Toll-like receptor 9 (TLR9) 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. TLR9 is activated by unmethylated cytidine-phosphate-guanosine (CpG) dinucleotides, which is more abundant in bacterial genomes or viral DNA compared to the vertebrate genomes [, , , ]. It acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. TLR9 controls lymphocyte response to Helicobacter infection [].
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 [].
This entry represents the death domain found in interleukin-1 receptor-associated kinase-like 2 (IRAK2) []. IRAK2 is an essential component of several signaling pathways, including NF-kappaB and the IL-1 signaling pathways. It is an inactive kinase that participates in septic shock mediated by TLR4 and TLR9 []. It plays a redundant role with IRAK1 in early NF-kB and MAPK responses, and remains present at later stages whereas IRAK1 disappears [, ].Interleukin-1 receptor-associated kinases (IRAKs) are essential components of innate immunity and inflammation in mammals and other vertebrates []. They are involved in signal transduction pathways involving IL-1 and IL-18 receptors, Toll-like receptors, nuclear factor-kappaB (NF-kB), and mitogen-activated protein kinases (MAPKs). IRAKs contain an N-terminal death domain (DD) and a C-terminal kinase domain [, , , ].Death domains (DDs) are protein-protein interaction domains found in a variety of domain architectures. Their common feature is that they form homodimers by self-association or heterodimers by associating with other members of the DD superfamily including CARD (Caspase activation and recruitment domain), DED (Death Effector Domain), and PYRIN. They serve as adaptors in signaling pathways and can recruit other proteins into signaling complexes [].
