| ENTPD1 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Aliases | ENTPD1 , ATPDase, CD39, NTPDase-1, SPG64, ectonucleoside triphosphate diphosphohydrolase 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 601752 MGI: 102805 HomoloGene: 20423 GeneCards: ENTPD1 | ||||||||||||||||||||||||||||||||||||||||||||||||||
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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]
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]
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.
Adenosine (symbol A) is an organic compound that occurs widely in nature in the form of diverse derivatives. The molecule consists of an adenine attached to a ribose via a β-N9-glycosidic bond. Adenosine is one of the four nucleoside building blocks of RNA (and its derivative deoxyadenosine is a building block of DNA), which are essential for all life on Earth. Its derivatives include the energy carriers adenosine mono-, di-, and triphosphate, also known as AMP/ADP/ATP. Cyclic adenosine monophosphate (cAMP) is pervasive in signal transduction. Adenosine is used as an intravenous medication for some cardiac arrhythmias.
ATPases (EC 3.6.1.3, Adenosine 5'-TriPhosphatase, adenylpyrophosphatase, ATP monophosphatase, triphosphatase, SV40 T-antigen, ATP hydrolase, complex V (mitochondrial electron transport), (Ca2+ + Mg2+)-ATPase, HCO3−-ATPase, adenosine triphosphatase) are a class of enzymes that catalyze the decomposition of ATP into ADP and a free phosphate ion or the inverse reaction. This dephosphorylation reaction releases energy, which the enzyme (in most cases) harnesses to drive other chemical reactions that would not otherwise occur. This process is widely used in all known forms of life.
Purinergic receptors, also known as purinoceptors, are a family of plasma membrane molecules that are found in almost all mammalian tissues. Within the field of purinergic signalling, these receptors have been implicated in learning and memory, locomotor and feeding behavior, and sleep. More specifically, they are involved in several cellular functions, including proliferation and migration of neural stem cells, vascular reactivity, apoptosis and cytokine secretion. These functions have not been well characterized and the effect of the extracellular microenvironment on their function is also poorly understood.
5′-Nucleotidase is an enzyme which catalyzes the phosphorylytic cleavage of 5′-nucleotides. Although originally found in snake venom, the activity of 5'nucleotidase has been described for bacteria and plant cells, and is widely distributed in vertebrate tissue. In mammalian cells the enzyme is predominantly located in the plasma membrane and its primary role is in the conversion of extracellular nucleotides, which are generally impermeable, to the corresponding nucleoside which can readily enter most cells. Consequently, the enzyme plays a key role in the metabolism of nucleotides.
VEGF receptors (VEGFRs) are receptors for vascular endothelial growth factor (VEGF). There are three main subtypes of VEGFR, numbered 1, 2 and 3. Depending on alternative splicing, they may be membrane-bound (mbVEGFR) or soluble (sVEGFR).
Ectonucleotidases consist of families of nucleotide metabolizing enzymes that are expressed on the plasma membrane and have externally oriented active sites. These enzymes metabolize nucleotides to nucleosides. The contribution of ectonucleotidases in the modulation of purinergic signaling depends on the availability and preference of substrates and on cell and tissue distribution.
Sphingosine-1-phosphate receptor 1, also known as endothelial differentiation gene 1 (EDG1) is a protein that in humans is encoded by the S1PR1 gene. S1PR1 is a G-protein-coupled receptor which binds the bioactive signaling molecule sphingosine 1-phosphate (S1P). S1PR1 belongs to a sphingosine-1-phosphate receptor subfamily comprising five members (S1PR1-5). S1PR1 was originally identified as an abundant transcript in endothelial cells and it has an important role in regulating endothelial cell cytoskeletal structure, migration, capillary-like network formation and vascular maturation. In addition, S1PR1 signaling is important in the regulation of lymphocyte maturation, migration and trafficking.
P2Y purinoceptor 1 is a protein that in humans is encoded by the P2RY1 gene.
Ectonucleotide pyrophosphatase/phosphodiesterase family member 1 is an enzyme that in humans is encoded by the ENPP1 gene.
5′-nucleotidase (5′-NT), also known as ecto-5′-nucleotidase or CD73, is an enzyme that in humans is encoded by the NT5E gene. CD73 commonly serves to convert AMP to adenosine.
P2 receptor may refer to:
Vascular endothelial growth factor B also known as VEGF-B is a protein that, in humans, is encoded by the VEGF-B gene. VEGF-B is a growth factor that belongs to the vascular endothelial growth factor family, of which VEGF-A is the best-known member.
Ectonucleoside triphosphate diphosphohydrolase 2 is an enzyme that in humans is encoded by the ENTPD2 gene.
Ectonucleoside triphosphate diphosphohydrolase 5 is an enzyme that in humans is encoded by the ENTPD5 gene.
Ectonucleoside triphosphate diphosphohydrolase 3 is an enzyme that in humans is encoded by the ENTPD3 gene.
BAY 60–6583 is a selective adenosine A2B receptor agonist. It has been shown to provide protection from ischemia in both the heart and kidney of test animals, and has also been shown to be beneficial in treatment of acute lung and brain injury, as well as claimed anti-aging and anti-obesity effects, showing a range of potential applications for selective A2B agonists.
Purinergic signalling is a form of extracellular signalling mediated by purine nucleotides and nucleosides such as adenosine and ATP. It involves the activation of purinergic receptors in the cell and/or in nearby cells, thereby regulating cellular functions.
Herbert Zimmermann is a German neuroscientist who pioneered the studies on the biochemical, structural and functional heterogeneity of cholinergic synaptic vesicles from the electric organ of the electric ray Torpedo, and the functional and biochemical characterization of enzymes hydrolyzing extracellular nucleotides.
20-Hydroxyeicosatetraenoic acid, also known as 20-HETE or 20-hydroxy-5Z,8Z,11Z,14Z-eicosatetraenoic acid, is an eicosanoid metabolite of arachidonic acid that has a wide range of effects on the vascular system including the regulation of vascular tone, blood flow to specific organs, sodium and fluid transport in the kidney, and vascular pathway remodeling. These vascular and kidney effects of 20-HETE have been shown to be responsible for regulating blood pressure and blood flow to specific organs in rodents; genetic and preclinical studies suggest that 20-HETE may similarly regulate blood pressure and contribute to the development of stroke and heart attacks. Additionally the loss of its production appears to be one cause of the human neurological disease, Hereditary spastic paraplegia. Preclinical studies also suggest that the overproduction of 20-HETE may contribute to the progression of certain human cancers, particularly those of the breast.
Arterial calcification due to CD73 deficiency or Calcification of joints and arteries is a rare genetic disorder affecting adults.
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