The equilibrative nucleoside transporter family, SLC29, consists of four members, called equilibrative nucleoside transporters (ENTs) due to the characteristics of the first family member hENT1 (SLC29A1). The proteins belonging to the widely distributed eukaryotic ENT family of equilibrative and concentrative nucleoside/nucleobase transporters. All four isoforms are widely distributed in mammalian tissues, although their relative abundance is different. In polarized cells, ENT1 and ENT2 are present in the basolateral membrane. They are in tandem with the SLC28 family of transporters, maybe function in transepithelial nucleoside transport. ENT2 is particularly abundant in skeletal muscle. All four members are strongly associated with the lysosomal membrane protein, CLN3, mutations in which cause neuronal ceroid lipofuscinosis. The predicted topology of 11 transmembrane helices with the cytoplasmic N-terminus and extracellular C-terminus of hENT1 has been experimentally confirmed. As the most characteristic members of this family, hENT1, and hENT2 have similar broad substrate specificities for pyrimidine and purine nucleosides. hENT2 can efficiently transport nucleobases. Recently, ENT3 and ENT4 have also been shown to be genuine nucleoside transporters. Transporters play a key role in nucleoside and nucleobase uptake in the salvage pathway for nucleotide synthesis. They are also responsible for cellular uptake of nucleoside analogs for the treatment of viral diseases and cancer. Moreover, by modulating the concentration of adenosine available to cell surface receptors, they affect many physiological processes, from cardiovascular activity to neurotransmission.
Fig.1 Phylogenetic tree of the human SLC29 amino acid sequences, showing a distant relationship to the human CLN3 protein (GenBank accession NP_000077). (Baldwin, 2004)
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