ENTPD1 explained
Ectonucleoside triphosphate diphosphohydrolase-1 (gene: ENTPD1; protein: NTPDase1) also known as CD39 (Cluster of Differentiation 39), is a typical cell surface enzyme with a catalytic site on the extracellular face.[1] [2] [3]
Function
NTPDase1 is an ectonucleotidase that catalyse the hydrolysis of γ- and β-phosphate residues of triphospho- and diphosphonucleosides to the monophosphonucleoside derivative.[4] [5] NTPDase1 hydrolyzes P2 receptor ligands, namely ATP, ADP, UTP and UDP with similar efficacy.[6] NTPDase1 can therefore affect P2 receptor activation and functions.[7]
Clinical significance
ATP causes a pro-inflammatory environment, whereas degradation of ATP into adenosine by the CD39/CD73 pathway leads to an anti-inflammatory environment.[8] CD39 converts ATP (or ADP) to adenosine monophosphate (AMP), which is converted into adenosine by CD73.[9] A substantial portion of the immune suppressive and anti-inflammatory activity of regulatory T cells (Tregs) is due to the adenosine produced by the CD39/CD73 pathway, insofar as Tregs express CD39 and CD73.
Adenosine produced by the CD39/CD73 pathway can protect against ischemia-reperfusion injury. On the other hand, high expression and activity of CD39 and CD73 on cancer cells can prevent the immune system from inhibiting the progression of cancer.
Biallelic pathogenic variant in ENTPD1 causes autosomal recessive spastic paraplegia 64 (SPG64).[10] [11] SPG64 is a complex hereditary spastic paraplegia characterized by childhood onset progressive spastic paraparesis, delayed developmental milestones, intellectual disability, dysarthria, and white matter abnormalities.
See also
Further reading
- Maliszewski CR, Delespesse GJ, Schoenborn MA, Armitage RJ, Fanslow WC, Nakajima T, Baker E, Sutherland GR, Poindexter K, Birks C . Grant Robert Sutherland . The CD39 lymphoid cell activation antigen. Molecular cloning and structural characterization . Journal of Immunology . 153 . 8 . 3574–83 . Oct 1994 . 10.4049/jimmunol.153.8.3574 . 7930580 . 34664153 .
- Christoforidis S, Papamarcaki T, Galaris D, Kellner R, Tsolas O . Purification and properties of human placental ATP diphosphohydrolase . European Journal of Biochemistry . 234 . 1 . 66–74 . Nov 1995 . 8529670 . 10.1111/j.1432-1033.1995.066_c.x . free .
- Wang TF, Guidotti G . CD39 is an ecto-(Ca2+,Mg2+)-apyrase . The Journal of Biological Chemistry . 271 . 17 . 9898–901 . Apr 1996 . 8626624 . 10.1074/jbc.271.17.9898 . free .
- Kaczmarek E, Koziak K, Sévigny J, Siegel JB, Anrather J, Beaudoin AR, Bach FH, Robson SC . Identification and characterization of CD39/vascular ATP diphosphohydrolase . The Journal of Biological Chemistry . 271 . 51 . 33116–22 . Dec 1996 . 8955160 . 10.1074/jbc.271.51.33116 . free .
- Robson SC, Kaczmarek E, Siegel JB, Candinas D, Koziak K, Millan M, Hancock WW, Bach FH . Loss of ATP diphosphohydrolase activity with endothelial cell activation . The Journal of Experimental Medicine . 185 . 1 . 153–63 . Jan 1997 . 8996251 . 2196106 . 10.1084/jem.185.1.153 .
- Gray IC, Fallowfield J, Ford S, Nobile C, Volpi EV, Spurr NK . An integrated physical and genetic map spanning chromosome band 10q24 . Genomics . 43 . 1 . 85–8 . Jul 1997 . 9226376 . 10.1006/geno.1997.4809 .
- Makita K, Shimoyama T, Sakurai Y, Yagi H, Matsumoto M, Narita N, Sakamoto Y, Saito S, Ikeda Y, Suzuki M, Titani K, Fujimura Y . Placental ecto-ATP diphosphohydrolase: its structural feature distinct from CD39, localization and inhibition on shear-induced platelet aggregation . International Journal of Hematology . 68 . 3 . 297–310 . Oct 1998 . 9846014 . 10.1016/S0925-5710(98)00080-2 . free .
- Matsumoto M, Sakurai Y, Kokubo T, Yagi H, Makita K, Matsui T, Titani K, Fujimura Y, Narita N . The cDNA cloning of human placental ecto-ATP diphosphohydrolases I and II . FEBS Letters . 453 . 3 . 335–40 . Jun 1999 . 10405171 . 10.1016/S0014-5793(99)00751-6 . 35474833 . free .
- Kittel A, Kaczmarek E, Sevigny J, Lengyel K, Csizmadia E, Robson SC . CD39 as a caveolar-associated ectonucleotidase . Biochemical and Biophysical Research Communications . 262 . 3 . 596–9 . Sep 1999 . 10471369 . 10.1006/bbrc.1999.1254 .
- Koziak K, Kaczmarek E, Kittel A, Sévigny J, Blusztajn JK, Schulte Am Esch J, Imai M, Guckelberger O, Goepfert C, Qawi I, Robson SC . Palmitoylation targets CD39/endothelial ATP diphosphohydrolase to caveolae . The Journal of Biological Chemistry . 275 . 3 . 2057–62 . Jan 2000 . 10636909 . 10.1074/jbc.275.3.2057 . O . Goepfert . Imai . Guckelberger . C . Schulte Am Esch J 2nd . M . free .
- Dias Neto E, Correa RG, Verjovski-Almeida S, Briones MR, Nagai MA, da Silva W, Zago MA, Bordin S, Costa FF, Goldman GH, Carvalho AF, Matsukuma A, Baia GS, Simpson DH, Brunstein A, de Oliveira PS, Bucher P, Jongeneel CV, O'Hare MJ, Soares F, Brentani RR, Reis LF, de Souza SJ, Simpson AJ . Shotgun sequencing of the human transcriptome with ORF expressed sequence tags . Proceedings of the National Academy of Sciences of the United States of America . 97 . 7 . 3491–6 . Mar 2000 . 10737800 . 16267 . 10.1073/pnas.97.7.3491 . 2000PNAS...97.3491D . free .
- Goepfert C, Imai M, Brouard S, Csizmadia E, Kaczmarek E, Robson SC . CD39 modulates endothelial cell activation and apoptosis . Molecular Medicine . 6 . 7 . 591–603 . Jul 2000 . 10997340 . 1949966 . 10.1007/BF03401797.
- Kittel A, Garrido M, Varga G . Localization of NTPDase1/CD39 in normal and transformed human pancreas . The Journal of Histochemistry and Cytochemistry . 50 . 4 . 549–56 . Apr 2002 . 11897808 . 10.1177/002215540205000412 . free .
- Kaneider NC, Egger P, Dunzendorfer S, Noris P, Balduini CL, Gritti D, Ricevuti G, Wiedermann CJ . Reversal of thrombin-induced deactivation of CD39/ATPDase in endothelial cells by HMG-CoA reductase inhibition: effects on Rho-GTPase and adenosine nucleotide metabolism . Arteriosclerosis, Thrombosis, and Vascular Biology . 22 . 6 . 894–900 . Jun 2002 . 12067895 . 10.1161/01.ATV.0000018305.95943.F7 . free .
- Drosopoulos JH . Roles of Asp54 and Asp213 in Ca2+ utilization by soluble human CD39/ecto-nucleotidase . Archives of Biochemistry and Biophysics . 406 . 1 . 85–95 . Oct 2002 . 12234494 . 10.1016/S0003-9861(02)00414-9 .
- Krötz F, Sohn HY, Keller M, Gloe T, Bolz SS, Becker BF, Pohl U . Depolarization of endothelial cells enhances platelet aggregation through oxidative inactivation of endothelial NTPDase . Arteriosclerosis, Thrombosis, and Vascular Biology . 22 . 12 . 2003–9 . Dec 2002 . 12482826 . 10.1161/01.ATV.0000043454.08172.51 . free .
- Rossatto ER, da Silva LB, Pereira GS, Bonan CD, Battastini AM, Ribeiro JP, Sarkis JJ . 24657425 . ATP diphosphohydrolase in human platelets from patients with coronary arteries heart disease . Platelets . 14 . 1 . 47–52 . Feb 2003 . 12623446 . 10.1080/0953710021000062923 .
- Sørensen CE, Amstrup J, Rasmussen HN, Ankorina-Stark I, Novak I . Rat pancreas secretes particulate ecto-nucleotidase CD39 . The Journal of Physiology . 551 . Pt 3 . 881–92 . Sep 2003 . 12832497 . 2343304 . 10.1113/jphysiol.2003.049411 .
- Sévigny J, Sundberg C, Braun N, Guckelberger O, Csizmadia E, Qawi I, Imai M, Zimmermann H, Robson SC . Differential catalytic properties and vascular topography of murine nucleoside triphosphate diphosphohydrolase 1 (NTPDase1) and NTPDase2 have implications for thromboregulation . Blood . 99 . 8 . 2801–9 . Apr 2002 . 11929769 . 10.1182/blood.v99.8.2801. free .
- Novarino G, Fenstermaker AG, Zaki MS, et al. . Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders . Science . 343 . 6170 . 506–511 . Jan 2014 . 24482476 . 4157572 . 10.1126/science.1247363 . 2014Sci...343..506N .
- Calame DG, Herman I, Maroofian R, et al. . Biallelic Variants in the Ectonucleotidase ENTPD1 Cause a Complex Neurodevelopmental Disorder with Intellectual Disability, Distinct White Matter Abnormalities, and Spastic Paraplegia . Ann Neurol . 92 . 2 . 304–321 . Aug 2022 . 35471564 . 10.1002/ana.26381 . 10054521 . 1887/3564840 . free .
Notes and References
- Web site: Entrez Gene: ENTPD1 Ectonucleoside triphosphate diphosphohydrolase 1.
- Sévigny J, Levesque FP, Grondin G, Beaudoin AR . Purification of the blood vessel ATP diphosphohydrolase, identification and localisation by immunological techniques . Biochimica et Biophysica Acta (BBA) - General Subjects . 1334 . 1 . 73–88 . Feb 1997 . 9042368 . 10.1016/s0304-4165(96)00079-7.
- Kaczmarek E, Koziak K, Sévigny J, Siegel JB, Anrather J, Beaudoin AR, Bach FH, Robson SC . Identification and characterization of CD39/vascular ATP diphosphohydrolase . The Journal of Biological Chemistry . 271 . 51 . 33116–22 . Dec 1996 . 8955160 . 10.1074/jbc.271.51.33116. free .
- Robson SC, Sévigny J, Zimmermann H . The E-NTPDase family of ectonucleotidases: Structure function relationships and pathophysiological significance . Purinergic Signalling . 2 . 2 . 409–30 . Jun 2006 . 18404480 . 2254478 . 10.1007/s11302-006-9003-5 .
- Yegutkin GG . Nucleotide- and nucleoside-converting ectoenzymes: Important modulators of purinergic signalling cascade . Biochimica et Biophysica Acta (BBA) - Molecular Cell Research . 1783 . 5 . 673–94 . May 2008 . 18302942 . 10.1016/j.bbamcr.2008.01.024 . free .
- Kukulski F, Lévesque SA, Lavoie EG, Lecka J, Bigonnesse F, Knowles AF, Robson SC, Kirley TL, Sévigny J . Comparative hydrolysis of P2 receptor agonists by NTPDases 1, 2, 3 and 8 . Purinergic Signalling . 1 . 2 . 193–204 . Jun 2005 . 18404504 . 2096530 . 10.1007/s11302-005-6217-x .
- Book: Kukulski F, Lévesque SA, Sévigny J . Pharmacology of Purine and Pyrimidine Receptors . Impact of ectoenzymes on p2 and p1 receptor signaling . Advances in Pharmacology . 61 . 263–99 . 2011-01-01 . 21586362 . 10.1016/B978-0-12-385526-8.00009-6 . 978-0-12-385526-8 .
- Antonioli L, Pacher P, Vizi ES, Haskó G . CD39 and CD73 in immunity and inflammation . . 19 . 6 . 355–367. 2013 . 10.1016/j.molmed.2013.03.005 . 3674206 . 23601906.
- Sepúlveda C, Palomo I, Fuentes E . Role of adenosine A2b receptor overexpression in tumor progression . . 166 . 92–99 . 2016 . 10.1016/j.lfs.2016.10.008 . 27729268.
- Novarino G, Fenstermaker AG, Zaki MS, et al. . Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders . Science . 343 . 6170 . 506–511 . Jan 2014 . 24482476 . 4157572 . 10.1126/science.1247363 . 2014Sci...343..506N .
- Calame DG, Herman I, Maroofian R, et al. . Biallelic Variants in the Ectonucleotidase ENTPD1 Cause a Complex Neurodevelopmental Disorder with Intellectual Disability, Distinct White Matter Abnormalities, and Spastic Paraplegia . Ann Neurol . 92 . 2 . 304–321 . Aug 2022 . 35471564 . 10.1002/ana.26381 . 10054521 . 1887/3564840 . free .