Alternative titles; symbols
HGNC Approved Gene Symbol: ENTPD6
Cytogenetic location: 20p11.21 Genomic coordinates (GRCh38): 20:25,195,712-25,228,075 (from NCBI)
Extracellular nucleotides serve as signaling molecules in many extracellular activities. The catabolism of extracellular nucleotides is mediated by several types of ectonucleotidases, including the divalent cation-dependent E-type nucleotidases (NTPases). The E-type NTPases include ectoapyrases, such as CD39 (601752), which show a significant rate of ADP hydrolysis compared to ATP hydrolysis. NTPases are characterized by the presence of 4 motifs known as apyrase-conserved regions (ACRs) (summary by Chadwick and Frischauf, 1998).
Chadwick et al. (1998) identified cDNAs encoding a mouse NTPase, symbolized MNTPase. By searching an EST database for sequences similar to that of MNTPase, Chadwick and Frischauf (1998) identified cDNAs corresponding to 2 human genes, CD39L2 and CD39L4 (603162). The predicted 484-amino acid CD39L2 protein contains all 4 ACRs, a single N-terminal transmembrane segment, and a large extracellular C-terminal domain. Northern blot analysis revealed that CD39L2 was expressed as a major 2.6-kb and minor 4.4-kb mRNA in all tissues tested. Homology searches yielded ESTs likely to represent the mouse cd39l2 gene.
By PCR and sequence analysis of cDNA libraries, and by Northern blot analysis, Yeung et al. (2000) detected CD39L2 predominantly in heart, with very low or no expression in other tissues. In situ hybridization analysis revealed expression distinctively in cardiac muscle and capillary endothelial cells. A larger variant, resulting from a 43-bp insertion in exon 14, was detected in fetal brain. Western blot analysis of cells expressing recombinant CD39L2 detected expression of an approximately 60-kD protein triplet primarily in the secreted fraction but also on membranes. Glycosidase treatment reduced the size of the protein to 57 kD, still greater than the predicted 53 kD, suggesting additional posttranslational modifications. Brefeldin A treatment decreased the secretion of CD39L2. Flow cytometric analysis demonstrated expression on the extracellular membrane. Functional analysis showed that, like CD39L4, CD39L2 preferentially hydrolyzes nucleotide diphosphates rather than triphospates. This hydrolysis is enhanced in the presence of magnesium or calcium. However, in contrast to CD39, calcium excess fails to inhibit CD39L2-mediated adenosine diphosphatase activity. On the basis of structural and biochemical features, Yeung et al. (2000) concluded that CD39L2 and CD39L4 are in a separate subclass, defined by the presence of only 1 N-terminal hydrophobic transmembrane domain, from CD39, CD39L1 (602012), and CD39L3 (603161), which have an N-terminal and a C-terminal transmembrane domain.
By analysis of radiation hybrid and somatic cell hybrid panels, Chadwick and Frischauf (1998) mapped the CD39L2 gene to 20q11.2.
Chadwick, B. P., Frischauf, A.-M. The CD39-like gene family: identification of three new human members (CD39L2, CD39L3, and CD39L4), their murine homologues, and a member of the gene family from Drosophila melanogaster. Genomics 50: 357-367, 1998. [PubMed: 9676430] [Full Text: https://doi.org/10.1006/geno.1998.5317]
Chadwick, B. P., Williamson, J., Sheer, D., Frischauf, A.-M. cDNA cloning and chromosomal mapping of a mouse gene with homology to NTPases. Mammalian Genome 9: 162-164, 1998. [PubMed: 9457681] [Full Text: https://doi.org/10.1007/s003359900710]
Yeung, G., Mulero, J. J., McGowan, D. W., Bajwa, S. S., Ford, J. E. CD39L2, a gene encoding a human nucleoside diphosphatase, predominantly expressed in the heart. Biochemistry 39: 12916-12923, 2000. [PubMed: 11041856] [Full Text: https://doi.org/10.1021/bi000959z]