ID TLR9_MOUSE Reviewed; 1032 AA. AC Q9EQU3; F8VPN5; Q4L0K3; Q4L0K4; Q99MF2; Q99MQ8; DT 31-JAN-2002, integrated into UniProtKB/Swiss-Prot. DT 14-DEC-2011, sequence version 3. DT 24-JAN-2024, entry version 191. DE RecName: Full=Toll-like receptor 9; DE AltName: CD_antigen=CD289; DE Flags: Precursor; GN Name=Tlr9; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. 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 [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Macrophage; RX PubMed=11470918; DOI=10.1073/pnas.161293498; RA Bauer S.M., Kirschning C.J., Hacker H., Redecke V., Hausmann S., Akira S., RA Wagner H., Lipford G.B.; RT "Human TLR9 confers responsiveness to bacterial DNA via species-specific RT CpG motif recognition."; RL Proc. Natl. Acad. Sci. U.S.A. 98:9237-9242(2001). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=BALB/cJ; RX PubMed=11867692; RA Chuang T.-H., Lee J., Kline L., Mathison J.C., Ulevitch R.J.; RT "Toll-like receptor 9 mediates CpG-DNA signaling."; RL J. Leukoc. Biol. 71:538-544(2002). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=C57BL/6J; RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112; RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S., RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., RA Eichler E.E., Ponting C.P.; RT "Lineage-specific biology revealed by a finished genome assembly of the RT mouse."; RL PLoS Biol. 7:E1000112-E1000112(2009). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-964, FUNCTION, TISSUE SPECIFICITY, RP INDUCTION, AND DISRUPTION PHENOTYPE. RC STRAIN=BALB/cJ, and C57BL/6J; RX PubMed=17474149; DOI=10.1002/eji.200636562; RA Anderson A.E., Worku M.L., Khamri W., Bamford K.B., Walker M.M., RA Thursz M.R.; RT "TLR9 polymorphisms determine murine lymphocyte responses to Helicobacter: RT results from a genome-wide scan."; RL Eur. J. Immunol. 37:1548-1561(2007). RN [6] RP FUNCTION IN CYTOMEGALOVIRUS INFECTION, AND MUTAGENESIS OF LEU-499. RX PubMed=14993594; DOI=10.1073/pnas.0400525101; RA Tabeta K., Georgel P., Janssen E., Du X., Hoebe K., Crozat K., Mudd S., RA Shamel L., Sovath S., Goode J., Alexopoulou L., Flavell R.A., Beutler B.; RT "Toll-like receptors 9 and 3 as essential components of innate immune RT defense against mouse cytomegalovirus infection."; RL Proc. Natl. Acad. Sci. U.S.A. 101:3516-3521(2004). RN [7] RP IDENTIFICATION BY MASS SPECTROMETRY, AND INTERACTION WITH UNC93B1. RX PubMed=17452530; DOI=10.1083/jcb.200612056; RA Brinkmann M.M., Spooner E., Hoebe K., Beutler B., Ploegh H.L., Kim Y.M.; RT "The interaction between the ER membrane protein UNC93B and TLR3, 7, and 9 RT is crucial for TLR signaling."; RL J. Cell Biol. 177:265-275(2007). RN [8] RP INTERACTION WITH CNPY3. RX PubMed=18780723; DOI=10.1093/intimm/dxn098; RA Kiyokawa T., Akashi-Takamura S., Shibata T., Matsumoto F., Nishitani C., RA Kuroki Y., Seto Y., Miyake K.; RT "A single base mutation in the PRAT4A gene reveals differential interaction RT of PRAT4A with Toll-like receptors."; RL Int. Immunol. 20:1407-1415(2008). RN [9] RP SUBCELLULAR LOCATION. RX PubMed=18305481; DOI=10.1038/nature06726; RA Kim Y.M., Brinkmann M.M., Paquet M.E., Ploegh H.L.; RT "UNC93B1 delivers nucleotide-sensing toll-like receptors to RT endolysosomes."; RL Nature 452:234-238(2008). RN [10] RP FUNCTION, INTERACTION WITH MYD88, SUBCELLULAR LOCATION, AND PROTEOLYTIC RP CLEAVAGE. RX PubMed=18820679; DOI=10.1038/nature07405; RA Ewald S.E., Lee B.L., Lau L., Wickliffe K.E., Shi G.P., Chapman H.A., RA Barton G.M.; RT "The ectodomain of Toll-like receptor 9 is cleaved to generate a functional RT receptor."; RL Nature 456:658-662(2008). RN [11] RP FUNCTION, INTERACTION WITH UNC93B1, SUBCELLULAR LOCATION, PROTEOLYTIC RP CLEAVAGE, AND 3D-STRUCTURE MODELING OF THE ECTODOMAIN. RX PubMed=18931679; DOI=10.1038/ni.1669; RA Park B., Brinkmann M.M., Spooner E., Lee C.C., Kim Y.M., Ploegh H.L.; RT "Proteolytic cleavage in an endolysosomal compartment is required for RT activation of Toll-like receptor 9."; RL Nat. Immunol. 9:1407-1414(2008). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Spleen; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [13] 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 [14] 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 [15] RP FUNCTION, AND PROTEOLYTIC CLEAVAGE. RX PubMed=21402738; DOI=10.1084/jem.20100682; RA Ewald S.E., Engel A., Lee J., Wang M., Bogyo M., Barton G.M.; RT "Nucleic acid recognition by Toll-like receptors is coupled to stepwise RT processing by cathepsins and asparagine endopeptidase."; RL J. Exp. Med. 208:643-651(2011). RN [16] RP INTERACTION WITH CD300LH. RX PubMed=21940676; DOI=10.4049/jimmunol.1003806; RA Wu Y., Zhu X., Li N., Chen T., Yang M., Yao M., Liu X., Jin B., Wang X., RA Cao X.; RT "CMRF-35-like molecule 3 preferentially promotes TLR9-triggered RT proinflammatory cytokine production in macrophages by enhancing TNF RT receptor-associated factor 6 ubiquitination."; RL J. Immunol. 187:4881-4889(2011). RN [17] RP INTERACTION WITH SMPDL3B. RX PubMed=26095358; DOI=10.1016/j.celrep.2015.05.006; RA Heinz L.X., Baumann C.L., Koeberlin M.S., Snijder B., Gawish R., Shui G., RA Sharif O., Aspalter I.M., Mueller A.C., Kandasamy R.K., Breitwieser F.P., RA Pichlmair A., Bruckner M., Rebsamen M., Blueml S., Karonitsch T., RA Fauster A., Colinge J., Bennett K.L., Knapp S., Wenk M.R., RA Superti-Furga G.; RT "The lipid-modifying enzyme SMPDL3B negatively regulates innate immunity."; RL Cell Rep. 11:1919-1928(2015). RN [18] RP SUBCELLULAR LOCATION. RX PubMed=25917084; DOI=10.4049/jimmunol.1402006; RA Kimura T., Endo S., Inui M., Saitoh S., Miyake K., Takai T.; RT "Endoplasmic Protein Nogo-B (RTN4-B) Interacts with GRAMD4 and Regulates RT TLR9-Mediated Innate Immune Responses."; RL J. Immunol. 194:5426-5436(2015). RN [19] RP X-RAY CRYSTALLOGRAPHY (1.96 ANGSTROMS) OF 26-818 OF UNLIGANDED REDUCED RP GLYCOSYLATION MUTANT AND IN COMPLEXES WITH INHIBITORY DNA, FUNCTION, RP GLYCOSYLATION AT ASN-210; ASN-332 AND ASN-732, DISULFIDE BONDS, AND RP MUTAGENESIS OF TRP-47; ARG-74; SER-104; PHE-108; TYR-132; HIS-152; TYR-179; RP TYR-229; HIS-642; PHE-668 AND ASN-695. RX PubMed=25686612; DOI=10.1038/nature14138; RA Ohto U., Shibata T., Tanji H., Ishida H., Krayukhina E., Uchiyama S., RA Miyake K., Shimizu T.; RT "Structural basis of CpG and inhibitory DNA recognition by Toll-like RT receptor 9."; RL Nature 520:702-705(2015). 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:18931679, PubMed:21402738, CC PubMed:14993594, PubMed:17474149, PubMed:25686612, PubMed:18820679). CC Plays a role in defense against systemic mouse cytomegalovirus CC infection (PubMed:14993594). Controls lymphocyte response to CC Helicobacter infection (PubMed:17474149). Upon CpG stimulation, induces CC B-cell proliferation, activation, survival and antibody production (By CC similarity). {ECO:0000250|UniProtKB:Q9NR96, CC ECO:0000269|PubMed:14993594, ECO:0000269|PubMed:17474149, CC ECO:0000269|PubMed:18820679, ECO:0000269|PubMed:18931679, CC ECO:0000269|PubMed:21402738, ECO:0000269|PubMed:25686612}. 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 (PubMed:18820679). Interacts with BTK (By CC similarity). Interacts (via transmembrane domain) with UNC93B1 CC (PubMed:17452530, PubMed:18931679). Interacts with CD300LH; the CC interaction may promote full activation of TLR9-triggered innate CC responses (PubMed:21940676). Interacts with CNPY3 and HSP90B1; this CC interaction is required for proper folding in the endoplasmic reticulum CC (PubMed:18780723, PubMed:20865800). Interacts with SMPDL3B CC (PubMed:26095358). {ECO:0000250|UniProtKB:Q2EEY0, CC ECO:0000250|UniProtKB:Q9NR96, ECO:0000269|PubMed:17452530, CC ECO:0000269|PubMed:18780723, ECO:0000269|PubMed:18820679, CC ECO:0000269|PubMed:18931679, ECO:0000269|PubMed:20865800, CC ECO:0000269|PubMed:21940676, ECO:0000269|PubMed:26095358}. CC -!- INTERACTION: CC Q9EQU3; P11507: Atp2a2; Xeno; NbExp=4; IntAct=EBI-9979528, EBI-916319; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000269|PubMed:18305481}; Single-pass type I membrane protein CC {ECO:0000269|PubMed:18305481}. Endosome {ECO:0000269|PubMed:18305481, CC ECO:0000269|PubMed:25917084}. Lysosome {ECO:0000269|PubMed:18305481, CC ECO:0000269|PubMed:18820679, ECO:0000269|PubMed:25917084}. Cytoplasmic CC vesicle, phagosome {ECO:0000269|PubMed:18305481, CC ECO:0000269|PubMed:18820679}. Note=Relocalizes from endoplasmic CC reticulum to endosome and lysosome upon stimulation with agonist CC (PubMed:18305481). Exit from the ER requires UNC93B1 (PubMed:18820679). CC Endolysosomal localization is required for proteolytic cleavage and CC subsequent activation (PubMed:18931679, PubMed:18820679). Intracellular CC localization of the active receptor may prevent from responding to self CC nucleic acid (PubMed:18820679). {ECO:0000269|PubMed:18305481, CC ECO:0000269|PubMed:18820679, ECO:0000269|PubMed:18931679}. CC -!- TISSUE SPECIFICITY: Expressed in the basolateral region of gastric CC epithelial cells with high levels detected in antrum and body mucosa CC (at protein level). Detected in spleen and stomach at higher levels in CC C57BL/6 mice than BALB/C. {ECO:0000269|PubMed:17474149}. CC -!- INDUCTION: Following Helicobacter infection, down-regulated in C57BL/6 CC mice and up-regulated in BALB/C mice. {ECO:0000269|PubMed:17474149}. CC -!- PTM: Activated by proteolytic cleavage of the flexible loop between CC repeats LRR14 and LRR15 within the ectodomain (PubMed:18931679, CC PubMed:18820679). Cleavage requires UNC93B1 (PubMed:18820679). CC Proteolytically processed by first removing the majority of the CC 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 (PubMed:21402738). CC {ECO:0000269|PubMed:18820679, ECO:0000269|PubMed:18931679, CC ECO:0000269|PubMed:21402738}. CC -!- DISRUPTION PHENOTYPE: Reduced proliferation of lymphocytes, reduced CC interferon-gamma production by splenocytes and reduced neutrophil CC numbers following Helicobacter infection. CC {ECO:0000269|PubMed:17474149}. CC -!- SIMILARITY: Belongs to the Toll-like receptor family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AB045181; BAB19260.1; -; mRNA. DR EMBL; AF348140; AAK29625.1; -; mRNA. DR EMBL; AF314224; AAK28488.1; -; mRNA. DR EMBL; AC164430; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AY649790; AAU04980.1; -; Genomic_DNA. DR EMBL; AY649791; AAU04981.1; -; Genomic_DNA. DR CCDS; CCDS40755.1; -. DR RefSeq; NP_112455.2; NM_031178.2. DR PDB; 3WPF; X-ray; 1.96 A; A=26-818. DR PDB; 3WPG; X-ray; 2.25 A; A=26-818. DR PDB; 3WPH; X-ray; 2.33 A; A=26-818. DR PDB; 3WPI; X-ray; 2.25 A; A=26-818. DR PDB; 4QDH; X-ray; 2.40 A; A/B=480-753. DR PDB; 5ZLN; X-ray; 2.30 A; A/B=26-818. DR