Solute Carrier Family 28

The concentrative nucleoside transporter family, SLC28, consists of three subtypes of sodium-dependent, concentrative nucleoside transporters, CNT1 (SLC28A1), CNT2 (also called the sodium-dependent purine nucleoside transporter SPNT, SLC28A2), and CNT3 (SLC28A3). These proteins are membrane-bound transporters that transport nucleosides and nucleoside analogs actively into cells by coupling transport to the inwardly directed sodium gradient. They transport both naturally occurring nucleosides and synthetic nucleoside analogs for the treatment of various diseases.

Although there is no known disease state associated with this family, these transporters play a role in the pharmacokinetics and pharmacodynamics of antineoplastic and antiviral nucleoside analogs due to their tissue localization and specificity for therapeutic nucleoside analogs. Early studies in isolated mammalian tissues and cell lines have shown that nucleoside uptake is characterized by low-affinity and high-affinity systems and that the high-affinity system(s) is active, concentrative, and Na⁺-dependent. The low-affinity system is now considered to be the equilibrative nucleoside transporter (ENT) family, SLC29, while SLC28 is responsible for high-affinity transport.

Members of the SLC28 actively transport nucleosides and nucleoside analogs into cells by coupling transport to the inwardly directed sodium gradient. CNT1 preferentially transports pyrimidine nucleosides; CNT2 preferentially transports purine nucleosides; CNT3 transports both pyrimidine and purine nucleosides. CNT3 has a 1:2 nucleoside to sodium ratio. Fig.1 SLC28 family members transport purine and pyrimidine nucleosides. (Gray, 2004)

Here show three subtypes of SLC28 family, SLC28A1, SLC28A2, and SLC28A3, which differ in their substrate specificities. SLC28A1 is pyrimidine nucleoside preferring. CNT2 is purine-nucleoside preferring, and CNT3 transports both pyrimidine and purine nucleosides.

Human SLC28 Family Members
SLC28A1	SLC28A2	SLC28A3

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Reference

Gray J H, et al. (2004). The concentrative nucleoside transporter family, SLC28. Pflugers Arch. 447(5): 728-34.

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