UniProtKB - Q9NYK1 (TLR7_HUMAN)
Protein
Toll-like receptor 7
Gene
TLR7
Organism
Homo sapiens (Human)
Status
Functioni
Endosomal receptor that plays a key role in innate and adaptive immunity (PubMed:14976261, PubMed:32433612). Controls host immune response against pathogens through recognition of uridine-containing single strand RNAs (ssRNAs) of viral origin or guanosine analogs (PubMed:31608988, PubMed:27742543, PubMed:12738885). 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 (PubMed:27742543). 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 (PubMed:27742543).5 Publications
Activity regulationi
Activated by guanosine analogs including deoxyguanosine, 7-thia-8-oxoguanosine or 7-deazaguanosine in a RNA-independent manner.2 Publications
GO - Molecular functioni
- double-stranded RNA binding Source: UniProtKB
- drug binding Source: Ensembl
- pattern recognition receptor activity Source: GO_Central
- single-stranded RNA binding Source: UniProtKB
- siRNA binding Source: UniProtKB
- transmembrane signaling receptor activity Source: InterPro
GO - Biological processi
- cellular response to mechanical stimulus Source: UniProtKB
- defense response to virus Source: UniProtKB
- I-kappaB kinase/NF-kappaB signaling Source: GO_Central
- I-kappaB phosphorylation Source: BHF-UCL
- immune response Source: GO_Central
- innate immune response Source: UniProtKB-KW
- microglial cell activation Source: Ensembl
- MyD88-dependent toll-like receptor signaling pathway Source: InterPro
- positive regulation of chemokine production Source: BHF-UCL
- positive regulation of inflammatory response Source: BHF-UCL
- 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-6 production Source: GO_Central
- positive regulation of interleukin-8 production Source: BHF-UCL
- positive regulation of NIK/NF-kappaB signaling Source: BHF-UCL
- regulation of protein phosphorylation Source: Ensembl
- toll-like receptor 7 signaling pathway Source: GO_Central
- toll-like receptor 9 signaling pathway Source: Reactome
- toll-like receptor signaling pathway Source: GO_Central
Keywordsi
Molecular function | Receptor |
Biological process | Immunity, Inflammatory response, Innate immunity |
Enzyme and pathway databases
PathwayCommonsi | Q9NYK1 |
Reactomei | R-HSA-1679131, Trafficking and processing of endosomal TLR R-HSA-168181, Toll Like Receptor 7/8 (TLR7/8) Cascade R-HSA-9679191, Potential therapeutics for SARS R-HSA-975110, TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling R-HSA-975138, TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation R-HSA-975155, MyD88 dependent cascade initiated on endosome |
SIGNORi | Q9NYK1 |
Names & Taxonomyi
Protein namesi | Recommended name: Toll-like receptor 7 |
Gene namesi | Name:TLR7 ORF Names:UNQ248/PRO285 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000196664.4 |
HGNCi | HGNC:15631, TLR7 |
MIMi | 300365, gene |
neXtProti | NX_Q9NYK1 |
Subcellular locationi
Endosome
- Endosome By similarity
Lysosome
- Lysosome By similarity
Endoplasmic reticulum
- Endoplasmic reticulum membrane By similarity; Single-pass type I membrane protein By similarity
Other locations
