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TLR9 toll like receptor 9 [ Homo sapiens (human) ]

Gene ID: 54106, updated on 17-Jun-2019

Summary

Official Symbol
TLR9provided by HGNC
Official Full Name
toll like receptor 9provided by HGNC
Primary source
HGNC:HGNC:15633
See related
Ensembl:ENSG00000239732 MIM:605474
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
CD289
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. 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, Aug 2017]
Expression
Broad expression in lymph node (RPKM 2.9), spleen (RPKM 1.9) and 16 other tissues See more
Orthologs

Genomic context

See TLR9 in Genome Data Viewer
Location:
3p21.2
Exon count:
2
Annotation release Status Assembly Chr Location
109.20190607 current GRCh38.p13 (GCF_000001405.39) 3 NC_000003.12 (52221080..52226163, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (52255096..52260179, complement)

Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene ALDOA pseudogene 1 Neighboring gene 5'-aminolevulinate synthase 1 Neighboring gene Sharpr-MPRA regulatory region 10522 Neighboring gene twinfilin actin binding protein 2 Neighboring gene uncharacterized LOC101929054

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Phenotypes

NHGRI GWAS Catalog

Description
Genome-wide association analysis identifies 13 new risk loci for schizophrenia.
NHGRI GWA Catalog
Large-scale genome-wide association analysis of bipolar disorder identifies a new susceptibility locus near ODZ4.
NHGRI GWA Catalog

HIV-1 interactions

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env HIV-1 gp120 inhibits TLR9-mediated upregulation of CD83 and the secretion of inflammatory cytokines TNF-alpha and IL-6, and chemokine IP10 in plasmacytoid dendritic cells (pDC) PubMed
env TLR-9-induced IFN-alpha production is inhibited by both monomeric and trimeric HIV-1 gp120 in plasmacytoid dendritic cells (pDC) PubMed
env Treatment of HIV-1 gp120 to astroglia displays significant decreases in TLR9 PubMed
Envelope surface glycoprotein gp160, precursor env Combined activation of TLR7/8 and TLR9 by TLR7/8 and TLR9 agonists induces the highest titers of binding, neutralizing, and antibody-dependent cellular cytotoxicity-mediating antibodies against HIV-1 Env/gp140 PubMed
Tat tat Treatment of HIV-1 Tat to astroglia displays significant decreases in TLR9 expression PubMed

