TLR9_HORSE
ID TLR9_HORSE Reviewed; 1031 AA.
AC Q2EEY0;
DT 10-MAY-2017, integrated into UniProtKB/Swiss-Prot.
DT 21-MAR-2006, sequence version 1.
DT 03-AUG-2022, entry version 122.
DE RecName: Full=Toll-like receptor 9 {ECO:0000303|PubMed:18462806, ECO:0000312|EMBL:ABD36388.2};
DE AltName: CD_antigen=CD289 {ECO:0000305};
DE Flags: Precursor;
GN Name=TLR9 {ECO:0000303|PubMed:18462806, ECO:0000312|EMBL:ABD36388.2,
GN ECO:0000312|Ensembl:ENSECAP00000011919};
OS Equus caballus (Horse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Perissodactyla; Equidae; Equus.
OX NCBI_TaxID=9796 {ECO:0000312|EMBL:ABD36388.2};
RN [1] {ECO:0000312|EMBL:ABD36388.2}
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, INDUCTION, AND PHYLOGENETIC
RP ANALYSIS.
RX PubMed=18462806; DOI=10.1016/j.vetimm.2008.03.005;
RA Zhang Y.W., Davis E.G., Blecha F., Wilkerson M.J.;
RT "Molecular cloning and characterization of equine Toll-like receptor 9.";
RL Vet. Immunol. Immunopathol. 124:209-219(2008).
RN [2] {ECO:0000312|Ensembl:ENSECAP00000011919}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Thoroughbred {ECO:0000312|Ensembl:ENSECAP00000011919};
RX PubMed=19892987; DOI=10.1126/science.1178158;
RA Wade C.M., Giulotto E., Sigurdsson S., Zoli M., Gnerre S., Imsland F.,
RA Lear T.L., Adelson D.L., Bailey E., Bellone R.R., Bloecker H., Distl O.,
RA Edgar R.C., Garber M., Leeb T., Mauceli E., MacLeod J.N., Penedo M.C.T.,
RA Raison J.M., Sharpe T., Vogel J., Andersson L., Antczak D.F., Biagi T.,
RA Binns M.M., Chowdhary B.P., Coleman S.J., Della Valle G., Fryc S.,
RA Guerin G., Hasegawa T., Hill E.W., Jurka J., Kiialainen A., Lindgren G.,
RA Liu J., Magnani E., Mickelson J.R., Murray J., Nergadze S.G., Onofrio R.,
RA Pedroni S., Piras M.F., Raudsepp T., Rocchi M., Roeed K.H., Ryder O.A.,
RA Searle S., Skow L., Swinburne J.E., Syvaenen A.C., Tozaki T., Valberg S.J.,
RA Vaudin M., White J.R., Zody M.C., Lander E.S., Lindblad-Toh K.;
RT "Genome sequence, comparative analysis, and population genetics of the
RT domestic horse.";
RL Science 326:865-867(2009).
RN [3]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=19548205; DOI=10.1002/ar.20927;
RA Schneberger D., Caldwell S., Suri S.S., Singh B.;
RT "Expression of toll-like receptor 9 in horse lungs.";
RL Anat. Rec. (Hoboken) 292:1068-1077(2009).
RN [4]
RP DEVELOPMENTAL STAGE, AND INDUCTION.
RX PubMed=19819162; DOI=10.1016/j.cyto.2009.08.012;
RA Liu M., Liu T., Bordin A., Nerren J., Cohen N.;
RT "Activation of foal neutrophils at different ages by CpG
RT oligodeoxynucleotides and Rhodococcus equi.";
RL Cytokine 48:280-289(2009).
RN [5]
RP TISSUE SPECIFICITY.
RX PubMed=21292331; DOI=10.1016/j.vetimm.2010.12.008;
RA Quintana A.M., Landolt G.A., Annis K.M., Hussey G.S.;
RT "Immunological characterization of the equine airway epithelium and of a
RT primary equine airway epithelial cell culture model.";
RL Vet. Immunol. Immunopathol. 140:226-236(2011).
RN [6]
RP DEVELOPMENTAL STAGE, AND INDUCTION.
RX PubMed=22197007; DOI=10.1016/j.vetimm.2011.11.012;
RA Bordin A.I., Liu M., Nerren J.R., Buntain S.L., Brake C.N., Kogut M.H.,
RA Cohen N.D.;
RT "Neutrophil function of neonatal foals is enhanced in vitro by CpG
RT oligodeoxynucleotide stimulation.";
RL Vet. Immunol. Immunopathol. 145:290-297(2012).
RN [7]
RP INDUCTION.
RX PubMed=25066759; DOI=10.1016/j.intimp.2014.07.016;
RA Manuja A., Kumar P., Kumar R., Kumar B., Singha H., Sharma R.K.,
RA Yadav S.C.;
RT "CpG-ODN class C-mediated immunostimulation and its potential against
RT Trypanosoma evansi in equines.";
RL Int. Immunopharmacol. 22:366-370(2014).
RN [8]
RP INDUCTION.
RX PubMed=24560592; DOI=10.1016/j.vetmic.2014.01.018;
RA Soboll Hussey G., Ashton L.V., Quintana A.M., Lunn D.P., Goehring L.S.,
RA Annis K., Landolt G.;
RT "Innate immune responses of airway epithelial cells to infection with
RT equine herpesvirus-1.";
RL Vet. Microbiol. 170:28-38(2014).
RN [9]
RP TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=27270960; DOI=10.1111/evj.12597;
RA Kennedy R., Lappin D.F., Dixon P.M., Bennett D., Riggio M.P.;
RT "Gingival Toll-like receptor and cytokine messenger RNA levels in equine
RT periodontitis and oral health.";
RL Equine Vet. J. 49:294-299(2017).
RN [10] {ECO:0007744|PDB:3WPB, ECO:0007744|PDB:3WPC, ECO:0007744|PDB:3WPD}
RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 26-817 OF UNLIGANDED AND IN
RP COMPLEX WITH AGONIST CPG-DNA AND INHIBITORY DNA, FUNCTION, SUBUNIT,
RP GLYCOSYLATION AT ASN-200; ASN-210; ASN-242; ASN-309; ASN-513; ASN-567;
RP ASN-694 AND ASN-731, DISULFIDE BONDS, AND MUTAGENESIS OF TRP-47; TRP-96 AND
RP PHE-108.
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. Upon CpG stimulation, induces B-cell
CC proliferation, activation, survival and antibody production (By
CC similarity). {ECO:0000250|UniProtKB:Q9NR96,
CC 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 (PubMed:25686612). Interacts with MYD88 via their
CC respective TIR domains (By similarity). Interacts with BTK (By
CC similarity). Interacts (via transmembrane domain) with UNC93B1.
CC Interacts with CD300LH; the interaction may promote full activation of
CC TLR9-triggered innate responses. Interacts with CNPY3 and HSP90B1; this
CC interaction is required for proper folding in the endoplasmic
CC reticulum. Interacts with SMPDL3B (By similarity).
CC {ECO:0000250|UniProtKB:Q9EQU3, ECO:0000250|UniProtKB:Q9NR96,
CC ECO:0000269|PubMed:25686612}.
CC -!- INTERACTION:
CC Q2EEY0; Q2EEY0: TLR9; NbExp=2; IntAct=EBI-16145055, EBI-16145055;
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
CC {ECO:0000250|UniProtKB:Q9EQU3}. Cytoplasmic vesicle, phagosome
CC {ECO:0000250|UniProtKB:Q9EQU3}. Cell membrane
CC {ECO:0000269|PubMed:19548205}. Cytoplasm {ECO:0000269|PubMed:19548205}.
CC Nucleus {ECO:0000269|PubMed:19548205}. Note=Relocalizes from
CC endoplasmic reticulum to endosome and lysosome upon stimulation with
CC agonist. Exit from the ER requires UNC93B1. Endolysosomal localization
CC is required for proteolytic cleavage and subsequent activation.
CC Intracellular localization of the active receptor may prevent from
CC responding to self nucleic acid. {ECO:0000250|UniProtKB:Q9EQU3}.
CC -!- TISSUE SPECIFICITY: Expressed in airway epithelium, vascular
CC endothelium and inflammatory cells in blood vessels of the lungs (at
CC protein level). Highly expressed in pulmonary intravascular macrophages
CC (PIMs) and to a lesser extent in alveolar macrophages, neutrophiles,
CC type-II alveolar epithelial cells and bronchial epithelial cells of the
CC lungs (at protein level) (PubMed:19548205). High constitutive
CC intracellular expression in leukocytes including polymorphonuclear
CC leukocytes (PMNs), CD4 and CD8 T cells (at protein level)
CC (PubMed:18462806). Expressed throughout the respiratory tract including
CC larynx, upper, middle and lower trachea, and bronchus in isolated
CC equine respiratory epithelial cells (ERECs) and in fully differentiated
CC ERECs cultured at the air-fluid interface (AFI) (at protein level)
CC (PubMed:21292331). Constitutively expressed in peripheral blood
CC mononuclear cells (PBMCs), lymph nodes and spleen. The level of
CC expression in PBMCs is about 2- to 3-fold higher than that in lymph
CC nodes and spleen. Very low expression in liver, heart, lung, kidney,
CC small intestine, colon and stomach (PubMed:18462806). Low expression in
CC the airway tissue epithelium of the larynx, upper trachea, middle
CC tranchea, lower trachea, bronchus and spleen, and more abundant
CC expression in mesenteric lymph node. Not expressed in fully
CC differentiated bronchus epithelial cells cultured at the AFI for four
CC weeks (PubMed:21292331). Expressed in gingival tissue
CC (PubMed:27270960). {ECO:0000269|PubMed:18462806,
CC ECO:0000269|PubMed:19548205, ECO:0000269|PubMed:21292331,
CC ECO:0000269|PubMed:27270960}.
CC -!- DEVELOPMENTAL STAGE: Expression increases with age in neutrophils of an
CC individual foal aged between 2 to 56 days (PubMed:22197007). Expression
CC in neutrophils of a foal at age 1 day, another different foal at age 56
CC days, and of an adult horse is constitutive at a very low level
CC (PubMed:19819162). {ECO:0000269|PubMed:19819162,
CC ECO:0000269|PubMed:22197007}.
CC -!- INDUCTION: By mitogen phytohaemagglutinin (PHA) in peripheral blood
CC mononuclear cells (PBMCs) (PubMed:18462806). By lipopolysaccharide
CC (LPS) in cells of the lung septa. This induction is abolished by
CC gadolinium chloride treatment which depletes pulmonary intravascular
CC macrophages (PIMs) (PubMed:19548205). By synthetic class C cytidine-
CC phosphate-guanosine oligodeoxynucleotides (CpG-ODNs) in PBMCs
CC (PubMed:25066759). Synthetic class B CpG-ODN does not induce a
CC significant increase of expression in vitro in neutrophils of foals
CC aged between 2 to 56 days nor in adult horses (PubMed:22197007,
CC PubMed:19819162). Expression level in neutrophils is not significantly
CC changed by virulent strain of R.equi bacterium (PubMed:19819162). Up-
CC regulated by neuropathogenic equine herpesvirus-1 (EHV-1) infection in
CC fully differentiated equine respiratory epithelial cells (ERECs)
CC cultured at the air-fluid interface (AFI) (PubMed:24560592). Up-
CC regulated in gingival tissue in individuals with equine periodontal
CC disease. 16-fold increase in expression at diseased sites of the gums
CC compared to healthy sites of the same animal (PubMed:27270960).
CC {ECO:0000269|PubMed:18462806, ECO:0000269|PubMed:19548205,
CC ECO:0000269|PubMed:19819162, ECO:0000269|PubMed:22197007,
CC ECO:0000269|PubMed:24560592, ECO:0000269|PubMed:25066759,
CC ECO:0000269|PubMed:27270960}.
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; DQ390541; ABD36388.2; -; mRNA.
DR EMBL; AAWR02008456; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_001075259.1; NM_001081790.2.
DR PDB; 3WPB; X-ray; 2.40 A; A=26-817.
DR PDB; 3WPC; X-ray; 1.60 A; A/B=26-817.
DR PDB; 3WPD; X-ray; 2.75 A; A=26-817.
DR PDB; 5Y3J; X-ray; 1.81 A; A/B=26-819.
DR PDB; 5Y3K; X-ray; 2.70 A; A/B=26-819.
DR PDB; 5Y3L; X-ray; 2.60 A; A/B=26-819.
DR PDBsum; 3WPB; -.
DR PDBsum; 3WPC; -.
DR PDBsum; 3WPD; -.
DR PDBsum; 5Y3J; -.
DR PDBsum; 5Y3K; -.
DR PDBsum; 5Y3L; -.
DR AlphaFoldDB; Q2EEY0; -.
DR SMR; Q2EEY0; -.
DR DIP; DIP-61513N; -.
DR STRING; 9796.ENSECAP00000011919; -.
DR iPTMnet; Q2EEY0; -.
DR PaxDb; Q2EEY0; -.
DR PRIDE; Q2EEY0; -.
DR Ensembl; ENSECAT00000014884; ENSECAP00000011919; ENSECAG00000014294.
DR GeneID; 100009693; -.
