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FLASH GENE
Symbol TLR7 contributors: mct - updated : 18-10-2017
HGNC name toll-like receptor 7
HGNC id 15631
Location Xp22.2      Physical location : 12.885.201 - 12.908.479
Synonym name Drosophila transmembrane receptor Toll homolog 7
DNA
TYPE functioning gene
SPECIAL FEATURE arranged in tandem
text arranged in tandem with TLR8
STRUCTURE 23.28 kb     3 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status confirmed
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
3 - 4992 - 1049 - 2000 11022120
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Endocrineparathyroid   highly
Lymphoid/Immunelymph node   highly
 spleen   predominantly
 tonsils   lowly
Reproductivefemale systemuterus  predominantly
 female systemoviduct   
Respiratorylung   predominantly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Blood / Hematopoieticbone marrow   
Epithelialbarrier liningendometrium  
cells
SystemCellPubmedSpeciesStageRna symbol
Blood/Hematopoieticmonocyte
Lymphoid/ImmuneB cell Homo sapiens
Lymphoid/Immunedendritic cell Homo sapiens
cell lineage
cell lines
fluid/secretion
at STAGE
physiological period pregnancy
Text placenta
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N-terminus with a novel role as a molecular chaperone that provides processed TLR7 with the correct targeting instructions to reach the endosomal compartment, hence ensuring its biological activity and preventing inadvertent cell surface responses to self-RNA
  • 27 leucine-rich repeats (LRR)
  • a ToL N homology domain common to the Toll and IL1 receptors (also called TIR domain)
  • conjugated GlycoP
    HOMOLOGY
    interspecies homolog to Drosophila transmembrane receptor Toll,7
    homolog to murine Tlr7
    Homologene
    FAMILY
  • toll-like receptor family
  • CATEGORY immunity/defense , receptor membrane
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,organelle,endosome
    intracellular,cytoplasm,organelle,lysosome
    text sequestered in the endoplasmic reticulum (ER) in a resting state and traffic to endolysosomes upon ligand-induced stimulation
    basic FUNCTION
  • can recognize nucleic acids and trigger signalling cascades that activate plasmacytoid dendritic cells to produce interferon-alpha (thus contributing to the pathogenesis of systemic lupus erythematosus)
  • pathogen recognition and activation of innate immunity
  • acting via MYD88 and TRAF6, leading to the activation of NF-KappaB signaling pathway
  • inducing TNF production in plasmacytoid dendritic cells precursor and IL12 in immature (CD11C+) myeloid cells
  • acting as the host sensor for human parechovirus 1
  • potentially involved in modulating the recognition of CpG motifs
  • acting as the host sensors for human parechovirus 1, a single-stranded RNA (ssRNA) virus
  • play critical roles in pathogen recognition and activation of innate immunity
  • may confer susceptibility to asthma and related atopic disorders
  • initiate immune responses to infection by recognizing microbial nucleic acid
  • implicated in the sequence-dependent detection of RNA oligonucleotides in immune cells
  • involved in sequence-specific sensing of single-stranded RNAs in macrophages
  • requirement for processing of TLR7 may represent an evolutionary strategy to ensure proper self/non-self discrimination based on nucleic acid recognition
  • recognize pathogen-derived nucleotides in intracellular compartments and respond to host-derived nucleotides as well, and they have been implicated in a variety of autoimmune diseases
  • with TLR8, activate similar signaling pathways that play different roles in dendritic cells maturation, depending on which TLR is triggered
  • with TLR9, are required for plasmacytoid dendritic cells
  • TLR7-dependent EDN1 secretion by infiltrating macrophages attempting clearance of immune complexes bound apoptotic cardiocytes may be positioned as a direct inducer of the fibroblast secretion of TGFbeta
  • exerts B-cell–intrinsic effects in promoting spontaneous germinal center (GC) and plasmablast B-cell development
  • exerts B-cell–specific effects that influence B-cell fate and development of spontaneous autoimmunity
