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 effect 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]
^Sévigny J, Levesque FP, Grondin G, Beaudoin AR (Feb 1997). "Purification of the blood vessel ATP diphosphohydrolase, identification and localisation by immunological techniques". Biochimica et Biophysica Acta (BBA) - General Subjects. 1334 (1): 73–88. doi:10.1016/s0304-4165(96)00079-7. PMID9042368.
^Kukulski F, Lévesque SA, Sévigny J (2011-01-01). "Impact of ectoenzymes on p2 and p1 receptor signaling". Pharmacology of Purine and Pyrimidine Receptors. Advances in Pharmacology. Vol. 61. pp. 263–99. doi:10.1016/B978-0-12-385526-8.00009-6. ISBN9780123855268. PMID21586362.
Maliszewski CR, Delespesse GJ, Schoenborn MA, Armitage RJ, Fanslow WC, Nakajima T, Baker E, Sutherland GR, Poindexter K, Birks C (Oct 1994). "The CD39 lymphoid cell activation antigen. Molecular cloning and structural characterization". Journal of Immunology. 153 (8): 3574–83. PMID7930580.
Christoforidis S, Papamarcaki T, Galaris D, Kellner R, Tsolas O (Nov 1995). "Purification and properties of human placental ATP diphosphohydrolase". European Journal of Biochemistry / FEBS. 234 (1): 66–74. doi:10.1111/j.1432-1033.1995.066_c.x. PMID8529670.
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. doi:10.1016/S0014-5793(99)00751-6. PMID10405171.
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. doi:10.1006/bbrc.1999.1254. PMID10471369.
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. doi:10.1073/pnas.97.7.3491. PMC16267. PMID10737800.
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. doi:10.1016/S0003-9861(02)00414-9. PMID12234494.