Go to the HIV-1, Human Interaction Database

Pathways from BioSystems

  • African trypanosomiasis, organism-specific biosystem (from KEGG)
    African trypanosomiasis, organism-specific biosystemTrypanosoma brucei, the parasite responsible for African trypanosomiasis (sleeping sickness), are spread by the tsetse fly in sub-Saharan Africa. The parasites are able to pass through the blood-brai...
  • African trypanosomiasis, conserved biosystem (from KEGG)
    African trypanosomiasis, conserved biosystemTrypanosoma brucei, the parasite responsible for African trypanosomiasis (sleeping sickness), are spread by the tsetse fly in sub-Saharan Africa. The parasites are able to pass through the blood-brai...
  • Chagas disease (American trypanosomiasis), organism-specific biosystem (from KEGG)
    Chagas disease (American trypanosomiasis), organism-specific biosystemTrypanosoma cruzi is an intracellular protozoan parasite that causes Chagas disease. The parasite life cycle involves hematophagous reduviid bugs as vectors. Once parasites enter the host body, they ...
  • Chagas disease (American trypanosomiasis), conserved biosystem (from KEGG)
    Chagas disease (American trypanosomiasis), conserved biosystemTrypanosoma cruzi is an intracellular protozoan parasite that causes Chagas disease. The parasite life cycle involves hematophagous reduviid bugs as vectors. Once parasites enter the host body, they ...
  • Herpes simplex infection, organism-specific biosystem (from KEGG)
    Herpes simplex infection, organism-specific biosystemHerpes simplex virus (HSV) infections are very common worldwide, with the prevalence of HSV-1 reaching up to 80%-90%. Primary infection with HSV takes place in the mucosa, followed by the establishme...
  • Herpes simplex infection, conserved biosystem (from KEGG)
    Herpes simplex infection, conserved biosystemHerpes simplex virus (HSV) infections are very common worldwide, with the prevalence of HSV-1 reaching up to 80%-90%. Primary infection with HSV takes place in the mucosa, followed by the establishme...
  • IGF1R signaling cascade, organism-specific biosystem (from REACTOME)
    IGF1R signaling cascade, organism-specific biosystemAfter autophosphorylation the type 1 insulin-like growth factor receptor (IGF1R) binds and phosphorylates scaffold proteins, IRS1/2/4 and SHC1, which in turn bind effectors possessing enzymatic activ...
  • IRS-mediated signalling, organism-specific biosystem (from REACTOME)
    IRS-mediated signalling, organism-specific biosystemRelease of phospho-IRS from the insulin receptor triggers a cascade of signalling events via PI3K, SOS, RAF and the MAP kinases.
  • IRS-related events triggered by IGF1R, organism-specific biosystem (from REACTOME)
    IRS-related events triggered by IGF1R, organism-specific biosystemThe phosphorylated type 1 insulin-like growth factor receptor phosphorylates IR1, IRS2, IRS4 and possibly other IRS/DOK family members (reviewed in Pavelic et al. 2007, Chitnis et al. 2008, Maki et a...
  • Immune System, organism-specific biosystem (from REACTOME)
    Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
  • Innate Immune System, organism-specific biosystem (from REACTOME)
    Innate Immune System, organism-specific biosystemInnate immunity encompases the nonspecific part of immunity tha are part of an individual's natural biologic makeup
  • Insulin receptor signalling cascade, organism-specific biosystem (from REACTOME)
    Insulin receptor signalling cascade, organism-specific biosystemAutophosphorylation of the insulin receptor triggers a series of signalling events, mediated by SHC or IRS, and resulting in activation of the Ras/RAF and MAP kinase cascades. A second effect of the ...
  • Malaria, organism-specific biosystem (from KEGG)
    Malaria, organism-specific biosystemPlasmodium protozoa are parasites that account for malaria infection. Sporozoite forms of the parasite are injected by mosquito bites under the skin and are carried to the liver where they develop in...
  • Malaria, conserved biosystem (from KEGG)
    Malaria, conserved biosystemPlasmodium protozoa are parasites that account for malaria infection. Sporozoite forms of the parasite are injected by mosquito bites under the skin and are carried to the liver where they develop in...
  • Measles, organism-specific biosystem (from KEGG)
    Measles, organism-specific biosystemMeasles virus (MV) is highly contagious virus that leads infant death worldwide. Humans are the unique natural reservoir for this virus. It causes severe immunosuppression favouring secondary bacteri...
  • Measles, conserved biosystem (from KEGG)
    Measles, conserved biosystemMeasles virus (MV) is highly contagious virus that leads infant death worldwide. Humans are the unique natural reservoir for this virus. It causes severe immunosuppression favouring secondary bacteri...
  • MyD88 dependent cascade initiated on endosome, organism-specific biosystem (from REACTOME)
    MyD88 dependent cascade initiated on endosome, organism-specific biosystemUpon binding of their ligands, TLR7/8 and TLR9 recruit a cytoplasmic adaptor MyD88 and IRAKs, downstream of which the signaling pathways are divided to induce either inflammatory cytokines or type I ...
  • PI3K Cascade, organism-specific biosystem (from REACTOME)
    PI3K Cascade, organism-specific biosystem
    PI3K Cascade
  • Regulation of toll-like receptor signaling pathway, organism-specific biosystem (from WikiPathways)
    Regulation of toll-like receptor signaling pathway, organism-specific biosystem
