Q9EQU3 (TLR9_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Toll-like receptor 9

Alternative name(s):
CD_antigen=CD289

Gene names

Name:

Tlr9

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	1032 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 vesicle › phagosome. 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 process	Immunity Inflammatory response Innate immunity
Cellular component	Cytoplasmic vesicle Endoplasmic reticulum Endosome Lysosome Membrane
Domain	Leucine-rich repeat Repeat Signal Transmembrane Transmembrane helix
Molecular function	Receptor
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	MyD88-dependent toll-like receptor signaling pathway Inferred from electronic annotation. Source: InterPro defense response to virus Inferred from genetic interaction PubMed 18250457. 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 negative regulation of interleukin-6 production Inferred from mutant phenotype PubMed 18203139. Source: BHF-UCL 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 toll-like receptor 9 signaling pathway Inferred from electronic annotation. Source: InterPro
Cellular_component	early 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 to 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_function	siRNA binding Inferred from sequence or structural similarity. Source: UniProtKB transmembrane signaling receptor activity Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 25	25	Potential
	Chain	26 – 1032	1007	Toll-like receptor 9		PRO_0000034738
Regions
	Topological domain	26 – 818	793	Extracellular Potential
	Transmembrane	819 – 839	21	Helical; Potential
	Topological domain	840 – 1032	193	Cytoplasmic Potential
	Repeat	62 – 85	24	LRR 1
	Repeat	87 – 110	24	LRR 2
	Repeat	122 – 147	26	LRR 3
	Repeat	150 – 166	17	LRR 4
	Repeat	167 – 190	24	LRR 5
	Repeat	198 – 221	24	LRR 6
	Repeat	223 – 242	20	LRR 7
	Repeat	243 – 268	26	LRR 8
	Repeat	283 – 306	24	LRR 9
	Repeat	308 – 332	25	LRR 10
	Repeat	333 – 356	24	LRR 11
	Repeat	363 – 386	24	LRR 12
	Repeat	390 – 413	24	LRR 13
	Repeat	415 – 440	26	LRR 14
	Repeat	471 – 495	25	LRR 15
	Repeat	497 – 520	24	LRR 16
	Repeat	521 – 544	24	LRR 17
	Repeat	546 – 573	28	LRR 18
	Repeat	575 – 599	25	LRR 19
	Repeat	601 – 623	23	LRR 20
	Repeat	628 – 651	24	LRR 21
	Repeat	653 – 676	24	LRR 22
	Repeat	677 – 700	24	LRR 23
	Repeat	702 – 724	23	LRR 24
	Repeat	725 – 748	24	LRR 25
	Repeat	750 – 773	24	LRR 26
	Domain	868 – 1016	149	TIR
Amino acid modifications
	Glycosylation	64	1	N-linked (GlcNAc...) Potential
	Glycosylation	129	1	N-linked (GlcNAc...) Potential
	Glycosylation	147	1	N-linked (GlcNAc...) Potential
	Glycosylation	200	1	N-linked (GlcNAc...) Potential
	Glycosylation	210	1	N-linked (GlcNAc...) Potential
	Glycosylation	242	1	N-linked (GlcNAc...) Potential
	Glycosylation	300	1	N-linked (GlcNAc...) Potential
	Glycosylation	309	1	N-linked (GlcNAc...) Potential
	Glycosylation	332	1	N-linked (GlcNAc...) Potential
	Glycosylation	340	1	N-linked (GlcNAc...) Potential
	Glycosylation	495	1	N-linked (GlcNAc...) Potential
	Glycosylation	514	1	N-linked (GlcNAc...) Potential
	Glycosylation	568	1	N-linked (GlcNAc...) Potential
	Glycosylation	670	1	N-linked (GlcNAc...) Potential
	Glycosylation	695	1	N-linked (GlcNAc...) Potential
	Glycosylation	700	1	N-linked (GlcNAc...) Potential
	Glycosylation	732	1	N-linked (GlcNAc...) Potential
	Glycosylation	752	1	N-linked (GlcNAc...) Potential
Experimental info
	Mutagenesis	499	1	L → P: Highly susceptible to mouse cytomegalovirus infection. Shows low level of cytokine induction and natural killer activation on viral infection. Ref.6
	Sequence conflict	325	1	T → N in BAB19260. Ref.1
	Sequence conflict	325	1	T → N in AAK29625. Ref.2
	Sequence conflict	325	1	T → N in AAK28488. Ref.3
	Sequence conflict	325	1	T → N in AAU04980. Ref.5
	Sequence conflict	378	1	L → S in BAB19260. Ref.1
	Sequence conflict	378	1	L → S in AAK29625. Ref.2
	Sequence conflict	378	1	L → S in AAK28488. Ref.3
	Sequence conflict	378	1	L → S in AAU04980. Ref.5
	Sequence conflict	554	1	S → G in AAK28488. Ref.3
	Sequence conflict	562	1	M → I in AAK28488. Ref.3
	Sequence conflict	573	1	T → A in AAK29625. Ref.2
	Sequence conflict	573	1	T → A in AAK28488. Ref.3
	Sequence conflict	573	1	T → A in AAU04980. Ref.5
	Sequence conflict	579	1	Q → H in AAK29625. Ref.2
	Sequence conflict	579	1	Q → H in AAK28488. Ref.3
	Sequence conflict	579	1	Q → H in AAU04980. Ref.5
	Sequence conflict	867	1	T → A in AAK29625. Ref.2
	Sequence conflict	867	1	T → A in AAK28488. Ref.3
	Sequence conflict	867	1	T → A in AAU04980. Ref.5
	Sequence conflict	897	1	E → G in AAK28488. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Q9EQU3 [UniParc]. Last modified December 14, 2011. Version 3. Checksum: C13A7888588CE297	FASTA	1,032	116,412
	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

