SUMMARY PARAGRAPH for FCY2
Fcy2p is a purine-cytosine permease that mediates the active transport of adenine, hypoxanthine, guanine and cytosine through the plasma membrane and into the cell (6, 7, 3, 4, 8). Fcy2p also shows a low affinity for cytidine, and mediates its transport into the cell, but is unable to transport uracil or ATP (6, 9, 10). The amino acids at positions 374 and 377 modulate the affinity of Fcy2p towards its substrates (11).
Fcy2p may be required for adenine repression of ADE genes (2), and its localization to the plasma membrane requires a functional secretory pathway and is reduced in mnn9 mutants (12, 3). Lithium chloride represses the transcription of FCY2 during growth on galactose (13), and Fcy2p activity is inhibited by 2,4-dinitrophenyl, sodium azide, chlorohexidine and 8-azidoadenine (14, 15). Fcy2p is phosphorylated in vivo either between the Golgi apparatus and the plasma membrane or in the plasma membrane itself (16), but the functional significance of this phosphorylation has not yet been determined (14). Fcy2p has also been reported to be glycosylated in vivo (10), but it was later shown that N-linked glycosylation is not required for the permease activity, and may not actually occur (17).
fcy2 null mutants are viable, but do not display normal repression of ADE5,7 and ADE1 in the presence of adenine, or of IMD2 in the presence of guanine. In addition, they are unable to take up guanine, adenine, hypoxanthine, 5-methylcytosine, or cytosine (18, 19, 3, 20). Further, fcy2 mutants are resistant to 8-azaadenine, 8-azaguanine, 5-fluorocytosine, 5-fluorouracil and the anti-cancer drug Cisplatin, and show weak resistance to the anti-cancer drug doxorubicin (18, 2, 19).
Although FCY2 is similar to FCY21 and FCY22, it does not appear that Fcy21p or Fcy22p are able to complement fcy2 mutants (21, 4). The hypoxanthine uptake defects of an fcy2 null mutant are functionally complemented by human ENT2, which is an equilibrative (Na+-independent) nucleoside transporter belonging to a family of integral membrane proteins with 11 transmembrane domains (TMs) that are distinguished functionally by differences in sensitivity to inhibition by nitrobenzylthioinosine and coronary vasoactive drugs. This family also includes human ENT1, and rat rENT1 and rENT2 (20).
Last updated: 2005-11-15