ID FCY1_YEAST Reviewed; 158 AA. AC Q12178; D6W467; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1996, sequence version 1. DT 27-MAR-2024, entry version 188. DE RecName: Full=Cytosine deaminase {ECO:0000303|PubMed:9000374}; DE Short=yCD; DE EC=3.5.4.1 {ECO:0000269|PubMed:9000374}; DE AltName: Full=Cytosine aminohydrolase; DE AltName: Full=Fluorocytosine resistance protein 1 {ECO:0000303|PubMed:9000374}; GN Name=FCY1 {ECO:0000303|PubMed:9000374}; OrderedLocusNames=YPR062W; GN ORFNames=YP9499.17; OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast). OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes; OC Saccharomycetales; Saccharomycetaceae; Saccharomyces. OX NCBI_TaxID=559292; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND CATALYTIC ACTIVITY. RC STRAIN=ATCC 28383 / FL100 / VTT C-80102; RX PubMed=9000374; DOI=10.1007/s002940050169; RA Erbs P., Exinger F., Jund R.; RT "Characterization of the Saccharomyces cerevisiae FCY1 gene encoding RT cytosine deaminase and its homologue FCA1 of Candida albicans."; RL Curr. Genet. 31:1-6(1997). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=334; RA Senter P.D., Su P.C.D., Marquardt H., Hayden M.S., Linsley P.S.; RT "Isolation of thermally stable cytosine deaminase from baker's yeast."; RL Submitted (AUG-1997) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 204508 / S288c; RX PubMed=9169875; RA Bussey H., Storms R.K., Ahmed A., Albermann K., Allen E., Ansorge W., RA Araujo R., Aparicio A., Barrell B.G., Badcock K., Benes V., Botstein D., RA Bowman S., Brueckner M., Carpenter J., Cherry J.M., Chung E., RA Churcher C.M., Coster F., Davis K., Davis R.W., Dietrich F.S., Delius H., RA DiPaolo T., Dubois E., Duesterhoeft A., Duncan M., Floeth M., Fortin N., RA Friesen J.D., Fritz C., Goffeau A., Hall J., Hebling U., Heumann K., RA Hilbert H., Hillier L.W., Hunicke-Smith S., Hyman R.W., Johnston M., RA Kalman S., Kleine K., Komp C., Kurdi O., Lashkari D., Lew H., Lin A., RA Lin D., Louis E.J., Marathe R., Messenguy F., Mewes H.-W., Mirtipati S., RA Moestl D., Mueller-Auer S., Namath A., Nentwich U., Oefner P., Pearson D., RA Petel F.X., Pohl T.M., Purnelle B., Rajandream M.A., Rechmann S., RA Rieger M., Riles L., Roberts D., Schaefer M., Scharfe M., Scherens B., RA Schramm S., Schroeder M., Sdicu A.-M., Tettelin H., Urrestarazu L.A., RA Ushinsky S., Vierendeels F., Vissers S., Voss H., Walsh S.V., Wambutt R., RA Wang Y., Wedler E., Wedler H., Winnett E., Zhong W.-W., Zollner A., RA Vo D.H., Hani J.; RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome XVI."; RL Nature 387:103-105(1997). RN [4] RP GENOME REANNOTATION. RC STRAIN=ATCC 204508 / S288c; RX PubMed=24374639; DOI=10.1534/g3.113.008995; RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R., RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S., RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.; RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now."; RL G3 (Bethesda) 4:389-398(2014). RN [5] RP FUNCTION, AND PATHWAY. RX PubMed=10501935; DOI=10.1007/s002940050482; RA Kurtz J.-E., Exinger F., Erbs P., Jund R.; RT "New insights into the pyrimidine salvage pathway of Saccharomyces RT cerevisiae: requirement of six genes for cytidine metabolism."; RL Curr. Genet. 