Toll-like receptor 7 (TLR7) is a 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. TLR7 is a nucleotide-sensing TLR, which is activated by single-stranded RNA, acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response [, ].
UNC93B1 is a multi-transmembrane domain-containing protein that plays an essential role in signalling by the nucleotide-sensing Toll-like receptors (TLRs), including TLR3, TLR7 and TLR9 [, ]. UNC93B1 delivers the nucleotide-sensing receptors TLR7 and TLR9 from the ER to endolysosomes []. It has been shown to recruit Syntenin-1 and dampen TLR7 signalling and prevent autoimmunity []. It also binds TLR9, and the release of TLR9 from UNC93B1 is required for TLR9 to function []. Mutations in the UNC93B1 gene that result in aberrant TLR trafficking can lead to autoimmune disease [].
Interferon regulatory factor 5 (IRF5) is a transcription factor involved in the induction of interferons IFNA and INFB and inflammatory cytokines upon virus infection []. It is activated by TLR7 or TLR8 signalling []. Its structure has been revealed []. Variations of the IRF5 gene affects the susceptibility of a few diseases, such as inflammatory bowel disease 14 (IBD14) [], systemic lupus erythematosus 10 (SLEB10) []and Rheumatoid arthritis (RA).
The proteins in this family are represented by UNC-93 from Caenorhabditis elegans and also includes protein unc-93 homologue A (UNC93A), protein unc-93 homologue B1 (UNC93B1), and UNC93-like protein MFSD11 (also called major facilitator superfamily domain-containing protein 11 or protein ET). UNC-93 colocalizes with SUP-10 and SUP-9 within muscle cells. UNC-93 acts as a regulatory subunit of a multi-subunit potassium channel complex that may function in coordinating muscle contraction in C. elegans []. UNC93B1 controls intracellular trafficking and transport of a subset of Toll-like receptors (TLRs), including TLR3, TLR7 and TLR9, from the endoplasmic reticulum to endolysosomes where they can engage pathogen nucleotides and activate signalling cascades []. MFSD11 is ubiquitously expressed in the periphery and the central nervous system of mice, where it is expressed in excitatory and inhibitory mouse brain neurons [].This group of proteins also includes Notoamide biosynthesis cluster protein O' from Aspergillus versicolor, which is involved in the biosynthesis of notoamide, a fungal indole alkaloid that belongs to a family of natural products containing a characteristic bicyclo[2.2.2]diazaoctane core [].
