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FLASH GENE
Symbol TLR2 contributors: mct/npt - updated : 20-04-2016
HGNC name toll-like receptor 2
HGNC id 11848
Location 4q31.3      Physical location : 154.605.440 - 154.627.240
Synonym name
  • toll/interleukin 1 receptor-like 4
  • Drosophila transmembrane receptor Toll homolog 2
  • CD282 antigen
  • Synonym symbol(s) TIL4, CD282
    DNA
    TYPE functioning gene
    STRUCTURE 21.80 kb     3 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Physical map
    LOC283341 4q31.23 similar to Adenylate kinase isoenzyme 4, mitochondrial (ATP-AMP transphosphorylase) RPS3A 4q31.2-q31.3 ribosomal protein S3A U73B 4q31.2-q31.3 RNA, U73B small nucleolar DKFZp434D0215 4q31.23 SH3 domain protein D19 LOC391704 4 similar to Prss32 protein ESSPL 4q31.23 epidermis-specific serine protease-like protein LOC391705 4 similar to RIKEN cDNA 9930021J17 PET112L 4q27-q28 PET112-like (yeast) LOC389232 4 LOC389232 LOC389233 4 LOC389233 FBXW7 4q31.23 F-box and WD-40 domain protein 7 (archipelago homolog, Drosophila) LOC391706 4 similar to ribosomal protein S3a; 40S ribosomal protein S3a; v-fos transformation effector protein 1 FLJ32028 4q31.3 hypothetical protein FLJ32028 TIGD4 4q31.23 tigger transposable element derived 4 ARFIP1 4q31.3 ADP-ribosylation factor interacting protein 1 (arfaptin 1) LOC152667 4q31.3 similar to NEFA-interacting nuclear protein NIP30 KIAA1727 4q31.3 KIAA1727 protein LOC389234 4 LOC389234 TRIM2 4q31.3 tripartite motif-containing 2 ANXA2P1 4q21-q31 annexin A2 pseudogene 1 GAJ 4q31.3 GAJ protein KIAA0922 4q31.23 GAJ protein LOC285532 4q31.3 similar to JM5 protein TLR2 4q32 toll-like receptor 2 LOC285533 4q31.3 hypothetical protein LOC285533 SFRP2 4q31.3 secreted frizzled-related protein 2 FLJ20047 4q31.3 hypothetical protein FLJ20047 LOC389235 4 similar to protocadherin 16 precursor; fibroblast cadherin FIB1; fibroblast cadherin 1; dachsous homologue PLRG1 4q31.2-q32.1 pleiotropic regulator 1 (PRL1homolog, Arabidopsis) FGB 4q28 fibrinogen, B beta polypeptide FGA 4q28 fibrinogen, A alpha polypeptide FGG 4q28 fibrinogen, G gamma polypeptide LRAT 4q31.1-q31.23 lecithin retinol acyltransferase (phosphatidylcholine--retinol O-acyltransferase) MGC27016 4q31.3 hypothetical protein MGC27016 LOC389236 4 LOC389236 NPY2R 4q31 neuropeptide Y receptor Y2 LOC389237 4 LOC389237 FLJ21159 4q31.3 hypothetical protein FLJ21159 GUCY1A3 4q31.1-q31.2 guanylate cyclase 1, soluble, alpha 3 GUCY1B3 4q31.3-q33 guanylate cyclase 1, soluble, beta 3 ACCN5 4q31.3-q32 amiloride-sensitive cation channel 5, intestinal TDO2 4q31-q32 tryptophan 2,3-dioxygenase CTSO 4q31-q32 cathepsin O FTHP2 4q31-q32 ferritin, heavy polypeptide pseudogene 2
    RNA
    TRANSCRIPTS type messenger
    text with two alternatively spliced variants, one expressed in lung, the other in heart, brain, muscle (Rock)
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    3 - 3417 - 784 - 1998 9435236
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Reproductivefemale systemovary  highly Homo sapiens
    Respiratoryrespiratory tracttrachea  highly
    Skin/Tegumentskin     Homo sapiensFetal
    Urinarybladder   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticmonocyte
    Reproductiveepithelial cell Homo sapiens
    cell lineage myelomonocytic cells, dendritic cell precursors
    cell lines in benign conditions, epithelial tumors, and in ovarian cancer cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • an extracellular part composed of 19 leucine-rich repeats (LRR)
  • a cysteine rich region
  • a transmembrane segment
  • a cytoplasmic domain, the TolN homology domain (TH), common to the Toll and IL1 receptor genes (also called TIR domain, Toll/Interleukin-1 receptor playing an important role in innate host defense signaling)
  • HOMOLOGY
    interspecies homolog to Drosophila transmembrane receptor Toll,2
    Homologene
    FAMILY
  • Toll-like receptor family
  • CATEGORY immunity/defense , receptor membrane
    SUBCELLULAR LOCALIZATION     plasma membrane
    text
  • TLR1, TLR2, TLR6, and TLR10 are displayed on the plasma membrane where they are best available to contact bacterial and fungal cell wall constituents
  • basic FUNCTION
  • plays a central role for the response to a wide variety of microbial and endogenous danger signals
  • involved in innate immunity through the recruitment of MYD88
