TLR9 | Toll-like receptor family | IUPHAR/BPS Guide to PHARMACOLOGY

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TLR9

target has curated data in GtoImmuPdb

Target id: 1759

Nomenclature: TLR9

Family: Toll-like receptor family

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 1007 3p21.3 TLR9 toll like receptor 9
Mouse - 1007 9 57.46 cM Tlr9 toll-like receptor 9
Rat - - 8 Tlr9 toll-like receptor 9
Previous and Unofficial Names
CD289 | toll-like receptor 9
Database Links
CATH/Gene3D
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
UniProtKB
Wikipedia

Download all structure-activity data for this target as a CSV file

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
agatolimod Hs Agonist - - 5
[5]
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
hydroxychloroquine Hs Antagonist 7.1 pIC50 3
pIC50 7.1 (IC50 8x10-8 M) [3]
Description: Inhibition of hTLR9 CpG2006-induced luciferase reporter gene activation.
Immunopharmacology Comments
TLR9 is an endosomal receptor detecting viral and bacterial CpG DNA and genomic DNA from some protozoan species [4]. Activated TLR9 receptors expressed by B cells and plasmacytoid dendritic cells, stimulate human B-cell proliferation, enhance antigen-specific antibody production and induce IFN-α production, IL-10 secretion and natural killer cell activity.
Immuno Process Associations
Immuno Process:  B cell (activation)
GO Annotations:  Associated to 4 GO processes
GO:0030890 positive regulation of B cell proliferation IDA
GO:0045577 regulation of B cell differentiation IDA
GO:0050864 regulation of B cell activation IGI
GO:0050871 positive regulation of B cell activation IDA
Immuno Process:  Inflammation
GO Annotations:  Associated to 14 GO processes
GO:0001774 microglial cell activation ISO
GO:0002218 activation of innate immune response IDA
GO:0002224 toll-like receptor signaling pathway IBA
GO:0008329 signaling pattern recognition receptor activity IBA
GO:0034122 negative regulation of toll-like receptor signaling pathway IDA
GO:0034123 positive regulation of toll-like receptor signaling pathway IDA
GO:0034162 toll-like receptor 9 signaling pathway TAS
GO:0034163 regulation of toll-like receptor 9 signaling pathway IDA
GO:0034165 positive regulation of toll-like receptor 9 signaling pathway IMP
GO:0045087 innate immune response TAS
GO:0050727 regulation of inflammatory response IMP
GO:0050729 positive regulation of inflammatory response IC
click arrow to show/hide IEA associations
GO:0002755 MyD88-dependent toll-like receptor signaling pathway IEA
GO:0006954 inflammatory response IEA
Immuno Process:  Immune system development
GO Annotations:  Associated to 1 GO processes
GO:0045577 regulation of B cell differentiation IDA
Immuno Process:  Immune regulation
GO Annotations:  Associated to 17 GO processes
GO:0002218 activation of innate immune response IDA
GO:0002224 toll-like receptor signaling pathway IBA
GO:0002639 positive regulation of immunoglobulin production IDA
GO:0002730 regulation of dendritic cell cytokine production IDA
GO:0008329 signaling pattern recognition receptor activity IBA
GO:0030890 positive regulation of B cell proliferation IDA
GO:0034122 negative regulation of toll-like receptor signaling pathway IDA
GO:0034123 positive regulation of toll-like receptor signaling pathway IDA
GO:0034162 toll-like receptor 9 signaling pathway TAS
GO:0034163 regulation of toll-like receptor 9 signaling pathway IDA
GO:0034165 positive regulation of toll-like receptor 9 signaling pathway IMP
GO:0045577 regulation of B cell differentiation IDA
GO:0050727 regulation of inflammatory response IMP
GO:0050729 positive regulation of inflammatory response IC
GO:0050864 regulation of B cell activation IGI
GO:0050871 positive regulation of B cell activation IDA
click arrow to show/hide IEA associations
GO:0002755 MyD88-dependent toll-like receptor signaling pathway IEA
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 19 GO processes
GO:0001816 cytokine production IDA
GO:0002730 regulation of dendritic cell cytokine production IDA
GO:0032640 tumor necrosis factor production IDA
GO:0032715 negative regulation of interleukin-6 production ISS
GO:0032717 negative regulation of interleukin-8 production IDA
GO:0032722 positive regulation of chemokine production IDA
GO:0032725 positive regulation of granulocyte macrophage colony-stimulating factor production IDA
GO:0032728 positive regulation of interferon-beta production ISS
GO:0032733 positive regulation of interleukin-10 production ISS
GO:0032735 positive regulation of interleukin-12 production ISS
GO:0032741 positive regulation of interleukin-18 production ISS
