Genomes and Genes
Summary: A calcium-activated enzyme that catalyzes the hydrolysis of ATP to yield AMP and orthophosphate. It can also act on ADP and other nucleoside triphosphates and diphosphates. EC 126.96.36.199.
- Clark G, Wu M, Wat N, Onyirimba J, Pham T, Herz N, et al. Both the stimulation and inhibition of root hair growth induced by extracellular nucleotides in Arabidopsis are mediated by nitric oxide and reactive oxygen species. Plant Mol Biol. 2010;74:423-35 pubmed publisher..Two mammalian purinoceptor antagonists also blocked the growth responses induced by extracellular nucleotides, suggesting that they were initiated by a receptor-based mechanism. ..
- Hart M, Gorzolla I, Schittenhelm J, Robson S, Eltzschig H. SP1-dependent induction of CD39 facilitates hepatic ischemic preconditioning. J Immunol. 2010;184:4017-24 pubmed publisher..Therapeutic studies to mimic IP with i.p. apyrase (a soluble ectonucleoside triphosphate diphosphohydrolase, NTPDase) in the absence of IP attenuated hepatic ..
- Clark G, Torres J, Finlayson S, Guan X, Handley C, Lee J, et al. Apyrase (nucleoside triphosphate-diphosphohydrolase) and extracellular nucleotides regulate cotton fiber elongation in cultured ovules. Plant Physiol. 2010;152:1073-83 pubmed publisher..release ATP as they grow, and when their ectoapyrase activity is blocked by the addition of polyclonal anti-apyrase antibodies or by two different small molecule inhibitors, the medium ATP level rises and fiber growth is ..
- Rajakumar S, Lu B, Crikis S, Robson S, d Apice A, Cowan P, et al. Deficiency or inhibition of CD73 protects in mild kidney ischemia-reperfusion injury. Transplantation. 2010;90:1260-4 pubmed publisher..Investigating the mechanisms by which AMP mediates protection may lead to new targets for research in kidney IRI. ..
- García Hernández M, Portales Cervantes L, Cortez Espinosa N, Vargas Morales J, Fritche Salazar J, Rivera López E, et al. Expression and function of P2X(7) receptor and CD39/Entpd1 in patients with type 2 diabetes and their association with biochemical parameters. Cell Immunol. 2011;269:135-43 pubmed publisher..Therefore, CD39(+) cells could have a balancing regulatory role in the inflammatory process observed in patients with T2D. ..
- Nilsson P, Engberg A, Bäck J, Faxälv L, Lindahl T, Nilsson B, et al. The creation of an antithrombotic surface by apyrase immobilization. Biomaterials. 2010;31:4484-91 pubmed publisher..The goal of this study was to immobilize apyrase on a biomaterial surface in order to develop an enzymatically active surface that would have the capacity to ..
- Mandapathil M, Hilldorfer B, Szczepanski M, Czystowska M, Szajnik M, Ren J, et al. Generation and accumulation of immunosuppressive adenosine by human CD4+CD25highFOXP3+ regulatory T cells. J Biol Chem. 2010;285:7176-86 pubmed publisher..The data suggest that the adenosinergic pathway represents a potential therapeutic target for regulation of immunosuppression in a broad variety of human diseases. ..
- Pinheiro C, Martins Duarte E, Ferraro R, Fonseca de Souza A, Gomes M, Lopes A, et al. Leishmania amazonensis: Biological and biochemical characterization of ecto-nucleoside triphosphate diphosphohydrolase activities. Exp Parasitol. 2006;114:16-25 pubmed..amazonensis ecto-NTPDase expression. Also, adenosine and anti-NTPDase antibodies induced a significant diminishing in the interaction between promastigotes of L. amazonensis and mouse peritoneal macrophages. ..
- Morrone F, Oliveira D, Gamermann P, Stella J, Wofchuk S, Wink M, et al. In vivo glioblastoma growth is reduced by apyrase activity in a rat glioma model. BMC Cancer. 2006;6:226 pubmed..To deplete the extracellular ATP, the enzyme apyrase was tested on the treatment of gliomas implanted in the rats CNS...
- Deaglio S, Dwyer K, Gao W, Friedman D, Usheva A, Erat A, et al. Adenosine generation catalyzed by CD39 and CD73 expressed on regulatory T cells mediates immune suppression. J Exp Med. 2007;204:1257-65 pubmed..We conclude that CD39 and CD73 are surface markers of T reg cells that impart a specific biochemical signature characterized by adenosine generation that has functional relevance for cellular immunoregulation. ..
