ENTPD1

Function

NTPDase1 is an ectonucleotidase that catalyse the hydrolysis of γ- and β-phosphate residues of triphospho- and diphosphonucleosides to the monophosphonucleoside derivative. NTPDase1 hydrolyzes P2 receptor ligands, namely ATP, ADP, UTP and UDP with similar efficacy. NTPDase1 can therefore affect P2 receptor activation and functions.

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. CD39 converts ATP (or ADP) to adenosine monophosphate (AMP), which is converted into adenosine by CD73. 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.

Adenosine produced by the CD39/CD73 pathway can protect against ischemia-reperfusion injury. 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.

Biallelic pathogenic variant in ENTPD1 causes autosomal recessive spastic paraplegia 64 (SPG64). SPG64 is a complex hereditary spastic paraplegia characterized by childhood onset progressive spastic paraparesis, delayed developmental milestones, intellectual disability, dysarthria, and white matter abnormalities.

References

References

1. "Entrez Gene: ENTPD1 Ectonucleoside triphosphate diphosphohydrolase 1".
2. (Feb 1997). "Purification of the blood vessel ATP diphosphohydrolase, identification and localisation by immunological techniques". Biochimica et Biophysica Acta (BBA) - General Subjects.
3. (Dec 1996). "Identification and characterization of CD39/vascular ATP diphosphohydrolase". The Journal of Biological Chemistry.
4. (Jun 2006). "The E-NTPDase family of ectonucleotidases: Structure function relationships and pathophysiological significance". Purinergic Signalling.
5. (May 2008). "Nucleotide- and nucleoside-converting ectoenzymes: Important modulators of purinergic signalling cascade". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research.
6. (Jun 2005). "Comparative hydrolysis of P2 receptor agonists by NTPDases 1, 2, 3 and 8". Purinergic Signalling.
7. (2011-01-01). "Pharmacology of Purine and Pyrimidine Receptors".
8. (2013). "CD39 and CD73 in immunity and inflammation". [[Trends in Molecular Medicine]].
9. (2016). "Role of adenosine A2b receptor overexpression in tumor progression". [[Life Sciences (journal).
10. (Jan 2014). "Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders". Science.
11. (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.