, Inflammatory response, Innate immunity

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 8

Organism-specific databases

MGIiMGI:2156367 Tlr3

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

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

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...) asparagineSequence analysis1
Glycosylationi58N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi71N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi96 ↔ 1231 Publication
Glycosylationi125N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi197N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi248N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi253N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi276N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi292N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi399N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi414N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi425N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi508N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi650 ↔ 6781 Publication
Disulfide bondi652 ↔ 6971 Publication
Glycosylationi663N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi668N-linked (GlcNAc...) asparagine1 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 Expressed in 228 organ(s), highest expression level in cochlea
CleanExiMM_TLR3
ExpressionAtlasiQ99MB1 baseline and differential
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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi228338, 8 interactors
IntActiQ99MB1, 2 interactors
MINTiQ99MB1
STRINGi10090.ENSMUSP00000034056

Structurei

Secondary structure

1905
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

Keywords - Domaini

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

Phylogenomic databases

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

Family and domain databases

Gene3Di3.40.50.10140, 1 hit
3.80.10.10, 1 hit
InterProiView protein in InterPro
IPR000483 Cys-rich_flank_reg_C
IPR001611 Leu-rich_rpt
IPR003591 Leu-rich_rpt_typical-subtyp
IPR032675 LRR_dom_sf
IPR000157 TIR_dom
IPR027173 TLR3
IPR035897 Toll_tir_struct_dom_sf
PANTHERiPTHR44599 PTHR44599, 1 hit
PfamiView protein in Pfam
PF00560 LRR_1, 1 hit
PF13855 LRR_8, 5 hits
PF01582 TIR, 1 hit
SMARTiView protein in SMART
SM00369 LRR_TYP, 16 hits
SM00082 LRRCT, 1 hit
SM00255 TIR, 1 hit
SUPFAMiSSF52200 SSF52200, 1 hit
PROSITEiView protein in PROSITE
PS51450 LRR, 18 hits
PS50104 TIR, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

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

This entry has 1 described isoform and 4 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A1B0GS40A0A1B0GS40_MOUSE
Toll-like receptor 3
Tlr3
306Annotation score:
A0A1B0GSY9A0A1B0GSY9_MOUSE
Toll-like receptor 3
Tlr3
93Annotation score:
A0A1Y7VI41A0A1Y7VI41_MOUSE
Toll-like receptor 3
Tlr3
7Annotation score:
A0A1B0GTA2A0A1B0GTA2_MOUSE
Toll-like receptor 3
Tlr3
15Annotation score:

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

Similar proteinsi

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, 2 interactors
MINTiQ99MB1
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
OMAiHLLKDPL
OrthoDBiEOG091G02Q2
PhylomeDBiQ99MB1
TreeFamiTF325595

Enzyme and pathway databases

ReactomeiR-MMU-1679131 Trafficking and processing of endosomal TLR

Miscellaneous databases

EvolutionaryTraceiQ99MB1
PROiPR:Q99MB1
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000031639 Expressed in 228 organ(s), highest expression level in cochlea
CleanExiMM_TLR3
ExpressionAtlasiQ99MB1 baseline and differential
GenevisibleiQ99MB1 MM

Family and domain databases

Gene3Di3.40.50.10140, 1 hit
3.80.10.10, 1 hit
InterProiView protein in InterPro
IPR000483 Cys-rich_flank_reg_C
IPR001611 Leu-rich_rpt
IPR003591 Leu-rich_rpt_typical-subtyp
IPR032675 LRR_dom_sf
IPR000157 TIR_dom
IPR027173 TLR3
IPR035897 Toll_tir_struct_dom_sf
PANTHERiPTHR44599 PTHR44599, 1 hit
PfamiView protein in Pfam
PF00560 LRR_1, 1 hit
PF13855 LRR_8, 5 hits
PF01582 TIR, 1 hit
SMARTiView protein in SMART
SM00369 LRR_TYP, 16 hits
SM00082 LRRCT, 1 hit
SM00255 TIR, 1 hit
SUPFAMiSSF52200 SSF52200, 1 hit
PROSITEiView protein in PROSITE
PS51450 LRR, 18 hits
PS50104 TIR, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiTLR3_MOUSE
AccessioniPrimary (citable) accession number: Q99MB1
Secondary accession number(s): Q91ZM4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 31, 2002
Last sequence update: January 31, 2002
Last modified: September 12, 2018
This is version 164 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

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