    Regulation of toll-like receptor signaling pathway
  • Signal Transduction, organism-specific biosystem (from REACTOME)
    Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
  • Signaling by Insulin receptor, organism-specific biosystem (from REACTOME)
    Signaling by Insulin receptor, organism-specific biosystemInsulin binding to its receptor results in receptor autophosphorylation on tyrosine residues and the tyrosine phosphorylation of insulin receptor substrates (e.g. IRS and Shc) by the insulin receptor...
  • Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R), organism-specific biosystem (from REACTOME)
    Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R), organism-specific biosystemBinding of IGF1 (IGF-I) or IGF2 (IGF-II) to the extracellular alpha peptides of the type 1 insulin-like growth factor receptor (IGF1R) triggers the activation of two major signaling pathways: the SOS...
  • Simplified Depiction of MYD88 Distinct Input-Output Pathway, organism-specific biosystem (from WikiPathways)
    Simplified Depiction of MYD88 Distinct Input-Output Pathway, organism-specific biosystemThis pathway is based on figure 7 from Li et al. Formation of MyD88 dimer catalyzes formation of IRAK1/TRAF6 complex. UEV1A and Ubc13 ubiquinate TRAF6 which allow for the activation of NFKB and AP-1 ...
  • TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling, organism-specific biosystem (from REACTOME)
    TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling, organism-specific biosystemIn plasmacytoid dendritic cell induction of type I IFNs critically depends on IFN regulatory factor 7 in TLR7 and 9 signaling (Honda et al 2005). IRF-7, but not IRF3, interacts with MyD88, TRAF6, and...
  • TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation, organism-specific biosystem (from REACTOME)
    TRAF6 mediated induction of NFkB and MAP kinases upon TLR7/8 or 9 activation, organism-specific biosystemTRAF6 mediates NFkB activation via canonical phosphorylation of IKK complex by TAK1. TRAF6 and TAK1 also regulate MAPK cascades leading to the activation of AP-1.
  • Toll Like Receptor 7/8 (TLR7/8) Cascade, organism-specific biosystem (from REACTOME)
    Toll Like Receptor 7/8 (TLR7/8) Cascade, organism-specific biosystemRNA can serve as a danger signal, both in its double-stranded form (that is associated with viral infection), as well as single-stranded RNA (ssRNA). Specifically, guanosine (G)- and uridine (U)-rich...
  • Toll Like Receptor 9 (TLR9) Cascade, organism-specific biosystem (from REACTOME)
    Toll Like Receptor 9 (TLR9) Cascade, organism-specific biosystemCpG DNA is an unusual Pathogen-Associated Molecular Pattern (PAMP). Cytosine methylation exists in mammalian but not bacterial cells, and most (but not all) CpG in the mammalian genome is methylated....
  • Toll-Like Receptors Cascades, organism-specific biosystem (from REACTOME)
    Toll-Like Receptors Cascades, organism-specific biosystemIn human, ten members of the Toll-like receptor (TLR) family (TLR1-TLR10) have been identified (TLR11 has been found in mouse, but not in human). All TLRs have a similar Toll/IL-1 receptor (TIR) doma...
  • Toll-like Receptor Signaling, organism-specific biosystem (from WikiPathways)
    Toll-like Receptor Signaling, organism-specific biosystemThis pathway is based on the figure 1 of "Genetic variation in TLR or NFkappaB pathways and the risk of breast cancer: a case-control study" (see bibliography). TLR and NFkB are important in inflamma...
  • Toll-like Receptor Signaling Pathway, organism-specific biosystem (from WikiPathways)
    Toll-like Receptor Signaling Pathway, organism-specific biosystemSpecific families of pattern recognition receptors are responsible for detecting microbial pathogens and generating innate immune responses. Toll-like receptors (TLRs) are membrane-bound receptors id...
  • Toll-like receptor signaling pathway, organism-specific biosystem (from KEGG)
    Toll-like receptor signaling pathway, organism-specific biosystemSpecific families of pattern recognition receptors are responsible for detecting microbial pathogens and generating innate immune responses. Toll-like receptors (TLRs) are membrane-bound receptors id...
  • Toll-like receptor signaling pathway, conserved biosystem (from KEGG)
    Toll-like receptor signaling pathway, conserved biosystemSpecific families of pattern recognition receptors are responsible for detecting microbial pathogens and generating innate immune responses. Toll-like receptors (TLRs) are membrane-bound receptors id...
  • Trafficking and processing of endosomal TLR, organism-specific biosystem (from REACTOME)
    Trafficking and processing of endosomal TLR, organism-specific biosystemMammalian TLR3, TLR7, TLR8, TLR9 are endosomal receptors that sense nucleic acids that have been released from endocytosed/phagocytosed bacteria, viruses or parasites. These TLRs have a ligand-recogn...
  • Tuberculosis, organism-specific biosystem (from KEGG)
    Tuberculosis, organism-specific biosystemTuberculosis, or TB, is an infectious disease caused by Mycobacterium tuberculosis. One third of the world's population is thought to be infected with TB. About 90% of those infected result in latent...
  • Tuberculosis, conserved biosystem (from KEGG)
    Tuberculosis, conserved biosystemTuberculosis, or TB, is an infectious disease caused by Mycobacterium tuberculosis. One third of the world's population is thought to be infected with TB. About 90% of those infected result in latent...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Potential readthrough