PDBsum; 3WPF; -. DR PDBsum; 3WPG; -. DR PDBsum; 3WPH; -. DR PDBsum; 3WPI; -. DR PDBsum; 4QDH; -. DR PDBsum; 5ZLN; -. DR AlphaFoldDB; Q9EQU3; -. DR SMR; Q9EQU3; -. DR BioGRID; 219897; 2. DR CORUM; Q9EQU3; -. DR IntAct; Q9EQU3; 28. DR MINT; Q9EQU3; -. DR STRING; 10090.ENSMUSP00000082207; -. DR BindingDB; Q9EQU3; -. DR ChEMBL; CHEMBL6128; -. DR GlyCosmos; Q9EQU3; 18 sites, No reported glycans. DR GlyGen; Q9EQU3; 19 sites, 1 O-linked glycan (1 site). DR iPTMnet; Q9EQU3; -. DR PhosphoSitePlus; Q9EQU3; -. DR SwissPalm; Q9EQU3; -. DR EPD; Q9EQU3; -. DR MaxQB; Q9EQU3; -. DR PaxDb; 10090-ENSMUSP00000082207; -. DR PeptideAtlas; Q9EQU3; -. DR ProteomicsDB; 258897; -. DR ABCD; Q9EQU3; 1 sequenced antibody. DR DNASU; 81897; -. DR Ensembl; ENSMUST00000062241.11; ENSMUSP00000082207.7; ENSMUSG00000045322.11. DR GeneID; 81897; -. DR KEGG; mmu:81897; -. DR UCSC; uc009rjh.1; mouse. DR AGR; MGI:1932389; -. DR CTD; 54106; -. DR MGI; MGI:1932389; Tlr9. DR VEuPathDB; HostDB:ENSMUSG00000045322; -. DR eggNOG; KOG4641; Eukaryota. DR GeneTree; ENSGT00940000162493; -. DR HOGENOM; CLU_006000_2_0_1; -. DR InParanoid; Q9EQU3; -. DR OMA; YNQNFCR; -. DR OrthoDB; 4603490at2759; -. DR PhylomeDB; Q9EQU3; -. DR TreeFam; TF325595; -. DR Reactome; R-MMU-109704; PI3K Cascade. DR Reactome; R-MMU-1679131; Trafficking and processing of endosomal TLR. DR Reactome; R-MMU-168138; Toll Like Receptor 9 (TLR9) Cascade. DR BioGRID-ORCS; 81897; 2 hits in 75 CRISPR screens. DR PRO; PR:Q9EQU3; -. DR Proteomes; UP000000589; Chromosome 9. DR RNAct; Q9EQU3; Protein. DR Bgee; ENSMUSG00000045322; Expressed in animal zygote and 36 other cell types or tissues. DR GO; GO:0016324; C:apical plasma membrane; ISO:MGI. DR GO; GO:0016323; C:basolateral plasma membrane; ISO:MGI. DR GO; GO:0005737; C:cytoplasm; ISO:MGI. DR GO; GO:0032009; C:early phagosome; IDA:UniProtKB. DR GO; GO:0036019; C:endolysosome; IDA:UniProtKB. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005768; C:endosome; IDA:UniProtKB. DR GO; GO:0005764; C:lysosome; IDA:UniProtKB. DR GO; GO:0045335; C:phagocytic vesicle; IGI:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:MGI. DR GO; GO:0005149; F:interleukin-1 receptor binding; ISO:MGI. DR GO; GO:0038187; F:pattern recognition receptor activity; ISO:MGI. DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB. DR GO; GO:0035197; F:siRNA binding; ISS:UniProtKB. DR GO; GO:0045322; F:unmethylated CpG binding; ISS:UniProtKB. DR GO; GO:0002218; P:activation of innate immune response; IDA:UniProtKB. DR GO; GO:0007249; P:canonical NF-kappaB signal transduction; IDA:UniProtKB. DR GO; GO:1902350; P:cellular response to chloroquine; IDA:MGI. 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:0050829; P:defense response to Gram-negative bacterium; ISO:MGI. DR GO; GO:0051607; P:defense response to virus; IGI:MGI. DR GO; GO:0032490; P:detection of molecule of bacterial origin; ISO:MGI. DR GO; GO:0006955; P:immune response; IMP:MGI. DR GO; GO:0045087; P:innate immune response; TAS:BHF-UCL. DR GO; GO:0030277; P:maintenance of gastrointestinal epithelium; IMP:BHF-UCL. DR GO; GO:0008584; P:male gonad development; IEA:Ensembl. DR GO; GO:0001774; P:microglial cell activation; ISO:MGI. DR GO; GO:0002755; P:MyD88-dependent toll-like receptor signaling pathway; IPI:UniProtKB. DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; IGI:MGI. DR GO; GO:0010508; P:positive regulation of autophagy; ISO:MGI. DR GO; GO:0050871; P:positive regulation of B cell activation; ISS:UniProtKB. DR GO; GO:0030890; P:positive regulation of B cell proliferation; ISS:UniProtKB. DR