TLR7

Domain

Contains two binding domains, first site for small ligands and second site for ssRNA.

Function

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:12738885, PubMed:27742543, PubMed:31608988, PubMed:32706371, PubMed:35477763). 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 pro-inflammatory cytokines and interferons, respectively (PubMed:27742543, PubMed:32706371).

Involvement in disease

Immunodeficiency 74, COVID19-related, X-linked

IMD74

An X-linked recessive immunologic disorder characterized by impaired type I and type II interferon responses due to defective TLR7 signaling. Individuals with TLR7 deficiency develop severe respiratory insufficiency in response to infection with SARS-CoV-2 coronavirus. Death from respiratory failure may occur.

None

The disease is caused by variants affecting the gene represented in this entry.

Systemic lupus erythematosus 17

SLEB17

A form of systemic lupus erythematosus, a chronic, relapsing, inflammatory, and often febrile multisystemic disorder of connective tissue, characterized principally by involvement of the skin, joints, kidneys and serosal membranes. The disease is marked by a wide range of system dysfunctions, an elevated erythrocyte sedimentation rate, and the formation of LE cells in the blood or bone marrow. SLEB17 is an X-linked dominant form characterized by onset of systemic autoinflammatory symptoms in the first decades of life.

None

The disease is caused by variants affecting the gene represented in this entry.

Sequence Similarities

Belongs to the Toll-like receptor family.

Tissue Specificity

Detected in brain, placenta, spleen, stomach, small intestine, lung and in plasmacytoid pre-dendritic cells. Expressed in peripheral mononuclear blood cells (PubMed:32706371).

Cellular localization

• Endoplasmic reticulum membrane
• Single-pass type I membrane protein
• Endosome
• Lysosome
• Cytoplasmic vesicle
• Phagosome
• Relocalizes from endoplasmic reticulum to endosome and lysosome upon stimulation with agonist.

Alternative names

UNQ248/PRO285, TLR7, Toll-like receptor 7

Database links

swissprot:Q9NYK1 entrezGene:51284 omim:300365

Other research areas

• Immuno-oncology