UniProtKB - P58682 (TLR8_MOUSE)
Protein
Toll-like receptor 8
Gene
Tlr8
Organism
Mus musculus (Mouse)
Status
Functioni
Endosomal receptor that plays a key role in innate and adaptive immunity. Controls host immune response against pathogens through recognition of RNA degradation products specific to microorganisms that are initially processed by RNASET2. Upon binding to agonists, undergoes dimerization that brings TIR domains from the two molecules into direct contact, leading to the recruitment of TIR-containing downstream adapter MYD88 through homotypic interaction. In turn, the Myddosome signaling complex is formed involving IRAK4, IRAK1, TRAF6, TRAF3 leading to activation of downstream transcription factors NF-kappa-B and IRF7 to induce proinflammatory cytokines and interferons, respectively.By similarity
Activity regulationi
Activated by RNAs having enough uridines.By similarity
GO - Molecular functioni
- DNA binding Source: UniProtKB
- double-stranded RNA binding Source: UniProtKB
- drug binding Source: MGI
- identical protein binding Source: MGI
- pattern recognition receptor activity Source: GO_Central
- single-stranded RNA binding Source: UniProtKB
- transmembrane signaling receptor activity Source: InterPro
GO - Biological processi
- cellular response to mechanical stimulus Source: Ensembl
- defense response to virus Source: UniProtKB
- I-kappaB kinase/NF-kappaB signaling Source: MGI
- immune response Source: GO_Central
- innate immune response Source: UniProtKB-KW
- microglial cell activation Source: MGI
- MyD88-dependent toll-like receptor signaling pathway Source: InterPro
- negative regulation of interleukin-12 production Source: MGI
- positive regulation of innate immune response Source: UniProtKB
- positive regulation of interferon-alpha production Source: UniProtKB
- positive regulation of interferon-beta production Source: UniProtKB
- positive regulation of interferon-gamma production Source: UniProtKB
- positive regulation of interleukin-1 beta production Source: MGI
- positive regulation of interleukin-6 production Source: MGI
- positive regulation of interleukin-8 production Source: UniProtKB
- regulation of cytokine secretion Source: InterPro
- regulation of protein phosphorylation Source: MGI
- response to virus Source: MGI
- toll-like receptor 8 signaling pathway Source: MGI
- toll-like receptor signaling pathway Source: MGI
Keywordsi
Molecular function | Receptor |
Biological process | Immunity, Inflammatory response, Innate immunity |
Enzyme and pathway databases
Reactomei | R-MMU-1679131, Trafficking and processing of endosomal TLR |
Names & Taxonomyi
Protein namesi | Recommended name: Toll-like receptor 8Alternative name(s): CD_antigen: CD288 |
Gene namesi | Name:Tlr8 |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:2176887, Tlr8 |
Subcellular locationi
Endosome
- Endosome membrane By similarity; Single-pass type I membrane protein By similarity
Note: Endosomal localization confers distinctive proteolytic processing.By similarity
Endosome
- endosome membrane Source: UniProtKB-SubCell
Plasma Membrane
- external side of plasma membrane Source: MGI
- plasma membrane Source: GO_Central
Other locations
- integral component of membrane Source: UniProtKB-KW
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 24 – 818 | ExtracellularSequence analysisAdd BLAST | 795 | |
Transmembranei | 819 – 839 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 840 – 1032 | CytoplasmicSequence analysisAdd BLAST | 193 |
