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Q9EQU3 (TLR9_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 124. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Toll-like receptor 9
Alternative name(s):
CD_antigen=CD289
Gene names
Name:Tlr9
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1032 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Key component of innate and adaptive immunity. TLRs (Toll-like receptors) control host immune response against pathogens through recognition of molecular patterns specific to microorganisms. TLR9 is a nucleotide-sensing TLR which is activated by unmethylated cytidine-phosphate-guanosine (CpG) dinucleotides. Acts via MYD88 and TRAF6, leading to NF-kappa-B activation, cytokine secretion and the inflammatory response. Plays a role in defense against systemic mouse cytomegalovirus infection. Controls lymphocyte response to Helicobacter infection. Ref.5 Ref.6

Subunit structure

Interacts with MYD88 via their respective TIR domains By similarity. Interacts with BTK By similarity. Interacts (via transmembrane domain) with UNC93B1. Interacts with CD300LH; the interaction may promote full activation of TLR9-triggered innate responses. Interacts with CNPY3 and HSP90B1; this interaction is required for proper folding in the endoplasmic reticulum. Ref.7 Ref.8 Ref.10 Ref.12

Subcellular location

Endoplasmic reticulum membrane; Single-pass type I membrane protein. Endosome. Lysosome. Cytoplasmic vesiclephagosome. Note: Relocalizes from endoplasmic reticulum to endosome and lysosome upon stimulation with agonist. Ref.9

Tissue specificity

Expressed in the basolateral region of gastric epithelial cells with high levels detected in antrum and body mucosa (at protein level). Detected in spleen and stomach at higher levels in C57BL/6 mice than BALB/C. Ref.5

Induction

Following Helicobacter infection, down-regulated in C57BL/6 mice and up-regulated in BALB/C mice. Ref.5

Disruption phenotype

Reduced proliferation of lymphocytes, reduced interferon-gamma production by splenocytes and reduced neutrophil numbers following Helicobacter infection. Ref.5

Sequence similarities

Belongs to the Toll-like receptor family.

Contains 26 LRR (leucine-rich) repeats.

Contains 1 TIR domain.

Ontologies

Keywords
   Biological processImmunity
Inflammatory response
Innate immunity
   Cellular componentCytoplasmic vesicle
Endoplasmic reticulum
Endosome
Lysosome
Membrane
   DomainLeucine-rich repeat
Repeat
Signal
Transmembrane
Transmembrane helix
   Molecular functionReceptor
   PTMGlycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processMyD88-dependent toll-like receptor signaling pathway

Inferred from electronic annotation. Source: InterPro

cellular response to lipopolysaccharide

Inferred from electronic annotation. Source: Ensembl

cellular response to metal ion

Inferred from electronic annotation. Source: Ensembl

defense response to bacterium

Inferred from electronic annotation. Source: Ensembl

defense response to virus

Inferred from genetic interaction PubMed 18250457. Source: MGI

immune response

Inferred from mutant phenotype Ref.1. Source: MGI

inflammatory response

Inferred from electronic annotation. Source: UniProtKB-KW

innate immune response

Traceable author statement PubMed 15356140. Source: BHF-UCL

maintenance of gastrointestinal epithelium

Inferred from mutant phenotype PubMed 17128265. Source: BHF-UCL

male gonad development

Inferred from electronic annotation. Source: Ensembl

microglial cell activation involved in immune response

Inferred from electronic annotation. Source: Ensembl

negative regulation of interleukin-6 production

Inferred from mutant phenotype PubMed 18203139. Source: BHF-UCL

pathogen-associated molecular pattern dependent induction by symbiont of host innate immune response

Inferred from electronic annotation. Source: Ensembl

positive regulation of autophagy

Inferred from electronic annotation. Source: Ensembl

positive regulation of inflammatory response

Inferred from electronic annotation. Source: InterPro

positive regulation of interferon-alpha biosynthetic process

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of interferon-beta biosynthetic process

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of interferon-beta production