DR KEGG; ecb:100009693; -.
DR CTD; 54106; -.
DR GeneTree; ENSGT00940000162493; -.
DR HOGENOM; CLU_006000_2_0_1; -.
DR InParanoid; Q2EEY0; -.
DR OMA; LSWDCFG; -.
DR TreeFam; TF325595; -.
DR Proteomes; UP000002281; Chromosome 16.
DR Bgee; ENSECAG00000014294; Expressed in blood and 8 other tissues.
DR GO; GO:0016324; C:apical plasma membrane; IEA:Ensembl.
DR GO; GO:0016323; C:basolateral plasma membrane; IEA:Ensembl.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0032009; C:early phagosome; IEA:Ensembl.
DR GO; GO:0036019; C:endolysosome; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005764; C:lysosome; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0045335; C:phagocytic vesicle; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0005149; F:interleukin-1 receptor binding; IEA:Ensembl.
DR GO; GO:0038187; F:pattern recognition receptor activity; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0035197; F:siRNA binding; ISS:UniProtKB.
DR GO; GO:0004888; F:transmembrane signaling receptor activity; IEA:InterPro.
DR GO; GO:0045322; F:unmethylated CpG binding; IDA:UniProtKB.
DR GO; GO:0002218; P:activation of innate immune response; IDA:UniProtKB.
DR GO; GO:1902350; P:cellular response to chloroquine; IEA:Ensembl.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IEA:Ensembl.
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; IEA:Ensembl.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0030277; P:maintenance of gastrointestinal epithelium; 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; IEA:Ensembl.
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; IEA:Ensembl.
DR GO; GO:0032717; P:negative regulation of interleukin-8 production; IEA:Ensembl.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IEA:Ensembl.
DR GO; GO:0034122; P:negative regulation of toll-like receptor signaling pathway; IEA:Ensembl.
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:0032722; P:positive regulation of chemokine production; IEA:Ensembl.
DR GO; GO:0032725; P:positive regulation of granulocyte macrophage colony-stimulating factor production; IEA:Ensembl.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB signaling; IEA:Ensembl.
DR GO; GO:0002639; P:positive regulation of immunoglobulin production; ISS:UniProtKB.
DR GO; GO:0050729; P:positive regulation of inflammatory response; IEA:InterPro.
DR GO; GO:0032727; P:positive regulation of interferon-alpha production; ISS:UniProtKB.
DR GO; GO:0032728; P:positive regulation of interferon-beta production; ISS:UniProtKB.
DR GO; GO:0032729; P:positive regulation of interferon-gamma production; ISS:UniProtKB.
DR GO; GO:0032733; P:positive regulation of interleukin-10 production; IEA:Ensembl.
DR GO; GO:0032735; P:positive regulation of interleukin-12 production; IEA:Ensembl.
DR GO; GO:0032741; P:positive regulation of interleukin-18 production; IEA:Ensembl.
DR GO; GO:0032755; P:positive regulation of interleukin-6 production; IBA:GO_Central.
DR GO; GO:0032757; P:positive regulation of interleukin-8 production; IEA:Ensembl.
DR GO; GO:0043507; P:positive regulation of JUN kinase activity; IEA:Ensembl.
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 NIK/NF-kappaB signaling; IEA:Ensembl.
DR GO; GO:0051770; P:positive regulation of nitric-oxide synthase biosynthetic process; IEA:Ensembl.
DR GO; GO:0034165; P:positive regulation of toll-like receptor 9 signaling pathway; IDA:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IEA:Ensembl.
DR GO; GO:0045577; P:regulation of B cell differentiation; ISS:UniProtKB.
DR GO; GO:0002730; P:regulation of dendritic cell cytokine production; IEA:Ensembl.
DR GO; GO:0002237; P:response to molecule of bacterial origin; IEA:InterPro.
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; 1.
DR Pfam; PF13855; LRR_8; 3.
DR Pfam; PF01582; TIR; 1.
DR SMART; SM00369; LRR_TYP; 16.
DR SMART; SM00255; TIR; 1.
DR SUPFAM; SSF52200; SSF52200; 1.
DR PROSITE; PS51450; LRR; 18.
DR PROSITE; PS50104; TIR; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Cytoplasm; Cytoplasmic vesicle;
KW Disulfide bond; Endoplasmic reticulum; Endosome; Glycoprotein; Immunity;
KW Inflammatory response; Innate immunity; Leucine-rich repeat; Lysosome;
KW Membrane; Nucleus; Receptor; Reference proteome; Repeat; Signal;
KW Transmembrane; Transmembrane helix.
FT SIGNAL 1..25
FT /evidence="ECO:0000255"
FT CHAIN 26..1031
FT /note="Toll-like receptor 9"
FT /evidence="ECO:0000255"
FT /id="PRO_5009710270"
FT TOPO_DOM 26..817
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 818..838
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 839..1031
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REPEAT 62..85
FT /note="LRR 1"
FT /evidence="ECO:0000255"
FT REPEAT 87..110
FT /note="LRR 2"
FT /evidence="ECO:0000255"
FT REPEAT 122..147
FT /note="LRR 3"
FT /evidence="ECO:0000255"
FT REPEAT 150..166
FT /note="LRR 4"
FT /evidence="ECO:0000255"
FT REPEAT 167..190
FT /note="LRR 5"
FT /evidence="ECO:0000255"
FT REPEAT 198..221
FT /note="LRR 6"
FT /evidence="ECO:0000255"
FT REPEAT 223..242
FT /note="LRR 7"
FT /evidence="ECO:0000255"
FT REPEAT 243..268
FT /note="LRR 8"
FT /evidence="ECO:0000255"
FT REPEAT 283..306
FT /note="LRR 9"
FT /evidence="ECO:0000255"
FT REPEAT 308..332
FT /note="LRR 10"
FT /evidence="ECO:0000255"
FT REPEAT 333..356
FT /note="LRR 11"
FT /evidence="ECO:0000255"
FT REPEAT 363..386
FT /note="LRR 12"
FT /evidence="ECO:0000255"
FT REPEAT 390..413
FT /note="LRR 13"
FT /evidence="ECO:0000255"
FT REPEAT 414..438
FT /note="LRR 14"
FT /evidence="ECO:0000255"
FT REPEAT 470..494
FT /note="LRR 15"
FT /evidence="ECO:0000255"
FT REPEAT 496..519
FT /note="LRR 16"
FT /evidence="ECO:0000255"
FT REPEAT 520..543
FT /note="LRR 17"
FT /evidence="ECO:0000255"
FT REPEAT 545..567
FT /note="LRR 18"
FT /evidence="ECO:0000255"
FT REPEAT 574..598
FT /note="LRR 19"
FT /evidence="ECO:0000255"
FT REPEAT 600..622
FT /note="LRR 20"
FT /evidence="ECO:0000255"
FT REPEAT 627..650
FT /note="LRR 21"
FT /evidence="ECO:0000255"
FT REPEAT 652..675
FT /note="LRR 22"
FT /evidence="ECO:0000255"
FT REPEAT 676..699
FT /note="LRR 23"
FT /evidence="ECO:0000255"
FT REPEAT 701..723
FT /note="LRR 24"
FT /evidence="ECO:0000255"
FT REPEAT 724..747
FT /note="LRR 25"
FT /evidence="ECO:0000255"
FT REPEAT 749..772
FT /note="LRR 26"
FT /evidence="ECO:0000255"
FT DOMAIN 866..1011
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:0000269|PubMed:25686612,
FT ECO:0007744|PDB:3WPC"
FT BINDING 72..77
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /ligand_note="CpG-containing DNA"
FT /evidence="ECO:0000269|PubMed:25686612,
FT ECO:0007744|PDB:3WPC"
FT BINDING 95..109
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /ligand_note="CpG-containing DNA"
FT /evidence="ECO:0000269|PubMed:25686612,
FT ECO:0007744|PDB:3WPC"
FT BINDING 132
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /ligand_note="CpG-containing DNA"
FT /evidence="ECO:0000269|PubMed:25686612,
FT ECO:0007744|PDB:3WPC"
FT BINDING 152
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /ligand_note="CpG-containing DNA"
FT /evidence="ECO:0000269|PubMed:25686612,
FT ECO:0007744|PDB:3WPC"
FT BINDING 179..181
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /ligand_note="CpG-containing DNA"
FT /evidence="ECO:0000269|PubMed:25686612,
FT ECO:0007744|PDB:3WPC"
FT BINDING 208
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /ligand_note="CpG-containing DNA"