Keywords - Cellular componenti
Endosome, MembranePTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 23 | Sequence analysisAdd BLAST | 23 | |
ChainiPRO_0000034736 | 24 – 1032 | Toll-like receptor 8Add BLAST | 1009 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 29 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 36 ↔ 49 | By similarity | ||
Glycosylationi | 88 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 111 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 122 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 160 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 177 ↔ 181 | By similarity | ||
Glycosylationi | 182 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 231 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 242 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 252 ↔ 265 | By similarity | ||
Disulfide bondi | 255 ↔ 262 | By similarity | ||
Glycosylationi | 268 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 288 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 304 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 353 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 357 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 411 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 470 ↔ 500 | By similarity | ||
Glycosylationi | 502 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 513 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 581 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 671 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 743 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 754 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 783 | N-linked (GlcNAc...) asparagineSequence analysis | 1 |
Post-translational modificationi
Ubiquitinated by RNF216; leading to degradation by the proteasome.By similarity
Proteolytic processing occurs in monocytes and monocyte-derived macrophages by both furin-like proprotein convertase and cathepsins. The cleavage is necessary for dimer formation and subsequent activation.By similarity
Keywords - PTMi
Disulfide bond, Glycoprotein, Ubl conjugationProteomic databases
MaxQBi | P58682 |
PaxDbi | P58682 |
PeptideAtlasi | P58682 |
PRIDEi | P58682 |
PTM databases
GlyGeni | P58682, 21 sites |
iPTMneti | P58682 |
PhosphoSitePlusi | P58682 |
Expressioni
Gene expression databases
Bgeei | ENSMUSG00000040522, Expressed in bone marrow macrophage and 50 other tissues |
ExpressionAtlasi | P58682, baseline and differential |
Genevisiblei | P58682, MM |
Interactioni
Subunit structurei
GO - Molecular functioni
- identical protein binding Source: MGI
Protein-protein interaction databases
BioGRIDi | 228410, 1 interactor |
IntActi | P58682, 2 interactors |
STRINGi | 10090.ENSMUSP00000107793 |
Miscellaneous databases
RNActi | P58682, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Repeati | 41 – 61 | LRR 1Add BLAST | 21 | |
Repeati | 62 – 85 | LRR 2Add BLAST | 24 | |
Repeati | 87 – 109 | LRR 3Add BLAST | 23 | |
Repeati | 120 – 143 | LRR 4Add BLAST | 24 | |
Repeati | 145 – 165 | LRR 5Add BLAST | 21 | |
Repeati | 166 – 194 | LRR 6Add BLAST | 29 | |
Repeati | 195 – 218 | LRR 7Add BLAST | 24 | |
Repeati | 220 – 239 | LRR 8Add BLAST | 20 | |
Repeati | 240 – 267 | LRR 9Add BLAST | 28 | |
Repeati | 281 – 304 | LRR 10Add BLAST | 24 | |
Repeati | 306 – 329 | LRR 11Add BLAST | 24 | |
Repeati | 331 – 360 | LRR 12Add BLAST | 30 | |