36:130-136(1999). RN [6] RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS]. RX PubMed=14562095; DOI=10.1038/nature02026; RA Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W., RA Weissman J.S., O'Shea E.K.; RT "Global analysis of protein localization in budding yeast."; RL Nature 425:686-691(2003). RN [7] RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS]. RX PubMed=14562106; DOI=10.1038/nature02046; RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N., RA O'Shea E.K., Weissman J.S.; RT "Global analysis of protein expression in yeast."; RL Nature 425:737-741(2003). RN [8] RP FUNCTION. RX PubMed=15535715; DOI=10.1021/ja046462k; RA Sklenak S., Yao L., Cukier R.I., Yan H.; RT "Catalytic mechanism of yeast cytosine deaminase: an ONIOM computational RT study."; RL J. Am. Chem. Soc. 126:14879-14889(2004). RN [9] RP CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND BIOTECHNOLOGY. RX PubMed=15823054; DOI=10.1021/bi050095n; RA Yao L., Li Y., Wu Y., Liu A., Yan H.; RT "Product release is rate-limiting in the activation of the prodrug 5- RT fluorocytosine by yeast cytosine deaminase."; RL Biochemistry 44:5940-5947(2005). RN [10] RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) IN COMPLEX WITH SUBSTRATE ANALOG AND RP ZINC IONS, AND ACTIVE SITE. RX PubMed=12637534; DOI=10.1074/jbc.m300874200; RA Ko T.-P., Lin J.-J., Hu C.-Y., Hsu Y.-H., Wang A.H.-J., Liaw S.-H.; RT "Crystal structure of yeast cytosine deaminase. Insights into enzyme RT mechanism and evolution."; RL J. Biol. Chem. 278:19111-19117(2003). RN [11] RP X-RAY CRYSTALLOGRAPHY (1.14 ANGSTROMS) IN COMPLEX WITH SUBSTRATE ANALOG AND RP ZINC IONS, AND SUBUNIT. RX PubMed=12906827; DOI=10.1016/s0969-2126(03)00153-9; RA Ireton G.C., Black M.E., Stoddard B.L.; RT "The 1.14 A crystal structure of yeast cytosine deaminase: evolution of RT nucleotide salvage enzymes and implications for genetic chemotherapy."; RL Structure 11:961-972(2003). RN [12] RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) IN COMPLEX WITH ZINC IONS. RX PubMed=15879217; DOI=10.1126/science.1107387; RA Korkegian A., Black M.E., Baker D., Stoddard B.L.; RT "Computational thermostabilization of an enzyme."; RL Science 308:857-860(2005). CC -!- FUNCTION: Catalyzes the hydrolytic deamination of cytosine to uracil or CC 5-methylcytosine to thymine. Is involved in the pyrimidine salvage CC pathway, which allows the cell to utilize cytosine for pyrimidine CC nucleotide synthesis. {ECO:0000269|PubMed:10501935, CC ECO:0000269|PubMed:9000374}. CC -!- CATALYTIC ACTIVITY: CC Reaction=cytosine + H(+) + H2O = NH4(+) + uracil; Xref=Rhea:RHEA:20605, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:16040, CC ChEBI:CHEBI:17568, ChEBI:CHEBI:28938; EC=3.5.4.1; CC Evidence={ECO:0000269|PubMed:9000374}; CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; CC Evidence={ECO:0000269|PubMed:12637534, ECO:0000269|PubMed:12906827, CC ECO:0000269|PubMed:15879217}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=1.1 mM for cytosine {ECO:0000269|PubMed:15823054}; CC KM=0.16 mM for 5-fluorocytosine {ECO:0000269|PubMed:15823054}; CC Note=kcat is 91 sec(-1) with cytosine as substrate and 17 sec(-1) CC with 5-fluorocytosine as substrate. {ECO:0000269|PubMed:15823054}; CC -!- PATHWAY: Pyrimidine metabolism; UMP biosynthesis via salvage pathway; CC uracil from cytosine: step 1/1. {ECO:0000269|PubMed:10501935, CC ECO:0000305|PubMed:10501935}. CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:12906827}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14562095}. Nucleus CC {ECO:0000269|PubMed:14562095}. CC -!- BIOTECHNOLOGY: Also catalyzes the conversion of 5-fluorocytosine (5FC) CC to 5-fluorouracil (5FU); this activity allows the formation of a CC cytotoxic chemotherapeutic agent from a non-cytotoxic precursor. CC yCD/5FC is one of the most widely used enzyme/prodrug combinations for CC gene-directed enzyme prodrug therapy (GDEPT) for the treatment of CC cancers. 5FU is an anticancer drug used to treat breast, colon, rectal, CC stomach, and pancreatic cancers, and is the drug of choice for treating CC colorectal carcinoma. However, the drug has high gastrointestinal and CC hematological toxicities. In contrast, the prodrug 5FC is fairly non- CC toxic to human, because of the lack of CD activity in human cells. By CC producing 5FU in the tumor, the CD/5FC system minimizes the undesired CC toxic effects of 5FU. {ECO:0000305|PubMed:15823054}. CC -!