Biology:ENTPD1
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Short description: Mammalian protein found in Homo sapiens
 Generic protein structure example |
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.[8][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.[8] [9]
Adenosine produced by the CD39/CD73 pathway can protect against ischemia-reperfusion injury.[8] 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.[8]
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
References
- ↑ "Entrez Gene: ENTPD1 Ectonucleoside triphosphate diphosphohydrolase 1". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=953.
- ↑ "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. doi:10.1016/s0304-4165(96)00079-7. PMID 9042368.
- ↑ "Identification and characterization of CD39/vascular ATP diphosphohydrolase". The Journal of Biological Chemistry 271 (51): 33116–22. Dec 1996. doi:10.1074/jbc.271.51.33116. PMID 8955160.
- ↑ "The E-NTPDase family of ectonucleotidases: Structure function relationships and pathophysiological significance". Purinergic Signalling 2 (2): 409–30. Jun 2006. doi:10.1007/s11302-006-9003-5. PMID 18404480.
- ↑ "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. doi:10.1016/j.bbamcr.2008.01.024. PMID 18302942.
- ↑ "Comparative hydrolysis of P2 receptor agonists by NTPDases 1, 2, 3 and 8". Purinergic Signalling 1 (2): 193–204. Jun 2005. doi:10.1007/s11302-005-6217-x. PMID 18404504.
- ↑ "Impact of ectoenzymes on p2 and p1 receptor signaling". Pharmacology of Purine and Pyrimidine Receptors. Advances in Pharmacology. 61. 2011-01-01. pp. 263–99. doi:10.1016/B978-0-12-385526-8.00009-6. ISBN 9780123855268.
- ↑ 8.0 8.1 8.2 8.3 8.4 "CD39 and CD73 in immunity and inflammation". Trends in Molecular Medicine 19 (6): 355–367. 2013. doi:10.1016/j.molmed.2013.03.005. PMID 23601906.
- ↑ 9.0 9.1 "Role of adenosine A2b receptor overexpression in tumor progression". Life Sciences 166: 92–99. 2016. doi:10.1016/j.lfs.2016.10.008. PMID 27729268.
- ↑ "Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders". Science 343 (6170): 506–511. Jan 2014. doi:10.1126/science.1247363. PMID 24482476.
- ↑ "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. doi:10.1002/ana.26381. PMID 35471564.
Further reading
- "The CD39 lymphoid cell activation antigen. Molecular cloning and structural characterization". Journal of Immunology 153 (8): 3574–83. Oct 1994. doi:10.4049/jimmunol.153.8.3574. PMID 7930580.
- "Purification and properties of human placental ATP diphosphohydrolase". European Journal of Biochemistry 234 (1): 66–74. Nov 1995. doi:10.1111/j.1432-1033.1995.066_c.x. PMID 8529670.
- "CD39 is an ecto-(Ca2+,Mg2+)-apyrase". The Journal of Biological Chemistry 271 (17): 9898–901. Apr 1996. doi:10.1074/jbc.271.17.9898. PMID 8626624.
- "Identification and characterization of CD39/vascular ATP diphosphohydrolase". The Journal of Biological Chemistry 271 (51): 33116–22. Dec 1996. doi:10.1074/jbc.271.51.33116. PMID 8955160.
- "Loss of ATP diphosphohydrolase activity with endothelial cell activation". The Journal of Experimental Medicine 185 (1): 153–63. Jan 1997. doi:10.1084/jem.185.1.153. PMID 8996251.
- "An integrated physical and genetic map spanning chromosome band 10q24". Genomics 43 (1): 85–8. Jul 1997. doi:10.1006/geno.1997.4809. PMID 9226376.
- "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. Oct 1998. doi:10.1016/S0925-5710(98)00080-2. PMID 9846014.
- "The cDNA cloning of human placental ecto-ATP diphosphohydrolases I and II". FEBS Letters 453 (3): 335–40. Jun 1999. doi:10.1016/S0014-5793(99)00751-6. PMID 10405171.
- "CD39 as a caveolar-associated ectonucleotidase". Biochemical and Biophysical Research Communications 262 (3): 596–9. Sep 1999. doi:10.1006/bbrc.1999.1254. PMID 10471369.
- "Palmitoylation targets CD39/endothelial ATP diphosphohydrolase to caveolae". The Journal of Biological Chemistry 275 (3): 2057–62. Jan 2000. doi:10.1074/jbc.275.3.2057. PMID 10636909.
- "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. Mar 2000. doi:10.1073/pnas.97.7.3491. PMID 10737800. Bibcode: 2000PNAS...97.3491D.
- "CD39 modulates endothelial cell activation and apoptosis". Molecular Medicine 6 (7): 591–603. Jul 2000. doi:10.1007/BF03401797. PMID 10997340.
- "Localization of NTPDase1/CD39 in normal and transformed human pancreas". The Journal of Histochemistry and Cytochemistry 50 (4): 549–56. Apr 2002. doi:10.1177/002215540205000412. PMID 11897808.
- "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. Jun 2002. doi:10.1161/01.ATV.0000018305.95943.F7. PMID 12067895.
- "Roles of Asp54 and Asp213 in Ca2+ utilization by soluble human CD39/ecto-nucleotidase". Archives of Biochemistry and Biophysics 406 (1): 85–95. Oct 2002. doi:10.1016/S0003-9861(02)00414-9. PMID 12234494.
- "Depolarization of endothelial cells enhances platelet aggregation through oxidative inactivation of endothelial NTPDase". Arteriosclerosis, Thrombosis, and Vascular Biology 22 (12): 2003–9. Dec 2002. doi:10.1161/01.ATV.0000043454.08172.51. PMID 12482826.
- "ATP diphosphohydrolase in human platelets from patients with coronary arteries heart disease". Platelets 14 (1): 47–52. Feb 2003. doi:10.1080/0953710021000062923. PMID 12623446.
- "Rat pancreas secretes particulate ecto-nucleotidase CD39". The Journal of Physiology 551 (Pt 3): 881–92. Sep 2003. doi:10.1113/jphysiol.2003.049411. PMID 12832497.
- "Differential catalytic properties and vascular topography of murine nucleoside triphosphate diphosphohydrolase 1 (NTPDase1) and NTPDase2 have implications for thromboregulation". Blood 99 (8): 2801–9. Apr 2002. doi:10.1182/blood.v99.8.2801. PMID 11929769.
- "Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders". Science 343 (6170): 506–511. Jan 2014. doi:10.1126/science.1247363. PMID 24482476.
- "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. doi:10.1002/ana.26381. PMID 35471564.
External links
- ENTPD1+protein,+human at the US National Library of Medicine Medical Subject Headings (MeSH)
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