Inferred from direct assay PubMed 15356140. Source: BHF-UCL

positive regulation of interferon-gamma biosynthetic process

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of interleukin-10 production

Inferred from direct assay PubMed 15356140. Source: BHF-UCL

positive regulation of interleukin-12 production

Inferred from direct assay PubMed 15356140. Source: BHF-UCL

positive regulation of interleukin-18 production

Inferred from direct assay PubMed 15356140. Source: BHF-UCL

positive regulation of interleukin-6 production

Inferred from direct assay PubMed 15356140. Source: BHF-UCL

positive regulation of nitric-oxide synthase biosynthetic process

Inferred from direct assay PubMed 15356140. Source: BHF-UCL

positive regulation of transcription from RNA polymerase II promoter

Inferred from direct assay PubMed 15356140. Source: BHF-UCL

positive regulation of tumor necrosis factor production

Inferred from direct assay PubMed 15356140. Source: BHF-UCL

regulation of cytokine secretion

Inferred from electronic annotation. Source: InterPro

regulation of inflammatory response

Inferred from mutant phenotype PubMed 18203139. Source: BHF-UCL

response to molecule of bacterial origin

Traceable author statement PubMed 15356140. Source: BHF-UCL

response to virus

Inferred from mutant phenotype Ref.6. Source: MGI

toll-like receptor 9 signaling pathway

Inferred from electronic annotation. Source: InterPro

   Cellular_componentearly phagosome

Inferred from direct assay Ref.9. Source: UniProtKB

endoplasmic reticulum

Inferred from direct assay Ref.9. Source: UniProtKB

endoplasmic reticulum membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

endosome

Inferred from direct assay Ref.9. Source: UniProtKB

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

lysosome

Inferred from direct assay Ref.9. Source: UniProtKB

plasma membrane

Inferred from direct assay PubMed 16415873. Source: MGI

   Molecular_functionprotein binding

Inferred from physical interaction Ref.7. Source: UniProtKB

siRNA binding

Inferred from sequence or structural similarity. Source: UniProtKB

transmembrane signaling receptor activity

Inferred from electronic annotation. Source: InterPro

unmethylated CpG binding

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2525 Potential
Chain26 – 10321007Toll-like receptor 9
PRO_0000034738

Regions

Topological domain26 – 818793Extracellular Potential
Transmembrane819 – 83921Helical; Potential
Topological domain840 – 1032193Cytoplasmic Potential
Repeat62 – 8524LRR 1
Repeat87 – 11024LRR 2
Repeat122 – 14726LRR 3
Repeat150 – 16617LRR 4
Repeat167 – 19024LRR 5
Repeat198 – 22124LRR 6
Repeat223 – 24220LRR 7
Repeat243 – 26826LRR 8
Repeat283 – 30624LRR 9
Repeat308 – 33225LRR 10
Repeat333 – 35624LRR 11
Repeat363 – 38624LRR 12
Repeat390 – 41324LRR 13
Repeat415 – 44026LRR 14
Repeat471 – 49525LRR 15
Repeat497 – 52024LRR 16
Repeat521 – 54424LRR 17
Repeat546 – 57328LRR 18
Repeat575 – 59925LRR 19
Repeat601 – 62323LRR 20
Repeat628 – 65124LRR 21
Repeat653 – 67624LRR 22
Repeat677 – 70024LRR 23
Repeat702 – 72423LRR 24
Repeat725 – 74824LRR 25
Repeat750 – 77324LRR 26
Domain868 – 1016149TIR

