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    TLR3 toll-like receptor 3 [ Homo sapiens (human) ]

    Gene ID: 7098, updated on 26-Jul-2015
    Official Symbol
    TLR3provided by HGNC
    Official Full Name
    toll-like receptor 3provided by HGNC
    Primary source
    HGNC:HGNC:11849
    See related
    HPRD:04324; MIM:603029
    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
    CD283; IIAE2
    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 receptor is most abundantly expressed in placenta and pancreas, and is restricted to the dendritic subpopulation of the leukocytes. It recognizes dsRNA associated with viral infection, and induces the activation of NF-kappaB and the production of type I interferons. It may thus play a role in host defense against viruses. Use of alternative polyadenylation sites to generate different length transcripts has been noted for this gene. [provided by RefSeq, Jul 2008]
    Orthologs
    See TLR3 in Epigenomics, MapViewer
    Location:
    4q35
    Exon count:
    5
    Annotation release Status Assembly Chr Location
    107 current GRCh38.p2 (GCF_000001405.28) 4 NC_000004.12 (186069155..186085098)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) 4 NC_000004.11 (186990309..187006252)

    Chromosome 4 - NC_000004.12Genomic Context describing neighboring genes Neighboring gene sorbin and SH3 domain containing 2 Neighboring gene uncharacterized LOC101928929 Neighboring gene uncharacterized LOC105377593 Neighboring gene uncharacterized LOC105377592 Neighboring gene protein FAM149A-like Neighboring gene 40S ribosomal protein SA-like Neighboring gene family with sequence similarity 149, member A

