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

Notes and References

  1. Web site: Entrez Gene: ENTPD1 Ectonucleoside triphosphate diphosphohydrolase 1.
  2. 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.
  3. 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 .
  4. 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 .
  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 .
  6. 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 .
  7. 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 .
  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.
  9. 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.
  10. 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 .
  11. 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 .