Included gene: TWF2

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
interleukin-1 receptor binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein homodimerization activity ISS
Inferred from Sequence or Structural Similarity
more info
 
siRNA binding IMP
Inferred from Mutant Phenotype
more info
PubMed 
signaling pattern recognition receptor activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
transmembrane signaling receptor activity IEA
Inferred from Electronic Annotation
more info
 
unmethylated CpG binding ISS
Inferred from Sequence or Structural Similarity
more info
 
Process Evidence Code Pubs
I-kappaB kinase/NF-kappaB signaling IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
I-kappaB phosphorylation IDA
Inferred from Direct Assay
more info
PubMed 
MyD88-dependent toll-like receptor signaling pathway IEA
Inferred from Electronic Annotation
more info
 
defense response to Gram-negative bacterium IMP
Inferred from Mutant Phenotype
more info
PubMed 
defense response to bacterium NAS
Non-traceable Author Statement
more info
PubMed 
defense response to virus IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
immune response IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
inflammatory response IEA
Inferred from Electronic Annotation
more info
 
innate immune response TAS
Traceable Author Statement
more info
PubMed 
maintenance of gastrointestinal epithelium ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of NF-kappaB transcription factor activity IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of calcium-transporting ATPase activity IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of interleukin-6 production ISS
Inferred from Sequence or Structural Similarity
more info
 
negative regulation of interleukin-8 production IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of toll-like receptor signaling pathway IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of B cell activation IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of B cell proliferation IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of I-kappaB kinase/NF-kappaB signaling IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of JNK cascade IC
Inferred by Curator
more info
PubMed 
positive regulation of JUN kinase activity IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of MAPK cascade IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of NF-kappaB transcription factor activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
positive regulation of NF-kappaB transcription factor activity IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of NIK/NF-kappaB signaling IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of chemokine production IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of gene expression IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of granulocyte macrophage colony-stimulating factor production IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of immunoglobulin production IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of inflammatory response IC
Inferred by Curator
more info
PubMed 
positive regulation of interferon-alpha biosynthetic process IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of interferon-beta biosynthetic process IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
positive regulation of interferon-beta biosynthetic process IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of interferon-beta production ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of interferon-gamma biosynthetic process IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
positive regulation of interferon-gamma biosynthetic process IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of interleukin-10 production ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of interleukin-12 production ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of interleukin-18 production ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of interleukin-6 production IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
positive regulation of interleukin-6 production IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of interleukin-8 biosynthetic process IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
positive regulation of interleukin-8 production IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of nitric-oxide synthase biosynthetic process ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of toll-like receptor signaling pathway IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of transcription by RNA polymerase II ISS
Inferred from Sequence or Structural Similarity
more info
 
positive regulation of tumor necrosis factor production ISS
Inferred from Sequence or Structural Similarity
more info
 
regulation of B cell differentiation IDA
Inferred from Direct Assay
more info
PubMed 
regulation of cytokine secretion IEA
Inferred from Electronic Annotation
more info
 
regulation of toll-like receptor 9 signaling pathway IDA
Inferred from Direct Assay
more info
PubMed 
response to molecule of bacterial origin TAS
Traceable Author Statement
more info
PubMed 
toll-like receptor 9 signaling pathway TAS
Traceable Author Statement
more info
 
toll-like receptor signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
toll-like receptor signaling pathway TAS
Traceable Author Statement
more info
 
tumor necrosis factor production IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
tumor necrosis factor production IDA
Inferred from Direct Assay
more info
PubMed 
Component Evidence Code Pubs
Golgi membrane TAS
Traceable Author Statement
more info
 
apical plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
basolateral plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 
cytoplasm IDA
Inferred from Direct Assay
more info
PubMed 
early phagosome ISS
Inferred from Sequence or Structural Similarity
more info
 
endolysosome ISS
Inferred from Sequence or Structural Similarity
more info
 
endolysosome membrane TAS
Traceable Author Statement
more info
 
endoplasmic reticulum ISS
Inferred from Sequence or Structural Similarity
more info
 
endoplasmic reticulum membrane TAS
Traceable Author Statement
more info
 
endosome ISS
Inferred from Sequence or Structural Similarity
more info
 
endosome membrane TAS
Traceable Author Statement
more info
 
extracellular region NAS
Non-traceable Author Statement
more info
PubMed 
integral component of membrane IEA
Inferred from Electronic Annotation
more info
 
lysosome ISS
Inferred from Sequence or Structural Similarity
more info
 
plasma membrane IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
plasma membrane IDA
Inferred from Direct Assay
more info
PubMed 

NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_033933.1 RefSeqGene

    Range
    5001..10084
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_017442.3NP_059138.1  toll-like receptor 9 precursor

    See identical proteins and their annotated locations for NP_059138.1

    Status: REVIEWED

    Source sequence(s)
    AF245704, AF259262, BC032713
    Consensus CDS
    CCDS2848.1
    UniProtKB/Swiss-Prot
    Q9NR96
    Related
    ENSP00000353874.2, ENST00000360658.2
    Conserved Domains (4) summary
    cd00116
    Location:476739
    LRR_RI; Leucine-rich repeats (LRRs), ribonuclease inhibitor (RI)-like subfamily. LRRs are 20-29 residue sequence motifs present in many proteins that participate in protein-protein interactions and have different functions and cellular locations. LRRs correspond ...
    sd00033
    Location:476497
    LRR_RI; leucine-rich repeat [structural motif]
    pfam13855
    Location:496555
    LRR_8; Leucine rich repeat
    cl23749
    Location:8701009
    TIR_2; TIR domain

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000003.12 Reference GRCh38.p13 Primary Assembly

    Range
    52221080..52226163 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_138688.1: Suppressed sequence

    Description
    NM_138688.1: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.
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