TLR9

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:14716310). Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response (PubMed:11564765, PubMed:17932028). Controls lymphocyte response to Helicobacter infection (By similarity). Upon CpG stimulation, induces B-cell proliferation, activation, survival and antibody production (PubMed:23857366).

Activated by proteolytic cleavage of the flexible loop between repeats LRR14 and LRR15 within the ectodomain. Cleavage requires UNC93B1. 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.

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.

Belongs to the Toll-like receptor family.

Highly expressed in spleen, lymph node, tonsil and peripheral blood leukocytes, especially in plasmacytoid pre-dendritic cells. Levels are much lower in monocytes and CD11c+ immature dendritic cells. Also detected in lung and liver.

• Endoplasmic reticulum membrane
• Single-pass type I membrane protein
• Early endosome membrane
• Lysosome
• Cytoplasmic vesicle
• Phagosome
• Golgi apparatus membrane
• Relocalizes from endoplasmic reticulum to endosome and lysosome upon stimulation with agonist. Exit from the ER requires UNC93B1. Endolysosomal localization is required for proteolytic cleavage and subsequent activation. Intracellular localization of the active receptor may prevent from responding to self nucleic acid.

CD289, UNQ5798/PRO19605, TLR9, Toll-like receptor 9

• entrezGene:54106
• omim:605474
• swissprot:Q9NR96

Proteins

Immunology & Infectious Disease

• Immuno-oncology

115860Da