Amino acid modifications

Glycosylation641N-linked (GlcNAc...) Potential
Glycosylation1291N-linked (GlcNAc...) Potential
Glycosylation1471N-linked (GlcNAc...) Potential
Glycosylation2001N-linked (GlcNAc...) Potential
Glycosylation2101N-linked (GlcNAc...) Potential
Glycosylation2421N-linked (GlcNAc...) Potential
Glycosylation3001N-linked (GlcNAc...) Potential
Glycosylation3091N-linked (GlcNAc...) Potential
Glycosylation3321N-linked (GlcNAc...) Potential
Glycosylation3401N-linked (GlcNAc...) Potential
Glycosylation4951N-linked (GlcNAc...) Potential
Glycosylation5141N-linked (GlcNAc...) Potential
Glycosylation5681N-linked (GlcNAc...) Potential
Glycosylation6701N-linked (GlcNAc...) Potential
Glycosylation6951N-linked (GlcNAc...) Potential
Glycosylation7001N-linked (GlcNAc...) Potential
Glycosylation7321N-linked (GlcNAc...) Potential
Glycosylation7521N-linked (GlcNAc...) Potential

Experimental info

Mutagenesis4991L → P: Highly susceptible to mouse cytomegalovirus infection. Shows low level of cytokine induction and natural killer activation on viral infection. Ref.6
Sequence conflict3251T → N in BAB19260. Ref.1
Sequence conflict3251T → N in AAK29625. Ref.2
Sequence conflict3251T → N in AAK28488. Ref.3
Sequence conflict3251T → N in AAU04980. Ref.5
Sequence conflict3781L → S in BAB19260. Ref.1
Sequence conflict3781L → S in AAK29625. Ref.2
Sequence conflict3781L → S in AAK28488. Ref.3
Sequence conflict3781L → S in AAU04980. Ref.5
Sequence conflict5541S → G in AAK28488. Ref.3
Sequence conflict5621M → I in AAK28488. Ref.3
Sequence conflict5731T → A in AAK29625. Ref.2
Sequence conflict5731T → A in AAK28488. Ref.3
Sequence conflict5731T → A in AAU04980. Ref.5
Sequence conflict5791Q → H in AAK29625. Ref.2
Sequence conflict5791Q → H in AAK28488. Ref.3
Sequence conflict5791Q → H in AAU04980. Ref.5
Sequence conflict8671T → A in AAK29625. Ref.2
Sequence conflict8671T → A in AAK28488. Ref.3
Sequence conflict8671T → A in AAU04980. Ref.5
Sequence conflict8971E → G in AAK28488. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Q9EQU3 [UniParc].

Last modified December 14, 2011. Version 3.
Checksum: C13A7888588CE297

FASTA1,032116,412
        10         20         30         40         50         60 
MVLRRRTLHP LSLLVQAAVL AETLALGTLP AFLPCELKPH GLVDCNWLFL KSVPRFSAAA 

        70         80         90        100        110        120 
SCSNITRLSL ISNRIHHLHN SDFVHLSNLR QLNLKWNCPP TGLSPLHFSC HMTIEPRTFL 

       130        140        150        160        170        180 
AMRTLEELNL SYNGITTVPR LPSSLVNLSL SHTNILVLDA NSLAGLYSLR VLFMDGNCYY 

       190        200        210        220        230        240 
KNPCTGAVKV TPGALLGLSN LTHLSLKYNN LTKVPRQLPP SLEYLLVSYN LIVKLGPEDL 

       250        260        270        280        290        300 
ANLTSLRVLD VGGNCRRCDH APNPCIECGQ KSLHLHPETF HHLSHLEGLV LKDSSLHTLN 

       310        320        330        340        350        360 
SSWFQGLVNL SVLDLSENFL YESITHTNAF QNLTRLRKLN LSFNYRKKVS FARLHLASSF 

       370        380        390        400        410        420 
KNLVSLQELN MNGIFFRLLN KYTLRWLADL PKLHTLHLQM NFINQAQLSI FGTFRALRFV 

       430        440        450        460        470        480 
DLSDNRISGP STLSEATPEE ADDAEQEELL SADPHPAPLS TPASKNFMDR CKNFKFTMDL 

       490        500        510        520        530        540 
SRNNLVTIKP EMFVNLSRLQ CLSLSHNSIA QAVNGSQFLP LTNLQVLDLS HNKLDLYHWK 

       550        560        570        580        590        600 
SFSELPQLQA LDLSYNSQPF SMKGIGHNFS FVTHLSMLQS LSLAHNDIHT RVSSHLNSNS 

