ENTPD1

ENTPD1
Identifiers
AliasesENTPD1, ATPDase, CD39, NTPDase-1, SPG64, ectonucleoside triphosphate diphosphohydrolase 1
External IDsOMIM: 601752; MGI: 102805; HomoloGene: 20423; GeneCards: ENTPD1; OMA:ENTPD1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_009848
NM_001304721

RefSeq (protein)

NP_001291650
NP_033978

Location (UCSC)Chr 10: 95.71 – 95.88 MbChr 19: 40.6 – 40.73 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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

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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

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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

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References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000138185Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000048120Ensembl, 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. Vol. 61. pp. 263–99. doi:10.1016/B978-0-12-385526-8.00009-6. ISBN 978-0-12-385526-8. PMID 21586362.
  12. ^ 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.
  13. ^ 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.
  14. ^ 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.
  15. ^ 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

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