TLR9_PIG
ID TLR9_PIG Reviewed; 1030 AA.
AC Q5I2M3;
DT 07-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 15-FEB-2005, sequence version 1.
DT 03-AUG-2022, entry version 105.
DE RecName: Full=Toll-like receptor 9;
DE AltName: CD_antigen=CD289;
DE Flags: Precursor;
GN Name=TLR9;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
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 "Sus scrofa 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; AY859728; AAW50956.1; -; mRNA.
DR AlphaFoldDB; Q5I2M3; -.
DR SMR; Q5I2M3; -.
DR STRING; 9823.ENSSSCP00000012188; -.
DR PaxDb; Q5I2M3; -.
DR PRIDE; Q5I2M3; -.
DR Ensembl; ENSSSCT00000012516; ENSSSCP00000012188; ENSSSCG00000011436.
DR Ensembl; ENSSSCT00015108303; ENSSSCP00015045894; ENSSSCG00015079750.
DR Ensembl; ENSSSCT00025019535; ENSSSCP00025007918; ENSSSCG00025014654.
DR Ensembl; ENSSSCT00030041455; ENSSSCP00030018844; ENSSSCG00030029843.
DR Ensembl; ENSSSCT00035100877; ENSSSCP00035042886; ENSSSCG00035074286.
DR Ensembl; ENSSSCT00040046162; ENSSSCP00040019360; ENSSSCG00040034305.
DR Ensembl; ENSSSCT00055031924; ENSSSCP00055025414; ENSSSCG00055016203.
DR Ensembl; ENSSSCT00060034526; ENSSSCP00060014780; ENSSSCG00060025471.
DR Ensembl; ENSSSCT00065051391; ENSSSCP00065022310; ENSSSCG00065037626.
DR eggNOG; KOG4641; Eukaryota.
DR GeneTree; ENSGT00940000162493; -.
DR HOGENOM; CLU_006000_2_0_1; -.
DR InParanoid; Q5I2M3; -.
DR OMA; LSWDCFG; -.
DR TreeFam; TF325595; -.
DR Reactome; R-SSC-109704; PI3K Cascade.
DR Reactome; R-SSC-1679131; Trafficking and processing of endosomal TLR.
DR Reactome; R-SSC-168138; Toll Like Receptor 9 (TLR9) Cascade.
DR Proteomes; UP000008227; Chromosome 13.
DR Proteomes; UP000314985; Unplaced.
DR Bgee; ENSSSCG00000011436; Expressed in spleen and 12 other tissues.
DR Genevisible; Q5I2M3; SS.
DR GO; GO:0016324; C:apical plasma membrane; IEA:Ensembl.
DR GO; GO:0016323; C:basolateral plasma membrane; IEA:Ensembl.
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:0005149; F:interleukin-1 receptor binding; IEA:Ensembl.
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: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; IBA:GO_Central.
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; 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: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; 17.
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..24
FT /evidence="ECO:0000255"
FT CHAIN 25..1030
FT /note="Toll-like receptor 9"
FT /id="PRO_0000227009"
FT TOPO_DOM 25..816
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 817..837
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 838..1030
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 61..84
FT /note="LRR 1"
FT REPEAT 86..109
FT /note="LRR 2"
FT REPEAT 121..146
FT /note="LRR 3"
FT REPEAT 149..165
FT /note="LRR 4"
FT REPEAT 166..189
FT /note="LRR 5"
FT REPEAT 197..220
FT /note="LRR 6"
FT REPEAT 222..241
FT /note="LRR 7"
FT REPEAT 242..267
FT /note="LRR 8"
FT REPEAT 282..305
FT /note="LRR 9"
FT REPEAT 307..331
FT /note="LRR 10"
FT REPEAT 332..355
FT /note="LRR 11"
FT REPEAT 362..385
FT /note="LRR 12"
FT REPEAT 389..412
FT /note="LRR 13"
FT REPEAT 414..439
FT /note="LRR 14"
FT REPEAT 469..493
FT /note="LRR 15"
FT REPEAT 495..518
FT /note="LRR 16"
FT REPEAT 519..542
FT /note="LRR 17"
FT REPEAT 544..571
FT /note="LRR 18"
FT REPEAT 573..597
FT /note="LRR 19"
FT REPEAT 599..621
FT /note="LRR 20"
FT REPEAT 626..649
FT /note="LRR 21"
FT REPEAT 651..674
FT /note="LRR 22"
FT REPEAT 675..698
FT /note="LRR 23"
FT REPEAT 700..722
FT /note="LRR 24"
FT REPEAT 723..746
FT /note="LRR 25"
FT REPEAT 748..771
FT /note="LRR 26"
FT DOMAIN 865..1010
FT /note="TIR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00204"
FT BINDING 46..50
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /ligand_note="CpG-containing DNA"
FT /evidence="ECO:0000250|UniProtKB:Q2EEY0"
FT BINDING 71..76
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /ligand_note="CpG-containing DNA"
FT /evidence="ECO:0000250|UniProtKB:Q2EEY0"
FT BINDING 94..108
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /ligand_note="CpG-containing DNA"
FT /evidence="ECO:0000250|UniProtKB:Q2EEY0"
FT BINDING 131
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /ligand_note="CpG-containing DNA"
FT /evidence="ECO:0000250|UniProtKB:Q2EEY0"
FT BINDING 151
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /ligand_note="CpG-containing DNA"
FT /evidence="ECO:0000250|UniProtKB:Q2EEY0"
FT BINDING 178..180
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /ligand_note="CpG-containing DNA"
FT /evidence="ECO:0000250|UniProtKB:Q2EEY0"
FT BINDING 207
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /ligand_note="CpG-containing DNA"
FT /evidence="ECO:0000250|UniProtKB:Q2EEY0"
FT BINDING 261
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /ligand_note="CpG-containing DNA"
FT /evidence="ECO:0000250|UniProtKB:Q2EEY0"
FT CARBOHYD 63
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 128
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 199
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 209
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 241
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 339
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 512
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 566
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 668
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 693
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 730
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 34..44
FT /evidence="ECO:0000250|UniProtKB:Q2EEY0"
FT DISULFID 97..109
FT /evidence="ECO:0000250|UniProtKB:Q2EEY0"
FT DISULFID 177..183
FT /evidence="ECO:0000250|UniProtKB:Q2EEY0"
FT DISULFID 254..267
FT /evidence="ECO:0000250|UniProtKB:Q2EEY0"
FT DISULFID 257..264
FT /evidence="ECO:0000250|UniProtKB:Q2EEY0"
FT DISULFID 469..499
FT /evidence="ECO:0000250|UniProtKB:Q2EEY0"
FT DISULFID 763..789
FT /evidence="ECO:0000250|UniProtKB:Q2EEY0"
FT DISULFID 765..808
FT /evidence="ECO:0000250|UniProtKB:Q2EEY0"
SQ SEQUENCE 1030 AA; 115883 MW; 5D81A7DC80EE4D32 CRC64;
MGPRCTLHPL SLLVQVTALA AALAQGRLPA FLPCELQPHG LVNCNWLFLK SVPHFSAAAP
RANVTSLSLL SNRIHHLHDS DFVHLSSLRT LNLKWNCPPA GLSPMHFPCH MTIEPNTFLA
VPTLEELNLS YNSITTVPAL PDSLVSLSLS RTNILVLDPT HLTGLHALRY LYMDGNCYYK
NPCQGALEVV PGALLGLGNL THLSLKYNNL TEVPRSLPPS LETLLLSYNH IVTLTPEDLA
NLTALRVLDV GGNCRRCDHA RNPCRECPKD HPKLHSDTFS HLSRLEGLVL KDSSLYNLDT
RWFRGLDRLQ VLDLSENFLY DCITKTTAFQ GLARLRSLNL SFNYHKKVSF AHLHLAPSFG
HLRSLKELDM HGIFFRSLSE TTLQPLVQLP MLQTLRLQMN FINQAQLSIF GAFPGLLYVD
LSDNRISGAA RPVAITREVD GRERVWLPSR NLAPRPLDTL RSEDFMPNCK AFSFTLDLSR
NNLVTIQSEM FARLSRLECL RLSHNSISQA VNGSQFVPLT SLRVLDLSHN KLDLYHGRSF
TELPRLEALD LSYNSQPFTM QGVGHNLSFV AQLPALRYLS LAHNDIHSRV SQQLCSASLC
ALDFSGNDLS RMWAEGDLYL RFFQGLRSLV WLDLSQNHLH TLLPRALDNL PKSLKHLHLR
DNNLAFFNWS SLTLLPKLET LDLAGNQLKA LSNGSLPSGT QLRRLDLSGN SIGFVNPGFF
ALAKQLEELN LSANALKTVE PSWFGSMVGN LKVLDVSANP LHCACGATFV GFLLEVQAAV
PGLPSRVKCG SPGQLQGHSI FAQDLRLCLD ETLSWNCFGI SLLAMALGLV VPMLHHLCGW
DLWYCFHLCL AWLPHRGQRR GADALFYDAF VVFDKAQSAV ADWVYNELRV QLEERRGRRA
LRLCLEERDW LPGKTLFENL WASVYSSRKT LFVLAHTDRV SGLLRASFLL AQQRLLEDRK
DVVVLVILRP DAYRSRYVRL RQRLCRQSVL LWPHQPRGQG SFWAQLGTAL TRDNHHFYNR
NFCRGPTTAE