       610        620        630        640        650        660 
VRFLDFSGNG MGRMWDEGGL YLHFFQGLSG LLKLDLSQNN LHILRPQNLD NLPKSLKLLS 

       670        680        690        700        710        720 
LRDNYLSFFN WTSLSFLPNL EVLDLAGNQL KALTNGTLPN GTLLQKLDVS SNSIVSVVPA 

       730        740        750        760        770        780 
FFALAVELKE VNLSHNILKT VDRSWFGPIV MNLTVLDVRS NPLHCACGAA FVDLLLEVQT 

       790        800        810        820        830        840 
KVPGLANGVK CGSPGQLQGR SIFAQDLRLC LDEVLSWDCF GLSLLAVAVG MVVPILHHLC 

       850        860        870        880        890        900 
GWDVWYCFHL CLAWLPLLAR SRRSAQTLPY DAFVVFDKAQ SAVADWVYNE LRVRLEERRG 

       910        920        930        940        950        960 
RRALRLCLED RDWLPGQTLF ENLWASIYGS RKTLFVLAHT DRVSGLLRTS FLLAQQRLLE 

       970        980        990       1000       1010       1020 
DRKDVVVLVI LRPDAHRSRY VRLRQRLCRQ SVLFWPQQPN GQGGFWAQLS TALTRDNRHF 

      1030 
YNQNFCRGPT AE 

« Hide

References

« Hide 'large scale' references
[1]"A Toll-like receptor recognizes bacterial DNA."
Hemmi H., Takeuchi O., Kawai T., Kaisho T., Sato S., Sanjo H., Matsumoto M., Hoshino K., Wagner H., Takeda K., Akira S.
Nature 408:740-745(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"Human TLR9 confers responsiveness to bacterial DNA via species-specific CpG motif recognition."
Bauer S.M., Kirschning C.J., Hacker H., Redecke V., Hausmann S., Akira S., Wagner H., Lipford G.B.
Proc. Natl. Acad. Sci. U.S.A. 98:9237-9242(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Macrophage.
[3]"Toll-like receptor 9 mediates CpG-DNA signaling."
Chuang T.-H., Lee J., Kline L., Mathison J.C., Ulevitch R.J.
J. Leukoc. Biol. 71:538-544(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: BALB/c.
[4]"Lineage-specific biology revealed by a finished genome assembly of the mouse."
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. expand/collapse author list , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: C57BL/6J.
[5]"TLR9 polymorphisms determine murine lymphocyte responses to Helicobacter: results from a genome-wide scan."
Anderson A.E., Worku M.L., Khamri W., Bamford K.B., Walker M.M., Thursz M.R.
Eur. J. Immunol. 37:1548-1561(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-964, FUNCTION, TISSUE SPECIFICITY, INDUCTION, DISRUPTION PHENOTYPE.
Strain: BALB/c and C57BL/6.
[6]"Toll-like receptors 9 and 3 as essential components of innate immune defense against mouse cytomegalovirus infection."
Tabeta K., Georgel P., Janssen E., Du X., Hoebe K., Crozat K., Mudd S., Shamel L., Sovath S., Goode J., Alexopoulou L., Flavell R.A., Beutler B.
Proc. Natl. Acad. Sci. U.S.A. 101:3516-3521(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CYTOMEGALOVIRUS INFECTION, MUTAGENESIS OF LEU-499.
[7]"The interaction between the ER membrane protein UNC93B and TLR3, 7, and 9 is crucial for TLR signaling."
Brinkmann M.M., Spooner E., Hoebe K., Beutler B., Ploegh H.L., Kim Y.M.
J. Cell Biol. 177:265-275(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY, INTERACTION WITH UNC93B1.
[8]"A single base mutation in the PRAT4A gene reveals differential interaction of PRAT4A with Toll-like receptors."
Kiyokawa T., Akashi-Takamura S., Shibata T., Matsumoto F., Nishitani C., Kuroki Y., Seto Y., Miyake K.
Int. Immunol. 20:1407-1415(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CNPY3.
[9]"UNC93B1 delivers nucleotide-sensing toll-like receptors to endolysosomes."
Kim Y.M., Brinkmann M.M., Paquet M.E., Ploegh H.L.
Nature 452:234-238(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[10]"Folding of Toll-like receptors by the HSP90 paralogue gp96 requires a substrate-specific cochaperone."
Liu B., Yang Y., Qiu Z., Staron M., Hong F., Li Y., Wu S., Li Y., Hao B., Bona R., Han D., Li Z.
Nat. Commun. 1:79-79(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CNPY3 AND HSP90B1.
[11]Erratum
Liu B., Yang Y., Qiu Z., Staron M., Hong F., Li Y., Wu S., Li Y., Hao B., Bona R., Han D., Li Z.
Nat. Commun. 3:653-653(2012)
[12]"CMRF-35-like molecule 3 preferentially promotes TLR9-triggered proinflammatory cytokine production in macrophages by enhancing TNF receptor-associated factor 6 ubiquitination."
Wu Y., Zhu X., Li N., Chen T., Yang M., Yao M., Liu X., Jin B., Wang X., Cao X.
J. Immunol. 187:4881-4889(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CD300LH.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB045181 mRNA. Translation: BAB19260.1.
AF348140 mRNA. Translation: AAK29625.1.
AF314224 mRNA. Translation: AAK28488.1.
AC164430 Genomic DNA. No translation available.
AY649790 Genomic DNA. Translation: AAU04980.1.
AY649791 Genomic DNA. Translation: AAU04981.1.
CCDSCCDS40755.1.
RefSeqNP_112455.2. NM_031178.2.
UniGeneMm.44889.