FT /evidence="ECO:0000269|PubMed:25686612,
FT ECO:0007744|PDB:3WPC"
FT BINDING 262
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /ligand_note="CpG-containing DNA"
FT /evidence="ECO:0000269|PubMed:25686612,
FT ECO:0007744|PDB:3WPC"
FT CARBOHYD 64
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 129
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 200
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498,
FT ECO:0000269|PubMed:25686612, ECO:0007744|PDB:3WPC"
FT CARBOHYD 210
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498,
FT ECO:0000269|PubMed:25686612, ECO:0007744|PDB:3WPB,
FT ECO:0007744|PDB:3WPC, ECO:0007744|PDB:3WPD"
FT CARBOHYD 242
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498,
FT ECO:0000269|PubMed:25686612, ECO:0007744|PDB:3WPC"
FT CARBOHYD 309
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498,
FT ECO:0000269|PubMed:25686612, ECO:0007744|PDB:3WPC"
FT CARBOHYD 340
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 472
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 513
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498,
FT ECO:0000269|PubMed:25686612, ECO:0007744|PDB:3WPC"
FT CARBOHYD 567
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498,
FT ECO:0000269|PubMed:25686612, ECO:0007744|PDB:3WPB,
FT ECO:0007744|PDB:3WPC, ECO:0007744|PDB:3WPD"
FT CARBOHYD 669
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 694
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498,
FT ECO:0000269|PubMed:25686612, ECO:0007744|PDB:3WPC"
FT CARBOHYD 731
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498,
FT ECO:0000269|PubMed:25686612, ECO:0007744|PDB:3WPB,
FT ECO:0007744|PDB:3WPC, ECO:0007744|PDB:3WPD"
FT DISULFID 35..45
FT /evidence="ECO:0000269|PubMed:25686612,
FT ECO:0007744|PDB:3WPB, ECO:0007744|PDB:3WPC,
FT ECO:0007744|PDB:3WPD"
FT DISULFID 98..110
FT /evidence="ECO:0000269|PubMed:25686612,
FT ECO:0007744|PDB:3WPB, ECO:0007744|PDB:3WPC,
FT ECO:0007744|PDB:3WPD"
FT DISULFID 178..184
FT /evidence="ECO:0000269|PubMed:25686612,
FT ECO:0007744|PDB:3WPB, ECO:0007744|PDB:3WPC,
FT ECO:0007744|PDB:3WPD"
FT DISULFID 255..268
FT /evidence="ECO:0000269|PubMed:25686612,
FT ECO:0007744|PDB:3WPB, ECO:0007744|PDB:3WPC,
FT ECO:0007744|PDB:3WPD"
FT DISULFID 258..265
FT /evidence="ECO:0000269|PubMed:25686612,
FT ECO:0007744|PDB:3WPB, ECO:0007744|PDB:3WPC,
FT ECO:0007744|PDB:3WPD"
FT DISULFID 470..500
FT /evidence="ECO:0000269|PubMed:25686612,
FT ECO:0007744|PDB:3WPB, ECO:0007744|PDB:3WPC,
FT ECO:0007744|PDB:3WPD"
FT DISULFID 764..790
FT /evidence="ECO:0000269|PubMed:25686612,
FT ECO:0007744|PDB:3WPB, ECO:0007744|PDB:3WPC,
FT ECO:0007744|PDB:3WPD"
FT DISULFID 766..809
FT /evidence="ECO:0000269|PubMed:25686612,
FT ECO:0007744|PDB:3WPB, ECO:0007744|PDB:3WPD"
FT MUTAGEN 47
FT /note="W->A: Significantly decreased binding to agonist
FT CpG-DNA."
FT /evidence="ECO:0000269|PubMed:25686612"
FT MUTAGEN 96
FT /note="W->A: Significantly decreased binding to agonist
FT CpG-DNA."
FT /evidence="ECO:0000269|PubMed:25686612"
FT MUTAGEN 108
FT /note="F->A: Significantly decreased binding to agonist
FT CpG-DNA."
FT /evidence="ECO:0000269|PubMed:25686612"
FT TURN 31..34
FT /evidence="ECO:0007829|PDB:3WPC"
FT STRAND 35..38
FT /evidence="ECO:0007829|PDB:3WPC"
FT TURN 39..41
FT /evidence="ECO:0007829|PDB:3WPC"
FT STRAND 42..44
FT /evidence="ECO:0007829|PDB:3WPC"
FT STRAND 58..60
FT /evidence="ECO:0007829|PDB:5Y3L"
FT HELIX 62..64
FT /evidence="ECO:0007829|PDB:3WPC"
FT STRAND 66..69
FT /evidence="ECO:0007829|PDB:3WPC"
FT TURN 80..85
FT /evidence="ECO:0007829|PDB:5Y3L"
FT STRAND 91..93
FT /evidence="ECO:0007829|PDB:3WPC"
FT STRAND 96..98
FT /evidence="ECO:0007829|PDB:3WPB"
FT TURN 101..103
FT /evidence="ECO:0007829|PDB:3WPC"
FT TURN 116..121
FT /evidence="ECO:0007829|PDB:3WPC"
FT STRAND 127..129
FT /evidence="ECO:0007829|PDB:3WPC"
FT STRAND 147..149
FT /evidence="ECO:0007829|PDB:3WPC"
FT TURN 160..162
FT /evidence="ECO:0007829|PDB:3WPC"
FT STRAND 171..173
FT /evidence="ECO:0007829|PDB:3WPC"
FT STRAND 177..179
FT /evidence="ECO:0007829|PDB:3WPC"
FT TURN 192..197
FT /evidence="ECO:0007829|PDB:3WPC"
FT STRAND 203..205
FT /evidence="ECO:0007829|PDB:3WPC"
FT STRAND 223..226
FT /evidence="ECO:0007829|PDB:3WPC"
FT HELIX 237..240
FT /evidence="ECO:0007829|PDB:3WPC"
FT STRAND 247..250
FT /evidence="ECO:0007829|PDB:3WPC"
FT STRAND 253..256
FT /evidence="ECO:0007829|PDB:3WPB"
FT HELIX 258..260
FT /evidence="ECO:0007829|PDB:3WPC"
FT TURN 277..282
FT /evidence="ECO:0007829|PDB:3WPC"
FT STRAND 288..290
FT /evidence="ECO:0007829|PDB:3WPC"
FT HELIX 301..303
FT /evidence="ECO:0007829|PDB:3WPC"
FT TURN 304..306
FT /evidence="ECO:0007829|PDB:3WPC"
FT STRAND 312..314
FT /evidence="ECO:0007829|PDB:3WPC"
FT TURN 320..322
FT /evidence="ECO:0007829|PDB:5Y3L"
FT HELIX 323..326
FT /evidence="ECO:0007829|PDB:3WPC"
FT TURN 329..332
FT /evidence="ECO:0007829|PDB:3WPC"
FT STRAND 338..340
FT /evidence="ECO:0007829|PDB:3WPC"
FT TURN 347..349
FT /evidence="ECO:0007829|PDB:3WPD"
FT HELIX 358..362
FT /evidence="ECO:0007829|PDB:3WPC"
FT STRAND 368..370
FT /evidence="ECO:0007829|PDB:3WPC"
FT STRAND 376..379
FT /evidence="ECO:0007829|PDB:3WPC"
FT TURN 381..384
FT /evidence="ECO:0007829|PDB:3WPC"
FT HELIX 385..387
FT /evidence="ECO:0007829|PDB:3WPC"
FT STRAND 395..397
FT /evidence="ECO:0007829|PDB:3WPC"
FT HELIX 408..411
FT /evidence="ECO:0007829|PDB:3WPC"
FT STRAND 419..421
FT /evidence="ECO:0007829|PDB:3WPC"
FT TURN 464..466
FT /evidence="ECO:0007829|PDB:5Y3J"
FT STRAND 470..474
FT /evidence="ECO:0007829|PDB:3WPD"
FT STRAND 476..478
FT /evidence="ECO:0007829|PDB:3WPC"
FT HELIX 489..492
FT /evidence="ECO:0007829|PDB:3WPC"
FT STRAND 499..502
FT /evidence="ECO:0007829|PDB:3WPC"
FT STRAND 512..514
FT /evidence="ECO:0007829|PDB:3WPB"
FT TURN 516..519
FT /evidence="ECO:0007829|PDB:3WPC"
FT STRAND 525..527
FT /evidence="ECO:0007829|PDB:3WPC"
FT TURN 538..543
FT /evidence="ECO:0007829|PDB:3WPC"
FT STRAND 549..551
FT /evidence="ECO:0007829|PDB:3WPC"
FT HELIX 556..559
FT /evidence="ECO:0007829|PDB:3WPC"
FT HELIX 569..573
FT /evidence="ECO:0007829|PDB:3WPC"
FT STRAND 579..581
FT /evidence="ECO:0007829|PDB:3WPC"
FT STRAND 589..591
FT /evidence="ECO:0007829|PDB:3WPC"
FT STRAND 596..599
FT /evidence="ECO:0007829|PDB:3WPC"
FT STRAND 602..604
FT /evidence="ECO:0007829|PDB:3WPC"
FT HELIX 610..614
FT /evidence="ECO:0007829|PDB:3WPC"
FT TURN 617..625
FT /evidence="ECO:0007829|PDB:3WPC"
FT STRAND 632..634
FT /evidence="ECO:0007829|PDB:3WPC"
FT HELIX 645..648
FT /evidence="ECO:0007829|PDB:3WPC"
FT STRAND 657..659
FT /evidence="ECO:0007829|PDB:3WPC"
FT HELIX 670..675
FT /evidence="ECO:0007829|PDB:3WPC"
FT STRAND 681..683
FT /evidence="ECO:0007829|PDB:3WPC"
FT STRAND 690..692
FT /evidence="ECO:0007829|PDB:5Y3K"
FT STRAND 705..707
FT /evidence="ECO:0007829|PDB:3WPC"
FT TURN 718..723
FT /evidence="ECO:0007829|PDB:3WPC"
FT STRAND 729..731
FT /evidence="ECO:0007829|PDB:3WPC"
FT HELIX 742..745
FT /evidence="ECO:0007829|PDB:3WPC"
FT HELIX 749..751
FT /evidence="ECO:0007829|PDB:5Y3J"
FT STRAND 753..756
FT /evidence="ECO:0007829|PDB:3WPC"
FT HELIX 770..776
FT /evidence="ECO:0007829|PDB:3WPC"
FT HELIX 778..780
FT /evidence="ECO:0007829|PDB:3WPC"
FT HELIX 784..787
FT /evidence="ECO:0007829|PDB:3WPC"
FT STRAND 789..793
FT /evidence="ECO:0007829|PDB:3WPC"
FT HELIX 794..796
FT /evidence="ECO:0007829|PDB:3WPC"
FT HELIX 801..803
FT /evidence="ECO:0007829|PDB:5Y3L"
FT HELIX 804..807
FT /evidence="ECO:0007829|PDB:3WPB"
SQ SEQUENCE 1031 AA; 115592 MW; 1B6EA2A08EE693C9 CRC64;
MGPCHGALQP LSLLVQAAML AVALAQGTLP PFLPCELQPH GLVNCNWLFL KSVPHFSAAA
PRDNVTSLSL LSNRIHHLHD SDFAQLSNLQ KLNLKWNCPP AGLSPMHFPC HMTIEPNTFL
AVPTLEELNL SYNGITTVPA LPSSLVSLIL SRTNILQLDP TSLTGLHALR FLYMDGNCYY
KNPCGRALEV APGALLGLGN LTHLSLKYNN LTTVPRSLPP SLEYLLLSYN HIVTLAPEDL
ANLTALRVLD VGGNCRRCDH ARNPCVECPH KFPQLHSDTF SHLSRLEGLV LKDSSLYQLN
PRWFRGLGNL TVLDLSENFL YDCITKTKAF QGLAQLRRLN LSFNYHKKVS FAHLTLAPSF
GSLLSLQELD MHGIFFRSLS QKTLQPLARL PMLQRLYLQM NFINQAQLGI FKDFPGLRYI
DLSDNRISGA VEPVATTGEV DGGKKVWLTS RDLTPGPLDT PSSEDFMPSC KNLSFTLDLS
RNNLVTVQPE MFAQLSRLQC LRLSHNSISQ AVNGSQFVPL TSLQVLDLSH NKLDLYHGRS
FTELPRLEAL DLSYNSQPFS MRGVGHNLSF VAQLPTLRYL SLAHNGIHSR VSQQLCSTSL
WALDFSGNSL SQMWAEGDLY LRFFQGLRSL IRLDLSQNRL HTLLPCTLGN LPKSLQLLRL
RNNYLAFFNW SSLTLLPNLE TLDLAGNQLK ALSNGSLPSG TQLQRLDVSR NSIIFVVPGF
FALATRLREL NLSANALRTV EPSWFGFLAG SLEVLDVSAN PLHCACGAAF VDFLLQVQAA
VPGLPSRVKC GSPGQLQGRS IFAQDLRLCL DESLSWDCFG LSLLVVALGL AMPMLHHLCG
WDLWYCFHLG LAWLPRRGWQ RGADALSYDA FVVFDKAQSA VADWVYNELR VRLEERRGRR
ALRLCLEERD WLPGKTLFEN LWASVYSSRK MLFVLAHTDQ VSGLLRASFL LAQQRLLEDR
KDVVVLVILS PDARRSRYVR LRQRLCRQSV LFWPHQPSGQ RSFWAQLGMA LTRDNRHFYN
QNFCRGPTMA E
