ENTPD1

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.^[5][6][7]

Function

NTPDase1 is an ectonucleotidase that catalyse the hydrolysis of γ- and β-phosphate residues of triphospho- and diphosphonucleosides to the monophosphonucleoside derivative.^[8][9] NTPDase1 hydrolyzes P2 receptor ligands, namely ATP, ADP, UTP and UDP with similar efficacy.^[10] NTPDase1 can therefore affect P2 receptor activation and functions.^[11]

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.^[12] CD39 converts ATP (or ADP) to adenosine monophosphate (AMP), which is converted into adenosine by CD73.^[12][13] 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.^{[12] [13]}

Adenosine produced by the CD39/CD73 pathway can protect against ischemia-reperfusion injury.^[12] 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.^[12]

Biallelic pathogenic variant in ENTPD1 causes autosomal recessive spastic paraplegia 64 (SPG64).^[14][15] 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

• Cluster of differentiation

References

Further reading

• Maliszewski CR, Delespesse GJ, Schoenborn MA, Armitage RJ, Fanslow WC, Nakajima T, Baker E,
  S2CID 34664153
  .
• Christoforidis S, Papamarcaki T, Galaris D, Kellner R, Tsolas O (Nov 1995). "Purification and properties of human placental ATP diphosphohydrolase". European Journal of Biochemistry. 234 (1): 66–74.
  PMID 8529670
  .
• Wang TF, Guidotti G (Apr 1996). "CD39 is an ecto-(Ca2+,Mg2+)-apyrase". The Journal of Biological Chemistry. 271 (17): 9898–901.
  PMID 8626624
  .
• Kaczmarek E, Koziak K, Sévigny J, Siegel JB, Anrather J, Beaudoin AR, Bach FH, Robson SC (Dec 1996). "Identification and characterization of CD39/vascular ATP diphosphohydrolase". The Journal of Biological Chemistry. 271 (51): 33116–22.
  PMID 8955160
  .
• Robson SC, Kaczmarek E, Siegel JB, Candinas D, Koziak K, Millan M, Hancock WW, Bach FH (Jan 1997). "Loss of ATP diphosphohydrolase activity with endothelial cell activation". The Journal of Experimental Medicine. 185 (1): 153–63.
  PMID 8996251
  .
• Gray IC, Fallowfield J, Ford S, Nobile C, Volpi EV, Spurr NK (Jul 1997). "An integrated physical and genetic map spanning chromosome band 10q24". Genomics. 43 (1): 85–8.
  PMID 9226376
  .
• Makita K, Shimoyama T, Sakurai Y, Yagi H, Matsumoto M, Narita N, Sakamoto Y, Saito S, Ikeda Y, Suzuki M, Titani K, Fujimura Y (Oct 1998). "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.
  PMID 9846014
  .
• Matsumoto M, Sakurai Y, Kokubo T, Yagi H, Makita K, Matsui T, Titani K, Fujimura Y, Narita N (Jun 1999). "The cDNA cloning of human placental ecto-ATP diphosphohydrolases I and II". FEBS Letters. 453 (3): 335–40.
  S2CID 35474833
  .
• Kittel A, Kaczmarek E, Sevigny J, Lengyel K, Csizmadia E, Robson SC (Sep 1999). "CD39 as a caveolar-associated ectonucleotidase". Biochemical and Biophysical Research Communications. 262 (3): 596–9.
  PMID 10471369
  .
• Koziak K, Kaczmarek E, Kittel A, Sévigny J, Blusztajn JK, Schulte Am Esch J, Imai M, Guckelberger O, Goepfert C, Qawi I, Robson SC (Jan 2000). "Palmitoylation targets CD39/endothelial ATP diphosphohydrolase to caveolae". The Journal of Biological Chemistry. 275 (3): 2057–62.
  PMID 10636909
  .
• 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 (Mar 2000). "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.
  PMID 10737800
  .
• Goepfert C, Imai M, Brouard S, Csizmadia E, Kaczmarek E, Robson SC (Jul 2000). "CD39 modulates endothelial cell activation and apoptosis". Molecular Medicine. 6 (7): 591–603.
  PMID 10997340
  .
• Kittel A, Garrido M, Varga G (Apr 2002). "Localization of NTPDase1/CD39 in normal and transformed human pancreas". The Journal of Histochemistry and Cytochemistry. 50 (4): 549–56.
  PMID 11897808
  .
• Kaneider NC, Egger P, Dunzendorfer S, Noris P, Balduini CL, Gritti D, Ricevuti G, Wiedermann CJ (Jun 2002). "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.
  PMID 12067895
  .
• Drosopoulos JH (Oct 2002). "Roles of Asp54 and Asp213 in Ca2+ utilization by soluble human CD39/ecto-nucleotidase". Archives of Biochemistry and Biophysics. 406 (1): 85–95.
  PMID 12234494
  .
• Krötz F, Sohn HY, Keller M, Gloe T, Bolz SS, Becker BF, Pohl U (Dec 2002). "Depolarization of endothelial cells enhances platelet aggregation through oxidative inactivation of endothelial NTPDase". Arteriosclerosis, Thrombosis, and Vascular Biology. 22 (12): 2003–9.
  PMID 12482826
  .
• Rossatto ER, da Silva LB, Pereira GS, Bonan CD, Battastini AM, Ribeiro JP, Sarkis JJ (Feb 2003). "ATP diphosphohydrolase in human platelets from patients with coronary arteries heart disease". Platelets. 14 (1): 47–52.
  S2CID 24657425
  .
• Sørensen CE, Amstrup J, Rasmussen HN, Ankorina-Stark I, Novak I (Sep 2003). "Rat pancreas secretes particulate ecto-nucleotidase CD39". The Journal of Physiology. 551 (Pt 3): 881–92.
  PMID 12832497
  .
• Sévigny J, Sundberg C, Braun N, Guckelberger O, Csizmadia E, Qawi I, Imai M, Zimmermann H, Robson SC (Apr 2002). "Differential catalytic properties and vascular topography of murine nucleoside triphosphate diphosphohydrolase 1 (NTPDase1) and NTPDase2 have implications for thromboregulation". Blood. 99 (8): 2801–9.
  PMID 11929769
  .
• Novarino G, Fenstermaker AG, Zaki MS, et al. (Jan 2014). "Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders". Science. 343 (6170): 506–511.
  PMID 24482476
  .
• Calame DG, Herman I, Maroofian R, et al. (Aug 2022). "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.
  PMID 35471564
  .

External links

• ENTPD1+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

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