- phagosome By similarity
Note: Relocalizes from endoplasmic reticulum to endosome and lysosome upon stimulation with agonist.By similarity
Endoplasmic reticulum
- endoplasmic reticulum Source: UniProtKB
- endoplasmic reticulum membrane Source: Reactome
Endosome
- endolysosome membrane Source: Reactome
- endosome Source: UniProtKB
- endosome membrane Source: Reactome
Golgi apparatus
- Golgi membrane Source: Reactome
Lysosome
- endolysosome membrane Source: Reactome
- lysosome Source: UniProtKB
Plasma Membrane
- plasma membrane Source: BHF-UCL
Other locations
- cytoplasm Source: BHF-UCL
- early phagosome Source: UniProtKB
- integral component of membrane Source: UniProtKB-KW
- receptor complex Source: MGI
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 27 – 839 | ExtracellularSequence analysisAdd BLAST | 813 | |
Transmembranei | 840 – 860 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 861 – 1049 | CytoplasmicSequence analysisAdd BLAST | 189 |
Keywords - Cellular componenti
Cytoplasmic vesicle, Endoplasmic reticulum, Endosome, Lysosome, MembranePathology & Biotechi
Organism-specific databases
DisGeNETi | 51284 |
OpenTargetsi | ENSG00000196664 |
PharmGKBi | PA38008 |
Miscellaneous databases
Pharosi | Q9NYK1, Tclin |
Chemistry databases
ChEMBLi | CHEMBL5936 |
DrugBanki | DB05127, ANA971 DB05475, Golotimod DB01611, Hydroxychloroquine DB00724, Imiquimod DB04860, Isatoribine DB06530, Resiquimod |
DrugCentrali | Q9NYK1 |
GuidetoPHARMACOLOGYi | 1757 |
Polymorphism and mutation databases
BioMutai | TLR7 |
DMDMi | 20140876 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 26 | Sequence analysisAdd BLAST | 26 | |
ChainiPRO_0000034733 | 27 – 1049 | Toll-like receptor 7Add BLAST | 1023 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 66 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 69 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 167 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 202 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 215 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 361 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 413 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 488 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 523 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 534 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 590 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 679 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 720 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 799 | N-linked (GlcNAc...) asparagineSequence analysis | 1 |
Keywords - PTMi
GlycoproteinProteomic databases
jPOSTi | Q9NYK1 |
MassIVEi | Q9NYK1 |
PaxDbi | Q9NYK1 |
PeptideAtlasi | Q9NYK1 |
PRIDEi | Q9NYK1 |
ProteomicsDBi | 83240 |
PTM databases
GlyGeni | Q9NYK1, 14 sites |
iPTMneti | Q9NYK1 |
PhosphoSitePlusi | Q9NYK1 |
Expressioni
Tissue specificityi
Detected in brain, placenta, spleen, stomach, small intestine, lung and in plasmacytoid pre-dendritic cells.
Gene expression databases
Bgeei | ENSG00000196664, Expressed in leukocyte and 131 other tissues |
ExpressionAtlasi | Q9NYK1, baseline and differential |
Genevisiblei | Q9NYK1, HS |
Organism-specific databases
HPAi | ENSG00000196664, Tissue enhanced (brain) |
Interactioni
Subunit structurei
Homodimer (PubMed:27742543).
Interacts with MYD88 via their respective TIR domains (Probable).
Interacts with UNC93B1 (By similarity).
Interacts with SMPDL3B (By similarity).
By similarityCurated1 PublicationProtein-protein interaction databases
BioGRIDi | 119436, 2 interactors |
IntActi | Q9NYK1, 11 interactors |
STRINGi | 9606.ENSP00000370034 |
Chemistry databases
BindingDBi | Q9NYK1 |
Miscellaneous databases
RNActi | Q9NYK1, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Repeati | 43 – 64 | LRR 1Add BLAST | 22 | |
Repeati | 65 – 87 | LRR 2Add BLAST | 23 | |
Repeati | 110 – 126 | LRR 3Add BLAST | 17 | |
Repeati | 127 – 149 | LRR 4Add BLAST | 23 | |
Repeati | 151 – 170 | LRR 5Add BLAST | 20 | |
Repeati | 171 – 195 | LRR 6Add BLAST | 25 | |
Repeati | 203 – 226 | LRR 7Add BLAST | 24 | |
Repeati | 228 – 247 | LRR 8Add BLAST | 20 | |
Repeati | 248 – 275 | LRR 9Add BLAST | 28 | |
Repeati | 289 – 312 | LRR 10Add BLAST | 24 | |
Repeati | 314 – 337 | LRR 11Add BLAST | 24 | |
Repeati | 339 – 368 | LRR 12Add BLAST | 30 | |
Repeati | 369 – 392 | LRR 13Add BLAST | 24 | |
Repeati | 396 – 419 | LRR 14Add BLAST | 24 | |
Repeati | 421 – 443 | LRR 15Add BLAST | 23 | |
Repeati | 492 – 515 | LRR 16Add BLAST | 24 | |
Repeati | 516 – 540 | LRR 17Add BLAST | 25 | |
Repeati | 541 – 564 | LRR 18Add BLAST | 24 | |
Repeati | 566 – 588 | LRR 19Add BLAST | 23 | |
Repeati | 595 – 618 | LRR 20Add BLAST | 24 | |
Repeati | 619 – 644 | LRR 21Add BLAST | 26 | |
Repeati | 649 – 672 | LRR 22Add BLAST | 24 | |
Repeati | 674 – 697 | LRR 23Add BLAST | 24 | |
Repeati | 698 – 721 | LRR 24Add BLAST | 24 | |
Repeati | 723 – 745 | LRR 25Add BLAST | 23 | |
Repeati | 746 – 769 | LRR 26Add BLAST | 24 | |
Repeati | 772 – 795 | LRR 27Add BLAST | 24 | |
Domaini | 889 – 1033 | TIRPROSITE-ProRule annotationAdd BLAST | 145 |
Domaini
Contains two binding domains, first site for small ligands and second site for ssRNA.1 Publication
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 | ENSGT00940000159771 |
HOGENOMi | CLU_006000_2_0_1 |
InParanoidi | Q9NYK1 |
OMAi | DPAVSEW |
OrthoDBi | 303561at2759 |
PhylomeDBi | Q9NYK1 |
TreeFami | TF325595 |
Family and domain databases
Gene3Di | 3.40.50.10140, 1 hit 3.80.10.10, 1 hit |
InterProi | View protein in InterPro IPR000483, Cys-rich_flank_reg_C IPR001611, Leu-rich_rpt IPR003591, Leu-rich_rpt_typical-subtyp IPR026906, LRR_5 IPR032675, LRR_dom_sf IPR000157, TIR_dom IPR026880, TLR7 IPR035897, Toll_tir_struct_dom_sf |
PANTHERi | PTHR47410:SF2, PTHR47410:SF2, 1 hit |
Pfami | View protein in Pfam PF13306, LRR_5, 1 hit PF13855, LRR_8, 3 hits PF01582, TIR, 1 hit |
SMARTi | View protein in SMART SM00369, LRR_TYP, 12 hits SM00082, LRRCT, 1 hit SM00255, TIR, 1 hit |
SUPFAMi | SSF52200, SSF52200, 1 hit |
PROSITEi | View protein in PROSITE PS51450, LRR, 18 hits PS50104, TIR, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
Q9NYK1-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MVFPMWTLKR QILILFNIIL ISKLLGARWF PKTLPCDVTL DVPKNHVIVD
60 70 80 90 100