  • innate immune sensor for microbial RNA, erroneously responds to self-derived RNA
  • essential role for TLR7-unique cysteines in an intramolecular disulfide bond, proteolytic cleavage and RNA sensing
  • TLR7 is likely the major TLR recognizing single-stranded RNA (ssRNA) in brains
  • TLR7 plays a central role in early immune activation during malaria infection, whereas TLR7 and TLR9 contribute combinatorially to immune responses as infection progresses
  • B cell-intrinsic TLR7 signaling is essential for the development of spontaneous germinal centers (PID: 25252960)
  • distinct roles for TLR7 and TLR9 in the differentiation of autoreactive B cells that explain the capacity of TLR9 to limit, as well as TLR7 to promote, the clinical features of systemic erythematosus lupus
  • mediates innate immune responses to viral RNA in endocytic compartments
  • TLR7 and TLR8 on trophoblastic cells play an important role in the prevention of intrauterine HBV transmission by inhibiting HBV translocation across trophoblast
  • activation of TLR7 signaling in T cells can inhibit Th17 cell differentiation from naive T cells and IL17 production in established Th17 cells
  • CELLULAR PROCESS cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS immunity/defense , inflammation
    text apoptosis of infected cells
    PATHWAY
    metabolism
    signaling signal transduction
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • binding MYD88 via the TIR domains
  • MARCH5 positively regulates TLR7 signaling
  • upon activation, TLR7 and 9 are transported from the endoplasmic reticulum (ER) to endolysosomes for nucleic acid sensing by an ER-resident protein, UNC93B1
  • IRF5 is a transcription factor activated by toll like receptor TLR7 and TLR9 during innate immune responses
  • BTK is an important player for TLR9 but not TLR7 signaling in human Plasmacytoid dendritic cells (PDCs)
  • link between platelets and their response to single-stranded RNA viruses involves activation of TLR7
  • IRF5 is degraded following TLR7 activation and TRIM21 is involved in this process
  • plays a, hitherto unappreciated, role in TLR7 signaling through a novel signaling axis containing, but not limited to, MYD88, TICAM2 and IRF3 towards the activation of anti-viral immunity
  • to restrict Nucleic acid (NA)-sensing in endolysosomes, TLR7/9 trafficking is tightly controlled by a multiple transmembrane protein UNC93B1
  • MCOLN1 positively regulates TLR7 responses in dendritic cells by facilitating RNA transportation to lysosomes
  • TRIM35 is a negative feedback regulator of TLR7/9-mediated type I IFN production due to its ability to suppress the stability of IRF7
  • SARM1, mediates TLR7/TLR9-induced apoptosis in neurons
  • GFI1 plays a critical role in the prevention of spontaneous lupus autoimmunity by negatively regulating TLR7 signaling
  • signaling via TLR7 leads to an upregulation of XBP1 and IFNA1-production
  • central role of XBP1 in TLR7-induced IFNA1 production
  • TLR7/TLR8 activation in neutrophils impairs immune complex phagocytosis through shedding of FCGR2A
  • critical role of CD180 in regulating TLR7- and TLR9-mediated activation of macrophages and Dendritics cells
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    significantly elevated in Relapsing Remitting Multiple Sclerosis (RRMS) patients than healthy controls
    constitutional       gain of function
    expression of mRNA for TLR7 was up-regulated in pulmonary alveolar macrophages (AMs) during Respiratory syncytial virus (RSV) infection
    Susceptibility to male systemic lupus erythematosus (SLE)
    Variant & Polymorphism SNP association of the TLR7 3&
    8242;UTR SNP rs3853839, that may confer elevated expression of TLR7, with male SLE
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    diabete  
    inhibiting TLR7 suppressed diabetic retinopathy by reducing inflammation
    cancerendocrinepancreas
    activation of TLR7 suppresses the progression of pancreatic cancer
    ANIMAL & CELL MODELS
  • germinal center (GC) B cell response(GC B) in Tlr7-deficient mice proliferated to a lesser extent and had a greater proportion of cells with phenotypic characteristics of light zone, relative to dark zone, GC B cells