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]

ENTPD1
Identifiers
AliasesENTPD1, ATPDase, CD39, NTPDase-1, SPG64, ectonucleoside triphosphate diphosphohydrolase 1
External IDsOMIM: 601752 MGI: 102805 HomoloGene: 20423 GeneCards: ENTPD1
Gene location (Human)
Chr.Chromosome 10 (human)[1]
Band10q24.1Start95,711,779 bp[1]
End95,877,266 bp[1]
RNA expression pattern




More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

953

12495

Ensembl

ENSG00000138185

ENSMUSG00000048120

UniProt

P49961

P55772

RefSeq (mRNA)

NM_009848
NM_001304721

RefSeq (protein)

NP_001291650
NP_033978

Location (UCSC)Chr 10: 95.71 – 95.88 MbChr 19: 40.61 – 40.74 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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]

See also

References
  1. GRCh38: Ensembl release 89: ENSG00000138185 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000048120 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. "Entrez Gene: ENTPD1 Ectonucleoside triphosphate diphosphohydrolase 1".
  6. 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. PMID 9042368.
  7. 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.
  8. 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.
  9. 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. doi:10.1016/j.bbamcr.2008.01.024. PMID 18302942.
  10. 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.
  11. 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. 61. pp. 263–99. doi:10.1016/B978-0-12-385526-8.00009-6. ISBN 9780123855268. PMID 21586362.
  12. 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.
  13. 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.

Further reading


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