- Friedman D, Talbert M, Bowden D, Freedman B, Mukanya Y, Enjyoji K, et al. Functional ENTPD1 polymorphisms in African Americans with diabetes and end-stage renal disease. Diabetes. 2009;58:999-1006 pubmed publisher..Studies in human cell lines and in vivo mouse data support a potential role for ENTPD1 genetic variation in susceptibility to type 2 diabetes. ..
- Santos R, Pôssa M, Bastos M, Guedes P, Almeida M, DeMarco R, et al. Influence of Ecto-nucleoside triphosphate diphosphohydrolase activity on Trypanosoma cruzi infectivity and virulence. PLoS Negl Trop Dis. 2009;3:e387 pubmed publisher..Our results suggest that Ecto-ATPDases act as facilitators of infection and virulence in vitro and in vivo and emerge as target candidates in chemotherapy of Chagas disease. ..
- Visovatti S, Hyman M, Bouïs D, Neubig R, McLaughlin V, Pinsky D. Increased CD39 nucleotidase activity on microparticles from patients with idiopathic pulmonary arterial hypertension. PLoS ONE. 2012;7:e40829 pubmed publisher..Further research is needed to elucidate whether these findings identify an important trigger for the development of the disease, or reflect a physiologic response to IPAH. ..
- Liao H, Hyman M, Baek A, Fukase K, Pinsky D. cAMP/CREB-mediated transcriptional regulation of ectonucleoside triphosphate diphosphohydrolase 1 (CD39) expression. J Biol Chem. 2010;285:14791-805 pubmed publisher..These data identify cAMP as a crucial regulator of macrophage CD39 expression and demonstrate that cAMP acts through the PKA/CREB, PKA/PI3K/ATF2, and PKA/ERK/ATF2 pathways to control a key vascular homeostatic mediator. ..
- Pulte E, Broekman M, Olson K, Drosopoulos J, Kizer J, Islam N, et al. CD39/NTPDase-1 activity and expression in normal leukocytes. Thromb Res. 2007;121:309-17 pubmed..We conclude that CD39 activity and expression are present to varying degrees on all leukocytes types examined. Differences between leukocyte types should be considered when examining CD39 in disease states. ..
- Ndhlovu L, Leal F, Eccles James I, Jha A, Lanteri M, Norris P, et al. A novel human CD4+ T-cell inducer subset with potent immunostimulatory properties. Eur J Immunol. 2010;40:134-41 pubmed publisher..We propose that this novel CD4+ T-cell population counterbalances the suppressive activity of suppressor Treg in peripheral blood and serves as a calibrator of immunoregulation. ..
- Lu B, Rajakumar S, Robson S, Lee E, Crikis S, d Apice A, et al. The impact of purinergic signaling on renal ischemia-reperfusion injury. Transplantation. 2008;86:1707-12 pubmed publisher..Deletion of CD39 was associated with severe renal injury. Administration of apyrase, a soluble form of CD39, decreased global apoptosis and I/RI induced renal injury in wild-type mice...
- Dwyer K, Mysore T, Crikis S, Robson S, Nandurkar H, Cowan P, et al. The transgenic expression of human CD39 on murine islets inhibits clotting of human blood. Transplantation. 2006;82:428-32 pubmed..These results suggest that transgenic expression of human CD39 does not interfere with islet function and may be a useful strategy to inhibit thrombosis induced by intraportal administration of islet xenografts. ..
- Banz Y, Beldi G, Wu Y, Atkinson B, Usheva A, Robson S. CD39 is incorporated into plasma microparticles where it maintains functional properties and impacts endothelial activation. Br J Haematol. 2008;142:627-37 pubmed publisher..Our data also suggest a modulatory role for CD39 within MP in the exchange of regulatory signals between leucocytes and vascular cells. ..
- Corriden R, Chen Y, Inoue Y, Beldi G, Robson S, Insel P, et al. Ecto-nucleoside triphosphate diphosphohydrolase 1 (E-NTPDase1/CD39) regulates neutrophil chemotaxis by hydrolyzing released ATP to adenosine. J Biol Chem. 2008;283:28480-6 pubmed publisher..Thus, E-NTPDase1 plays an important role in regulating neutrophil chemotaxis by facilitating the hydrolysis of extracellular ATP. ..
