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FLASH GENE
Symbol ENTPD1 contributors: mct - updated : 05-12-2016
HGNC name ectonucleoside triphosphate diphosphohydrolase 1
HGNC id 3363
Corresponding disease
SPG64 spastic paraplegia 64
Location 10q24.1      Physical location : 97.471.535 - 97.637.022
Synonym name
  • vascular ATP diphosphohydrolase
  • CD39 antigen
  • nucleoside triphosphate diphosphohydrolase (NTPDase)-1
  • cell differentiation antigen CD39, identified by monoclonal antibody B721
  • ecto-ATP diphosphohydrolase
  • ecto-apyrase
  • NTPDase 1
  • Synonym symbol(s) CD39, ATPDase, FLJ40921, FLJ40959, NTPDase-1, DKFZp686D194, DKFZp686I093, SPG64
    EC.number 3.6.1.5
    DNA
    TYPE functioning gene
    SPECIAL FEATURE head to head
    text vascular ATP diphosphohydrolase
    STRUCTURE 165.49 kb     10 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Map see WNT8B
    Physical map
    PLCE1 10q23 phospholipase C, epsilon 1 AD24 10q23.33 AD24 protein KIAA0608 10q23.33 KIAA0608 protein HELLS 10q23-q24 helicase, lymphoid-specific CYP2C18 10q24 cytochrome P450, family 2, subfamily C, polypeptide 18 CYP2C19 10q24 cytochrome P450, family 2, subfamily C, polypeptide 19 CYP2C9 10q24.1 cytochrome P450, family 2, subfamily C, polypeptide 9 CYP2C8 10q23.33 cytochrome P450, family 2, subfamily C, polypeptide 8 LOC387705 10 LOC387705 LOC142827 10q24.1 similar to Hypothetical protein MGC56918 PDLIM1 10q22-q26.3 PDZ and LIM domain 1 (elfin) SORBS1 10q23.3-q24.1 sorbin and SH3 domain containing 1 LOC389999 10 similar to ribosomal protein S3a; 40S ribosomal protein S3a; v-fos transformation effector protein 1 PYCS 10q24.3 pyrroline-5-carboxylate synthetase (glutamate gamma-semialdehyde synthetase) DKFZP564D116 10q24.1 DKFZP564D116 protein ENTPD1 10q24 ectonucleoside triphosphate diphosphohydrolase 1 LOC387706 10 LOC387706 LOC387707 10 similar to RIKEN cDNA 5730509K17 gene FLJ10895 10pter-q26.12 hypothetical protein FLJ10895 KIAA0335 10cen-q26.11 hypothetical protein FLJ10895 LOC387708 10 similar to nucleophosmin 1; nucleolar phosphoprotein B23; numatrin; nucleophosmin/nucleoplasmin family, member 1 BLNK 10q23.2 B-cell linker DNTT 10q24 deoxynucleotidyltransferase, terminal TMEM10 10q23-q24 transmembrane protein 10 TLL2 10q23-q24 tolloid-like 2 SMBP 10q24.2 SM-11044 binding protein PIK3AP1 10q24.2 phosphoinositide-3-kinase adaptor protein 1 LOC283340 10q24.2 similar to ribosomal protein L13a; 60S ribosomal protein L13a; 23 kD highly basic protein LOC387709 10 LOC387709 C10orf12 10q24.2 chromosome 10 open reading frame 12 SLIT1 10q23.3-q24 slit homolog 1 (Drosophila) ARHGAP19 10q24.2 Rho GTPase activating protein 19 FRAT1 10q24.1 frequently rearranged in advanced T-cell lymphomas FRAT2 10q23-q24.1 frequently rearranged in advanced T-cell lymphomas 2 KIAA0690 10q23.33 frequently rearranged in advanced T-cell lymphomas 2 PGAM1 10q25.3 phosphoglycerate mutase 1 (brain) CSL4 10q24 exosomal core protein CSL4 ZDHHC16 10q24.1 zinc finger, DHHC domain containing 16 MMS19L 10q24-q25 MMS19-like (MET18 homolog, S. cerevisiae) FLJ11807 10q24.2 hypothetical protein FLJ11807
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    10 - 12887 - 510 - 2015 26226423
    9 - 12615 - 517 - 2015 26226423
    10 - 12515 - 522 - 2015 26226423
    10 - 12617 - 469 - 2015 26226423
    9 - 12387 - 402 - 2015 26226423
    9 - 12589 - 372 - 2015 26226423
    8 - 12471 - 372 - 2015 26226423
    10 - 12561 - 402 - 2015 26226423
    10 - 2171 - 482 - 2015 26226423
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrineparathyroid   highly
    Hearing/Equilibriumear   highly Homo sapiens
    Reproductivefemale systemplacenta  highly Homo sapiens
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Lymphoid    
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/Immunelymphocyte
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period pregnancy
    Text placenta
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • basic leucine zipper (bZIP) like structure
  • four apyrase conserved regions in N terminal region (ACR)
  • site of binding to RANBP9
  • conjugated GlycoP
    HOMOLOGY
    interspecies homolog to rattus brain E type ecto ATPase
    Homologene
    FAMILY
  • GDA1/CD39 NTPase family
  • ectonucleoside triphosphate diphosphohydrolase (ENTPDase) family
  • CATEGORY adhesion , enzyme , transcription factor , antigen
    SUBCELLULAR LOCALIZATION     plasma membrane
    text
  • localized in caveolae, which are plasma membrane invaginations with distinct lipid composition, similar to dynamic lipid microdomains, called rafts
  • expressed at the sympathetic neuromuscular junction, where ATP is co-released with norepinephrine
  • basic FUNCTION
  • ectoenzyme that degrades ATP to AMP
  • modulating P2 receptor signaling by controlling nucleotides concentrations at the cell surface
  • ecto-nucleotidase influencing P2 receptor activation to regulate vascular and immune cell adhesion and signaling events pivotal in inflammation
  • regulates purinergic receptor signaling by controlling the levels of extracellular nucleotides
  • having a role in thromboregulation (through its localization in cholesterol-rich domains of the membrane)
  • by hydrolyzing ATP and ADP to AMP, regulates ligand availability to a large family of P2 (purinergic) receptors (Friedman 2007)
  • vascular protective factor in diabetic nephropathy that modulates glomerular inflammation and thromboregulation (Friedman 2007)
  • controls IL8 production by human neutrophils via the regulation of P2Y(2) activation
  • has anti-inflammatory properties as it hydrolyzes proinflammatory extracellular ATP, generates anti-inflammatory adenosine, and also protects regulatory T cells from ATP-induced cell death
  • is an integral component of regulatory T cells (Treg), which are central to immunological tolerance and maintenance of normal pregnancy
  • cellular homeostasis and fibrotic response involve the integration of signaling that is pro-fibrotic by ATP and anti-fibrotic by adenosine and that is regulated by ENTPD1 and ENTPD2
  • is a key "molecular switch" that allows macrophages to self-limit their activation state
  • extracellular adenosine, generated in tandem by ecto-enzymes ENTPD1 and NT5E, promotes dermal fibrogenesis
  • ENTPD1 modulates local renin release and thus, RAS activation, ultimately exerting a cardioprotective effect
  • expression of ENTPD1 in Tregs is primarily genetically driven, and this may determine interindividual differences in the control of inflammatory responses
  • marker of regulatory immune cells and catalyzes extracellular hydrolysis of nucleotides to generate AMP and, in tandem with NT5E, adenosine
  • ENTPD1, NT5E are two ectonucleotidases that cooperate in the generation of extracellular adenosine through ATP hydrolysis, thus tilting the balance towards immunosuppressive microenvironments
  • catalyzes the phosphohydrolysis of extracellular ATP (eATP) and ADP (eADP) released under conditions of inflammatory stress and cell injury
  • plays a dominant role in the purinergic regulation of inflammation and the immune response because its expression is influenced by genetic and environmental factors
  • CELLULAR PROCESS cell life, cell death/apoptosis
    nucleotide, transcription
    PHYSIOLOGICAL PROCESS coagulation/hemostasis , immunity/defense
    text prevention of platelet aggregation
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • associations with RANBP9 having the potential to regulate NTPDase catalytic activity( this intermolecular interaction may have important implications for the regulation of extracellular nucleotide-mediated signaling)
  • is a negative regulator of P2RX7-mediated inflammatory cell death in mast cells
  • KLRB1 and ENTPD1 have direct interactions that are further linked with acid sphingomyelinase (ASM)
  • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) SPG64
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    correlated with better long-term survival after tumor resection in patients with pancreatic cancer
    tumoral     --over  
    in malignant epithelial cells of human rectal adenocarcinoma
    Susceptibility
    Variant & Polymorphism
    Candidate gene marker of a Treg subset likely involved in the control of the inflammatory autoimmune disease
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    dermatologyskin 
    biochemical or biological inhibitors of ENTPD1 and/or NT5E may hold promise in the treatment of dermal fibrosis in diseases such as scleroderma
    cancerhemopathy 
    may serve as a future target for the development of novel therapies with immune-modulating antitumor agents in chronic lymphocytic leukemia
    ANIMAL & CELL MODELS
  • Entpd1 null mice exhibit decreased synaptic efficacy, presumably due to desensitization P2X1 receptors
  • in rat models of DNA damage, inhibiting Entpd1-driven ATP hydrolysis with POM-1 protected the heart and lung tissues against chemically induced DNA damage