Toll-like receptor 7

Function

Endosomal receptor that plays a key role in innate and adaptive immunity. Controls host immune response against pathogens through recognition of uridine-containing single strand RNAs (ssRNAs) of viral origin or guanosine analogs. 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 pro-inflammatory cytokines and interferons, respectively. In plasmacytoid dendritic cells, RNASET2 endonuclease cooperates with PLD3 or PLD4 5'->3' exonucleases to process RNA and release 2',3'-cyclic guanosine monophosphate (2',3'-cGMP) and cytidine-rich RNA fragments that occupy TLR7 ligand-binding pockets and trigger a signaling-competent state.

Classification

Family (Pfam)

PF13855 LRR_8, PF01582 TIR

InterPro

Cys-rich_flank_reg_C, Leu-rich_rpt, Leu-rich_rpt_typical-subtyp, LRR_dom_sf, TIR_dom, Toll_tir_struct_dom_sf

Functional cluster

Immunoglobulin-Domain Cell Adhesion Proteins

Experimental structures · PDB · 1

• 7CYN EM 4.20A

A predicted model is available from AlphaFold.

Gene Ontology · 35

• GO:0005737 cytoplasm
• GO:0032009 early phagosome
• GO:0036020 endolysosome membrane
• GO:0005783 endoplasmic reticulum
• GO:0005789 endoplasmic reticulum membrane
• GO:0005768 endosome
• GO:0010008 endosome membrane
• GO:0000139 Golgi membrane
• GO:0005764 lysosome
• GO:0005886 plasma membrane
• GO:0043235 receptor complex
• GO:0003725 double-stranded RNA binding
• GO:0038187 pattern recognition receptor activity
• GO:0003727 single-stranded RNA binding
• GO:0035197 siRNA binding
• GO:0007249 canonical NF-kappaB signal transduction
• GO:0071260 cellular response to mechanical stimulus
• GO:0098586 cellular response to virus
• GO:0051607 defense response to virus
• GO:0006954 inflammatory response
• GO:0045087 innate immune response
• GO:0007254 JNK cascade
• GO:0043123 positive regulation of canonical NF-kappaB signal transduction
• GO:0032722 positive regulation of chemokine production
• GO:0050729 positive regulation of inflammatory response
• GO:0032727 positive regulation of interferon-alpha production
• GO:0032728 positive regulation of interferon-beta production
• GO:0032755 positive regulation of interleukin-6 production
• GO:0032757 positive regulation of interleukin-8 production
• GO:0045944 positive regulation of transcription by RNA polymerase II
• GO:0032729 positive regulation of type II interferon production
• GO:0070305 response to cGMP
• GO:0034154 toll-like receptor 7 signaling pathway
• GO:0034158 toll-like receptor 8 signaling pathway
• GO:0002224 toll-like receptor signaling pathway

Disease associations

• immunodeficiency 74, COVID-19-related, X-linked MONDO:0026767
• systemic lupus erythematosus 17 MONDO:0859083

Drugs targeting this protein · 10

• IMIQUIMOD agonist
• HYDROXYCHLOROQUINE SULFATE antagonist
• VESATOLIMOD activator
• RESIQUIMOD agonist
• AZD-8848 agonist
• GSK-2245035 agonist
• TELRATOLIMOD agonist
• AFIMETORAN inhibitor
• ENPATORAN antagonist
• CPG-52852 agonist

Related proteins · sequence + function similarity

• Toll-like receptor 7 0.98
• Toll-like receptor 8 0.93
• Toll-like receptor 8 0.93
• Toll-like receptor 2 0.85
• Toll-like receptor 2 0.85
• Toll-like receptor 2 0.85
• Toll-like receptor 2 0.85
• Toll-like receptor 2 0.85
• Toll-like receptor 2 type-1 0.85
• Toll-like receptor 2 0.85
• Toll-like receptor 2 0.85
• Toll-like receptor 2 0.85

Co-cited proteins · studied together in the literature

• Toll-like receptor 7 2 shared papers
• Toll-like receptor 8 4 shared papers
• Toll-like receptor 9 3 shared papers
• Ribonuclease T2 1 shared papers
• TLR adapter interacting with SLC15A4 on the lysosome 1 shared papers
• Protein unc-93 homolog B1 1 shared papers
• 5'-3' exonuclease PLD4 1 shared papers
• Toll-like receptor 3 1 shared papers
• Protein unc-93 homolog B1 1 shared papers
• Interferon regulatory factor 5 1 shared papers
• Solute carrier family 15 member 4 1 shared papers
• Toll-like receptor 10 1 shared papers

Literature · 15 cited papers

• Lysosomal endonuclease RNase T2 and PLD exonucleases cooperatively generate RNA ligands for TLR7 activation. Immunity · 2024
• TLR7 gain-of-function genetic variation causes human lupus. Nature · 2022
• Cryo-EM structures of Toll-like receptors in complex with UNC93B1. Nat. Struct. Mol. Biol. · 2021
• Presence of Genetic Variants Among Young Men With Severe COVID-19. JAMA · 2020
• TASL is the SLC15A4-associated adaptor for IRF5 activation by TLR7-9. Nature · 2020
• Deoxyguanosine is a TLR7 agonist. Eur. J. Immunol. · 2020
• Structural Analysis Reveals that Toll-like Receptor 7 Is a Dual Receptor for Guanosine and Single-Stranded RNA. Immunity · 2016
• The heterogeneous allelic repertoire of human Toll-Like receptor (TLR) genes. PLoS ONE · 2009
• TLR7 is involved in sequence-specific sensing of single-stranded RNAs in human macrophages. J. Immunol. · 2008
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA. Science · 2004
• The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment. Genome Res. · 2003
• … and 3 more in the literature graph