3D structure databases

ProteinModelPortalQ9EQU3.
SMRQ9EQU3. Positions 34-1013.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING10090.ENSMUSP00000082207.

Chemistry

ChEMBLCHEMBL6128.

PTM databases

PhosphoSiteQ9EQU3.

Proteomic databases

PaxDbQ9EQU3.
PRIDEQ9EQU3.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000062241; ENSMUSP00000082207; ENSMUSG00000045322.
GeneID81897.
KEGGmmu:81897.
UCSCuc009rjh.1. mouse.

Organism-specific databases

CTD54106.
MGIMGI:1932389. Tlr9.

Phylogenomic databases

eggNOGCOG4886.
GeneTreeENSGT00750000117479.
HOGENOMHOG000230468.
HOVERGENHBG018601.
InParanoidQ4L0K3.
KOK10161.
OMALYLHFFQ.
OrthoDBEOG7C8GGD.
TreeFamTF325595.

Gene expression databases

BgeeQ9EQU3.
CleanExMM_TLR9.
GenevestigatorQ9EQU3.

Family and domain databases

Gene3D3.40.50.10140. 1 hit.
InterProIPR001611. Leu-rich_rpt.
IPR003591. Leu-rich_rpt_typical-subtyp.
IPR000157. TIR_dom.
IPR027181. TLR9.
[Graphical view]
PANTHERPTHR24373:SF37. PTHR24373:SF37. 1 hit.
PfamPF00560. LRR_1. 1 hit.
PF13855. LRR_8. 5 hits.
PF01582. TIR. 1 hit.
[Graphical view]
SMARTSM00369. LRR_TYP. 1 hit.
[Graphical view]
SUPFAMSSF52200. SSF52200. 1 hit.
PROSITEPS51450. LRR. 16 hits.
PS50104. TIR. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio350461.
PROQ9EQU3.
SOURCESearch...

Entry information

Entry nameTLR9_MOUSE
AccessionPrimary (citable) accession number: Q9EQU3
Secondary accession number(s): F8VPN5 expand/collapse secondary AC list , Q4L0K3, Q4L0K4, Q99MF2, Q99MQ8
Entry history
Integrated into UniProtKB/Swiss-Prot: January 31, 2002
Last sequence update: December 14, 2011
Last modified: July 9, 2014
This is version 124 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot