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FLASH GENE
Symbol TRPM2 contributors: mct - updated : 20-01-2015
HGNC name transient receptor potential cation channel, subfamily M, member 2
HGNC id 12339
Location 21q22.3      Physical location : 45.773.483 - 45.862.964
Synonym name
  • long transient receptor potential channel 2
  • transient receptor potential channel 7
  • estrogen responsive element associated gene 1
  • transient receptor potential Ca(2+) permeable channel melastatin type 2
  • Synonym symbol(s) KNP3, LTPCR2, TRPC7, EREG1, MGC133383, NUDT9H, NUDT9L1
    EC.number EC 3.6.1.13
    DNA
    TYPE functioning gene
    STRUCTURE 92.92 kb     32 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked Y status provisional
    Physical map
    C21orf124 21q22.3 chromosome 21 open reading frame 124 C21orf97 21q22.3 chromosome 21 open reading frame 97 CSTB 21q22.3 cystatin B (stefin B) D21S2056E 21q22.3 DNA segment on chromosome 21 (unique) 2056 expressed sequence LOC284837 21q22.3 hypothetical protein LOC284837 MYL6P 21q22.3 myosin, light polypeptide 6, pseudogene AGPAT3 21q22.3 1-acylglycerol-3-phosphate O-acyltransferase 3 TMEM1 21q22.3 transmembrane protein 1 H2AFZP 21q22.3 H2A histone family, member Z, pseudogene PWP2H 21q22.3 PWP2 periodic tryptophan protein homolog (yeast) C21orf33 21q22.3 chromosome 21 open reading frame 33 C21orf32 21q22.3 chromosome 21 open reading frame 32 ICOSL 21q22.3 inducible T-cell co-stimulator ligand DNMT3L 21q22.3 DNA (cytosine-5-)-methyltransferase 3-like AIRE 21q22.3 autoimmune regulator (autoimmune polyendocrinopathy candidiasis ectodermal dystrophy) PFKL 21q22.3 phosphofructokinase, liver C21orf2 21q22.3 chromosome 21 open reading frame 2 TRPM2 21q22.3 transient receptor potential cation channel, subfamily M, member 2 LRRC3 21q22.3 leucine-rich repeat-containing 3 C21orf29 21q22.3 chromosome 21 open reading frame 29 C21orf90 21q22.1 chromosome 21 open reading frame 90 KRTAP10-10 21q22.3 keratin associated protein 10-10 KRTAP12-2 21q22.3 keratin associated protein 12-2 IMMTP 21q22.3 inner membrane protein, mitochondrial (mitofilin) pseudogene KRTAP12-1 21q22.3 keratin associated protein 12-1 UBE2G2 21q22.3 ubiquitin-conjugating enzyme E2G 2 (UBC7 homolog, yeast) SMT3H1 21q22.3 SMT3 suppressor of mif two 3 homolog 1 (yeast) PTTG1IP 21q22.3 pituitary tumor-transforming 1 interacting protein ITGB2 21q22.3 integrin, beta 2 (antigen CD18 (p95), lymphocyte function-associated antigen 1; macrophage antigen 1 (mac-1) beta subunit)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    32 - 5876 - 1503 expressed in various tissues, significantly increased in neuroblastoma compared with adrenal gland 2013 23302782
  • TRPM2 lf, TRPM2L
  • N-terminal 214 AAs are removed
  • start from a novel 5' non-coding exon
  • - - 5227 - 1289 detected only in striatum (caudate nucleus and putamen) 2013 23302782
  • transcribed from the intron 4 of the TRPM2 gene
  • still maintained H2(O2)-induced Ca2+ influx activity
  • - - - - - significantly increased in neuroblastoma compared with adrenal gland 2013 23302782
  • basally associated with TRPM2 in the endothelial plasmalemma, and this interaction functioned to suppress TRPM2-dependent Ca2+ gating constitutively
  • EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart     Homo sapiens
    Digestiveliver     Homo sapiens
    Lymphoid/Immunespleen     Homo sapiens
    Nervousbrainbasal nucleicaudate nucleus highly Homo sapiens
     brainbasal nucleiputamen   Homo sapiens
     brainlimbic systemhippocampus   Homo sapiens
    Respiratorylung   highly Homo sapiens
    Urinarykidneytubuleconvoluted tubuleproximal tubulehighly Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow    Homo sapiens
    Muscularstriatumcardiac   Homo sapiens
    Nervouscentral    Homo sapiens
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticmonocyte Homo sapiens
    Blood/Hematopoieticneutrophil Homo sapiens
    Endocrineislet cell (alpha,beta...) Homo sapiens
    Lymphoid/Immunemacrophage Homo sapiens
    Muscularmyocyte Homo sapiens
    Nervousglia Homo sapiens
    Nervousneuron Homo sapiens
    Nervouspyramidal cell Homo sapiens
    cell lineage
    cell lines monocyte cell line HEK293
    fluid/secretion
    at STAGE
    physiological period fetal
    Text brain
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • two coiled-coil (CC) domains, one in the N-terminus required for protein expression and function, and the other in the C-terminus, playing an important, but not exclusive, role in the TRPM2 channel assembly
  • seven putative transmembrane domains protein
  • a highly conserved TRP (EWKFHR) domain and a nudix NUDT9 (nucleoside diphosphate linked moiety X-type motif 9) homology domain near the C terminus
  • a N-x-x-D motif playing specific roles in TRPM8 and TRPM2, reflecting different requirements for voltage-dependent and voltage-independent channel gating
  • seven predicted membrane-spanning domain
  • C terminal MutT motif
  • mono polymer homomer , heteromer , tetramer
    HOMOLOGY
    interspecies homolog to Drosophila store-operated channel (Soc)
    homolog to murine Trrp7
    intraspecies homolog to TRPC1
    Homologene
    FAMILY
  • TRP superfamily of Ca2+ cation channels, subfamily
  • melastatin subfamily of the mammalian transient receptor potential (TRP)2 proteins
  • CATEGORY receptor , transport channel
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,lysosome
    text
  • found in lysosomal membranes
  • basic FUNCTION
  • permeable non selective cation channel, enabling Ca2+ influx into cells
  • TRPM2-mediated Ca2+ influx induces chemokine production in monocytes that aggravates inflammatory neutrophil infiltration
  • mediates nuclear translocation of NFKB, and amplifies Erk signal via Pyk2 and Ras activation
  • implicated in cell death induced by oxidants
  • required for lipopolysaccharide-induced cytokine production in monocytes
  • essential for prostate cancer cell proliferation
  • fulfills an important role in oxidative stress signaling in immune and other cells, to which local extracellular acidosis is known to occur under physiological or pathological conditions and impose significant effects on their functions
  • calcium-permeable non-selective cation channel critically involved in aggravating reactive oxygen species (ROS)-induced inflammatory processes and has been implicated in cell death
  • TRPM2, TRPM4 and TRPM5 control insulin secretion levels by sensing intracellular Ca2+ increase, NAD metabolites, or hormone receptor activation
  • redox-sensitive channel, mediating cell death
  • imbalance of TRPM2 channel activity caused by excess copper or ROS may be one of the pathophysiological mechanisms for disruption of Ca2+ homeostasis in diabetes and neurodegenerative disorders
  • extracellular acidity limits Ca2+ influx through TRPM2 by driving the channels into a conformation similar to the C-type inactivated state
  • TRPM2 channels occupy a key role in cell proliferation and survival following oxidative stress in neuroblastoma
  • role of TRPM2 and TRPV1 cation channels in cellular responses to radiation-induced DNA damage
  • key factor that links oxidative stress to the NLRP3 inflammasome activation
  • crucial role of a positively charged amino acid residue at position 1110 for TRPM2 channel activity
  • TRPM2 channels protect the heart from ischemia/reperfusion (I/R) injury by ameliorating mitochondrial dysfunction and reducing reactive oxygen species levels
  • its activity is required for immune cell activation and insulin secretion and is responsible for postischemic neuronal cell death
  • is a simple ligand-gated channel that obeys an equilibrium gating mechanism uncoupled from its enzymatic activity
  • TRPM2 channel limits oxidative stress and preserves mitochondrial function
  • cardiac TRPM2-mediated Ca2+ influx is necessary to maintain mitochondrial function and protect against hypoxia-reoxygenation (H/R) injury
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    text calcium ion transport
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
  • Cu2+ is a potent TRPM2 channel blocker
  • protein
  • its activity could be modulated by certain pathological factors related to the diseases, such as Cu2+ that plays an important role in regulating oxidative status in a cell
  • cooperative interaction of trp melastatin channel transient receptor potential (TRPM2) with its splice variant TRPM2 short variant is essential for endothelial cell apoptosis
  • TRPM2-dependent RAC1 activation increases oxidant stress
  • cell & other
    REGULATION
    activated by nicotinamide adenine dinucleotide
    specifically activated by adenosine diphosphoribose (ADPR)
    by irradiation, via PARP1 activation, and contributes to irreversible loss of salivary gland function
    inhibited by intracellular adenosine trisphosphate
    Other adenosine 5'-diphosphoribose (ADPR)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
  • to bipolar diasease
  • to amyotrophic lateral sclerosis (ALS) and parkinsonism–dementia (PD)
  • Variant & Polymorphism other
  • variant increasing the risk of bipolar diasease
  • missense change in the channel protein, P1018L inactivate the ability of TRPM2 to maintain sustained ion influx is a physiologically important function and that its disruption may, under certain conditions, contribute to disease states (ALS and PD)
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerreproductiveprostate
    may be a potential target for the selective treatment of prostate cancer
    immunologyinflammatory 
    functional inhibition of TRPM2 channels is a new therapeutic strategy for treating inflammatory diseases
    miscelleaneousurinary 
    therapeutic approaches targeting TRPM2 and/or RAC1 may be effective in reducing ischemic kidney injury
    cancer  
    TRPM2 channels may represent a novel future therapeutic target in diseases involving oxidative stress
    ANIMAL & CELL MODELS
  • Trpm2-deficient mice were resistant to ischemic injury, as reflected by improved kidney function, reduced histologic damage, suppression of proapoptotic pathways, and reduced inflammation
  • neurons isolated from the brain of Trpm2-deficient mice have significantly longer neurites with a greater number of spines than those obtained from the brain of wild-type mice