InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Gene: TLR9

Summary

InnateDB Gene

IDBG-407857.3

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

TLR9

Gene Name

toll-like receptor 9

Synonyms

Species

Homo sapiens

Ensembl Gene

ENSG00000239732

Encoded Proteins

IDBP-38312

toll-like receptor 9

Protein Structure

Useful resources

Stemformatics EHFPI ImmGen

InnateDB Annotation

Summary

PMID 11130078

TLR9 acts as a receptor for unmethylated CpG-DNA and bacterial DNA to initiate a variety of immune responses.

PMID 18262306

TLR9 recognizes unmethylated DNA with CpG-motifs and the LR9 mediated signalling pathway is not only responsible for activation of innate immune cells, but also for mounting acquired responses.

PMID 14579267

TLR9, 8 and 7 form a functional subgroup within the TLR family that recognizes pathogen-associated molecular patterns in endosomal/lysosomal compartments.

PMID 11867692

TLR9 acts at the cell surface and engages an intracellular signalling pathway that includes MyD88, IRAK, and TRAF6.

PMID 20034855

TLR9/7-mediated innate immune responses are negatively regulated via selected TLR pathways by a human microsatellite DNA-mimicking oligodeoxynucleotide with CCT repeats.

PMID 20360853

TLR9 and TLR4 have both non-redundant and cooperative roles in lung innate responses during Gram-negative bacterial pneumonia and are both critical for IL-17 driven antibacterial host response.

PMID 18820679

TLR9 ectodomain is cleaved to generate a functional receptor; although both the full-length and cleaved forms of TLR9 are capable of binding ligand, only the processed form recruits MyD88 on activation, indicating that this truncated receptor, rather than the full-length form, is functional.

PMID 21376231

TLR9 signalling enhances the rate of acidification of Salmonella-containing phagosomes, 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 . (Demonstrated in murine model)

PMID 21389263

TLR9 triggers plasmacytoid dendritic cells in Systemic Lupus Erythematosus patients upon recognition of self-antigens such as neutrophil extracellular traps (NETs).

PMID 21402738

TLR9 requires proteolytic processing in endolysosome by asparagine endopeptidase and cathepsin in the endolysosome to initiate signalling in response to DNA. (Demonstrated in murine model)

PMID 21439959

TLR9 deficiency reduced pancreatic edema, inflammation and pro-IL1B expression in pacreatitis. (Demonstrated in murine model)

PMID 21482737

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.

PMID 21604257

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.

PMID 21721026

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. (Demonstrated in murine model)

PMID 21860217

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. (Demonstrated in murine model)

PMID 21947771

TLR9 is selectively compartmentalized to fungal phagosomes and negatively modulates macrophage anti-fungal effector functions. (Demonstrated in mice)

PMID 22342842

TLR9 expression and signalling capacity oscillate with the circadian clock. (Demonstrated in mice)

PMID 22535248

Mitochondrial DNA that escapes from autophagy induces TLR9 inflammatory responses in cardiomyocytes and is capable of inducing myocarditis and dilated cardiomyopathy. (Demonstrated in mice)

PMID 23071157

TLR9 activation by endogenous self-ligands generated during oxidative stress promotes platelet hyper-reactivity and thrombosis.

PMID 23752229

Human papillomavirus E7 protein forms a transcriptionally repressive complex over the promoter of TLR9 to suppress the interferon response.

Entrez Gene

Summary

The protein encoded by this gene is a member of the Toll-like receptor (TLR) family which plays a fundamental role in pathogen recognition and activation of innate immunity. TLRs are highly conserved from Drosophila to humans and share structural and functional similarities. They recognize pathogen-associated molecular patterns (PAMPs) that are expressed on infectious agents, and mediate the production of cytokines necessary for the development of effective immunity. The various TLRs exhibit different patterns of expression. This gene is preferentially expressed in immune cell rich tissues, such as spleen, lymph node, bone marrow and peripheral blood leukocytes. Studies in mice and human indicate that this receptor mediates cellular response to unmethylated CpG dinucleotides in bacterial DNA to mount an innate immune response. [provided by RefSeq, Jul 2008]

Gene Information

Type

Protein coding

Genomic Location

Chromosome 3:52221080-52226163

Strand

Reverse strand

Band

p21.2

Transcripts

ENST00000360658

ENSP00000353874

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 45 experimentally validated interaction(s) in this database.

Experimentally validated
Total	45 [view]
Protein-Protein	38 [view]
Protein-DNA	7 [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

Biological Process

GO:0002224	toll-like receptor signaling pathway
GO:0002237	response to molecule of bacterial origin
GO:0002755	MyD88-dependent toll-like receptor signaling pathway
GO:0006954	inflammatory response
GO:0007165	signal transduction
GO:0007252	I-kappaB phosphorylation
GO:0008286	insulin receptor signaling pathway
GO:0030277	maintenance of gastrointestinal epithelium
GO:0032088	negative regulation of NF-kappaB transcription factor activity
GO:0032715	negative regulation of interleukin-6 production
GO:0032717	negative regulation of interleukin-8 production
GO:0032722	positive regulation of chemokine 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:0042346	positive regulation of NF-kappaB import into nucleus
GO:0042742	defense response to bacterium
GO:0043123	positive regulation of I-kappaB kinase/NF-kappaB signaling
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:0045944	positive regulation of transcription from RNA polymerase II promoter
GO:0046330	positive regulation of JNK cascade
GO:0050707	regulation of cytokine secretion
GO:0050729	positive regulation of inflammatory response
GO:0050829	defense response to Gram-negative bacterium
GO:0051092	positive regulation of NF-kappaB transcription factor activity
GO:0051770	positive regulation of nitric-oxide synthase biosynthetic process

Cellular Component

GO:0000139	Golgi membrane
GO:0005576	extracellular region
GO:0005737	cytoplasm
GO:0005764	lysosome
GO:0005768	endosome
GO:0005783	endoplasmic reticulum
GO:0005789	endoplasmic reticulum membrane
GO:0005886	plasma membrane
GO:0010008	endosome membrane
GO:0016021	integral component of membrane
GO:0016323	basolateral plasma membrane
GO:0016324	apical plasma membrane
GO:0032009	early phagosome
GO:0036020	endolysosome membrane