Alternative titles; symbols
HGNC Approved Gene Symbol: ENTPD2
Cytogenetic location: 9q34.3 Genomic coordinates (GRCh38): 9:137,048,107-137,054,061 (from NCBI)
Plasma membrane-bound ectonucleoside trisphosphate diphosphohydrolases (ENTPDases), such as ENTPD2, modulate P2 receptor (see 600845) signaling by controlling extracellular nucleotide concentrations via nucleoside tri- and diphosphate hydrolysis (Munkonda et al., 2007).
Chadwick and Frischauf (1997) cloned and mapped a human gene sharing considerable amino acid identity with the chicken muscle ecto-ATPase and the human lymphoid cell activation antigen CD39 (601752). Biochemical studies had indicated that the human CD39 protein is an ectoapyrase. Ectoapyrases show high levels of amino acid sequence homology to ecto-ATPases. The full-length sequence of the CD39-like gene, symbolized CD39L1, encodes a putative 472-amino acid protein.
Masse et al. (2007) showed that purine-mediated signaling triggers both eye field transcription factor (EFTF) expression and eye development in Xenopus laevis. Overexpression of ENTPD2, an ectoenzyme that converts ATP to ADP, caused ectopic eye-like structures, with occasional complete duplication of the eye, and increased expression of Pax6 (607108), Rx1, and Six3 (603714). In contrast, downregulation of endogenous ENTPD2 decreased Rx1 and Pax6 expression. Masse et al. (2007) concluded that ENTPD2 therefore acts upstream of these EFTFs. To test whether ADP, the product of ENTPD2, might act to trigger eye development through P2Y1 receptors, selective in Xenopus for ADP, Masse et al. (2007) simultaneously knocked down expression of the genes encoding ENTPD2 and the P2Y1 receptor (601167). This prevented the expression of Rx1 and Pax6 and eye formation completely. Masse et al. (2007) next measured ATP release in the presumptive eye field, demonstrating a transient release of ATP at a time that could plausibly trigger (once converted to ADP) expression of the EFTFs. This role for transient purine-mediated signaling in eye development may be widely conserved, because alterations to the ENTPD2 locus on human chromosome 9 cause severe head and eye defects, including microphthalmia. Masse et al. (2007) concluded that their results suggested a new mechanism for the initiation of eye development.
By assaying cellular extracts of transfected COS-7 cells, Munkonda et al. (2007) showed that all P2 receptor antagonists tested, except MRS2179, an AMP analog, inhibited human and mouse ENTPDases, including ENTPD2.
Chadwick and Frischauf (1997) determined that the CD39L1 gene comprises 9 exons covering less than 7 kb.
Chadwick and Frischauf (1997) isolated the human CD39L1 gene from a cDNA library enriched for transcripts from regions of chromosome 9q. The presence of the human ABC2 gene (600047) on an overlapping cosmid and hybridization to somatic cell panels suggested to Chadwick and Frischauf (1997) that CD39L1 maps to 9q34. A mouse homolog was isolated that shares greater than 78% nucleotide sequence identity with CD39L1. They mapped the mouse gene by fluorescence in situ hybridization to mouse chromosome 2, the syntenic region of human 9q34.
Chadwick, B. P., Frischauf, A.-M. Cloning and mapping of a human and mouse gene with homology to ecto-ATPase genes. Mammalian Genome 8: 668-672, 1997. [PubMed: 9271669] [Full Text: https://doi.org/10.1007/s003359900534]
Masse, K., Bhamra, S., Eason, R., Dale, N., Jones, E. A. Purine-mediated signalling triggers eye development. Nature 449: 1058-1062, 2007. [PubMed: 17960245] [Full Text: https://doi.org/10.1038/nature06189]
Munkonda, M. N., Kauffenstein, G., Kukulski, F., Levesque, S. A., Legendre, C., Pelletier, J., Lavoie, E. G., Lecka, J., Sevigny, J. Inhibition of human and mouse plasma membrane bound NTPDases by P2 receptor antagonists. Biochem. Pharm. 74: 1524-1534, 2007. [PubMed: 17727821] [Full Text: https://doi.org/10.1016/j.bcp.2007.07.033]