Repeati | 361 – 384 | LRR 13Add BLAST | 24 | |
Repeati | 388 – 411 | LRR 14Add BLAST | 24 | |
Repeati | 413 – 436 | LRR 15Add BLAST | 24 | |
Repeati | 471 – 494 | LRR 16Add BLAST | 24 | |
Repeati | 520 – 543 | LRR 17Add BLAST | 24 | |
Repeati | 545 – 572 | LRR 18Add BLAST | 28 | |
Repeati | 574 – 598 | LRR 19Add BLAST | 25 | |
Repeati | 600 – 621 | LRR 20Add BLAST | 22 | |
Repeati | 629 – 652 | LRR 21Add BLAST | 24 | |
Repeati | 654 – 677 | LRR 22Add BLAST | 24 | |
Repeati | 678 – 701 | LRR 23Add BLAST | 24 | |
Repeati | 702 – 725 | LRR 24Add BLAST | 24 | |
Repeati | 727 – 749 | LRR 25Add BLAST | 23 | |
Repeati | 752 – 776 | LRR 26Add BLAST | 25 | |
Domaini | 869 – 1013 | TIRPROSITE-ProRule annotationAdd BLAST | 145 |
Sequence similaritiesi
Belongs to the Toll-like receptor family.Curated
Keywords - Domaini
Leucine-rich repeat, Repeat, Signal, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG4641, Eukaryota |
GeneTreei | ENSGT00940000160879 |
HOGENOMi | CLU_006000_2_0_1 |
InParanoidi | P58682 |
OMAi | HDIACLN |
OrthoDBi | 96378at2759 |
TreeFami | TF351113 |
Family and domain databases
Gene3Di | 3.40.50.10140, 1 hit 3.80.10.10, 1 hit |
InterProi | View protein in InterPro IPR001611, Leu-rich_rpt IPR003591, Leu-rich_rpt_typical-subtyp IPR026906, LRR_5 IPR032675, LRR_dom_sf IPR000157, TIR_dom IPR027175, TLR8 IPR035897, Toll_tir_struct_dom_sf |
PANTHERi | PTHR47410:SF1, PTHR47410:SF1, 1 hit |
Pfami | View protein in Pfam PF13306, LRR_5, 1 hit PF13855, LRR_8, 4 hits PF01582, TIR, 1 hit |
SMARTi | View protein in SMART SM00369, LRR_TYP, 13 hits SM00255, TIR, 1 hit |
SUPFAMi | SSF52200, SSF52200, 1 hit |
PROSITEi | View protein in PROSITE PS51450, LRR, 22 hits PS50104, TIR, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All
P58682-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MENMPPQSWI LTCFCLLSSG TSAIFHKANY SRSYPCDEIR HNSLVIAECN
60 70 80 90 100
HRQLHEVPQT IGKYVTNIDL SDNAITHITK ESFQKLQNLT KIDLNHNAKQ
110 120 130 140 150
QHPNENKNGM NITEGALLSL RNLTVLLLED NQLYTIPAGL PESLKELSLI
160 170 180 190 200
QNNIFQVTKN NTFGLRNLER LYLGWNCYFK CNQTFKVEDG AFKNLIHLKV
210 220 230 240 250
LSLSFNNLFY VPPKLPSSLR KLFLSNAKIM NITQEDFKGL ENLTLLDLSG
260 270 280 290 300
NCPRCYNAPF PCTPCKENSS IHIHPLAFQS LTQLLYLNLS STSLRTIPST
310 320 330 340 350
WFENLSNLKE LHLEFNYLVQ EIASGAFLTK LPSLQILDLS FNFQYKEYLQ
360 370 380 390 400
FINISSNFSK LRSLKKLHLR GYVFRELKKK HFEHLQSLPN LATINLGINF
410 420 430 440 450
IEKIDFKAFQ NFSKLDVIYL SGNRIASVLD GTDYSSWRNR LRKPLSTDDD
460 470 480 490 500
EFDPHVNFYH STKPLIKPQC TAYGKALDLS LNNIFIIGKS QFEGFQDIAC
510 520 530 540 550
LNLSFNANTQ VFNGTEFSSM PHIKYLDLTN NRLDFDDNNA FSDLHDLEVL
560 570 580 590 600
DLSHNAHYFS IAGVTHRLGF IQNLINLRVL NLSHNGIYTL TEESELKSIS
610 620 630 640 650
LKELVFSGNR LDRLWNANDG KYWSIFKSLQ NLIRLDLSYN NLQQIPNGAF
660 670 680 690 700
LNLPQSLQEL LISGNKLRFF NWTLLQYFPH LHLLDLSRNE LYFLPNCLSK
710 720 730 740 750
FAHSLETLLL SHNHFSHLPS GFLSEARNLV HLDLSFNTIK MINKSSLQTK
760 770 780 790 800
MKTNLSILEL HGNYFDCTCD ISDFRSWLDE NLNITIPKLV NVICSNPGDQ
810 820 830 840 850
KSKSIMSLDL TTCVSDTTAA VLFFLTFLTT SMVMLAALVH HLFYWDVWFI
860 870 880 890 900
YHMCSAKLKG YRTSSTSQTF YDAYISYDTK DASVTDWVIN ELRYHLEESE
910 920 930 940 950
DKSVLLCLEE RDWDPGLPII DNLMQSINQS KKTIFVLTKK YAKSWNFKTA
960 970 980 990 1000
FYLALQRLMD ENMDVIIFIL LEPVLQYSQY LRLRQRICKS SILQWPNNPK
1010 1020 1030
AENLFWQSLK NVVLTENDSR YDDLYIDSIR QY
