From Wikipedia, the free encyclopedia
Mammalian protein found in humans
Ectonucleoside triphosphate diphosphohydrolase-1 (gene: ENTPD1 ; protein: NTPDase1 ) also known as CD39 (C luster of D ifferentiation 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
References
^
a
b
c
GRCh38: Ensembl release 89: ENSG00000138185 –
Ensembl , May 2017
^
a
b
c
GRCm38: Ensembl release 89: ENSMUSG00000048120 –
Ensembl , May 2017
^
"Human PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^
"Mouse PubMed Reference:" . National Center for Biotechnology Information, U.S. National Library of Medicine .
^
"Entrez Gene: ENTPD1 Ectonucleoside triphosphate diphosphohydrolase 1" .
^ 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.
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10.1016/s0304-4165(96)00079-7 .
PMID
9042368 .
^ 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.
doi :
10.1074/jbc.271.51.33116 .
PMID
8955160 .
^ Robson SC, Sévigny J, Zimmermann H (Jun 2006).
"The E-NTPDase family of ectonucleotidases: Structure function relationships and pathophysiological significance" . Purinergic Signalling . 2 (2): 409–30.
doi :
10.1007/s11302-006-9003-5 .
PMC
2254478 .
PMID
18404480 .
^ Yegutkin GG (May 2008).
"Nucleotide- and nucleoside-converting ectoenzymes: Important modulators of purinergic signalling cascade" . Biochimica et Biophysica Acta (BBA) - Molecular Cell Research . 1783 (5): 673–94.
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10.1016/j.bbamcr.2008.01.024 .
PMID
18302942 .
^ Kukulski F, Lévesque SA, Lavoie EG, Lecka J, Bigonnesse F, Knowles AF, Robson SC, Kirley TL, Sévigny J (Jun 2005).
"Comparative hydrolysis of P2 receptor agonists by NTPDases 1, 2, 3 and 8" . Purinergic Signalling . 1 (2): 193–204.
doi :
10.1007/s11302-005-6217-x .
PMC
2096530 .
PMID
18404504 .
^ 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 .
ISBN
978-0-12-385526-8 .
PMID
21586362 .
^
a
b
c
d
e Antonioli L, Pacher P, Vizi ES, Haskó G (2013).
"CD39 and CD73 in immunity and inflammation" .
Trends in Molecular Medicine . 19 (6): 355–367.
doi :
10.1016/j.molmed.2013.03.005 .
PMC
3674206 .
PMID
23601906 .
^
a
b Sepúlveda C, Palomo I, Fuentes E (2016). "Role of adenosine A2b receptor overexpression in tumor progression".
Life Sciences . 166 : 92–99.
doi :
10.1016/j.lfs.2016.10.008 .
PMID
27729268 .
^ 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.
Bibcode :
2014Sci...343..506N .
doi :
10.1126/science.1247363 .
PMC
4157572 .
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.
doi :
10.1002/ana.26381 .
hdl :
1887/3564840 .
PMC
10054521 .
PMID
35471564 .
Further reading
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.
doi :
10.4049/jimmunol.153.8.3574 .
PMID
7930580 .
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.
doi :
10.1111/j.1432-1033.1995.066_c.x .
PMID
8529670 .
Wang TF, Guidotti G (Apr 1996).
"CD39 is an ecto-(Ca2+,Mg2+)-apyrase" . The Journal of Biological Chemistry . 271 (17): 9898–901.
doi :
10.1074/jbc.271.17.9898 .
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.
doi :
10.1074/jbc.271.51.33116 .
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.
doi :
10.1084/jem.185.1.153 .
PMC
2196106 .
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.
doi :
10.1006/geno.1997.4809 .
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.
doi :
10.1016/S0925-5710(98)00080-2 .
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.
doi :
10.1016/S0014-5793(99)00751-6 .
PMID
10405171 .
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.
doi :
10.1006/bbrc.1999.1254 .
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.
doi :
10.1074/jbc.275.3.2057 .
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.
Bibcode :
2000PNAS...97.3491D .
doi :
10.1073/pnas.97.7.3491 .
PMC
16267 .
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.
doi :
10.1007/BF03401797 .
PMC
1949966 .
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.
doi :
10.1177/002215540205000412 .
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.
doi :
10.1161/01.ATV.0000018305.95943.F7 .
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.
doi :
10.1016/S0003-9861(02)00414-9 .
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.
doi :
10.1161/01.ATV.0000043454.08172.51 .
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.
doi :
10.1080/0953710021000062923 .
PMID
12623446 .
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.
doi :
10.1113/jphysiol.2003.049411 .
PMC
2343304 .
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.
doi :
10.1182/blood.v99.8.2801 .
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.
Bibcode :
2014Sci...343..506N .
doi :
10.1126/science.1247363 .
PMC
4157572 .
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.
doi :
10.1002/ana.26381 .
hdl :
1887/3564840 .
PMC
10054521 .
PMID
35471564 .
External links
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