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Details on Person UniProt:Q9NR96 TLR9

Class:Id	ReferenceGeneProduct:168032
_chainChangeLog	signal peptide:1-25 added on Fri February 6 2015;chain:26-1032 added on Fri February 6 2015
_displayName	UniProt:Q9NR96 TLR9
_timestamp	2026-02-20 22:17:12
chain	signal peptide:1-25 chain:26-1032
checksum	71280AA9680EDCE2
comment	FUNCTION Key component of innate and adaptive immunity (PubMed:14716310). TLRs (Toll-like receptors) control host immune response against pathogens through recognition of molecular patterns specific to microorganisms (PubMed:14716310). 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). Also acts via ADCY7, leading to cyclic di-AMP (c-di-AMP) synthesis and activation of the NLRP3 inflammasome (By similarity). Plays a role in defense against systemic mouse cytomegalovirus infection (By similarity). Controls lymphocyte response to Helicobacter infection (By similarity). Upon CpG stimulation, induces B-cell proliferation, activation, survival and antibody production (PubMed:23857366).SUBUNIT Monomer and homodimer. Exists as a monomer in the absence of unmethylated cytidine-phosphate-guanosine (CpG) ligand. Proteolytic processing of an insertion loop (Z-loop) is required for homodimerization upon binding to the unmethylated CpG ligand leading to its activation (By similarity). Interacts with MYD88 via their respective TIR domains (By similarity). Interacts with BTK (PubMed:17932028). Interacts (via transmembrane domain) with UNC93B1. Interacts with CD300LH; the interaction may promote full activation of TLR9-triggered innate responses (By similarity). Interacts with CNPY3 and HSP90B1; this interaction is required for proper folding in the endoplasmic reticulum (PubMed:20865800). Interacts with SMPDL3B (By similarity). Interacts with CD82; this interaction is essential for TLR9-dependent myddosome formation in response to CpG stimulation (By similarity). Interacts with ADCY7; leading to ADCY7 activation, synthesis of cyclic di-AMP (c-di-AMP) and formation of the NLRP3 inflammasome (By similarity).SUBCELLULAR LOCATION 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.ALTERNATIVE PRODUCTS Additional isoforms seem to exist.TISSUE SPECIFICITY 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.PTM 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.PTM 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.SIMILARITY Belongs to the Toll-like receptor family.
created	[InstanceEdit:168000] Gillespie, ME, 2005-11-10 16:24:09
description	recommendedName: Toll-like receptor 9 cdAntigenNameCD289/cdAntigenName
geneName	TLR9 UNQ5798/PRO19605
identifier	Q9NR96
isSequenceChanged	FALSE
keyword	3D-structure Alternative splicing Cytoplasmic vesicle Disulfide bond Endoplasmic reticulum Endosome Glycoprotein Golgi apparatus Immunity Inflammatory response Innate immunity Leucine-rich repeat Lipoprotein Lysosome Membrane Palmitate Proteomics identification Receptor Reference proteome Repeat Signal Transmembrane Transmembrane helix
modified	[InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9841277] Weiser, Joel [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9983091] Weiser, Joel, 2026-02-20
name	TLR9
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:8993944] ENSEMBL:ENSG00000239732 TLR9 [Homo sapiens]
secondaryIdentifier	TLR9_HUMAN B3Y661 D1CS56 Q6UVZ2 Q9HD68 Q9HD69 Q9HD70 Q9NYC2 Q9NYC3
sequenceLength	1032
species	[Species:48887] Homo sapiens
(isoformParent)	[ReferenceIsoform:154963] UniProt:Q9NR96-2 TLR9 [Homo sapiens] [ReferenceIsoform:154964] UniProt:Q9NR96-3 TLR9 [Homo sapiens] [ReferenceIsoform:154965] UniProt:Q9NR96-4 TLR9 [Homo sapiens] [ReferenceIsoform:154966] UniProt:Q9NR96-5 TLR9 [Homo sapiens] [ReferenceIsoform:414721] UniProt:Q9NR96-1 TLR9 [Homo sapiens]
(referenceEntity)	[EntityWithAccessionedSequence:167979] TLR9 [endolysosome membrane] [Homo sapiens] [EntityWithAccessionedSequence:187882] TLR9 [endosome membrane] [Homo sapiens] [EntityWithAccessionedSequence:1678961] TLR9 [endoplasmic reticulum membrane] [Homo sapiens] [EntityWithAccessionedSequence:1678982] TLR9(?-1032) [endolysosome membrane] [Homo sapiens] [EntityWithAccessionedSequence:1678997] TLR9 [Golgi membrane] [Homo sapiens] [EntityWithAccessionedSequence:1679032] TLR9(1-?) [endolysosome membrane] [Homo sapiens] [EntityWithAccessionedSequence:1679573] TLR9(1-?) [endosome membrane] [Homo sapiens] [EntityWithAccessionedSequence:1679580] TLR9(?-1032) [endosome membrane] [Homo sapiens] [EntityWithAccessionedSequence:9678810] TLR9 [cytosol] [Homo sapiens]
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No pathways have been reviewed or authored by UniProt:Q9NR96 TLR9 (168032)