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketA2AHI8 | A2AHI8_MOUSE | Toll-like receptor 8 | Tlr8 | 100 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 613 | R → H in AAK62677 (Ref. 1) Curated | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AY035890 mRNA Translation: AAK62677.1 AL731735 Genomic DNA No translation available. BC132054 mRNA Translation: AAI32055.1 |
CCDSi | CCDS41209.1 |
RefSeqi | NP_001300689.1, NM_001313760.1 NP_001300690.1, NM_001313761.1 NP_573475.2, NM_133212.3 |
Genome annotation databases
Ensembli | ENSMUST00000049023; ENSMUSP00000036762; ENSMUSG00000040522 ENSMUST00000112170; ENSMUSP00000107793; ENSMUSG00000040522 |
GeneIDi | 170744 |
KEGGi | mmu:170744 |
UCSCi | uc009uwy.1, mouse |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AY035890 mRNA Translation: AAK62677.1 AL731735 Genomic DNA No translation available. BC132054 mRNA Translation: AAI32055.1 |
CCDSi | CCDS41209.1 |
RefSeqi | NP_001300689.1, NM_001313760.1 NP_001300690.1, NM_001313761.1 NP_573475.2, NM_133212.3 |
3D structure databases
SMRi | P58682 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 228410, 1 interactor |
IntActi | P58682, 2 interactors |
STRINGi | 10090.ENSMUSP00000107793 |
Chemistry databases
ChEMBLi | CHEMBL2146339 |
PTM databases
GlyGeni | P58682, 21 sites |
iPTMneti | P58682 |
PhosphoSitePlusi | P58682 |
Proteomic databases
MaxQBi | P58682 |
PaxDbi | P58682 |
PeptideAtlasi | P58682 |
PRIDEi | P58682 |
Protocols and materials databases
Antibodypediai | 458, 839 antibodies |
Genome annotation databases
Ensembli | ENSMUST00000049023; ENSMUSP00000036762; ENSMUSG00000040522 ENSMUST00000112170; ENSMUSP00000107793; ENSMUSG00000040522 |
GeneIDi | 170744 |
KEGGi | mmu:170744 |
UCSCi | uc009uwy.1, mouse |
Organism-specific databases
CTDi | 51311 |
MGIi | MGI:2176887, Tlr8 |
Phylogenomic databases
eggNOGi | KOG4641, Eukaryota |
GeneTreei | ENSGT00940000160879 |
HOGENOMi | CLU_006000_2_0_1 |
InParanoidi | P58682 |
OMAi | HDIACLN |
OrthoDBi | 96378at2759 |
TreeFami | TF351113 |
Enzyme and pathway databases
Reactomei | R-MMU-1679131, Trafficking and processing of endosomal TLR |
Miscellaneous databases
BioGRID-ORCSi | 170744, 1 hit in 17 CRISPR screens |
ChiTaRSi | Tlr8, mouse |
PROi | PR:P58682 |
RNActi | P58682, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSMUSG00000040522, Expressed in bone marrow macrophage and 50 other tissues |
ExpressionAtlasi | P58682, baseline and differential |
Genevisiblei | P58682, MM |
Family and domain databases
Gene3Di | 3.40.50.10140, 1 hit 3.80.10.10, 1 hit |
InterProi | View protein in InterPro IPR001611, Leu-rich_rpt IPR003591, Leu-rich_rpt_typical-subtyp IPR026906, LRR_5 IPR032675, LRR_dom_sf IPR000157, TIR_dom IPR027175, TLR8 IPR035897, Toll_tir_struct_dom_sf |
PANTHERi | PTHR47410:SF1, PTHR47410:SF1, 1 hit |
Pfami | View protein in Pfam PF13306, LRR_5, 1 hit PF13855, LRR_8, 4 hits PF01582, TIR, 1 hit |
SMARTi | View protein in SMART SM00369, LRR_TYP, 13 hits SM00255, TIR, 1 hit |
SUPFAMi | SSF52200, SSF52200, 1 hit |
PROSITEi | View protein in PROSITE PS51450, LRR, 22 hits PS50104, TIR, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | TLR8_MOUSE | |
Accessioni | P58682Primary (citable) accession number: P58682 Secondary accession number(s): A2AHI9, Q91XI7 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | January 31, 2002 |
Last sequence update: | July 27, 2011 | |
Last modified: | December 2, 2020 | |
This is version 162 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families