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
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.
^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.
PMID9042368.
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.
PMID10471369.
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.
PMID12234494.
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
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.
^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.
PMID9042368.
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.
PMID10471369.
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.
PMID12234494.