TLR9 | Toll-like receptor family | IUPHAR Guide to IMMUNOPHARMACOLOGY

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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 3 GO processes
GO:0030890 positive regulation of B cell proliferation IDA
GO:0045577 regulation of B cell differentiation IDA
GO:0050871 positive regulation of B cell activation IDA
Immuno Process:  Inflammation
GO Annotations:  Associated to 10 GO processes
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:0045087 innate immune response TAS
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 12 GO processes
GO:0002224 toll-like receptor signaling pathway IBA
GO:0002639 positive regulation of immunoglobulin 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:0045577 regulation of B cell differentiation IDA
GO:0050729 positive regulation of inflammatory response IC
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 17 GO processes
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 10 GO processes
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:0045577 regulation of B cell differentiation IDA
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
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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How to cite this page

Clare Bryant, Tom P. Monie.
Toll-like receptor family: TLR9. Last modified on 13/03/2018. Accessed on 26/08/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=1759.