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    • Activated TLR4 signalling, organism-specific biosystem (from REACTOME)
      Activated TLR4 signalling, organism-specific biosystemTLR4 is unique among the TLR family in its ability to recruit four adapters to activate two distinct signaling pathways. One pathway is activated by the pair of the adapters Mal or TIRAP (Toll/inter...
    • Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon, organism-specific biosystem (from REACTOME)
      Activation of IRF3/IRF7 mediated by TBK1/IKK epsilon, organism-specific biosystemCell stimulation with viral ds RNA leads to the activation of two IKK-related serine/threonine kinases, TBK1 and IKK-i which directly phosphorylate IRF3 and IRF7 promoting their dimerization and tran...
    • Apoptosis, organism-specific biosystem (from REACTOME)
      Apoptosis, organism-specific biosystemApoptosis is a distinct form of cell death that is functionally and morphologically different from necrosis. Nuclear chromatin condensation, cytoplasmic shrinking, dilated endoplasmic reticulum, and ...
    • Caspase activation via extrinsic apoptotic signalig pathway, organism-specific biosystem (from REACTOME)
      Caspase activation via extrinsic apoptotic signalig pathway, organism-specific biosystemKnown as the "death receptor pathway" the extrinsic or caspase 8/10 dependent pathway is activated by ligand binding. The "death receptors" are specialized cell-surface receptors including Fas/CD95, ...
    • Cytosolic sensors of pathogen-associated DNA, organism-specific biosystem (from REACTOME)
      Cytosolic sensors of pathogen-associated DNA, organism-specific biosystemPresence of pathogen-associated DNA in cytosol induces type I IFN production. Several intracellular receptors have been implicated to some degree. These include DNA-dependent activator of interferon ...
    • Disease, organism-specific biosystem (from REACTOME)
      Disease, organism-specific biosystemBiological processes are captured in Reactome by identifying the molecules (DNA, RNA, protein, small molecules) involved in them and describing the details of their interactions. From this molecular ...
    • Diseases associated with the TLR signaling cascade, organism-specific biosystem (from REACTOME)
      Diseases associated with the TLR signaling cascade, organism-specific biosystemToll like receptors (TLRs) are sensors of the innate immune system that detect danger signals derived from pathogens (pathogen-associated molecular patterns - PAMP) or damaged cells (damage-associate...
    • Diseases of Immune System, organism-specific biosystem (from REACTOME)
      Diseases of Immune System, organism-specific biosystemThe immune system is a complex network of the biological processes that provide defense mechanisms during infection or in response to an intrinsic danger signal. Compromised immune response may prese...
    • Hepatitis B, organism-specific biosystem (from KEGG)
      Hepatitis B, organism-specific biosystemHepatitis B virus (HBV) is an enveloped virus and contains a partially double-stranded relaxed circular DNA (RC-DNA) genome. After entry into hepatocytes, HBV RC-DNA is transported to the nucleus and...
    • Hepatitis C, organism-specific biosystem (from KEGG)
      Hepatitis C, organism-specific biosystemHepatitis C virus (HCV) is a major cause of chronic liver disease. The HCV employ several strategies to perturb host cell immunity. After invasion, HCV RNA genome functions directly as an mRNA in the...
    • Hepatitis C, conserved biosystem (from KEGG)
      Hepatitis C, conserved biosystemHepatitis C virus (HCV) is a major cause of chronic liver disease. The HCV employ several strategies to perturb host cell immunity. After invasion, HCV RNA genome functions directly as an mRNA in the...
    • 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...
    • IKK complex recruitment mediated by RIP1, organism-specific biosystem (from REACTOME)
      IKK complex recruitment mediated by RIP1, organism-specific biosystemReceptor-interacting protein 1 (RIP1) mediates the activation of proinflammatory cytokines via intermediate induction of IKK complex in NFkB pathways [Ea et al. 2006]. Poly(I-C) treatment stimulated ...
    • 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...
    • Influenza A, organism-specific biosystem (from KEGG)
      Influenza A, organism-specific biosystemInfluenza is a contagious respiratory disease caused by influenza virus infection. Influenza A virus is responsible for both annual seasonal epidemics and periodic worldwide pandemics. Novel strains ...
    • Influenza A, conserved biosystem (from KEGG)
      Influenza A, conserved biosystemInfluenza is a contagious respiratory disease caused by influenza virus infection. Influenza A virus is responsible for both annual seasonal epidemics and periodic worldwide pandemics. Novel strains ...
    • 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
    • Ligand-dependent caspase activation, organism-specific biosystem (from REACTOME)
