Tlr9

Function

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 a nucleotide-sensing TLR which is activated by unmethylated cytidine-phosphate-guanosine (CpG) dinucleotides (PubMed:31408613). Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response (PubMed:14993594, PubMed:17474149, PubMed:18820679, PubMed:18931679, PubMed:21402738, PubMed:25686612). Plays a role in defense against systemic mouse cytomegalovirus infection (PubMed:14993594). Controls lymphocyte response to Helicobacter infection (PubMed:17474149). Upon CpG stimulation, induces B-cell proliferation, activation, survival and antibody production (By similarity).

Post-translational modifications

Activated by proteolytic cleavage of the flexible loop between repeats LRR14 and LRR15 within the ectodomain (PubMed:18820679, PubMed:18931679). Cleavage requires UNC93B1 (PubMed:18820679). Proteolytically processed by first removing the majority of the ectodomain by either asparagine endopeptidase (AEP) or a cathepsin followed by a trimming event that is solely cathepsin mediated and required for optimal receptor signaling (PubMed:21402738).

Palmitoylated by ZDHHC3 in the Golgi regulates TLR9 trafficking from the Golgi to endosomes. Depalmitoylation by PPT1 controls the release of TLR9 from UNC93B1 in endosomes.

Sequence Similarities

Belongs to the Toll-like receptor family.

Tissue Specificity

Expressed in the basolateral region of gastric epithelial cells with high levels detected in antrum and body mucosa (at protein level). Detected in spleen and stomach at higher levels in C57BL/6 mice than BALB/C.

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 (PubMed:18305481). Exit from the ER requires UNC93B1 (PubMed:18820679). Endolysosomal localization is required for proteolytic cleavage and subsequent activation (PubMed:18820679, PubMed:18931679). Intracellular localization of the active receptor may prevent from responding to self nucleic acid (PubMed:18820679).

Alternative names

CD289, Toll-like receptor 9, Tlr9

Database links

swissprot:Q9EQU3 entrezGene:81897

Other research areas

• Immuno-oncology