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The GDA1_CD39 superfamily: NTPDases with diverse functions

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Abstract

The first comprehensive review of the ubiquitous “ecto-ATPases” by Plesner was published in 1995. A year later, a lymphoid cell activation antigen, CD39, that had been cloned previously, was shown to be an ecto-ATPase. A family of proteins, related to CD39 and a yeast GDPase, all containing the canonical apyrase conserved regions in their polypeptides, soon started to expand. They are now recognized as members of the GDA1_CD39 protein family. Because proteins in this family hydrolyze nucleoside triphosphates and diphosphates, a unifying nomenclature, nucleoside triphosphate diphopshohydrolases (NTPDases), was established in 2000. Membrane-bound NTPDases are either located on the cell surface or membranes of intracellular organelles. Soluble NTPDases exist in the cytosol and may be secreted. In the last 15 years, molecular cloning and functional expression have facilitated biochemical characterization of NTPDases of many organisms, culminating in the recent structural determination of the ecto-domain of a mammalian cell surface NTPDase and a bacterial NTPDase. The first goal of this review is to summarize the biochemical, mutagenesis, and structural studies of the NTPDases. Because of their ability in hydrolyzing extracellular nucleotides, the mammalian cell surface NTPDases (the ecto-NTPDases) which regulate purinergic signaling have received the most attention. Less appreciated are the functions of intracellular NTPDases and NTPDases of other organisms, e.g., bacteria, parasites, Drosophila, plants, etc. The second goal of this review is to summarize recent findings which demonstrate the involvement of the NTPDases in multiple and diverse physiological processes: pathogen-host interaction, plant growth, eukaryote cell protein and lipid glycosylation, eye development, and oncogenesis.

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Abbreviations

NTPDase:

Nucleoside triphosphate diphosphohydrolase

ATPDase:

ATP diphosphohydrolase

ACR:

Apyrase conserved regions

ConA:

Concanavalin A

TM:

Transmembrane

TMD:

Transmembrane domains

ECD:

Extracellular domain

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Acknowledgments

The contributions of Charles Caldwell, Mae Wu-Weis, Jerry Chiang, Takashi Mukasa, Kyoko Yarimizu, Yonghee Lee, Reem Javed, Nicole Pelletier, and Cheryl Li to research in the authors’ laboratory are gratefully acknowledged. I also thank Bill Stumph and Sandy Bernstein for support and the California Metabolic Research Foundation for research funding.

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  1. Department of Chemistry and Biochemistry, San Diego State University, 5500 Campanile Drive, San Diego, CA, 92182-1030, USA

    Aileen F. Knowles

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Knowles, A.F. The GDA1_CD39 superfamily: NTPDases with diverse functions. Purinergic Signalling 7, 21–45 (2011). https://doi.org/10.1007/s11302-010-9214-7

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