Disease relevance of ENTPD2

• A dramatic increase in ecto-ATPase activity above the level of normal melanocytes was demonstrated in the differentiated melanomas and was followed by a gradual decrease with tumor progression [1].
• Transcripts of ectonucleotidases (CD39 and CD39L1) together with P2R (P2X(7), P2Y(2), and P2Y(6)) are significantly increased in both chronic pancreatitis and pancreatic cancer [2].
• Cytomegalovirus infection increases the expression and activity of ecto-ATPase (CD39) and ecto-5'nucleotidase (CD73) on endothelial cells [3].
• Evidence for NTPDase2 expression was lacking in all cells except the mouse and human hepatoma cells [4].
• Neuroblasts-glia interaction. The effect of co-cultivation upon ecto-ATPase activity of neuroblastoma and glioma cells [5].

High impact information on ENTPD2

• We show that malignant T and null lymphocytes are deficient in ecto-ATPase activity [6].
• By comparison, ecto-ATPase and ecto-ADPase activities on cultured human umbilical vein endothelial cells were similar to those on leukocytes while endothelial 5'-nucleotidase per 10(6) cells was equivalent to the soluble activity in 1 ml of blood or plasma.(ABSTRACT TRUNCATED AT 250 WORDS)[7]
• The kinetic properties of the ecto-ATPase of human peripheral blood lymphocytes and of chronic lymphatic leukemia cells [8].
• The ecto-ATPase activities of preparations consisting predominantly of T or B cells were compared to each other and to the ecto-ATPase of the CLL peripheral blood lymphocytes (PBL) [8].
• On the basis of the kinetic properties, the ecto-ATPase of the B cell appears to be identical with that of the T cell [8].

Chemical compound and disease context of ENTPD2

• Interestingly, lipopolysaccharide, a component of cell walls of gram-negative bacteria that increase hemocyte aggregation and phagocytosis, increased the Mg2+-dependent ecto-ATPase activity in a dose-dependent manner but did not modify the Mg2+-independent ecto-ATPase activity [9].

Biological context of ENTPD2

• The genomic structure of CD39L1 reveals 9 exons covering less than 7 kb [10].
• The presence of the human ABC2 gene on an overlapping cosmid and hybridizations to somatic cell mapping panels suggest that CD39L1 maps to human Chr 9q34 [10].
• The human CD39-like-1 gene (CD39L1) was isolated from a selected cDNA library enriched for transcripts from regions of human Chromosome (Chr) 9q [10].
• Transmembrane domains confer different substrate specificities and adenosine diphosphate hydrolysis mechanisms on CD39, CD39L1, and chimeras [11].
• Like other members of the eNTPDase family, the human ecto-ATPase is a tetramer, the activity of which depends on its glycosylation [12].

Anatomical context of ENTPD2

• Nucleoside triphosphate diphosphohydrolase-2 (NTPDase2/CD39L1) is the dominant ectonucleotidase expressed by rat astrocytes [13].
• Mechanical loading stimulates ecto-ATPase activity in human tendon cells [14].
• Human ecto-ATPase (ecto-nucleoside triphosphate diphosphohydrolase 2 [eNTPDase2], also known as CD39L1) has been expressed and characterized in COS cells [12].
• Although all three enzyme forms were expressed heterologously to similar levels in Chinese hamster ovary cells clone K-1 (CHO-K1) cells, only the 495-amino acid protein (NTPDase2 alpha exhibited ecto-ATPase activity [15].
• Immunolocalization studies demonstrated that NTPDase2 alpha is fully processed and trafficked to the plasma membrane, whereas the NTPDase2 beta and -2 gamma splice variants were retained in not fully glycosylated forms in the endoplasmic reticulum [15].

Associations of ENTPD2 with chemical compounds

• NTPDase2 preferentially hydrolyzes nucleoside triphosphates, and the presence of NTPDase2 under either coexpression or coculture conditions did not change the EC(50) of 2MeSADP, ADP, or adenosine 5'-O-(2-thiodiphosphate) for activation of the P2Y(1) receptor [16].
• Ecto-ATPase may act as a co-modulator in ATP load-signal modulation by regulating the half-life of extracellular purine nucleotides [14].
• Hydrolysis of ATP by human ecto-ATPase is nonlinear with time, and its activity is stimulated/stabilized by both the lectin concanavalin A and the chemical cross-linking agent disuccinimidyl suberate [12].
• Mutation of Cys399, which is absent in NTPDase2 beta and -2 gamma, produced a protein completely devoid of nucleotidase activity, while mutation of Asn443 to Asp resulted in substantial loss of activity [15].
• Mutagenesis of arginine 146 to proline (R146P) essentially converted the eNTPDase-3 ecto-apyrase to an ecto-ATPase (eNTPDase-2), mainly by decreasing the hydrolysis rates for nucleoside diphosphates [17].

Regulatory relationships of ENTPD2

• Localisation of ecto-5'-nucleotidase and divalent cation-activated ecto-ATPase in chronic tonsillitis [18].

Other interactions of ENTPD2

• By quantitative real-time PCR, we identified Entpd2 (CD39L1) as the dominant Entpd gene expressed by rat hippocampal, cortical and cerebellar astrocytes [13].
• Those patterns, together with results of enzyme assays, Western blotting, or semiquantitative RT-PCR show that NTPDase2 is the main ectonucleotidase for murine and human hepatoma cells, NTPDase3 for chick hepatocytes and LMH cells, and an E-NPP enzyme for chick cardiac myocytes [4].
• NG108-15 cells expressed mRNA for the ecto-ATPase and nucleotide pyrophosphatase, but not for CD73 [19].
• This study examines whether the activity of the Mg2+-dependent ecto-ATPase of the surface membrane of the human lymphocyte is changed in chronic lymphocytic B-cell leukemia (CLL-B) and may be an indicator of malignant transformation [8].
• Successive additions of extracellular ATP can elicit repetitive Ca2+ transients if the initially added ATP is removed either through the action of native ecto-ATPase activity or exogenous hexokinase [20].

Analytical, diagnostic and therapeutic context of ENTPD2

• Purification and molecular cloning of ecto-ATPase and other canalicular proteins are complicated by an abundant canalicular plasma membrane protein, cCAM 105 [21].
• We characterized the ecto-ATPase activity on human blood cells with a [gamma 32P]ATP assay and HPLC measurements [22].
• Clinical relevance of immunohistochemical staining for ecto-AMPase and ecto-ATPase in chronic allograft nephropathy (CAN) [23].

References