Mus musculus Gene: Tlr9
Summary
InnateDB Gene IDBG-64760.1
Last Modified 2018-06-05 [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 20 experimentally validated interaction(s) in this database.
Experimentally validated
Total 20 [view]
Protein-Protein 12 [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:0005149 interleukin-1 receptor binding
GO:0005515 protein binding
GO:0035197 siRNA binding
GO:0042803 protein homodimerization activity
GO:0045322 unmethylated CpG binding
Biological Process
GO:0001774 microglial cell activation
GO:0001816 cytokine production
GO:0001932 regulation of protein phosphorylation
GO:0002218 activation of innate immune response
GO:0002224 toll-like receptor signaling pathway
GO:0002237 response to molecule of bacterial origin
GO:0002376 immune system process
GO:0002639 positive regulation of immunoglobulin production
GO:0002730 regulation of dendritic cell cytokine production
GO:0002755 MyD88-dependent toll-like receptor signaling pathway
GO:0006954 inflammatory response
GO:0006955 immune response
GO:0007165 signal transduction
GO:0007249 I-kappaB kinase/NF-kappaB signaling
GO:0007252 I-kappaB phosphorylation
GO:0007409 axonogenesis
GO:0008584 male gonad development
GO:0009615 response to virus
GO:0010508 positive regulation of autophagy
GO:0010628 positive regulation of gene expression
GO:0030277 maintenance of gastrointestinal epithelium
GO:0030890 positive regulation of B cell proliferation
GO:0032088 negative regulation of NF-kappaB transcription factor activity
GO:0032640 tumor necrosis factor production
GO:0032715 negative regulation of interleukin-6 production
GO:0032717 negative regulation of interleukin-8 production
GO:0032722 positive regulation of chemokine production
GO:0032725 positive regulation of granulocyte macrophage colony-stimulating factor 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:0032757 positive regulation of interleukin-8 production
GO:0032760 positive regulation of tumor necrosis factor production
GO:0034122 negative regulation of toll-like receptor signaling pathway
GO:0034123 positive regulation of toll-like receptor signaling pathway
GO:0034162 toll-like receptor 9 signaling pathway
GO:0034163 regulation of toll-like receptor 9 signaling pathway
GO:0034165 positive regulation of toll-like receptor 9 signaling pathway
GO:0042346 positive regulation of NF-kappaB import into nucleus
GO:0043123 positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:0043410 positive regulation of MAPK cascade
GO:0043507 positive regulation of JUN kinase activity
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:0045577 regulation of B cell differentiation
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:0050829 defense response to Gram-negative bacterium
GO:0050864 regulation of B cell activation
GO:0050871 positive regulation of B cell activation
GO:0051092 positive regulation of NF-kappaB transcription factor activity
GO:0051607 defense response to virus
GO:0051770 positive regulation of nitric-oxide synthase biosynthetic process
GO:0071222 cellular response to lipopolysaccharide
GO:0071248 cellular response to metal ion
GO:1901895 negative regulation of calcium-transporting ATPase activity
GO:1902350 cellular response to chloroquine
Cellular Component
GO:0005578 proteinaceous extracellular matrix
GO:0005615 extracellular space
GO:0005737 cytoplasm
GO:0005764 lysosome
GO:0005768 endosome
GO:0005783 endoplasmic reticulum
GO:0005789 endoplasmic reticulum membrane
GO:0005886 plasma membrane
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0016323 basolateral plasma membrane
GO:0016324 apical plasma membrane
GO:0031410 cytoplasmic vesicle
GO:0032009 early phagosome
GO:0036019 endolysosome
GO:0045335 phagocytic vesicle
Orthologs
No orthologs found for this gene
Pathways
NETPATH
REACTOME
Toll-Like Receptors Cascades pathway
Signaling by Insulin receptor pathway
TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling pathway
Innate Immune System pathway
Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) pathway
Trafficking and processing of endosomal TLR pathway
MyD88 dependent cascade initiated on endosome pathway
Toll Like Receptor 7/8 (TLR7/8) Cascade pathway
IGF1R signaling cascade pathway
IRS-related events triggered by IGF1R pathway
PI3K Cascade pathway
Signaling by Receptor Tyrosine Kinases pathway
Toll Like Receptor 9 (TLR9) Cascade pathway
Immune System pathway
Signal Transduction pathway
Insulin receptor signalling cascade pathway
IRS-mediated signalling pathway
TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation pathway
KEGG
Toll-like receptor signaling pathway pathway
Chagas disease (American trypanosomiasis) pathway
African trypanosomiasis pathway
Malaria pathway
Tuberculosis pathway
Measles pathway
Herpes simplex infection pathway
INOH
PID BIOCARTA
PID NCI
Cross-References
SwissProt
TrEMBL
UniProt Splice Variant
Entrez Gene
UniGene
RefSeq NM_031178
OMIM
CCDS CCDS40755
HPRD
IMGT
MGI ID
MGI Symbol
EMBL
GenPept
RNA Seq Atlas