TLR9_FELCA
ID TLR9_FELCA Reviewed; 1031 AA.
AC Q5I2M7; Q8HZ52;
DT 07-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 15-FEB-2005, sequence version 1.
DT 03-AUG-2022, entry version 90.
DE RecName: Full=Toll-like receptor 9;
DE AltName: CD_antigen=CD289;
DE Flags: Precursor;
GN Name=TLR9;
OS Felis catus (Cat) (Felis silvestris catus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Feliformia; Felidae; Felinae; Felis.
OX NCBI_TaxID=9685;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Spleen;
RA Wernette C.M., Smith B.F., Baker H.J.;
RT "Feline toll-like receptor 9 (tlr9).";
RL Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Spleen;
RA Brownlie R., Mookherjee N., Mutwiri G., Babiuk L., Hecker R., Lipford G.,
RA Griebel P.;
RT "Felis catus 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; AY137581; AAN15751.1; -; mRNA.
DR EMBL; AY859724; AAW50952.1; -; mRNA.
DR RefSeq; NP_001009285.1; NM_001009285.1.
DR AlphaFoldDB; Q5I2M7; -.
DR SMR; Q5I2M7; -.
DR PRIDE; Q5I2M7; -.
DR GeneID; 493839; -.
DR KEGG; fca:493839; -.
DR CTD; 54106; -.
DR InParanoid; Q5I2M7; -.
DR OrthoDB; 263937at2759; -.
DR TreeFam; TF325595; -.
DR Proteomes; UP000011712; Unplaced.
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: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:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0002755; P:MyD88-dependent toll-like receptor signaling pathway; IEA:InterPro.
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:0043410; P:positive regulation of MAPK cascade; ISS:UniProtKB.
DR GO; GO:0034165; P:positive regulation of toll-like receptor 9 signaling pathway; ISS:UniProtKB.
DR GO; GO:0045577; P:regulation of B cell differentiation; ISS:UniProtKB.
DR GO; GO:0034163; P:regulation of toll-like receptor 9 signaling pathway; ISS:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IEA:UniProt.
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 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; 15.
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..1031
FT /note="Toll-like receptor 9"
FT /id="PRO_0000227008"
FT TOPO_DOM 26..817
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 818..838
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 839..1031
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 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: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 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 669
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 699
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"
SQ SEQUENCE 1031 AA; 115029 MW; 74D37E2D3950CB25 CRC64;
MGPCHGALHP LSLLVQAAAL AVALAQGTLP AFLPCELQRH GLVNCDWLFL KSVPHFSAAA
PRGNVTSLSL YSNRIHHLHD SDFVHLSSLR RLNLKWNCPP ASLSPMHFPC HMTIEPHTFL
AVPTLEELNL SYNSITTVPA LPSSLVSLSL SRTNILVLDP ANLAGLHSLR FLFLDGNCYY
KNPCPQALQV APGALLGLGN LTHLSLKYNN LTAVPRGLPP SLEYLLLSYN HIITLAPEDL
ANLTALRVLD VGGNCRRCDH ARNPCMECPK GFPHLHPDTF SHLNHLEGLV LKDSSLYNLN
PRWFHALGNL MVLDLSENFL YDCITKTTAF QGLAQLRRLN LSFNYHKKVS FAHLHLAPSF
GSLLSLQQLD MHGIFFRSLS ETTLRSLVHL PMLQSLHLQM NFINQAQLSI FGAFPGLRYV
DLSDNRISGA MELAAATGEV DGGERVRLPS GDLALGPPGT PSSEGFMPGC KTLNFTLDLS
RNNLVTIQPE MFARLSRLQC LLLSRNSISQ AVNGSQFMPL TSLQVLDLSH NKLDLYHGRS
FTELPRLEAL DLSYNSQPFS MQGVGHNLSF VAQLPALRYL SLAHNDIHSR VSQQLCSASL
RALDFSGNAL SRMWAEGDLY LHFFRGLRSL VRLDLSQNRL HTLLPRTLDN LPKSLRLLRL
RDNYLAFFNW SSLVLLPRLE ALDLAGNQLK ALSNGSLPNG TQLQRLDLSS NSISFVASSF
FALATRLREL NLSANALKTV EPSWFGSLAG TLKVLDVTGN PLHCACGAAF VDFLLEVQAA
VPGLPGHVKC GSPGQLQGRS IFAQDLRLCL DEALSWDCFG LSLLTVALGL AVPMLHHLCG
WDLWYCFHLC LAWLPRRGRR RGADALPYDA FVVFDKAQSA VADWVYNELR VRLEERRGRR
ALRLCLEERD WLPGKTLFEN LWASVYSSRK MLFVLAHTDR VSGLLRASFL LAQQRLLEDR
KDVVVLVILR PDAHRSRYVR LRQRLCRQSV LLWPHQPSGQ RSFWAQLGTA LTRDNQHFYN
QNFCRGPTTA E