GO:0032755 positive regulation of interleukin-6 production IDA
GO:0032757 positive regulation of interleukin-8 production IDA
GO:0032760 positive regulation of tumor necrosis factor production ISS
GO:0045078 positive regulation of interferon-gamma biosynthetic process IDA
GO:0045356 positive regulation of interferon-alpha biosynthetic process IDA
GO:0045359 positive regulation of interferon-beta biosynthetic process IDA
GO:0045416 positive regulation of interleukin-8 biosynthetic process IBA
click arrow to show/hide IEA associations
GO:0050707 regulation of cytokine secretion IEA
Immuno Process:  Chemotaxis & migration
GO Annotations:  Associated to 1 GO processes
GO:0032722 positive regulation of chemokine production IDA
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 13 GO processes
GO:0001774 microglial cell activation ISO
GO:0002224 toll-like receptor signaling pathway IBA
GO:0008329 signaling pattern recognition receptor activity IBA
GO:0030890 positive regulation of B cell proliferation IDA
GO:0034122 negative regulation of toll-like receptor signaling pathway IDA
GO:0034123 positive regulation of toll-like receptor signaling pathway IDA
GO:0034162 toll-like receptor 9 signaling pathway TAS
GO:0034163 regulation of toll-like receptor 9 signaling pathway IDA
GO:0034165 positive regulation of toll-like receptor 9 signaling pathway IMP
GO:0045577 regulation of B cell differentiation IDA
GO:0050864 regulation of B cell activation IGI
GO:0050871 positive regulation of B cell activation IDA
click arrow to show/hide IEA associations
GO:0002755 MyD88-dependent toll-like receptor signaling pathway IEA
Clinically-Relevant Mutations and Pathophysiology
Disease:  Asthma, susceptibility to
Disease Ontology: DOID:2841
OMIM: 600807
Disease:  Cerebral malaria
Synonyms: Malaria, susceptibility to [OMIM: 611162]
Disease Ontology: DOID:14069
OMIM: 611162
Disease:  Cervical cancer
Disease Ontology: DOID:4362
OMIM: 603956
Disease:  Endometrial cancer
Disease Ontology: DOID:1380
OMIM: 608089
Disease:  Human immunodeficiency virus type 1, susceptibility to
Synonyms: Human immunodeficiency virus infectious disease [Disease Ontology: DOID:526]
Disease Ontology: DOID:526
OMIM: 609423
Orphanet: ORPHA319269
Disease:  Lupus nephritis
Disease:  Lymphoma, non-hodgkin, familial
Description: A lymphoma that is characterized as any kind of lymphoma except Hodgkin's lymphoma. Symptoms include enlarged lymph nodes, fever, night sweats, weight loss, and lethargy.
Synonyms: Non-Hodgkin lymphoma [Disease Ontology: DOID:0060060]
Disease Ontology: DOID:0060060
OMIM: 605027
Disease:  Prostate cancer
Disease Ontology: DOID:10283
OMIM: 176807
Disease:  Systemic lupus erythematosus
Description: SLE is a complex autoimmune disease that is characterised by inflammation of various connective tissues, and symptoms include dermatitis, arthritis, inflammation of the kidneys (glomerulonephritis), vasculitis, inflammation of the tissue surrounding the heart, and seizures. It is caused by the production of autoantibodies against widely expressed nuclear, cytoplasmic, and cell surface molecules. Extracellular RNA in the circulation in combination with the presence of autoantibodies potently stimulates interferon production and immune system activation.
Disease Ontology: DOID:9074
OMIM: 152700
Orphanet: ORPHA536
General Comments
TLR9 is an intracellular detector for pathogen-derived nucleic acids, in particular CpG dinucleotides. Trafficking of endosomal TLR9 is tightly controlled to prevent inappropriate activation [2].
The potential role of TLR9 in immuno-oncology is reviewed in [1].

References

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1. Adams JL, Smothers J, Srinivasan R, Hoos A. (2015) Big opportunities for small molecules in immuno-oncology. Nat Rev Drug Discov, 14 (9): 603-22. [PMID:26228631]

2. Babdor J, Descamps D, Adiko AC, Tohm√© M, Maschalidi S, Evnouchidou I, Vasconcellos LR, De Luca M, Mauvais FX, Garfa-Traore M et al.. (2017) IRAP+ endosomes restrict TLR9 activation and signaling. Nat. Immunol., 18 (5): 509-518. [PMID:28319098]

3. Lamphier M, Zheng W, Latz E, Spyvee M, Hansen H, Rose J, Genest M, Yang H, Shaffer C, Zhao Y et al.. (2014) Novel small molecule inhibitors of TLR7 and TLR9: mechanism of action and efficacy in vivo. Mol. Pharmacol., 85 (3): 429-40. [PMID:24342772]

4. Uematsu S, Akira S. (2008) Toll-Like receptors (TLRs) and their ligands. Handb Exp Pharmacol, (183): 1-20. [PMID:18071652]

5. (2006) CpG 7909: PF 3512676, PF-3512676. Drugs R D, 7 (5): 312-6. [PMID:16922592]

Contributors

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