References

	« Hide 'large scale' referencesShow '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. , 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.
IPI	IPI00318748. IPI01027735.
RefSeq	NP_112455.2. NM_031178.2.
UniGene	Mm.44889.
3D structure databases
ProteinModelPortal	Q9EQU3.
SMR	Q9EQU3. Positions 35-1013.
ModBase	Search...
Protein-protein interaction databases
STRING	10090.ENSMUSP00000082207.
PTM databases
PhosphoSite	Q9EQU3.
Proteomic databases
PaxDb	Q9EQU3.
PRIDE	Q9EQU3.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000062241; ENSMUSP00000082207; ENSMUSG00000045322.
GeneID	81897.
KEGG	mmu:81897.
Organism-specific databases
CTD	54106.
MGI	MGI:1932389. Tlr9.
Phylogenomic databases
eggNOG	COG4886.
GeneTree	ENSGT00680000099674.
HOGENOM	HOG000230468.
HOVERGEN	HBG018601.
InParanoid	Q4L0K3.
KO	K10161.
OMA	VGGNCRR.
OrthoDB	EOG47SSDD.
Gene expression databases
Bgee	Q9EQU3.
CleanEx	MM_TLR9.
Genevestigator	Q9EQU3.
GermOnline	ENSMUSG00000045322. Mus musculus.
Family and domain databases
InterPro	IPR001611. Leu-rich_rpt. IPR003591. Leu-rich_rpt_typical-subtyp. IPR000157. TIR_dom. IPR027181. TLR9. [Graphical view]
PANTHER	PTHR24373:SF37. PTHR24373:SF37. 1 hit.
Pfam	PF00560. LRR_1. 2 hits. PF01582. TIR. 1 hit. [Graphical view]
SMART	SM00369. LRR_TYP. 1 hit. [Graphical view]
SUPFAM	SSF52200. TIR. 1 hit.
PROSITE	PS51450. LRR. 16 hits. PS50104. TIR. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChEMBL	CHEMBL6128.
NextBio	350461.
SOURCE	Search...

Entry information

Entry name

TLR9_MOUSE

Accession

Primary (citable) accession number: Q9EQU3
Secondary accession number(s): F8VPN5 , Q4L0K3, Q4L0K4, Q99MF2, Q99MQ8

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 31, 2002
Last sequence update:	December 14, 2011
Last modified:	May 1, 2013
This is version 112 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program