GO; GO:0043123; P:positive regulation of canonical NF-kappaB signal transduction; ISO:MGI. DR GO; GO:0032722; P:positive regulation of chemokine production; ISO:MGI. DR GO; GO:0001819; P:positive regulation of cytokine production; IDA:UniProtKB. DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI. DR GO; GO:0032725; P:positive regulation of granulocyte macrophage colony-stimulating factor production; ISO:MGI. DR GO; GO:0002639; P:positive regulation of immunoglobulin production; ISS:UniProtKB. DR GO; GO:0032727; P:positive regulation of interferon-alpha production; ISS:UniProtKB. DR GO; GO:0032728; P:positive regulation of interferon-beta production; IDA:BHF-UCL. DR GO; GO:0032733; P:positive regulation of interleukin-10 production; IDA:BHF-UCL. DR GO; GO:0032735; P:positive regulation of interleukin-12 production; IDA:BHF-UCL. DR GO; GO:0032741; P:positive regulation of interleukin-18 production; IDA: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; ISO:MGI. DR GO; GO:1905300; P:positive regulation of intestinal epithelial cell development; IMP:BHF-UCL. DR GO; GO:0046330; P:positive regulation of JNK cascade; ISO:MGI. DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISS:UniProtKB. DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IDA:UniProtKB. DR GO; GO:1901224; P:positive regulation of non-canonical NF-kappaB signal transduction; ISO:MGI. DR GO; GO:0034165; P:positive regulation of toll-like receptor 9 signaling pathway; IMP:UniProtKB. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL. DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IDA:BHF-UCL. DR GO; GO:0032729; P:positive regulation of type II interferon production; ISS:UniProtKB. DR GO; GO:0050864; P:regulation of B cell activation; IGI:MGI. DR GO; GO:0045577; P:regulation of B cell differentiation; ISS:UniProtKB. DR GO; GO:0002730; P:regulation of dendritic cell cytokine production; IDA:MGI. DR GO; GO:0050727; P:regulation of inflammatory response; IMP:BHF-UCL. DR GO; GO:0001932; P:regulation of protein phosphorylation; IDA:MGI. DR GO; GO:0034163; P:regulation of toll-like receptor 9 signaling pathway; ISS:UniProtKB. DR GO; GO:0002237; P:response to molecule of bacterial origin; TAS:BHF-UCL. DR GO; GO:0009615; P:response to virus; IMP:MGI. DR GO; GO:0034162; P:toll-like receptor 9 signaling pathway; ISO:MGI. DR GO; GO:0002224; P:toll-like receptor signaling pathway; ISO:MGI. DR Gene3D; 3.80.10.10; Ribonuclease Inhibitor; 1. DR Gene3D; 3.40.50.10140; Toll/interleukin-1 receptor homology (TIR) domain; 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; IPR035897; Toll_tir_struct_dom_sf. DR PANTHER; PTHR47410; TOLL-LIKE RECEPTOR 7-RELATED; 1. DR PANTHER; PTHR47410:SF3; TOLL-LIKE RECEPTOR 9; 1. DR Pfam; PF18837; LRR_12; 1. DR Pfam; PF13855; LRR_8; 4. DR Pfam; PF01582; TIR; 1. DR PRINTS; PR00019; LEURICHRPT. DR SMART; SM00365; LRR_SD22; 9. DR SMART; SM00369; LRR_TYP; 15. DR SMART; SM00255; TIR; 1. DR SUPFAM; SSF52058; L domain-like; 1. DR SUPFAM; SSF52047; RNI-like; 1. DR SUPFAM; SSF52200; Toll/Interleukin receptor TIR domain; 1. DR PROSITE; PS51450; LRR; 16. DR PROSITE; PS50104; TIR; 1. DR Genevisible; Q9EQU3; MM. PE 1: Evidence at protein level; KW 3D-structure; Cytoplasmic vesicle; Disulfide bond; Endoplasmic reticulum; KW Endosome; Glycoprotein; Immunity; Inflammatory response; Innate immunity; KW Leucine-rich repeat; Lysosome; Membrane; Receptor; Reference proteome; KW Repeat; Signal; Transmembrane; Transmembrane helix. FT SIGNAL 1..25 FT /evidence="ECO:0000255" FT CHAIN 26..1032 FT /note="Toll-like receptor 9" FT /id="PRO_0000034738" 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 471..495 FT /note="LRR 15" FT REPEAT 497..520 FT /note="LRR 16" FT REPEAT 521..544 FT /note="LRR 17" FT REPEAT 546..573 FT /note="LRR 18" FT REPEAT 575..599 FT /note="LRR 19" FT REPEAT 601..623 FT /note="LRR 20" FT REPEAT 628..651 FT /note="LRR 21" FT REPEAT 653..676 FT /note="LRR 22" FT REPEAT 677..700 FT /note="LRR 23" FT REPEAT 702..724 FT /note="LRR 24" FT REPEAT 725..748 FT /note="LRR 25" FT REPEAT 750..773 FT /note="LRR 26" FT DOMAIN 868..1013 FT /note="TIR" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00204" FT REGION 430..462 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" 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 147 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, ECO:0000269|PubMed:25686612, FT ECO:0007744|PDB:3WPF" 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 309 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 332 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255, ECO:0000269|PubMed:25686612, FT ECO:0007744|PDB:3WPF, ECO:0007744|PDB:3WPH" FT CARBOHYD 340 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 495 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 514 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 568 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 670 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 695 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 700 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 732 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255, ECO:0000269|PubMed:25686612, FT ECO:0007744|PDB:3WPF, ECO:0007744|PDB:3WPG, FT ECO:0007744|PDB:3WPH, ECO:0007744|PDB:3WPI" FT CARBOHYD 752 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 35..45 FT /evidence="ECO:0000269|PubMed:25686612, FT ECO:0007744|PDB:3WPF, ECO:0007744|PDB:3WPG, FT ECO:0007744|PDB:3WPH, ECO:0007744|PDB:3WPI" FT DISULFID 98..110 FT /evidence="ECO:0000269|PubMed:25686612, FT ECO:0007744|PDB:3WPF, ECO:0007744|PDB:3WPG, FT ECO:0007744|PDB:3WPH, ECO:0007744|PDB:3WPI" FT DISULFID 178..184 FT /evidence="ECO:0000269|PubMed:25686612, FT ECO:0007744|PDB:3WPF, ECO:0007744|PDB:3WPG, FT ECO:0007744|PDB:3WPH, ECO:0007744|PDB:3WPI" FT DISULFID 255..268 FT /evidence="ECO:0000269|PubMed:25686612, FT ECO:0007744|PDB:3WPF, ECO:0007744|PDB:3WPG, FT ECO:0007744|PDB:3WPH, ECO:0007744|PDB:3WPI" FT DISULFID 258..265 FT /evidence="ECO:0000269|PubMed:25686612, FT ECO:0007744|PDB:3WPF, ECO:0007744|PDB:3WPG, FT ECO:0007744|PDB:3WPH, ECO:0007744|PDB:3WPI" FT DISULFID 471..501 FT /evidence="ECO:0000269|PubMed:25686612, FT ECO:0007744|PDB:3WPF, ECO:0007744|PDB:3WPG, FT ECO:0007744|PDB:3WPH, ECO:0007744|PDB:3WPI" FT DISULFID 765..791 FT /evidence="ECO:0000269|PubMed:25686612, FT ECO:0007744|PDB:3WPF, ECO:0007744|PDB:3WPG, FT ECO:0007744|PDB:3WPH, ECO:0007744|PDB:3WPI" FT DISULFID 767..810 FT /evidence="ECO:0000269|PubMed:25686612, FT ECO:0007744|PDB:3WPF, ECO:0007744|PDB:3WPG, FT ECO:0007744|PDB:3WPH, ECO:0007744|PDB:3WPI" FT MUTAGEN 47 FT /note="W->A: Significantly decreased NF-kappa-B FT activation." FT /evidence="ECO:0000269|PubMed:25686612" FT MUTAGEN 74 FT /note="R->A: Significantly decreased NF-kappa-B FT activation." FT /evidence="ECO:0000269|PubMed:25686612" FT MUTAGEN 104 FT /note="S->A: Significantly decreased NF-kappa-B FT activation." FT /evidence="ECO:0000269|PubMed:25686612" FT MUTAGEN 108 FT /note="F->A: Significantly decreased NF-kappa-B FT activation." FT /evidence="ECO:0000269|PubMed:25686612" FT MUTAGEN 132 FT /note="Y->A: Significantly decreased NF-kappa-B FT activation." FT /evidence="ECO:0000269|PubMed:25686612" FT MUTAGEN 152 FT /note="H->A: Significantly decreased NF-kappa-B FT activation." FT /evidence="ECO:0000269|PubMed:25686612" FT MUTAGEN 179 FT /note="Y->A: Significantly decreased NF-kappa-B FT activation." FT /evidence="ECO:0000269|PubMed:25686612" FT MUTAGEN 229 FT /note="Y->A: Significantly decreased NF-kappa-B FT activation." FT /evidence="ECO:0000269|PubMed:25686612" FT MUTAGEN 499 FT /note="L->P: Highly susceptible to mouse cytomegalovirus FT infection. Shows low level of cytokine induction and FT natural killer activation on viral infection." FT /evidence="ECO:0000269|PubMed:14993594" FT MUTAGEN 642 FT /note="H->A: Loss of NF-kappa-B activation." FT /evidence="ECO:0000269|PubMed:25686612" FT MUTAGEN 668 FT /note="F->A: Significantly decreased NF-kappa-B FT activation." FT /evidence="ECO:0000269|PubMed:25686612" FT MUTAGEN 695 FT /note="N->A: Significantly decreased NF-kappa-B FT activation." FT /evidence="ECO:0000269|PubMed:25686612" FT CONFLICT 325 FT /note="T -> N (in Ref. 1; BAB19260, 2; AAK29625, 3; FT AAK28488 and 5; AAU04980)" FT /evidence="ECO:0000305" FT CONFLICT 378 FT /note="L -> S (in Ref. 1; BAB19260, 2; AAK29625, 3; FT AAK28488 and 5; AAU04980)" FT /evidence="ECO:0000305" FT CONFLICT 554 FT /note="S -> G (in Ref. 3; AAK28488)" FT /evidence="ECO:0000305" FT CONFLICT 562 FT /note="M -> I (in Ref. 3; AAK28488)" FT /evidence="ECO:0000305" FT CONFLICT 573 FT /note="T -> A (in Ref. 2; AAK29625, 3; AAK28488 and 5; FT AAU04980)" FT /evidence="ECO:0000305" FT CONFLICT 579 FT /note="Q -> H (in Ref. 2; AAK29625, 3; AAK28488 and 5; FT AAU04980)" FT /evidence="ECO:0000305" FT CONFLICT 867 FT /note="T -> A (in Ref. 2; AAK29625, 3; AAK28488 and 5; FT AAU04980)" FT /evidence="ECO:0000305" FT CONFLICT 897 FT /note="E -> G (in Ref. 3; AAK28488)" FT /evidence="ECO:0000305" FT TURN 31..34 FT /evidence="ECO:0007829|PDB:3WPF" FT STRAND 35..38 FT /evidence="ECO:0007829|PDB:3WPF" FT TURN 39..41 FT /evidence="ECO:0007829|PDB:3WPF" FT STRAND 42..44 FT /evidence="ECO:0007829|PDB:3WPF" FT STRAND 67..69 FT /evidence="ECO:0007829|PDB:3WPF" FT TURN 80..83 FT /evidence="ECO:0007829|PDB:3WPF" FT HELIX 84..86 FT /evidence="ECO:0007829|PDB:3WPF" FT STRAND 90..93 FT /evidence="ECO:0007829|PDB:3WPF" FT STRAND 100..102 FT /evidence="ECO:0007829|PDB:3WPI" FT TURN 116..121 FT /evidence="ECO:0007829|PDB:3WPF" FT STRAND 127..129 FT /evidence="ECO:0007829|PDB:3WPF" FT STRAND 147..149 FT /evidence="ECO:0007829|PDB:3WPF" FT HELIX 160..163 FT /evidence="ECO:0007829|PDB:3WPF" FT STRAND 171..173 FT /evidence="ECO:0007829|PDB:3WPF" FT STRAND 177..179 FT /evidence="ECO:0007829|PDB:3WPF" FT TURN 192..197 FT /evidence="ECO:0007829|PDB:3WPF" FT STRAND 203..205 FT /evidence="ECO:0007829|PDB:3WPF" FT STRAND 223..226 FT /evidence="ECO:0007829|PDB:3WPF" FT HELIX 237..239 FT /evidence="ECO:0007829|PDB:3WPF" FT STRAND 247..250 FT /evidence="ECO:0007829|PDB:3WPF" FT STRAND 254..256 FT /evidence="ECO:0007829|PDB:3WPF" FT HELIX 258..260 FT /evidence="ECO:0007829|PDB:5ZLN" FT STRAND 269..272 FT /evidence="ECO:0007829|PDB:3WPF" FT TURN 277..282 FT /evidence="ECO:0007829|PDB:3WPF" FT STRAND 288..290 FT /evidence="ECO:0007829|PDB:3WPF" FT HELIX 301..304 FT /evidence="ECO:0007829|PDB:3WPF" FT STRAND 312..314 FT /evidence="ECO:0007829|PDB:3WPF" FT STRAND 317..319 FT /evidence="ECO:0007829|PDB:3WPF" FT HELIX 321..324 FT /evidence="ECO:0007829|PDB:3WPF" FT HELIX 329..332 FT /evidence="ECO:0007829|PDB:3WPI" FT STRAND 338..340 FT /evidence="ECO:0007829|PDB:3WPF" FT STRAND 347..349 FT /evidence="ECO:0007829|PDB:3WPF" FT HELIX 358..362 FT /evidence="ECO:0007829|PDB:3WPF" FT STRAND 368..370 FT /evidence="ECO:0007829|PDB:3WPF" FT STRAND 377..379 FT /evidence="ECO:0007829|PDB:3WPF" FT TURN 381..384 FT /evidence="ECO:0007829|PDB:3WPF" FT HELIX 385..387 FT /evidence="ECO:0007829|PDB:3WPF" FT STRAND 395..397 FT /evidence="ECO:0007829|PDB:3WPF" FT HELIX 408..412 FT /evidence="ECO:0007829|PDB:3WPF" FT STRAND 413..416 FT /evidence="ECO:0007829|PDB:3WPI" FT STRAND 419..421 FT /evidence="ECO:0007829|PDB:3WPF" FT HELIX 467..471 FT /evidence="ECO:0007829|PDB:5ZLN" FT STRAND 473..475 FT /evidence="ECO:0007829|PDB:3WPF" FT STRAND 477..479 FT /evidence="ECO:0007829|PDB:3WPF" FT HELIX 490..493 FT /evidence="ECO:0007829|PDB:3WPF" FT STRAND 501..503 FT /evidence="ECO:0007829|PDB:3WPF" FT TURN 517..520 FT /evidence="ECO:0007829|PDB:3WPH" FT STRAND 526..528 FT /evidence="ECO:0007829|PDB:3WPF" FT TURN 539..544 FT /evidence="ECO:0007829|PDB:3WPF" FT STRAND 550..552 FT /evidence="ECO:0007829|PDB:3WPF" FT HELIX 558..561 FT /evidence="ECO:0007829|PDB:5ZLN" FT HELIX 570..574 FT /evidence="ECO:0007829|PDB:3WPF" FT STRAND 580..582 FT /evidence="ECO:0007829|PDB:3WPF" FT STRAND 590..592 FT /evidence="ECO:0007829|PDB:5ZLN" FT STRAND 597..600 FT /evidence="ECO:0007829|PDB:3WPF" FT STRAND 603..605 FT /evidence="ECO:0007829|PDB:3WPF" FT HELIX 611..615 FT /evidence="ECO:0007829|PDB:3WPF" FT TURN 620..626 FT /evidence="ECO:0007829|PDB:3WPF" FT STRAND 633..635 FT /evidence="ECO:0007829|PDB:3WPF" FT HELIX 646..650 FT /evidence="ECO:0007829|PDB:3WPF" FT STRAND 658..660 FT /evidence="ECO:0007829|PDB:3WPF" FT HELIX 671..676 FT /evidence="ECO:0007829|PDB:3WPF" FT STRAND 682..684 FT /evidence="ECO:0007829|PDB:3WPF" FT STRAND 706..708 FT /evidence="ECO:0007829|PDB:3WPF" FT TURN 719..724 FT /evidence="ECO:0007829|PDB:3WPF" FT STRAND 730..732 FT /evidence="ECO:0007829|PDB:3WPF" FT HELIX 743..745 FT /evidence="ECO:0007829|PDB:3WPF" FT HELIX 747..751 FT /evidence="ECO:0007829|PDB:3WPF" FT STRAND 754..757 FT /evidence="ECO:0007829|PDB:3WPF" FT HELIX 771..777 FT /evidence="ECO:0007829|PDB:3WPF" FT HELIX 779..781 FT /evidence="ECO:0007829|PDB:3WPF" FT TURN 783..788 FT /evidence="ECO:0007829|PDB:3WPF" FT STRAND 789..794 FT /evidence="ECO:0007829|PDB:3WPF" FT TURN 795..797 FT /evidence="ECO:0007829|PDB:3WPF" FT HELIX 807..809 FT /evidence="ECO:0007829|PDB:3WPF" SQ SEQUENCE 1032 AA; 116412 MW; C13A7888588CE297 CRC64; MVLRRRTLHP LSLLVQAAVL AETLALGTLP AFLPCELKPH GLVDCNWLFL KSVPRFSAAA SCSNITRLSL ISNRIHHLHN SDFVHLSNLR QLNLKWNCPP TGLSPLHFSC HMTIEPRTFL AMRTLEELNL SYNGITTVPR LPSSLVNLSL SHTNILVLDA NSLAGLYSLR VLFMDGNCYY KNPCTGAVKV TPGALLGLSN LTHLSLKYNN LTKVPRQLPP SLEYLLVSYN LIVKLGPEDL ANLTSLRVLD VGGNCRRCDH APNPCIECGQ KSLHLHPETF HHLSHLEGLV LKDSSLHTLN SSWFQGLVNL SVLDLSENFL YESITHTNAF QNLTRLRKLN LSFNYRKKVS FARLHLASSF KNLVSLQELN MNGIFFRLLN KYTLRWLADL PKLHTLHLQM NFINQAQLSI FGTFRALRFV DLSDNRISGP STLSEATPEE ADDAEQEELL SADPHPAPLS TPASKNFMDR CKNFKFTMDL SRNNLVTIKP EMFVNLSRLQ CLSLSHNSIA QAVNGSQFLP LTNLQVLDLS HNKLDLYHWK SFSELPQLQA LDLSYNSQPF SMKGIGHNFS FVTHLSMLQS LSLAHNDIHT RVSSHLNSNS VRFLDFSGNG MGRMWDEGGL YLHFFQGLSG LLKLDLSQNN LHILRPQNLD NLPKSLKLLS LRDNYLSFFN WTSLSFLPNL EVLDLAGNQL KALTNGTLPN GTLLQKLDVS SNSIVSVVPA FFALAVELKE VNLSHNILKT VDRSWFGPIV MNLTVLDVRS NPLHCACGAA FVDLLLEVQT KVPGLANGVK CGSPGQLQGR SIFAQDLRLC LDEVLSWDCF GLSLLAVAVG MVVPILHHLC GWDVWYCFHL CLAWLPLLAR SRRSAQTLPY DAFVVFDKAQ SAVADWVYNE LRVRLEERRG RRALRLCLED RDWLPGQTLF ENLWASIYGS RKTLFVLAHT DRVSGLLRTS FLLAQQRLLE DRKDVVVLVI LRPDAHRSRY VRLRQRLCRQ SVLFWPQQPN GQGGFWAQLS TALTRDNRHF YNQNFCRGPT AE //