- Salcido Ochoa F, Tsang J, Tam P, Falk K, Rotzschke O. Regulatory T cells in transplantation: does extracellular adenosine triphosphate metabolism through CD39 play a crucial role?. Transplant Rev (Orlando). 2010;24:52-66 pubmed publisher..This is a comprehensive review on the fundamentals of Treg biology, the potential role of ATP metabolism in immunoregulation, and the potential use of Treg-based immunotherapy in transplantation. ..
- Sansom F, Newton H, Crikis S, Cianciotto N, Cowan P, d Apice A, et al. A bacterial ecto-triphosphate diphosphohydrolase similar to human CD39 is essential for intracellular multiplication of Legionella pneumophila. Cell Microbiol. 2007;9:1922-35 pubmed..The predicted products possess five apyrase conserved domains that are typical of eukaryotic ecto-NTPDases...
- Crikis S, Lu B, Murray Segal L, Selan C, Robson S, d Apice A, et al. Transgenic overexpression of CD39 protects against renal ischemia-reperfusion and transplant vascular injury. Am J Transplant. 2010;10:2586-95 pubmed publisher..Thus, systemic or local strategies to promote adenosine generation and signaling may have beneficial effects on warm and cold renal IRI, with implications for therapeutic application in clinical renal transplantation. ..
- Schulze zur Wiesch J, Thomssen A, Hartjen P, Tóth I, Lehmann C, Meyer Olson D, et al. Comprehensive analysis of frequency and phenotype of T regulatory cells in HIV infection: CD39 expression of FoxP3+ T regulatory cells correlates with progressive disease. J Virol. 2011;85:1287-97 pubmed publisher..The data presented here reconcile the seemingly contradictory results of previous studies looking at Tregs in HIV and highlight the complexity of Treg-mediated immunoregulation during human viral infections. ..
- Uluçkan O, Eagleton M, Floyd D, Morgan E, Hirbe A, Kramer M, et al. APT102, a novel adpase, cooperates with aspirin to disrupt bone metastasis in mice. J Cell Biochem. 2008;104:1311-23 pubmed publisher..We examined the role of a novel soluble apyrase/ADPase, APT102, and an inhibitor of TXA(2) synthesis, acetylsalicylic acid (aspirin or ASA), in mouse models of ..
- Borsellino G, Kleinewietfeld M, Di Mitri D, Sternjak A, Diamantini A, Giometto R, et al. Expression of ectonucleotidase CD39 by Foxp3+ Treg cells: hydrolysis of extracellular ATP and immune suppression. Blood. 2007;110:1225-32 pubmed..Thus, in humans CD39 is a marker of a Treg subset likely involved in the control of the inflammatory autoimmune disease. ..
- Friedman D, Rennke H, Csizmadia E, Enjyoji K, Robson S. The vascular ectonucleotidase ENTPD1 is a novel renoprotective factor in diabetic nephropathy. Diabetes. 2007;56:2371-9 pubmed..We conclude that ENTPD1 is a vascular protective factor in diabetic nephropathy that modulates glomerular inflammation and thromboregulation. ..
- Sun D, McNicol A, James A, Peng Z. Expression of functional recombinant mosquito salivary apyrase: a potential therapeutic platelet aggregation inhibitor. Platelets. 2006;17:178-84 pubmed..b>Apyrase, an ecto-enzyme with ADPase and ATPase activities, rapidly metabolizes ADP and ATP released from platelets and ..
- Kozakiewicz A, Neumann P, Banach M, Komoszyński M, Wojtczak A. Modeling studies of potato nucleoside triphosphate diphosphohydrolase NTPDase1: an insight into the catalytic mechanism. Acta Biochim Pol. 2008;55:141-50 pubmedNucleoside triphosphate diphosphohydrolase--NTPDase1 (apyrase, EC 188.8.131.52) was modeled based on sequence homology. The single polypeptide chain of apyrase is folded into two domains...
- Zebisch M, Strater N. Characterization of Rat NTPDase1, -2, and -3 ectodomains refolded from bacterial inclusion bodies. Biochemistry. 2007;46:11945-56 pubmed..The presented expression system will allow large scale production of active protein suitable for structural studies, development of inhibitors, and even clinical application. ..
- Sansom F, Riedmaier P, Newton H, Dunstone M, Muller C, Stephan H, et al. Enzymatic properties of an ecto-nucleoside triphosphate diphosphohydrolase from Legionella pneumophila: substrate specificity and requirement for virulence. J Biol Chem. 2008;283:12909-18 pubmed publisher..first prokaryotic member of the CD39/NTPDase1 family of enzymes, which are characterized by the presence of five apyrase conserved regions and the ability to hydrolyze nucleoside tri- and diphosphates...
- Clark G, Fraley D, Steinebrunner I, Cervantes A, Onyirimba J, Liu A, et al. Extracellular nucleotides and apyrases regulate stomatal aperture in Arabidopsis. Plant Physiol. 2011;156:1740-53 pubmed publisherThis study investigates the role of extracellular nucleotides and apyrase enzymes in regulating stomatal aperture...
- Martín Martín I, Molina R, Jimenez M. Molecular and immunogenic properties of apyrase SP01B and D7-related SP04 recombinant salivary proteins of Phlebotomus perniciosus from Madrid, Spain. Biomed Res Int. 2013;2013:526069 pubmed publisher..The apyrase SP01B and the D7-related protein SP04 were successfully cloned, expressed in Escherichia coli, and purified...
- Sugimoto S, Lin X, Lai J, Okazaki M, Das N, Li W, et al. Apyrase treatment prevents ischemia-reperfusion injury in rat lung isografts. J Thorac Cardiovasc Surg. 2009;138:752-9 pubmed publisherEndothelial cells express the ectoenzyme ectonucleoside adenosine triphosphate diphosphohydrolase, an apyrase that inhibits vascular inflammation by catalyzing the hydrolysis of adenosine triphosphate and adenosine diphosphate...
- Stutzer C, Mans B, Gaspar A, Neitz A, Maritz Olivier C. Ornithodoros savignyi: soft tick apyrase belongs to the 5'-nucleotidase family. Exp Parasitol. 2009;122:318-27 pubmed publisher..Cross-reactivity was demonstrated with polyclonal anti-apyrase antisera produced against O. savignyi apyrase. Subsequent Edman sequencing and MS/MS analysis of purified O...
- Uccelletti D, Pascoli A, Farina F, Alberti A, Mancini P, Hirschberg C, et al. APY-1, a novel Caenorhabditis elegans apyrase involved in unfolded protein response signalling and stress responses. Mol Biol Cell. 2008;19:1337-45 pubmed publisher..We report here that a UDP/GDPase, homologous to the human apyrase Scan-1, is present in the membranes of Caenorhabditis elegans, encoded by the ORF F08C6...
- Friedman D, Künzli B, A Rahim Y, Sevigny J, Berberat P, Enjyoji K, et al. From the Cover: CD39 deletion exacerbates experimental murine colitis and human polymorphisms increase susceptibility to inflammatory bowel disease. Proc Natl Acad Sci U S A. 2009;106:16788-93 pubmed publisher..005-0.0006). Our data indicate that CD39 deficiency exacerbates murine colitis and suggest that CD39 polymorphisms are associated with inflammatory bowel disease in humans. ..
- Okuhata R, Takishima T, Nishimura N, Ueda S, Tsuchiya T, Kanzawa N. Purification and biochemical characterization of a novel ecto-apyrase, MP67, from Mimosa pudica. Plant Physiol. 2011;157:464-75 pubmed publisherWe have previously reported the presence of an apyrase in Mimosa pudica. However, only limited information is available for this enzyme. Thus, in this study, the apyrase was purified to homogeneity...
- Schiller M, Massalski C, Kurth T, Steinebrunner I. The Arabidopsis apyrase AtAPY1 is localized in the Golgi instead of the extracellular space. BMC Plant Biol. 2012;12:123 pubmed publisher..The subcellular localization of AtAPY1 was investigated to corroborate an extracellular function...
- Bastid J, Cottalorda Regairaz A, Alberici G, Bonnefoy N, Eliaou J, Bensussan A. ENTPD1/CD39 is a promising therapeutic target in oncology. Oncogene. 2013;32:1743-51 pubmed publisher..Indeed, CD39 antagonistic antibodies could represent novel therapeutic tools for selectively inhibiting Treg function without depletion, a major limitation of current Treg-targeting strategies. ..
- Govindarajulu M, Kim S, Libault M, Berg R, Tanaka K, Stacey G, et al. GS52 ecto-apyrase plays a critical role during soybean nodulation. Plant Physiol. 2009;149:994-1004 pubmed publisher..GS52, a soybean (Glycine soja) ecto-apyrase, was previously shown to be induced very early in response to inoculation with the symbiotic bacterium ..
- Enjyoji K, Kotani K, Thukral C, Blumel B, Sun X, Wu Y, et al. Deletion of cd39/entpd1 results in hepatic insulin resistance. Diabetes. 2008;57:2311-20 pubmed publisher..Extracellular nucleotides serve as "metabolokines," indicating further links between inflammation and associated metabolic derangements. ..
- Riewe D, Grosman L, Fernie A, Wucke C, Geigenberger P. The potato-specific apyrase is apoplastically localized and has influence on gene expression, growth, and development. Plant Physiol. 2008;147:1092-109 pubmed publisher..we used reverse genetic and biochemical approaches to investigate the role of potato (Solanum tuberosum)-specific apyrase. Silencing of the apyrase gene family with RNA interference constructs under the control of the constitutive 35S ..
- Grenz A, Zhang H, Hermes M, Eckle T, Klingel K, Huang D, et al. Contribution of E-NTPDase1 (CD39) to renal protection from ischemia-reperfusion injury. FASEB J. 2007;21:2863-73 pubmed..Furthermore, administration of apyrase reconstituted renal protection by IP in cd39-/- mice...
- Moncrieffe H, Nistala K, Kamhieh Y, Evans J, Eddaoudi A, Eaton S, et al. High expression of the ectonucleotidase CD39 on T cells from the inflamed site identifies two distinct populations, one regulatory and one memory T cell population. J Immunol. 2010;185:134-43 pubmed publisher..Our data suggest that in human CD4(+) T cells from the inflamed site, CD39 can be highly expressed on two populations, one regulatory and the other of a memory phenotype. ..
- Eltzschig H, Kohler D, Eckle T, Kong T, Robson S, Colgan S. Central role of Sp1-regulated CD39 in hypoxia/ischemia protection. Blood. 2009;113:224-32 pubmed publisher..In summary, these results identify a novel Sp1-dependent regulatory pathway for CD39 and indicate the likelihood that CD39 is central to protective responses to hypoxia/ischemia. ..
- Hyman M, Petrovic Djergovic D, Visovatti S, Liao H, Yanamadala S, Bouïs D, et al. Self-regulation of inflammatory cell trafficking in mice by the leukocyte surface apyrase CD39. J Clin Invest. 2009;119:1136-49 pubmed publisher..Bone marrow reconstitution and provision of an apyrase, an enzyme that hydrolyzes nucleoside tri- and diphosphates, each normalized ischemic leukosequestration and ..
- Wu J, Steinebrunner I, Sun Y, Butterfield T, Torres J, Arnold D, et al. Apyrases (nucleoside triphosphate-diphosphohydrolases) play a key role in growth control in Arabidopsis. Plant Physiol. 2007;144:961-75 pubmedExpression of two Arabidopsis (Arabidopsis thaliana) apyrase (nucleoside triphosphate-diphosphohydrolase) genes with high similarity, APY1 and APY2, was analyzed during seedling development and under different light treatments using beta-..
- Parsons H, Christiansen K, Knierim B, Carroll A, Ito J, Batth T, et al. Isolation and proteomic characterization of the Arabidopsis Golgi defines functional and novel components involved in plant cell wall biosynthesis. Plant Physiol. 2012;159:12-26 pubmed publisher..Overall, these data show key proteins involved in primary cell wall synthesis and include a mixture of well-characterized and unknown proteins whose biological roles and importance as targets for future research can now be realized...
- Eltzschig H, Eckle T, Mager A, Küper N, Karcher C, Weissmüller T, et al. ATP release from activated neutrophils occurs via connexin 43 and modulates adenosine-dependent endothelial cell function. Circ Res. 2006;99:1100-8 pubmed..to adenosine required PMNs, and studies addressing these metabolic steps revealed that PMN express surface ecto-apyrase (CD39)...
- Hamasaki R, Kato H, Terayama Y, Iwata H, Valenzuela J. Functional characterization of a salivary apyrase from the sand fly, Phlebotomus duboscqi, a vector of Leishmania major. J Insect Physiol. 2009;55:1044-9 pubmed publisher..A recombinant P. duboscqi salivary apyrase was expressed in Escherichia coli and purified...
- Abraham E, Sterling K, Kim R, Salikhova A, Huffman H, Crockett M, et al. Erythrocyte membrane ATP binding cassette (ABC) proteins: MRP1 and CFTR as well as CD39 (ecto-apyrase) involved in RBC ATP transport and elevated blood plasma ATP of cystic fibrosis. Blood Cells Mol Dis. 2001;27:165-80 pubmed..Moreover, the presence of different ABC proteins in a single membrane implies that interaction among these proteins and with other membrane proteins may be the norm and not the exception in terms of modulation of their functions...