  • mediator of liposaccharide (LPS) induced response against Gram positive bacteria
  • significant role for in the occurrence of leprosy reversal reaction
  • can contribute to atherogenesis through transduction of inflammatory signals
  • role for TLR2 in atherosclerosis induced by atherogenic lipoproteins
  • as others Toll-like receptor (TLR), its stimulation plays a crucial role in the homeostasis of human B cells
  • initiates potent immune responses by recognizing diacylated and triacylated lipopeptides
  • key immune receptor in TLRs family with a large repertoire of ligands
  • required for morphine-induced neuronal cell death and apoptosis
  • TLR1, TLR2, TLR6, and TLR10, mediates immune responses to a variety of microbial cell wall components including lipoproteins and glycolipids
  • TLR2 has dual immune functions in the gut and TLR1 is a critical innate receptor for protective intestinal T(H)17 immunity
  • TLR1, when dimerized with TLR2, is a cell surface receptor that, upon recognition of bacterial lipoproteins, activates the innate immune system
  • TLR1, TLR2 and TLR6 were expressed on the surface of B cells, monocytes and dendritic cells in a manner dependent on TLR-specific chaperone CNPY3
  • lipopeptides elicit TLR1/2 and TLR2/6 signaling in the endolysosomes, but not on the cell surface
  • CELLULAR PROCESS cell life, cell death/apoptosis
    PHYSIOLOGICAL PROCESS immunity/defense
    text apoptosis of infected cells, pathogen recognition
    PATHWAY
    metabolism
    signaling signal transduction
    NF-kappa B signaling pathway, stress activated MAP kinase p38 pathway
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • activating NFkappa B in response to Gram+ bacteria
  • interaction with CD14 through the extracellular Toll-like receptor 2 domain
  • TLR4 requires myeloid differentiation (LY96), and both TLR2 and TLR4 signal need myeloid differentiation factor (MYD88)
  • RGS2 inhibits STAT3-mediated NOX1 transcription, and can itself be repressed by TLR2
  • MAP2K1 negatively regulates TLR2 signaling in endothelial cell, MAP2K1 promotes TLR2 signaling in monocytes
  • NOD1 cooperates with TLR2 to enhance T cell receptor-mediated activation in CD8 T cells
  • activation of PRKCH and PLD2 signaling pathway is an important mechanism for regulation of TLR2-induced ABCA1 expression
  • activation of TLR2 in the skin by commensal microbial products prevents excessive inflammation by blocking downstream TLR3 signaling
  • TICAM2 is required for the TLR2-dependent movement of MYD88 to endosomes following ligand engagement
  • MAPK7 mediates proinflammatory responses in primary human cells in response to stimulation of TLR2
  • PRG4 binds to TLR2 and TLR4 and this binding mediates a novel anti-inflammatory role for PRG4
  • activation of human mast cells by CAMP could be modified by TLR2 ligands and the function of human mast cells could be switched from allergic reactions to innate immune response
  • activation of TLR2 stimulates foam cell formation, which is a key early event in the process of atherosclerosis
  • CSF3 downregulates TLR1, TLR2 and TLR4 in a time- and dose-dependent fashion in human monocytes
  • critical role of SPI1 in the regulation of TLR1, 2, 4 and of CD14
  • cell & other
    REGULATION
    activated by MYD88
    induced by by inflammatory stimuli in alveolar macrophages in response to lipopolysaccharide (LPS), interleukin (IL)-1beta, or tumor necrosis factor-alpha
    hypoxia (coordinated induction of TLR2 and TLR6 during hypoxia suggesting tissue hypoxia in transcriptional adaptation of innate immune responses during acute infection or inflammation)
    Other recruited to macrophage phagosome in association with TLR6 where they recognize peptidoglycan, a gram+ pathogen component
    negative role of IMPDH2 in TLR2 signaling
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       loss of function
    is capable of preventing opioids-induced damage to neurons
    Susceptibility
  • to colorectal cancer
  • to leprosy (OMIM 246300)
  • to acute rheumatic fever(ARF)
  • to tuberculosis
  • Variant & Polymorphism SNP , insertion/deletion , other
  • GT polymorphism associated with colorectal cancer
  • Arg753Arg genotype was significantly decreased in the entire group of ARF cases (protecting against ARF)
  • SNP Arg753Gln increasing the risk for the development of tuberculosis
  • Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS