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

    Gene ID: 54106, updated on 31-Jan-2016
    Official Symbol
    TLR9provided by HGNC
    Official Full Name
    toll like receptor 9provided by HGNC
    Primary source
    HGNC:HGNC:15633
    See related
    Ensembl:ENSG00000239732; HPRD:05685; MIM:605474; Vega:OTTHUMG00000158106
    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. 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]
    Orthologs
    See TLR9 in Epigenomics, MapViewer
    Location:
    3p21.3
    Exon count:
    2
    Annotation release Status Assembly Chr Location
    107 current GRCh38.p2 (GCF_000001405.28) 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 aldolase, fructose-bisphosphate A pseudogene 1 Neighboring gene 5'-aminolevulinate synthase 1 Neighboring gene twinfilin actin binding protein 2 Neighboring gene uncharacterized LOC101929054

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    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

    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

    • 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...
    • 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 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, 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, 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...
    Products Interactant Other Gene Complex Source Pubs Description

    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 
    siRNA binding IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    transmembrane signaling receptor activity IEA
    Inferred from Electronic Annotation
    more info
     
    Process Evidence Code Pubs
    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
     
    NOT axonogenesis IBA
    Inferred from Biological aspect of Ancestor
    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 
    inflammatory response IEA
    Inferred from Electronic Annotation
    more info
     
    innate immune response TAS
    Traceable Author Statement
    more info
    PubMed 
    insulin receptor signaling pathway TAS
    Traceable Author Statement
    more info
     
    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 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 NF-kappaB import into nucleus IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of NF-kappaB transcription factor activity 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 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 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 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 IDA
    Inferred from Direct Assay
    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 from RNA polymerase II promoter 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 cytokine secretion IEA
    Inferred from Electronic Annotation
    more info
     
    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
     
    toll-like receptor signaling pathway TAS
    Traceable Author Statement
    more info
     
    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 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 IDA
    Inferred from Direct Assay
    more info
    PubMed 

    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, OTTHUMP00000212618, ENST00000360658, OTTHUMT00000350203
      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 ...
      pfam13855
      Location:496556
      LRR_8; Leucine rich repeat
      sd00033
      Location:476497
      LRR_RI; leucine-rich repeat [structural motif]
      cl22869
      Location:8721009
      TIR_2; TIR domain

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 107

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

    Reference GRCh38.p2 Primary Assembly

    Genomic

    1. NC_000003.12 Reference GRCh38.p2 Primary Assembly

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

    Alternate CHM1_1.1

    Genomic

    1. NC_018914.2 Alternate CHM1_1.1

      Range
      52207624..52212707 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.