CTDKHLTEIP GGIPTNTTNL TLTINHIPDI SPASFHRLDH LVEIDFRCNC
110 120 130 140 150
VPIPLGSKNN MCIKRLQIKP RSFSGLTYLK SLYLDGNQLL EIPQGLPPSL
160 170 180 190 200
QLLSLEANNI FSIRKENLTE LANIEILYLG QNCYYRNPCY VSYSIEKDAF
210 220 230 240 250
LNLTKLKVLS LKDNNVTAVP TVLPSTLTEL YLYNNMIAKI QEDDFNNLNQ
260 270 280 290 300
LQILDLSGNC PRCYNAPFPC APCKNNSPLQ IPVNAFDALT ELKVLRLHSN
310 320 330 340 350
SLQHVPPRWF KNINKLQELD LSQNFLAKEI GDAKFLHFLP SLIQLDLSFN
360 370 380 390 400
FELQVYRASM NLSQAFSSLK SLKILRIRGY VFKELKSFNL SPLHNLQNLE
410 420 430 440 450
VLDLGTNFIK IANLSMFKQF KRLKVIDLSV NKISPSGDSS EVGFCSNART
460 470 480 490 500
SVESYEPQVL EQLHYFRYDK YARSCRFKNK EASFMSVNES CYKYGQTLDL
510 520 530 540 550
SKNSIFFVKS SDFQHLSFLK CLNLSGNLIS QTLNGSEFQP LAELRYLDFS
560 570 580 590 600
NNRLDLLHST AFEELHKLEV LDISSNSHYF QSEGITHMLN FTKNLKVLQK
610 620 630 640 650
LMMNDNDISS STSRTMESES LRTLEFRGNH LDVLWREGDN RYLQLFKNLL
660 670 680 690 700
KLEELDISKN SLSFLPSGVF DGMPPNLKNL SLAKNGLKSF SWKKLQCLKN
710 720 730 740 750
LETLDLSHNQ LTTVPERLSN CSRSLKNLIL KNNQIRSLTK YFLQDAFQLR
760 770 780 790 800
YLDLSSNKIQ MIQKTSFPEN VLNNLKMLLL HHNRFLCTCD AVWFVWWVNH
810 820 830 840 850
TEVTIPYLAT DVTCVGPGAH KGQSVISLDL YTCELDLTNL ILFSLSISVS
860 870 880 890 900
LFLMVMMTAS HLYFWDVWYI YHFCKAKIKG YQRLISPDCC YDAFIVYDTK
910 920 930 940 950
DPAVTEWVLA ELVAKLEDPR EKHFNLCLEE RDWLPGQPVL ENLSQSIQLS
960 970 980 990 1000
KKTVFVMTDK YAKTENFKIA FYLSHQRLMD EKVDVIILIF LEKPFQKSKF
1010 1020 1030 1040
LQLRKRLCGS SVLEWPTNPQ AHPYFWQCLK NALATDNHVA YSQVFKETV
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 725 | L → H in AAF78035 (PubMed:11022120).Curated | 1 | |
Sequence conflicti | 738 | L → P in AAF78035 (PubMed:11022120).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_034554 | 11 | Q → L1 PublicationCorresponds to variant dbSNP:rs179008Ensembl. | 1 | |
Natural variantiVAR_024665 | 448 | A → V. Corresponds to variant dbSNP:rs5743781EnsemblClinVar. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF240467 mRNA Translation: AAF60188.1 AF245702 mRNA Translation: AAF78035.1 DQ022185 Genomic DNA Translation: AAZ99026.1 AY358292 mRNA Translation: AAQ88659.1 BC033651 mRNA Translation: AAH33651.1 |
CCDSi | CCDS14151.1 |
RefSeqi | NP_057646.1, NM_016562.3 |
Genome annotation databases
Ensembli | ENST00000380659; ENSP00000370034; ENSG00000196664 |
GeneIDi | 51284 |
KEGGi | hsa:51284 |
UCSCi | uc004cvc.4, human |
Keywords - Coding sequence diversityi
PolymorphismSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF240467 mRNA Translation: AAF60188.1 AF245702 mRNA Translation: AAF78035.1 DQ022185 Genomic DNA Translation: AAZ99026.1 AY358292 mRNA Translation: AAQ88659.1 BC033651 mRNA Translation: AAH33651.1 |
CCDSi | CCDS14151.1 |
RefSeqi | NP_057646.1, NM_016562.3 |
3D structure databases
SMRi | Q9NYK1 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 119436, 2 interactors |
IntActi | Q9NYK1, 11 interactors |
STRINGi | 9606.ENSP00000370034 |
Chemistry databases
BindingDBi | Q9NYK1 |
ChEMBLi | CHEMBL5936 |
DrugBanki | DB05127, ANA971 DB05475, Golotimod DB01611, Hydroxychloroquine DB00724, Imiquimod DB04860, Isatoribine DB06530, Resiquimod |
DrugCentrali | Q9NYK1 |
GuidetoPHARMACOLOGYi | 1757 |
PTM databases
GlyGeni | Q9NYK1, 14 sites |
iPTMneti | Q9NYK1 |
PhosphoSitePlusi | Q9NYK1 |
Polymorphism and mutation databases
BioMutai | TLR7 |
DMDMi | 20140876 |
Proteomic databases
jPOSTi | Q9NYK1 |
MassIVEi | Q9NYK1 |
PaxDbi | Q9NYK1 |
PeptideAtlasi | Q9NYK1 |
PRIDEi | Q9NYK1 |
ProteomicsDBi | 83240 |
Protocols and materials databases
Antibodypediai | 8500, 977 antibodies |
DNASUi | 51284 |
Genome annotation databases
Ensembli | ENST00000380659; ENSP00000370034; ENSG00000196664 |
GeneIDi | 51284 |
KEGGi | hsa:51284 |
UCSCi | uc004cvc.4, human |
Organism-specific databases
CTDi | 51284 |
DisGeNETi | 51284 |
EuPathDBi | HostDB:ENSG00000196664.4 |
GeneCardsi | TLR7 |
HGNCi | HGNC:15631, TLR7 |
HPAi | ENSG00000196664, Tissue enhanced (brain) |
MIMi | 300365, gene |
neXtProti | NX_Q9NYK1 |
OpenTargetsi | ENSG00000196664 |
PharmGKBi | PA38008 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG4641, Eukaryota |
GeneTreei | ENSGT00940000159771 |
HOGENOMi | CLU_006000_2_0_1 |
InParanoidi | Q9NYK1 |
OMAi | DPAVSEW |
OrthoDBi | 303561at2759 |
PhylomeDBi | Q9NYK1 |
TreeFami | TF325595 |
Enzyme and pathway databases
PathwayCommonsi | Q9NYK1 |
Reactomei | R-HSA-1679131, Trafficking and processing of endosomal TLR R-HSA-168181, Toll Like Receptor 7/8 (TLR7/8) Cascade R-HSA-9679191, Potential therapeutics for SARS R-HSA-975110, TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling R-HSA-975138, TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation R-HSA-975155, MyD88 dependent cascade initiated on endosome |
SIGNORi | Q9NYK1 |
Miscellaneous databases
BioGRID-ORCSi | 51284, 4 hits in 471 CRISPR screens |
ChiTaRSi | TLR7, human |
GeneWikii | TLR_7 |
GenomeRNAii | 51284 |
Pharosi | Q9NYK1, Tclin |
PROi | PR:Q9NYK1 |
RNActi | Q9NYK1, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000196664, Expressed in leukocyte and 131 other tissues |
ExpressionAtlasi | Q9NYK1, baseline and differential |
Genevisiblei | Q9NYK1, HS |
Family and domain databases
Gene3Di | 3.40.50.10140, 1 hit 3.80.10.10, 1 hit |
InterProi | View protein in InterPro IPR000483, Cys-rich_flank_reg_C IPR001611, Leu-rich_rpt IPR003591, Leu-rich_rpt_typical-subtyp IPR026906, LRR_5 IPR032675, LRR_dom_sf IPR000157, TIR_dom IPR026880, TLR7 IPR035897, Toll_tir_struct_dom_sf |
PANTHERi | PTHR47410:SF2, PTHR47410:SF2, 1 hit |
Pfami | View protein in Pfam PF13306, LRR_5, 1 hit PF13855, LRR_8, 3 hits PF01582, TIR, 1 hit |
SMARTi | View protein in SMART SM00369, LRR_TYP, 12 hits SM00082, LRRCT, 1 hit SM00255, TIR, 1 hit |
SUPFAMi | SSF52200, SSF52200, 1 hit |
PROSITEi | View protein in PROSITE PS51450, LRR, 18 hits PS50104, TIR, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | TLR7_HUMAN | |
Accessioni | Q9NYK1Primary (citable) accession number: Q9NYK1 Secondary accession number(s): D1CS69, Q9NR98 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | January 31, 2002 |
Last sequence update: | October 1, 2000 | |
Last modified: | December 2, 2020 | |
This is version 186 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families - Human chromosome X
Human chromosome X: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations