TLR9_HUMAN
ID TLR9_HUMAN Reviewed; 1032 AA.
AC Q9NR96; B3Y661; D1CS56; Q6UVZ2; Q9HD68; Q9HD69; Q9HD70; Q9NYC2; Q9NYC3;
DT 31-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT 31-JAN-2002, sequence version 2.
DT 03-AUG-2022, entry version 192.
DE RecName: Full=Toll-like receptor 9;
DE AltName: CD_antigen=CD289;
DE Flags: Precursor;
GN Name=TLR9; ORFNames=UNQ5798/PRO19605;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Monocytic leukemia;
RX PubMed=11022119;
RA Du X., Poltorak A., Wei Y., Beutler B.;
RT "Three novel mammalian Toll-like receptors: gene structure, expression, and
RT evolution.";
RL Eur. Cytokine Netw. 11:362-371(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 3; 4 AND 5).
RC TISSUE=Placenta;
RX PubMed=11022120;
RA Chuang T.-H., Ulevitch R.J.;
RT "Cloning and characterization of a sub-family of human Toll-like receptors:
RT hTLR7, hTLR8 and hTLR9.";
RL Eur. Cytokine Netw. 11:372-378(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=11130078; DOI=10.1038/35047123;
RA Hemmi H., Takeuchi O., Kawai T., Kaisho T., Sato S., Sanjo H.,
RA Matsumoto M., Hoshino K., Wagner H., Takeda K., Akira S.;
RT "A Toll-like receptor recognizes bacterial DNA.";
RL Nature 408:740-745(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Liu Z., Wang J., Xiao W.;
RL Submitted (SEP-2007) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=18810425; DOI=10.1007/s00251-008-0332-0;
RA Nakajima T., Ohtani H., Satta Y., Uno Y., Akari H., Ishida T., Kimura A.;
RT "Natural selection in the TLR-related genes in the course of primate
RT evolution.";
RL Immunogenetics 60:727-735(2008).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=19924287; DOI=10.1371/journal.pone.0007803;
RA Georgel P., Macquin C., Bahram S.;
RT "The heterogeneous allelic repertoire of human Toll-Like receptor (TLR)
RT genes.";
RL PLoS ONE 4:E7803-E7803(2009).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lymph;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP FUNCTION.
RX PubMed=11564765; DOI=10.4049/jimmunol.167.7.3555;
RA Takeshita F., Leifer C.A., Gursel I., Ishii K.J., Takeshita S., Gursel M.,
RA Klinman D.M.;
RT "Role of Toll-like receptor 9 in CpG DNA-induced activation of human
RT cells.";
RL J. Immunol. 167:3555-3558(2001).
RN [11]
RP FUNCTION, AND INTERACTION WITH BTK.
RX PubMed=17932028; DOI=10.1074/jbc.m707682200;
RA Doyle S.L., Jefferies C.A., Feighery C., O'Neill L.A.;
RT "Signaling by Toll-like receptors 8 and 9 requires Bruton's tyrosine
RT kinase.";
RL J. Biol. Chem. 282:36953-36960(2007).
RN [12]
RP INTERACTION WITH CNPY3 AND HSP90B1.
RX PubMed=20865800; DOI=10.1038/ncomms1070;
RA Liu B., Yang Y., Qiu Z., Staron M., Hong F., Li Y., Wu S., Li Y., Hao B.,
RA Bona R., Han D., Li Z.;
RT "Folding of Toll-like receptors by the HSP90 paralogue gp96 requires a
RT substrate-specific cochaperone.";
RL Nat. Commun. 1:79-79(2010).
RN [13]
RP ERRATUM OF PUBMED:20865800.
RA Liu B., Yang Y., Qiu Z., Staron M., Hong F., Li Y., Wu S., Li Y., Hao B.,
RA Bona R., Han D., Li Z.;
RL Nat. Commun. 3:653-653(2012).
RN [14]
RP FUNCTION.
RX PubMed=23857366; DOI=10.1002/eji.201243068;
RA Li F.J., Schreeder D.M., Li R., Wu J., Davis R.S.;
RT "FCRL3 promotes TLR9-induced B-cell activation and suppresses plasma cell
RT differentiation.";
RL Eur. J. Immunol. 43:2980-2992(2013).
RN [15]
RP VARIANTS [LARGE SCALE ANALYSIS] HIS-901 AND MET-933.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: Key component of innate and adaptive immunity. TLRs (Toll-
CC like receptors) control host immune response against pathogens through
CC recognition of molecular patterns specific to microorganisms. TLR9 is a
CC nucleotide-sensing TLR which is activated by unmethylated cytidine-
CC phosphate-guanosine (CpG) dinucleotides. Acts via MYD88 and TRAF6,
CC leading to NF-kappa-B activation, cytokine secretion and the
CC inflammatory response (PubMed:11564765, PubMed:17932028). Controls
CC lymphocyte response to Helicobacter infection (By similarity). Upon CpG
CC stimulation, induces B-cell proliferation, activation, survival and
CC antibody production (PubMed:23857366). {ECO:0000250|UniProtKB:Q9EQU3,
CC ECO:0000269|PubMed:11564765, ECO:0000269|PubMed:17932028,
CC ECO:0000269|PubMed:23857366}.
CC -!- SUBUNIT: Monomer and homodimer. Exists as a monomer in the absence of
CC unmethylated cytidine-phosphate-guanosine (CpG) ligand. Proteolytic
CC processing of an insertion loop (Z-loop) is required for
CC homodimerization upon binding to the unmethylated CpG ligand leading to
CC its activation (By similarity). Interacts with MYD88 via their
CC respective TIR domains (By similarity). Interacts with BTK
CC (PubMed:17932028). Interacts (via transmembrane domain) with UNC93B1.
CC Interacts with CD300LH; the interaction may promote full activation of
CC TLR9-triggered innate responses (By similarity). Interacts with CNPY3
CC and HSP90B1; this interaction is required for proper folding in the
CC endoplasmic reticulum (PubMed:20865800). Interacts with SMPDL3B (By
CC similarity). {ECO:0000250|UniProtKB:Q2EEY0,
CC ECO:0000250|UniProtKB:Q9EQU3, ECO:0000269|PubMed:17932028,
CC ECO:0000269|PubMed:20865800}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q9EQU3}; Single-pass type I membrane protein
CC {ECO:0000250|UniProtKB:Q9EQU3}. Endosome
CC {ECO:0000250|UniProtKB:Q9EQU3}. Lysosome
CC {ECO:0000250|UniProtKB:Q9EQU3}. Cytoplasmic vesicle, phagosome
CC {ECO:0000250|UniProtKB:Q9EQU3}. Note=Relocalizes from endoplasmic
CC reticulum to endosome and lysosome upon stimulation with agonist. Exit
CC from the ER requires UNC93B1. Endolysosomal localization is required
CC for proteolytic cleavage and subsequent activation. Intracellular
CC localization of the active receptor may prevent from responding to self
CC nucleic acid. {ECO:0000250|UniProtKB:Q9EQU3}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=5;
CC Comment=Additional isoforms seem to exist.;
CC Name=1; Synonyms=A;
CC IsoId=Q9NR96-1; Sequence=Displayed;
CC Name=2; Synonyms=B;
CC IsoId=Q9NR96-2; Sequence=VSP_006520;
CC Name=3;
CC IsoId=Q9NR96-3; Sequence=VSP_006521;
CC Name=4;
CC IsoId=Q9NR96-4; Sequence=VSP_006522;
CC Name=5;
CC IsoId=Q9NR96-5; Sequence=VSP_006523;
CC -!- TISSUE SPECIFICITY: Highly expressed in spleen, lymph node, tonsil and
CC peripheral blood leukocytes, especially in plasmacytoid pre-dendritic
CC cells. Levels are much lower in monocytes and CD11c+ immature dendritic
CC cells. Also detected in lung and liver.
CC -!- PTM: Activated by proteolytic cleavage of the flexible loop between
CC repeats LRR14 and LRR15 within the ectodomain. Cleavage requires
CC UNC93B1. Proteolytically processed by first removing the majority of
CC the ectodomain by either asparagine endopeptidase (AEP) or a cathepsin
CC followed by a trimming event that is solely cathepsin mediated and
CC required for optimal receptor signaling.
CC {ECO:0000250|UniProtKB:Q9EQU3}.
CC -!- SIMILARITY: Belongs to the Toll-like receptor family. {ECO:0000305}.
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DR EMBL; AF259262; AAF72189.1; -; mRNA.
DR EMBL; AF259263; AAF72190.1; -; mRNA.
DR EMBL; AF245704; AAF78037.1; -; mRNA.
DR EMBL; AF246972; AAG01734.1; -; mRNA.
DR EMBL; AF246973; AAG01735.1; -; mRNA.
DR EMBL; AF246974; AAG01736.1; -; mRNA.
DR EMBL; AB045180; BAB19259.1; -; mRNA.
DR EMBL; EU170540; ABW37075.1; -; Genomic_DNA.
DR EMBL; EU170541; ABW37076.1; -; Genomic_DNA.
DR EMBL; EU170542; ABW37077.1; -; Genomic_DNA.
DR EMBL; EU170543; ABW37078.1; -; Genomic_DNA.
DR EMBL; AB445673; BAG55070.1; -; mRNA.
DR EMBL; DQ019992; AAZ95513.1; -; Genomic_DNA.
DR EMBL; DQ019993; AAZ95514.1; -; Genomic_DNA.
DR EMBL; DQ019994; AAZ95515.1; -; Genomic_DNA.
DR EMBL; DQ019995; AAZ95516.1; -; Genomic_DNA.
DR EMBL; DQ019996; AAZ95517.1; -; Genomic_DNA.
DR EMBL; DQ019999; AAZ95520.1; -; Genomic_DNA.
DR EMBL; AY359085; AAQ89443.1; -; mRNA.
DR EMBL; CH471055; EAW65191.1; -; Genomic_DNA.
DR EMBL; BC032713; AAH32713.1; -; mRNA.
DR CCDS; CCDS2848.1; -. [Q9NR96-1]
DR RefSeq; NP_059138.1; NM_017442.3. [Q9NR96-1]
DR AlphaFoldDB; Q9NR96; -.
DR SMR; Q9NR96; -.
DR BioGRID; 119902; 148.
DR DIP; DIP-52371N; -.
DR IntAct; Q9NR96; 16.
DR STRING; 9606.ENSP00000353874; -.
DR BindingDB; Q9NR96; -.
DR ChEMBL; CHEMBL5804; -.
DR DrugBank; DB00608; Chloroquine.
DR DrugBank; DB05530; CPG 10101.
DR DrugBank; DB05475; Golotimod.
DR DrugBank; DB01611; Hydroxychloroquine.
DR DrugBank; DB05463; ISS-1018.
DR DrugCentral; Q9NR96; -.
DR GuidetoPHARMACOLOGY; 1759; -.
DR GlyGen; Q9NR96; 15 sites, 1 O-linked glycan (1 site).
DR iPTMnet; Q9NR96; -.
DR PhosphoSitePlus; Q9NR96; -.
DR BioMuta; TLR9; -.
DR DMDM; 20140872; -.
DR EPD; Q9NR96; -.
DR jPOST; Q9NR96; -.
DR MassIVE; Q9NR96; -.
DR MaxQB; Q9NR96; -.
DR PaxDb; Q9NR96; -.
DR PeptideAtlas; Q9NR96; -.
DR PRIDE; Q9NR96; -.
DR ABCD; Q9NR96; 1 sequenced antibody.
DR Antibodypedia; 34940; 1070 antibodies from 44 providers.
DR DNASU; 54106; -.
DR Ensembl; ENST00000360658.3; ENSP00000353874.2; ENSG00000239732.4. [Q9NR96-1]
DR GeneID; 54106; -.
DR KEGG; hsa:54106; -.
DR MANE-Select; ENST00000360658.3; ENSP00000353874.2; NM_017442.4; NP_059138.1.
DR UCSC; uc003dda.2; human. [Q9NR96-1]
DR CTD; 54106; -.
DR DisGeNET; 54106; -.
DR GeneCards; TLR9; -.
DR HGNC; HGNC:15633; TLR9.
DR HPA; ENSG00000239732; Tissue enhanced (brain, lymphoid tissue).
DR MIM; 605474; gene.
DR neXtProt; NX_Q9NR96; -.
DR OpenTargets; ENSG00000239732; -.
DR PharmGKB; PA38010; -.
DR VEuPathDB; HostDB:ENSG00000239732; -.
DR eggNOG; KOG1747; Eukaryota.
DR eggNOG; KOG4641; Eukaryota.
DR GeneTree; ENSGT00940000162493; -.
DR HOGENOM; CLU_006000_2_0_1; -.
DR InParanoid; Q9NR96; -.
DR OrthoDB; 264244at2759; -.
DR PhylomeDB; Q9NR96; -.
DR TreeFam; TF325595; -.
DR PathwayCommons; Q9NR96; -.
DR Reactome; R-HSA-109704; PI3K Cascade.
DR Reactome; R-HSA-1679131; Trafficking and processing of endosomal TLR.
DR Reactome; R-HSA-168138; Toll Like Receptor 9 (TLR9) Cascade.
DR Reactome; R-HSA-9679191; Potential therapeutics for SARS.
DR Reactome; R-HSA-975110; TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling.
DR Reactome; R-HSA-975138; TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation.
DR Reactome; R-HSA-975155; MyD88 dependent cascade initiated on endosome.
DR SignaLink; Q9NR96; -.
DR SIGNOR; Q9NR96; -.
DR BioGRID-ORCS; 54106; 12 hits in 1065 CRISPR screens.
DR GeneWiki; TLR9; -.
DR GenomeRNAi; 54106; -.
DR Pharos; Q9NR96; Tclin.
DR PRO; PR:Q9NR96; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q9NR96; protein.
DR Bgee; ENSG00000239732; Expressed in blood and 85 other tissues.
DR Genevisible; Q9NR96; HS.
DR GO; GO:0016324; C:apical plasma membrane; IDA:BHF-UCL.
DR GO; GO:0016323; C:basolateral plasma membrane; IDA:BHF-UCL.
DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
DR GO; GO:0032009; C:early phagosome; ISS:UniProtKB.
DR GO; GO:0036019; C:endolysosome; ISS:UniProtKB.
DR GO; GO:0036020; C:endolysosome membrane; TAS:Reactome.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0005768; C:endosome; ISS:UniProtKB.
DR GO; GO:0010008; C:endosome membrane; TAS:Reactome.
DR GO; GO:0005576; C:extracellular region; NAS:UniProtKB.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005764; C:lysosome; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:BHF-UCL.
DR GO; GO:0005149; F:interleukin-1 receptor binding; IPI:UniProtKB.
DR GO; GO:0038187; F:pattern recognition receptor activity; IBA:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0035197; F:siRNA binding; IMP:UniProtKB.
DR GO; GO:0004888; F:transmembrane signaling receptor activity; IEA:InterPro.
DR GO; GO:0045322; F:unmethylated CpG binding; ISS:UniProtKB.
DR GO; GO:0002218; P:activation of innate immune response; IEA:Ensembl.
DR GO; GO:1902350; P:cellular response to chloroquine; IEA:Ensembl.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEA:Ensembl.
DR GO; GO:0071248; P:cellular response to metal ion; IEA:Ensembl.
DR GO; GO:0042742; P:defense response to bacterium; NAS:UniProtKB.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IMP:UniProtKB.
DR GO; GO:0051607; P:defense response to virus; IBA:GO_Central.
DR GO; GO:0007249; P:I-kappaB kinase/NF-kappaB signaling; IBA:GO_Central.
DR GO; GO:0007252; P:I-kappaB phosphorylation; IDA:BHF-UCL.
DR GO; GO:0045087; P:innate immune response; TAS:BHF-UCL.
DR GO; GO:0030277; P:maintenance of gastrointestinal epithelium; ISS:BHF-UCL.
DR GO; GO:0008584; P:male gonad development; IEA:Ensembl.
DR GO; GO:0001774; P:microglial cell activation; IEA:Ensembl.
DR GO; GO:0002755; P:MyD88-dependent toll-like receptor signaling pathway; IEA:Ensembl.
DR GO; GO:1901895; P:negative regulation of ATPase-coupled calcium transmembrane transporter activity; IDA:CACAO.
DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; IEA:Ensembl.
DR GO; GO:0032715; P:negative regulation of interleukin-6 production; ISS:BHF-UCL.
DR GO; GO:0032717; P:negative regulation of interleukin-8 production; IDA:BHF-UCL.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IDA:BHF-UCL.
DR GO; GO:0034122; P:negative regulation of toll-like receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0010508; P:positive regulation of autophagy; IEA:Ensembl.
DR GO; GO:0050871; P:positive regulation of B cell activation; IDA:UniProtKB.
DR GO; GO:0030890; P:positive regulation of B cell proliferation; IDA:UniProtKB.
DR GO; GO:0032722; P:positive regulation of chemokine production; IDA:BHF-UCL.
DR GO; GO:0010628; P:positive regulation of gene expression; IDA:CACAO.
DR GO; GO:0032725; P:positive regulation of granulocyte macrophage colony-stimulating factor production; IDA:CACAO.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IDA:BHF-UCL.
DR GO; GO:0002639; P:positive regulation of immunoglobulin production; IDA:UniProtKB.
DR GO; GO:0050729; P:positive regulation of inflammatory response; IC:BHF-UCL.
DR GO; GO:0032727; P:positive regulation of interferon-alpha production; IDA:UniProtKB.
DR GO; GO:0032728; P:positive regulation of interferon-beta production; IDA:UniProtKB.
DR GO; GO:0032729; P:positive regulation of interferon-gamma production; IDA:UniProtKB.
DR GO; GO:0032733; P:positive regulation of interleukin-10 production; ISS:BHF-UCL.
DR GO; GO:0032735; P:positive regulation of interleukin-12 production; ISS:BHF-UCL.
DR GO; GO:0032741; P:positive regulation of interleukin-18 production; ISS:BHF-UCL.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IDA:BHF-UCL.
DR GO; GO:0032757; P:positive regulation of interleukin-8 production; IDA:BHF-UCL.
DR GO; GO:0046330; P:positive regulation of JNK cascade; IC:BHF-UCL.
DR GO; GO:0043507; P:positive regulation of JUN kinase activity; IDA:BHF-UCL.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IDA:UniProtKB.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IDA:BHF-UCL.
DR GO; GO:1901224; P:positive regulation of NIK/NF-kappaB signaling; IDA:BHF-UCL.
DR GO; GO:0051770; P:positive regulation of nitric-oxide synthase biosynthetic process; ISS:BHF-UCL.
DR GO; GO:0034165; P:positive regulation of toll-like receptor 9 signaling pathway; IEA:Ensembl.
DR GO; GO:0034123; P:positive regulation of toll-like receptor signaling pathway; IDA:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:BHF-UCL.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; ISS:BHF-UCL.
DR GO; GO:0045577; P:regulation of B cell differentiation; IDA:UniProtKB.
DR GO; GO:0002730; P:regulation of dendritic cell cytokine production; IEA:Ensembl.
DR GO; GO:0034163; P:regulation of toll-like receptor 9 signaling pathway; IDA:UniProtKB.
DR GO; GO:0002237; P:response to molecule of bacterial origin; TAS:BHF-UCL.
DR GO; GO:0034162; P:toll-like receptor 9 signaling pathway; IEA:InterPro.
DR GO; GO:0002224; P:toll-like receptor signaling pathway; IBA:GO_Central.
DR Gene3D; 3.40.50.10140; -; 1.
DR Gene3D; 3.80.10.10; -; 1.
DR InterPro; IPR001611; Leu-rich_rpt.
DR InterPro; IPR003591; Leu-rich_rpt_typical-subtyp.
DR InterPro; IPR041283; LRR_12.
DR InterPro; IPR032675; LRR_dom_sf.
DR InterPro; IPR000157; TIR_dom.
DR InterPro; IPR027181; TLR9.
DR InterPro; IPR035897; Toll_tir_struct_dom_sf.
DR PANTHER; PTHR47410:SF3; PTHR47410:SF3; 1.
DR Pfam; PF18837; LRR_12; 1.
DR Pfam; PF13516; LRR_6; 2.
DR Pfam; PF13855; LRR_8; 7.
DR Pfam; PF01582; TIR; 1.
DR SMART; SM00369; LRR_TYP; 18.
DR SMART; SM00255; TIR; 1.
DR SUPFAM; SSF52200; SSF52200; 1.
DR PROSITE; PS51450; LRR; 17.
DR PROSITE; PS50104; TIR; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cytoplasmic vesicle; Disulfide bond;
KW Endoplasmic reticulum; Endosome; Glycoprotein; Immunity;
KW Inflammatory response; Innate immunity; Leucine-rich repeat; Lysosome;
KW Membrane; Receptor; Reference proteome; Repeat; Signal; Transmembrane;
KW Transmembrane helix.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT CHAIN 26..1032
FT /note="Toll-like receptor 9"
FT /id="PRO_0000034737"
FT TOPO_DOM 26..818
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 819..839
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 840..1032
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 62..85
FT /note="LRR 1"
FT REPEAT 87..110
FT /note="LRR 2"
FT REPEAT 122..147
FT /note="LRR 3"
FT REPEAT 150..166
FT /note="LRR 4"
FT REPEAT 167..190
FT /note="LRR 5"
FT REPEAT 198..221
FT /note="LRR 6"
FT REPEAT 223..242
FT /note="LRR 7"
FT REPEAT 243..268
FT /note="LRR 8"
FT REPEAT 283..306
FT /note="LRR 9"
FT REPEAT 308..332
FT /note="LRR 10"
FT REPEAT 333..356
FT /note="LRR 11"
FT REPEAT 363..386
FT /note="LRR 12"
FT REPEAT 390..413
FT /note="LRR 13"
FT REPEAT 415..440
FT /note="LRR 14"
FT REPEAT 470..494
FT /note="LRR 15"
FT REPEAT 496..519
FT /note="LRR 16"
FT REPEAT 520..543
FT /note="LRR 17"
FT REPEAT 545..572
FT /note="LRR 18"
FT REPEAT 574..598
FT /note="LRR 19"
FT REPEAT 600..622
FT /note="LRR 20"
FT REPEAT 627..650
FT /note="LRR 21"
FT REPEAT 652..675
FT /note="LRR 22"
FT REPEAT 676..699
FT /note="LRR 23"
FT REPEAT 701..723
FT /note="LRR 24"
FT REPEAT 724..747
FT /note="LRR 25"
FT REPEAT 749..772
FT /note="LRR 26"
FT DOMAIN 868..1013
FT /note="TIR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00204"
FT BINDING 47..51
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /ligand_note="CpG-containing DNA"
FT /evidence="ECO:0000250|UniProtKB:Q2EEY0"
FT BINDING 72..77
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /ligand_note="CpG-containing DNA"
FT /evidence="ECO:0000250|UniProtKB:Q2EEY0"
FT BINDING 95..109
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /ligand_note="CpG-containing DNA"
FT /evidence="ECO:0000250|UniProtKB:Q2EEY0"
FT BINDING 132
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /ligand_note="CpG-containing DNA"
FT /evidence="ECO:0000250|UniProtKB:Q2EEY0"
FT BINDING 179..181
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /ligand_note="CpG-containing DNA"
FT /evidence="ECO:0000250|UniProtKB:Q2EEY0"
FT BINDING 208
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /ligand_note="CpG-containing DNA"
FT /evidence="ECO:0000250|UniProtKB:Q2EEY0"
FT CARBOHYD 64
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 129
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 200
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 210
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 242
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 300
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 340
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 469
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 474
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 513
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 567
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 694
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 731
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 35..45
FT /evidence="ECO:0000250|UniProtKB:Q2EEY0"
FT DISULFID 98..110
FT /evidence="ECO:0000250|UniProtKB:Q2EEY0"
FT DISULFID 178..184
FT /evidence="ECO:0000250|UniProtKB:Q2EEY0"
FT DISULFID 255..268
FT /evidence="ECO:0000250|UniProtKB:Q2EEY0"
FT DISULFID 258..265
FT /evidence="ECO:0000250|UniProtKB:Q2EEY0"
FT DISULFID 470..500
FT /evidence="ECO:0000250|UniProtKB:Q2EEY0"
FT DISULFID 764..790
FT /evidence="ECO:0000250|UniProtKB:Q2EEY0"
FT DISULFID 766..809
FT /evidence="ECO:0000250|UniProtKB:Q2EEY0"
FT VAR_SEQ 1..57
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11022119"
FT /id="VSP_006520"
FT VAR_SEQ 1..16
FT /note="MGFCRSALHPLSLLVQ -> M (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:11022120"
FT /id="VSP_006523"
FT VAR_SEQ 1
FT /note="M -> MPMKWSGWRWSWGPATHTALPPPQ (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:11022120"
FT /id="VSP_006521"
FT VAR_SEQ 1
FT /note="M -> MLYSSCKSRLLDSVEQDFHLEIAKK (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:11022120"
FT /id="VSP_006522"
FT VARIANT 5
FT /note="R -> C (in dbSNP:rs5743842)"
FT /id="VAR_024668"
FT VARIANT 79
FT /note="H -> Q (in dbSNP:rs5743843)"
FT /id="VAR_052364"
FT VARIANT 863
FT /note="R -> Q (in dbSNP:rs5743845)"
FT /id="VAR_034555"
FT VARIANT 882
FT /note="A -> T (in dbSNP:rs5743846)"
FT /id="VAR_052365"
FT VARIANT 901
FT /note="R -> H (in a colorectal cancer sample; somatic
FT mutation; dbSNP:rs755472700)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036077"
FT VARIANT 933
FT /note="T -> M (in a colorectal cancer sample; somatic
FT mutation; dbSNP:rs746622200)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036078"
FT CONFLICT 200
FT /note="N -> S (in Ref. 7; AAQ89443)"
FT /evidence="ECO:0000305"
FT CONFLICT 330
FT /note="F -> L (in Ref. 7; AAQ89443)"
FT /evidence="ECO:0000305"
FT CONFLICT 530
FT /note="H -> R (in Ref. 2; AAF78037)"
FT /evidence="ECO:0000305"
FT CONFLICT 688
FT /note="Q -> R (in Ref. 2; AAF78037)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1032 AA; 115860 MW; 71280AA9680EDCE2 CRC64;
MGFCRSALHP LSLLVQAIML AMTLALGTLP AFLPCELQPH GLVNCNWLFL KSVPHFSMAA
PRGNVTSLSL SSNRIHHLHD SDFAHLPSLR HLNLKWNCPP VGLSPMHFPC HMTIEPSTFL
AVPTLEELNL SYNNIMTVPA LPKSLISLSL SHTNILMLDS ASLAGLHALR FLFMDGNCYY
KNPCRQALEV APGALLGLGN LTHLSLKYNN LTVVPRNLPS SLEYLLLSYN RIVKLAPEDL
ANLTALRVLD VGGNCRRCDH APNPCMECPR HFPQLHPDTF SHLSRLEGLV LKDSSLSWLN
ASWFRGLGNL RVLDLSENFL YKCITKTKAF QGLTQLRKLN LSFNYQKRVS FAHLSLAPSF
GSLVALKELD MHGIFFRSLD ETTLRPLARL PMLQTLRLQM NFINQAQLGI FRAFPGLRYV
DLSDNRISGA SELTATMGEA DGGEKVWLQP GDLAPAPVDT PSSEDFRPNC STLNFTLDLS
RNNLVTVQPE MFAQLSHLQC LRLSHNCISQ AVNGSQFLPL TGLQVLDLSH NKLDLYHEHS
FTELPRLEAL DLSYNSQPFG MQGVGHNFSF VAHLRTLRHL SLAHNNIHSQ VSQQLCSTSL
RALDFSGNAL GHMWAEGDLY LHFFQGLSGL IWLDLSQNRL HTLLPQTLRN LPKSLQVLRL
RDNYLAFFKW WSLHFLPKLE VLDLAGNQLK ALTNGSLPAG TRLRRLDVSC NSISFVAPGF
FSKAKELREL NLSANALKTV DHSWFGPLAS ALQILDVSAN PLHCACGAAF MDFLLEVQAA
VPGLPSRVKC GSPGQLQGLS IFAQDLRLCL DEALSWDCFA LSLLAVALGL GVPMLHHLCG
WDLWYCFHLC LAWLPWRGRQ SGRDEDALPY DAFVVFDKTQ SAVADWVYNE LRGQLEECRG
RWALRLCLEE RDWLPGKTLF ENLWASVYGS RKTLFVLAHT DRVSGLLRAS FLLAQQRLLE
DRKDVVVLVI LSPDGRRSRY VRLRQRLCRQ SVLLWPHQPS GQRSFWAQLG MALTRDNHHF
YNRNFCQGPT AE
