Mus musculus Gene: Tlr9
Summary
InnateDB Gene IDBG-195818.6
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol Tlr9
Gene Name toll-like receptor 9
Synonyms
Species Mus musculus
Ensembl Gene ENSMUSG00000045322
Encoded Proteins
toll-like receptor 9
Protein Structure
Useful resources Stemformatics EHFPI ImmGen
InnateDB Annotation
Summary
Tlr9 binds CpG DNA and induces dendritic cell maturation in a MyD88-dependent manner in mice.
Tlr9 engages in signalling crosstalk with Tlr4 during activation, and as a result, amplifies the inflammatory response of murine macrophages.
Tlr9, 7, and 3 interact with the endoplasmic reticulum (ER) membrane protein Unc93b and this is essential for proper TLR signaling.
Tlr9 signalling enhances the rate of acidification of the Salmonella-containing phagosome, and this acidification induces the expression of Salmonella pathogenecity genes that are necessary for intracellular survival, growth, and systemic infection. Tlr9 deficiency rescues the high Salmonella susceptibility phenotype observed in Tlr2,Tlr4 double mutant mice.
Tlr9 triggers plasmacytoid dendritic cells in Systemic Lupus Erythematosus patients upon recognition of self-antigens such as neutrophil extracellular traps (NETs). (Demonstrated in human)
Tlr9 requires proteolytic processing in endolysosome by asparagine endopeptidase and cathepsin in the endolysosome to initiate signalling in response to DNA.
Tlr9 deficiency reduced pancreatic edema, inflammation and pro-Il1b expression in pacreatitis.
Tlr9 synergistically interacts with Tlr2::Tlr6 in lung epithelium to induce rapid pathogen killing, and can be used as a therapeutic target to treat otherwise lethal pneumonia.
Tlr9 is proteolytically cleaved in the endosome to form a soluble Tlr9 (sTlr9), which inhibits Tlr9-dependent signalling and contributes to the prevention of autoimmune disease.
Tlr9 activation is enhanced by increased levels of circulating histones, serving as a crucial link between initial damage and activation of innate immunity during sterile inflammation
Tlr9 promotes macrophage Hif1a levels, oxidative burst and nitric oxide production in response to group A Streptococcus (GAS), contributing to GAS clearance in vivo in both localized cutaneous and systemic infection models.
Tlr9 is selectively compartmentalized to fungal phagosomes and negatively modulates macrophage anti-fungal effector functions.
Tlr9 expression and signalling capacity oscillates with the circadian clock.
Mitochondrial DNA that escapes from autophagy induces Tlr9 inflammatory responses in cardiomyocytes and is capable of inducing myocarditis and dilated cardiomyopathy.
TLR9 activation by endogenous self-ligands generated during oxidative stress promotes platelet hyper-reactivity and thrombosis.
Tlr9 contributes to the control of activated endogenous retroviruses (ERVs) and ERV-induced tumours.
The N-terminal region of TLR9 is cleaved in the endolysosome to form an intracellular DNA sensor with the C-terminal TLR9.
Mir126-Kdr axis is an important regulator of the innate response. Mir126 controls the survival and function of plasmacytoid dendritic cells and regulates gene expression of Tlr7, Tlr9, Nfkb1 and Kdr.
Dnase2a is required for Tlr9 activation by bacterial genomic DNA.
Tyrosine phosphorylation is essential for Tlr9 protein stability and signalling.
Tlr9 activation requires a single CpG positioned 4-6 nucleotides from the 5'-end and this activation is augmented by a 5'TCC sequence one to three nucleotides from the CG.
Entrez Gene
Summary Currently no Entrez Summary Available. You might want to check the Summary Sections of the Orthologs.
Gene Information
Type Protein coding
Genomic Location Chromosome 9:106222598-106226883
Strand Forward strand
Band F1
Transcripts
ENSMUST00000062241 ENSMUSP00000082207
Interactions
Number of Interactions This gene and/or its encoded proteins are associated with 18 experimentally validated interaction(s) in this database.
Experimentally validated
Total 18 [view]
Protein-Protein 10 [view]
Protein-DNA 8 [view]
Protein-RNA 0
DNA-DNA 0
RNA-RNA 0
DNA-RNA 0
Gene Ontology

Molecular Function
Accession GO Term
GO:0004888 transmembrane signaling receptor activity
GO:0005515 protein binding
GO:0035197 siRNA binding
GO:0045322 unmethylated CpG binding
Biological Process
GO:0001774 microglial cell activation
GO:0002224 toll-like receptor signaling pathway
GO:0002237 response to molecule of bacterial origin
GO:0002282 microglial cell activation involved in immune response
GO:0002755 MyD88-dependent toll-like receptor signaling pathway
GO:0006954 inflammatory response
GO:0006955 immune response
GO:0007165 signal transduction
GO:0008584 male gonad development
GO:0009615 response to virus
GO:0010508 positive regulation of autophagy
GO:0030277 maintenance of gastrointestinal epithelium
GO:0032715 negative regulation of interleukin-6 production
GO:0032728 positive regulation of interferon-beta production
GO:0032733 positive regulation of interleukin-10 production
GO:0032735 positive regulation of interleukin-12 production
GO:0032741 positive regulation of interleukin-18 production
GO:0032755 positive regulation of interleukin-6 production
GO:0032760 positive regulation of tumor necrosis factor production
GO:0034162 toll-like receptor 9 signaling pathway
GO:0042742 defense response to bacterium
GO:0045078 positive regulation of interferon-gamma biosynthetic process
GO:0045087 innate immune response (InnateDB)
GO:0045356 positive regulation of interferon-alpha biosynthetic process
GO:0045359 positive regulation of interferon-beta biosynthetic process
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0050707 regulation of cytokine secretion
GO:0050727 regulation of inflammatory response
GO:0050729 positive regulation of inflammatory response
GO:0051607 defense response to virus
GO:0051770 positive regulation of nitric-oxide synthase biosynthetic process
GO:0052033 pathogen-associated molecular pattern dependent induction by symbiont of host innate immune response
GO:0071222 cellular response to lipopolysaccharide
GO:0071248 cellular response to metal ion
Cellular Component
GO:0005764 lysosome
GO:0005768 endosome
GO:0005783 endoplasmic reticulum
GO:0005789 endoplasmic reticulum membrane
GO:0005886 plasma membrane
GO:0016021 integral component of membrane
GO:0032009 early phagosome
Orthologs
No orthologs found for this gene
Pathways
NETPATH
REACTOME
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation pathway
Innate Immune System pathway
Trafficking and processing of endosomal TLR pathway
Signaling by Insulin receptor pathway
Immune System pathway
TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling pathway
Toll Like Receptor 9 (TLR9) Cascade pathway
Insulin receptor signalling cascade pathway
IRS-related events triggered by IGF1R pathway
IGF1R signaling cascade pathway
Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) pathway
PI3K Cascade pathway
Toll-Like Receptors Cascades pathway
MyD88 dependent cascade initiated on endosome pathway
IRS-related events pathway
IRS-mediated signalling pathway
Signal Transduction pathway
Toll Like Receptor 7/8 (TLR7/8) Cascade pathway
KEGG
Toll-like receptor signaling pathway pathway
Malaria pathway
Chagas disease (American trypanosomiasis) pathway
African trypanosomiasis pathway
INOH
PID NCI
Cross-References
SwissProt Q9EQU3
TrEMBL
UniProt Splice Variant
Entrez Gene 81897
UniGene Mm.44889
RefSeq NM_031178
OMIM
CCDS CCDS40755
HPRD
IMGT
MGI ID MGI:1932389
MGI Symbol Tlr9
EMBL AB045181 AC164430 AF314224 AF348140 AY649790 AY649791
GenPept AAK28488 AAK29625 AAU04980 AAU04981 BAB19260
RNA Seq Atlas 81897