TLR9_SHEEP
ID TLR9_SHEEP Reviewed; 1029 AA.
AC Q5I2M4;
DT 07-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 15-FEB-2005, sequence version 1.
DT 03-AUG-2022, entry version 82.
DE RecName: Full=Toll-like receptor 9;
DE AltName: CD_antigen=CD289;
DE Flags: Precursor;
GN Name=TLR9;
OS Ovis aries (Sheep).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Caprinae; Ovis.
OX NCBI_TaxID=9940;
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 "Ovis aries 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; AY859727; AAW50955.1; -; mRNA.
DR RefSeq; NP_001011555.1; NM_001011555.1.
DR AlphaFoldDB; Q5I2M4; -.
DR SMR; Q5I2M4; -.
DR STRING; 9940.ENSOARP00000006599; -.
DR GeneID; 494547; -.
DR KEGG; oas:494547; -.
DR CTD; 54106; -.
DR eggNOG; KOG4641; Eukaryota.
DR OrthoDB; 263937at2759; -.
DR Proteomes; UP000002356; 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; PF13516; LRR_6; 1.
DR Pfam; PF13855; LRR_8; 3.
DR Pfam; PF01582; TIR; 1.
DR SMART; SM00369; LRR_TYP; 17.
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..1029
FT /note="Toll-like receptor 9"
FT /id="PRO_0000227010"
FT TOPO_DOM 25..815
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 816..836
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 837..1029
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..492
FT /note="LRR 15"
FT REPEAT 494..517
FT /note="LRR 16"
FT REPEAT 518..541
FT /note="LRR 17"
FT REPEAT 543..570
FT /note="LRR 18"
FT REPEAT 572..596
FT /note="LRR 19"
FT REPEAT 598..620
FT /note="LRR 20"
FT REPEAT 625..648
FT /note="LRR 21"
FT REPEAT 650..673
FT /note="LRR 22"
FT REPEAT 674..697
FT /note="LRR 23"
FT REPEAT 699..721
FT /note="LRR 24"
FT REPEAT 722..745
FT /note="LRR 25"
FT REPEAT 747..770
FT /note="LRR 26"
FT DOMAIN 864..1009
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 331
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 380
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 472
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 511
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 565
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 667
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 692
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 729
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..498
FT /evidence="ECO:0000250|UniProtKB:Q2EEY0"
FT DISULFID 762..788
FT /evidence="ECO:0000250|UniProtKB:Q2EEY0"
FT DISULFID 764..807
FT /evidence="ECO:0000250|UniProtKB:Q2EEY0"
SQ SEQUENCE 1029 AA; 115638 MW; AE9ACBC6CC80ABA1 CRC64;
MGPYCAPHPL SLLVQAAALA AALAQGTLPA FLPCELQPRG KVNCNWLFLK SVPRFSAGAP
RANVTSLSLI SNRIHHLHDS DFVHLSNLRV LNLKWNCPPA GLSPMHFPCR MTIEPNTFLA
VPTLEELNLS YNGITTVPAL PSSLVSLSLS RTSILVLGPT HFTGLHALRF LYMDGNCYYK
NPCQQAVEVA PGALLGLGNL THLSLKYNNL TEVPRRLPPS LDTLLLSYNH IITLAPEDLA
NLTALRVLDV GGNCRRCDHA RNPCRECPKN FPKLHPDTFS HLSRLEGLVL KDSSLYKLEK
DWFRGLGRLQ VLDLSENFLY DYITKTTIFR NLTQLRRLNL SFNYHKKVSF AHLQLAPSFG
GLVSLEKLDM HGIFFRSLTN TTLRPLTQLP KLQSLSLQLN FINQAELSIF GAFPSLLFVD
LSDNRISGAA RPVAALGEVD SGVEVWRWPR GLAPGPLAAV SAKDFMPSCN LNFTLDLSRN
NLVTIQQEMF TRLSRLQCLR LSHNSISQAV NGSQFVPLTR LRVLDLSYNK LDLYHGRSFT
ELPQLEALDL SYNSQPFSMQ GVGHNLSFVA QLPSLRYLSL AHNGIHSRVS QKLSSASLRA
LDFSGNSLSQ MWAEGDLYLC FFKGLRNLVQ LDLSKNHLHT LLPRHLDNLP KSLRQLRLRD
NNLAFFNWSS LTVLPQLEAL DLAGNQLKAL SNGSLPPGTR LQKLDVSSNS IGFVTPGFFV
LANRLKELNL SANALKTVDP FWFGRLTETL KILDVSANPL HCACGAAFVD FLLEMQAAVP
GLSRRVTCGS PGQLQGRSIF AQDLRLCLDE TLSLDCFGFS LLMVALGLAV PMLHHLCGWD
LWYCFHLCLA HLPRRRRQRG EDTLLYDAFV VFDKAQSAVA DWVYNELRVQ LEERRGRRAL
RLCLEERDWL PGKTLFENLW ASVYSSRKTM FVLDHTDRVS GLLRASFLLA QQRLLEDRKD
VVVLVILRPA AYRSRYVRLR QRLCRQSVLL WPHQPSGQGS FWANLGMALT RDNRHFYNRN
FCRGPTTAE
