Concentrative nucleoside transporter (IPR008276)
Short name: C_nuclsd_transpt
Overlapping homologous superfamilies
- Concentrative nucleoside transporter (IPR008276)
Nucleosides are hydrophilic molecules and require specialised transport proteins for permeation of cell membranes. There are two types of nucleoside transport processes: equilibrative bidirectional processes driven by chemical gradients, and inwardly directed concentrative processes driven by an electrochemical gradient [PMID: 10353709]. The two types of nucleoside transporters are classified into two families: the solute carrier (SLC) 29 and SLC28 families, corresponding to equilibrative and concentrative nucleoside transporters, respectively [PMID: 23506887].
The microbial proteins include broad specificity transporters, such as the Escherichia coli NupC protein which transports all nucleosides (both ribo- and deoxyribonucleosides) except hypoxanthine and guanine nucleosides [PMID: 15678184]. Bacillus subtilis NupC transporter has been shown to be involved in transport of the pyrimidine nucleoside uridine [PMID: 8550462]. A recently characterised fungal protein, the first transporter of this type to be described in eukaryotes, exhibited transport activity for adenosine, uridine, inosine and guanosine but not cytidine, thymidine or the nucleobase hypoxanthine [PMID: 12794928].
The characterised mammalian proteins can be divided into three subgroups; CNT1, CNT2 and CNT3 [PMID: 16265592]. CNT1 preferentially transports pyrimidines and weakly transports adenosine. Several antiviral and anticancer nucleoside analogues, including AZT and dFdC are also substrates for CNT1. CNT2 selectively transports purines, and the human form has also been shown to facilitate the uptake of some antiviral compounds including ddI and ribavirin. CNT3 has a broader specificity, transporting both purines and pyrimidines. Several anticancer nucleoside analogues such as CdA, dFdC and FdU are also transported by CNT3. Substrate specificity appears to depend on a region containing transmembrane regions 7, 8 and 9. Mutation of just four residues in this region was sufficient to convert the activity of human CNT1 to that of CNT2. At least three other concentrative nucleoside transport activities have been described in mammalian cells, but the proteins responsible for these activities have not yet been identified.
This entry represents a family of Concentrative Nucleoside Transporter (CNT) proteins found in bacteria and eukaryotes. Most of the bacteria and fungi homologues identified are H+ symporters, while the mammalian members (CNT1/2/3) are mostly Na+ symporters. However, mammalian CNT3 exhibits uniquely broad cation interactions with Na+, H+, and Li+ and can couple transport of uridine to uptake of H(+) [PMID: 15870078, PMID: 17453413].
- PTHR10590 (PTHR10590)