FCY2/YER056C Summary Help

Standard Name FCY2 1
Systematic Name YER056C
Alias BRA7 2
Feature Type ORF, Verified
Description Purine-cytosine permease; mediates purine (adenine, guanine, and hypoxanthine) and cytosine accumulation; relative distribution to the vacuole increases upon DNA replication stress (3, 4, 5 and see Summary Paragraph)
Name Description FluoroCYtosine resistance
Chromosomal Location
ChrV:268113 to 266512 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Genetic position: 49 cM
Gene Ontology Annotations All FCY2 GO evidence and references
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Regulators 15 genes
Classical genetics
Large-scale survey
65 total interaction(s) for 46 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 4
  • Affinity Capture-RNA: 3
  • PCA: 6

Genetic Interactions
  • Negative Genetic: 44
  • Phenotypic Suppression: 1
  • Positive Genetic: 4
  • Synthetic Growth Defect: 2
  • Synthetic Rescue: 1

Expression Summary
Length (a.a.) 533
Molecular Weight (Da) 58,201
Isoelectric Point (pI) 4.96
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrV:268113 to 266512 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Genetic position: 49 cM
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Most Recent Updates
Coordinates Sequence
CDS 1..1602 268113..266512 2011-02-03 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
External Links All Associated Seq | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | TCDB | UniProtKB
Primary SGDIDS000000858

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 Contact SGD

References cited on this page View Complete Literature Guide for FCY2
1) Weber, E.  (1989) Personal Communication, Mortimer Map Edition 10
2) Guetsova ML, et al.  (1997) The isolation and characterization of Saccharomyces cerevisiae mutants that constitutively express purine biosynthetic genes. Genetics 147(2):383-97
3) Ferreira T, et al.  (1997) Functional analysis of mutated purine-cytosine permease from Saccharomyces cerevisiae. A possible role of the hydrophilic segment 371-377 in the active carrier conformation. J Biol Chem 272(15):9697-702
4) Wagner R, et al.  (2001) New plasmid system to select for Saccharomyces cerevisiae purine-cytosine permease affinity mutants. J Bacteriol 183(14):4386-8
5) Tkach JM, et al.  (2012) Dissecting DNA damage response pathways by analysing protein localization and abundance changes during DNA replication stress. Nat Cell Biol 14(9):966-76
6) Kurtz JE, et al.  (1999) New insights into the pyrimidine salvage pathway of Saccharomyces cerevisiae: requirement of six genes for cytidine metabolism. Curr Genet 36(3):130-6
7) Ferreira T, et al.  (1999) Screening of an intragenic second-site suppressor of purine-cytosine permease from Saccharomyces cerevisiae. Possible role of Ser272 in the base translocation process. Eur J Biochem 260(1):22-30
8) Hopkins P, et al.  (1992) Fluorocytosine causes uncoupled dissipation of the proton gradient and behaves as an imperfect substrate of the yeast cytosine permease. Yeast 8(12):1053-64
9) Mitterbauer R, et al.  (2002) Saccharomyces cerevisiae URH1 (encoding uridine-cytidine N-ribohydrolase): functional complementation by a nucleoside hydrolase from a protozoan parasite and by a mammalian uridine phosphorylase. Appl Environ Microbiol 68(3):1336-43
10) Schmidt R, et al.  (1984) Photoaffinity labeling and characterization of the cloned purine-cytosine transport system in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 81(20):6276-80
11) Bloch JC, et al.  (1992) Determination of a specific region of the purine-cytosine permease involved in the recognition of its substrates. Mol Microbiol 6(20):2989-97
12) Weber E, et al.  (1990) The purine-cytosine permease gene of Saccharomyces cerevisiae: primary structure and deduced protein sequence of the FCY2 gene product. Mol Microbiol 4(4):585-96
13) Mitterbauer R, et al.  (2003) A sensitive and inexpensive yeast bioassay for the mycotoxin zearalenone and other compounds with estrogenic activity. Appl Environ Microbiol 69(2):805-11
14) Vickers MF, et al.  (2001) Functional production of mammalian concentrative nucleoside transporters in Saccharomyces cerevisiae. Mol Membr Biol 18(1):73-9
15) Chirio MC, et al.  (1990) Photoaffinity labelling of the purine-cytosine permease of Saccharomyces cerevisiae. Eur J Biochem 194(1):293-9
16) Pinson B, et al.  (1996) In vivo phosphorylation of the purine/cytosine permease from the plasma membrane of the yeast Saccharomyces cerevisiae. Eur J Biochem 239(2):439-44
17) Rodriguez C, et al.  (1995) The immunodetected yeast purine-cytosine permease is not N-linked glycosylated, nor are glycosylation sequences required to have a functional permease. Yeast 11(1):15-23
18) Huang RY, et al.  (2005) Genome-wide screen identifies genes whose inactivation confer resistance to cisplatin in Saccharomyces cerevisiae. Cancer Res 65(13):5890-7
19) Escobar-Henriques M and Daignan-Fornier B  (2001) Transcriptional regulation of the yeast gmp synthesis pathway by its end products. J Biol Chem 276(2):1523-30
20) Yao SY, et al.  (2002) Functional and molecular characterization of nucleobase transport by recombinant human and rat equilibrative nucleoside transporters 1 and 2. Chimeric constructs reveal a role for the ENT2 helix 5-6 region in nucleobase translocation. J Biol Chem 277(28):24938-48
21) Nelissen B, et al.  (1995) Phylogenetic classification of the major superfamily of membrane transport facilitators, as deduced from yeast genome sequencing. FEBS Lett 377(2):232-6