TLR9_CANLF
ID TLR9_CANLF Reviewed; 1032 AA.
AC Q5I2M8;
DT 07-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 15-FEB-2005, sequence version 1.
DT 03-AUG-2022, entry version 112.
DE RecName: Full=Toll-like receptor 9;
DE AltName: CD_antigen=CD289;
DE Flags: Precursor;
GN Name=TLR9;
OS Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Spleen;
RA Brownlie R., Mookherjee N., Mutwiri G., Babiuk L., Hecker R., Lipford G.,
RA Griebel P.;
RT "Canis familiaris toll-like receptor 9 mRNA.";
RL Submitted (DEC-2004) to the EMBL/GenBank/DDBJ databases.
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:Q9EQU3,
CC ECO:0000250|UniProtKB:Q9NR96}.
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 (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:Q2EEY0, ECO:0000250|UniProtKB:Q9EQU3,
CC ECO:0000250|UniProtKB:Q9NR96}.
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 -!- 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; AY859723; AAW50951.1; -; mRNA.
DR RefSeq; XP_013977197.1; XM_014121722.1.
DR AlphaFoldDB; Q5I2M8; -.
DR SMR; Q5I2M8; -.
DR STRING; 9612.ENSCAFP00000030804; -.
DR PaxDb; Q5I2M8; -.
DR Ensembl; ENSCAFT00030014603; ENSCAFP00030012737; ENSCAFG00030007955.
DR GeneID; 403502; -.
DR CTD; 54106; -.
DR eggNOG; KOG4641; Eukaryota.
DR HOGENOM; CLU_006000_2_0_1; -.
DR InParanoid; Q5I2M8; -.
DR OMA; LSWDCFG; -.
DR TreeFam; TF325595; -.
DR Reactome; R-CFA-109704; PI3K Cascade.
DR Reactome; R-CFA-1679131; Trafficking and processing of endosomal TLR.
DR Reactome; R-CFA-168138; Toll Like Receptor 9 (TLR9) Cascade.
DR Proteomes; UP000002254; Unplaced.
DR Bgee; ENSCAFG00000023201; Expressed in granulocyte and 22 other tissues.
DR GO; GO:0032009; C:early phagosome; ISS:UniProtKB.
DR GO; GO:0036019; C:endolysosome; ISS:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005768; C:endosome; ISS:UniProtKB.
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; IBA:GO_Central.
DR GO; GO:0038187; F:pattern recognition receptor activity; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS: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; 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: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: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: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: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: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:0043410; P:positive regulation of MAPK cascade; ISS:UniProtKB.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; IBA:GO_Central.
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; ISS: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:0001932; P:regulation of protein phosphorylation; IEA:Ensembl.
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; 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; 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 2: Evidence at transcript level;
KW Cytoplasmic vesicle; Disulfide bond; Endoplasmic reticulum; Endosome;
KW 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_0000227007"
FT TOPO_DOM 26..815
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 816..836
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 837..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 472..496
FT /note="LRR 15"
FT REPEAT 498..521
FT /note="LRR 16"
FT REPEAT 522..545
FT /note="LRR 17"
FT REPEAT 547..574
FT /note="LRR 18"
FT REPEAT 576..600
FT /note="LRR 19"
FT REPEAT 602..624
FT /note="LRR 20"
FT REPEAT 629..652
FT /note="LRR 21"
FT REPEAT 654..677
FT /note="LRR 22"
FT REPEAT 678..701
FT /note="LRR 23"
FT REPEAT 703..725
FT /note="LRR 24"
FT REPEAT 726..749
FT /note="LRR 25"
FT REPEAT 751..774
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 152
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 BINDING 262
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 340
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 476
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 515
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 569
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 671
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 696
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 701
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 733
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 472..502
FT /evidence="ECO:0000250|UniProtKB:Q2EEY0"
FT DISULFID 766..792
FT /evidence="ECO:0000250|UniProtKB:Q2EEY0"
FT DISULFID 768..811
FT /evidence="ECO:0000250|UniProtKB:Q2EEY0"
SQ SEQUENCE 1032 AA; 115292 MW; 515C77FF681B74A2 CRC64;
MGPCRGALHP LSLLVQAAAL ALALAQGTLP AFLPCELQPH GLVNCNWLFL KSVPRFSAAA
PRGNVTSLSL YSNRIHHLHD YDFVHFVHLR RLNLKWNCPP ASLSPMHFPC HMTIEPNTFL
AVPTLEDLNL SYNSITTVPA LPSSLVSLSL SRTNILVLDP ATLAGLYALR FLFLDGNCYY
KNPCQQALQV APGALLGLGN LTHLSLKYNN LTVVPRGLPP SLEYLLLSYN HIITLAPEDL
ANLTALRVLD VGGNCRRCDH ARNPCRECPK GFPQLHPNTF GHLSHLEGLV LRDSSLYSLD
PRWFHGLGNL MVLDLSENFL YDCITKTKAF YGLARLRRLN LSFNYHKKVS FAHLHLASSF
GSLLSLQELD IHGIFFRSLS KTTLQSLAHL PMLQRLHLQL NFISQAQLSI FGAFPGLRYV
DLSDNRISGA AEPAAATGEV EADCGERVWP QSRDLALGPL GTPGSEAFMP SCRTLNFTLD
LSRNNLVTVQ PEMFVRLARL QCLGLSHNSI SQAVNGSQFV PLSNLRVLDL SHNKLDLYHG
RSFTELPRLE ALDLSYNSQP FSMRGVGHNL SFVAQLPALR YLSLAHNGIH SRVSQQLRSA
SLRALDFSGN TLSQMWAEGD LYLRFFQGLR SLVQLDLSQN RLHTLLPRNL DNLPKSLRLL
RLRDNYLAFF NWSSLALLPK LEALDLAGNQ LKALSNGSLP NGTQLQRLDL SGNSIGFVVP
SFFALAVRLR ELNLSANALK TVEPSWFGSL AGALKVLDVT ANPLHCACGA TFVDFLLEVQ
AAVPGLPSRV KCGSPGQLQG RSIFAQDLRL CLDEALSWVC FSLSLLAVAL SLAVPMLHQL
CGWDLWYCFH LCLAWLPRRG RRRGVDALAY DAFVVFDKAQ SSVADWVYNE LRVQLEERRG
RRALRLCLEE RDWVPGKTLF ENLWASVYSS RKTLFVLART DRVSGLLRAS FLLAQQRLLE
DRKDVVVLVI LCPDAHRSRY VRLRQRLCRQ SVLLWPHQPS GQRSFWAQLG TALTRDNRHF
YNQNFCRGPT TA