      Ligand-dependent caspase activation, organism-specific biosystemCaspase-8 is synthesized as zymogen (procaspase-8) and is formed from procaspase-8 as a cleavage product. However, the cleavage itself appears not to be sufficient for the formation of an active casp...
    • MyD88-independent TLR3/TLR4 cascade, organism-specific biosystem (from REACTOME)
      MyD88-independent TLR3/TLR4 cascade, organism-specific biosystemMyD88-independent signaling pathway is shared by TLR3 and TLR4 cascades. TIR-domain-containing adapter-inducing interferon-beta (TRIF or TICAM1) is a key adapter molecule in transducing signals from ...
    • Programmed Cell Death, organism-specific biosystem (from REACTOME)
      Programmed Cell Death, organism-specific biosystemCell death is a fundamental cellular response that has a crucial role in shaping our bodies during development and in regulating tissue homeostasis by eliminating unwanted cells. There are a number o...
    • RIP-mediated NFkB activation via ZBP1, organism-specific biosystem (from REACTOME)
      RIP-mediated NFkB activation via ZBP1, organism-specific biosystemOverexpression of human or murine ZBP1 (DAI) in human embryonic kidney 293T cells (HEK293T) activated NF-kB-dependent promoter in a dose-dependent manner. Two RHIM-contaning kinases RIP1 and RIP3 are...
    • 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
    • TICAM1 deficiency - HSE, organism-specific biosystem (from REACTOME)
      TICAM1 deficiency - HSE, organism-specific biosystemInborn errors of interferon immunity due to defects in toll like receptor 3 (TLR3)-mediated signaling underlie pathogenesis of herpes simplex virus type 1 (HSV1) encephalitis (HSE) in some children (...
    • TLR3 deficiency - HSE, organism-specific biosystem (from REACTOME)
      TLR3 deficiency - HSE, organism-specific biosystemToll like receptor 3 (TLR3) recognizes double-stranded RNA (dsRNA), an intermediate product during viral replication for most viruses. TLR3 is expressed in various tissues and cells including cells o...
    • TRAF3 deficiency - HSE, organism-specific biosystem (from REACTOME)
      TRAF3 deficiency - HSE, organism-specific biosystemTNF Receptor Associated Factor 3 (TRAF3) is a cytoplasmic adaptor protein utilized by the tumor necrosis factor receptor superfamily and toll-like receptors (TLRs). TRAF3 deficiency is thought to mim...
    • TRAF6 mediated induction of TAK1 complex, organism-specific biosystem (from REACTOME)
      TRAF6 mediated induction of TAK1 complex, organism-specific biosystemIn human, together with ubiquitin-conjugating E2-type enzymes UBC13 and UEV1A (also known as UBE2V1), TRAF6 catalyses Lys63-linked ubiquitination. It is believed that auto polyubiquitination and oli...
    • TRIF-mediated TLR3/TLR4 signaling, organism-specific biosystem (from REACTOME)
      TRIF-mediated TLR3/TLR4 signaling, organism-specific biosystemTRIF(TICAM1) was shown to induce IRF3/7 and NF-?B activation and apoptosis through distinct intracellular signaling pathways [Han KJ et al 2004; Kaiser WJ and Offermann MK et al 2005]. TRIF consists...
    • TRIF-mediated programmed cell death, organism-specific biosystem (from REACTOME)
      TRIF-mediated programmed cell death, organism-specific biosystemTLR3 and -4 trigger TRIF-dependent programmed cell death in various human and mouse cells (Kalai M et al. 2002; Han KJ et al. 2004; Kaiser WJ and Offermann MK 2005; Estornes Y et al. 2012; He S et al...
    • Toll Like Receptor 3 (TLR3) Cascade, organism-specific biosystem (from REACTOME)
      Toll Like Receptor 3 (TLR3) Cascade, organism-specific biosystemToll-like receptor 3 (TLR3) as was shown for mammals is expressed on myeloid dendritic cells, respiratory epithelium, macrophages, and appears to play a central role in mediating the antiviral and in...
    • Toll Like Receptor 4 (TLR4) Cascade, organism-specific biosystem (from REACTOME)
      Toll Like Receptor 4 (TLR4) Cascade, organism-specific biosystemToll-like Receptor 4 is a Microbe Associated Molecular Pattern receptor well known for it's sensitivity to Bacterial Lipopolysaccharides (LPS). LPS is assembled within diverse Gram-negative bacteria,...
    • 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...
    • UNC93B1 deficiency - HSE, organism-specific biosystem (from REACTOME)
      UNC93B1 deficiency - HSE, organism-specific biosystemUNC93B1 is an endoplasmic reticulum protein with 12 membrane-spanning domains. Signaling cascades of nucleotide-sensing endosomal toll like receptors (TLR3 and TLR7-9) depends on functional UNC93B1, ...
    • ZBP1(DAI) mediated induction of type I IFNs, organism-specific biosystem (from REACTOME)
      ZBP1(DAI) mediated induction of type I IFNs, organism-specific biosystemZ-DNA-binding protein-1 (ZBP1), also known as, DNA-dependent activator of IFN-regulatory factors (DAI) was reported to initiate innate immune responses in murine L929 cells upon stimulation by multip...
    Products Interactant Other Gene Complex Source Pubs Description

    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    double-stranded RNA binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    double-stranded RNA binding NAS
    Non-traceable Author Statement
    more info
    PubMed 
    identical protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    receptor activity TAS
    Traceable Author Statement
    more info
    PubMed 
    transmembrane signaling receptor activity NAS
    Non-traceable Author Statement
    more info
    PubMed 
    Process Evidence Code Pubs
    I-kappaB kinase/NF-kappaB signaling TAS
    Traceable Author Statement
    more info
     
    I-kappaB phosphorylation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    MyD88-independent toll-like receptor signaling pathway TAS
    Traceable Author Statement
    more info
     
    TRIF-dependent toll-like receptor signaling pathway TAS
    Traceable Author Statement
    more info
     
    activation of NF-kappaB-inducing kinase activity NAS
    Non-traceable Author Statement
    more info
    PubMed 
    activation of cysteine-type endopeptidase activity involved in apoptotic signaling pathway TAS
    Traceable Author Statement
    more info
     
    apoptotic process TAS
    Traceable Author Statement
    more info
     
    cellular response to mechanical stimulus IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    defense response to bacterium TAS
    Traceable Author Statement
    more info
    PubMed 
    defense response to virus TAS
    Traceable Author Statement
    more info
    PubMed 
    detection of virus NAS
    Non-traceable Author Statement
    more info
    PubMed 
    extrinsic apoptotic signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    extrinsic apoptotic signaling pathway TAS
    Traceable Author Statement
    more info
     
    hyperosmotic response 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 
    necroptotic signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    negative regulation of osteoclast differentiation NAS
    Non-traceable Author Statement
    more info
    PubMed 
    positive regulation of JNK cascade IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of NF-kappaB import into nucleus IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of NF-kappaB transcription factor activity IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of chemokine biosynthetic process IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of chemokine production IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of gene expression IMP
    Inferred from Mutant Phenotype
    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 biosynthetic process IMP
    Inferred from Mutant Phenotype
    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-12 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 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
     
    positive regulation of type III interferon production IEA
    Inferred from Electronic Annotation
    more info
     
    programmed cell death TAS
    Traceable Author Statement
    more info
     
    regulation of dendritic cell cytokine production IEA
    Inferred from Electronic Annotation
    more info
     
    response to exogenous dsRNA IDA
    Inferred from Direct Assay
    more info
    PubMed 
    signal transduction TAS
    Traceable Author Statement
    more info
    PubMed 
    toll-like receptor 3 signaling pathway TAS
    Traceable Author Statement
    more info
     
    toll-like receptor 4 signaling pathway TAS
    Traceable Author Statement
    more info
     
    toll-like receptor signaling pathway TAS
    Traceable Author Statement
    more info
     
    Component Evidence Code Pubs
    Golgi membrane TAS
    Traceable Author Statement
    more info
     
    NOT cell surface IDA
    Inferred from Direct Assay
    more info
    PubMed 
    cytoplasm IDA
    Inferred from Direct Assay
    more info
    PubMed 
    endolysosome membrane TAS
    Traceable Author Statement
    more info
     
    endoplasmic reticulum membrane TAS
    Traceable Author Statement
    more info
     
    endosome membrane TAS
    Traceable Author Statement
    more info
     
    integral component of plasma membrane TAS
    Traceable Author Statement
    more info
    PubMed 
    intracellular IDA
    Inferred from Direct Assay
    more info
    PubMed 
    lysosomal membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    membrane NAS
    Non-traceable Author Statement
    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_007278.1 RefSeqGene

      Range
      5001..20944
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_117

    mRNA and Protein(s)

    1. NM_003265.2NP_003256.1  toll-like receptor 3 precursor

      See identical proteins and their annotated locations for NP_003256.1

      Status: REVIEWED

      Source sequence(s)
      BC096333, BU624267, DA374150, U88879
      Consensus CDS
      CCDS3846.1
      UniProtKB/Swiss-Prot
      O15455
      Conserved Domains (7) summary
      smart00013
      Location:2854
      LRRNT; Leucine rich repeat N-terminal domain
      smart00082
      Location:645697
      LRRCT; Leucine rich repeat C-terminal domain
      cd00116
      Location:531647
      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 ...
      pfam01582
      Location:758896
      TIR; TIR domain
      pfam13855
      Location:75135
      LRR_8; Leucine rich repeat
      sd00031
      Location:532563
      LRR_1; leucine-rich repeat [structural motif]
      sd00033
      Location:3352
      LRR_RI; leucine-rich repeat [structural motif]

    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_000004.12 Reference GRCh38.p2 Primary Assembly

      Range
      186069155..186085098
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate CHM1_1.1

    Genomic

    1. NC_018915.2 Alternate CHM1_1.1

      Range
      186966756..186982686
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)