Purine-cytosine permease (FCY2) (FCY2)

Fungal cytosine permease, primarily encoded by the FCY2 gene, is a membrane-bound transporter responsible for the uptake of cytosine and purines such as adenine, guanine, and hypoxanthine into fungal cells [UniProt, PubMed]. It belongs to the Nucleobase-Cation Symporter-1 (NCS1) family and operates as an energy-dependent symporter [PubMed, NIH]. This protein is a critical therapeutic target because it facilitates the entry of the antifungal prodrug flucytosine (5-fluorocytosine) into susceptible fungi, such as Candida and Cryptococcus species [NIH, MDPI]. Once inside the cell, flucytosine is converted by cytosine deaminase into 5-fluorouracil, which subsequently inhibits DNA and RNA synthesis [NIH, PubMed]. Because human cells lack a functional equivalent of this specific cytosine permease, the pathway provides a high degree of selective toxicity [NIH]. However, mutations in the FCY2 gene are a common mechanism of clinical resistance to flucytosine, often necessitating its use in combination with other antifungals like amphotericin B [MDPI, PubMed].

Other names

Cytosine permeaseCytosine-purine permeasePurine-cytosine transporterFCY2pNucleobase transport protein

Facilitates the intracellular uptake of the prodrug flucytosine into fungal cells.