- MISCELLANEOUS: Present with 5180 molecules/cell in log phase SD medium. CC {ECO:0000269|PubMed:14562106}. CC -!- SIMILARITY: Belongs to the cytidine and deoxycytidylate deaminase CC family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U55193; AAC13409.1; -; Genomic_DNA. DR EMBL; AF005261; AAB67713.1; -; Genomic_DNA. DR EMBL; Z71255; CAA95006.1; -; Genomic_DNA. DR EMBL; Z49219; CAA89179.1; -; Genomic_DNA. DR EMBL; BK006949; DAA11483.1; -; Genomic_DNA. DR PIR; S54083; S54083. DR RefSeq; NP_015387.1; NM_001184159.1. DR PDB; 1OX7; X-ray; 1.43 A; A/B=1-158. DR PDB; 1P6O; X-ray; 1.14 A; A/B=1-158. DR PDB; 1RB7; X-ray; 2.10 A; A/B=1-158. DR PDB; 1UAQ; X-ray; 1.60 A; A/B=1-158. DR PDB; 1YSB; X-ray; 1.70 A; A/B=1-158. DR PDB; 1YSD; X-ray; 1.90 A; A/B=1-158. DR PDB; 2O3K; X-ray; 2.30 A; A/B=1-158. DR PDBsum; 1OX7; -. DR PDBsum; 1P6O; -. DR PDBsum; 1RB7; -. DR PDBsum; 1UAQ; -. DR PDBsum; 1YSB; -. DR PDBsum; 1YSD; -. DR PDBsum; 2O3K; -. DR AlphaFoldDB; Q12178; -. DR SMR; Q12178; -. DR BioGRID; 36235; 63. DR DIP; DIP-1662N; -. DR IntAct; Q12178; 2. DR MINT; Q12178; -. DR STRING; 4932.YPR062W; -. DR iPTMnet; Q12178; -. DR MaxQB; Q12178; -. DR PaxDb; 4932-YPR062W; -. DR PeptideAtlas; Q12178; -. DR EnsemblFungi; YPR062W_mRNA; YPR062W; YPR062W. DR GeneID; 856175; -. DR KEGG; sce:YPR062W; -. DR AGR; SGD:S000006266; -. DR SGD; S000006266; FCY1. DR VEuPathDB; FungiDB:YPR062W; -. DR eggNOG; KOG1018; Eukaryota. DR HOGENOM; CLU_025810_7_2_1; -. DR InParanoid; Q12178; -. DR OMA; MCTGACL; -. DR OrthoDB; 1126721at2759; -. DR BioCyc; MetaCyc:YPR062W-MONOMER; -. DR BioCyc; YEAST:YPR062W-MONOMER; -. DR BRENDA; 3.5.4.1; 984. DR UniPathway; UPA00574; UER00635. DR BioGRID-ORCS; 856175; 1 hit in 10 CRISPR screens. DR EvolutionaryTrace; Q12178; -. DR PRO; PR:Q12178; -. DR Proteomes; UP000002311; Chromosome XVI. DR RNAct; Q12178; Protein. DR GO; GO:0005737; C:cytoplasm; HDA:SGD. DR GO; GO:0005634; C:nucleus; HDA:SGD. DR GO; GO:0102480; F:5-fluorocytosine deaminase activity; IEA:UniProtKB-EC. DR GO; GO:0004131; F:cytosine deaminase activity; IDA:SGD. DR GO; GO:0008835; F:diaminohydroxyphosphoribosylaminopyrimidine deaminase activity; IBA:GO_Central. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0046087; P:cytidine metabolic process; IMP:SGD. DR GO; GO:0019858; P:cytosine metabolic process; IMP:SGD. DR GO; GO:0008655; P:pyrimidine-containing compound salvage; IMP:SGD. DR GO; GO:0044206; P:UMP salvage; IEA:UniProtKB-UniPathway. DR CDD; cd00786; cytidine_deaminase-like; 1. DR Gene3D; 3.40.140.10; Cytidine Deaminase, domain 2; 1. DR InterPro; IPR016192; APOBEC/CMP_deaminase_Zn-bd. DR InterPro; IPR002125; CMP_dCMP_dom. DR InterPro; IPR016193; Cytidine_deaminase-like. DR PANTHER; PTHR11079:SF179; CYTOSINE DEAMINASE; 1. DR PANTHER; PTHR11079; CYTOSINE DEAMINASE FAMILY MEMBER; 1. DR Pfam; PF00383; dCMP_cyt_deam_1; 1. DR SUPFAM; SSF53927; Cytidine deaminase-like; 1. DR PROSITE; PS00903; CYT_DCMP_DEAMINASES_1; 1. DR PROSITE; PS51747; CYT_DCMP_DEAMINASES_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Cytoplasm; Hydrolase; Metal-binding; Nucleus; KW Reference proteome; Zinc. FT CHAIN 1..158 FT /note="Cytosine deaminase" FT /id="PRO_0000171702" FT DOMAIN 9..129 FT /note="CMP/dCMP-type deaminase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01083" FT ACT_SITE 64 FT /note="Proton donor" FT /evidence="ECO:0000269|PubMed:12637534, FT ECO:0007744|PDB:1UAQ" FT BINDING 51 FT /ligand="substrate" FT /evidence="ECO:0000269|PubMed:12637534, FT ECO:0000269|PubMed:12906827, ECO:0007744|PDB:1P6O, FT ECO:0007744|PDB:1UAQ" FT BINDING 62 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:12637534, FT ECO:0000269|PubMed:12906827, ECO:0000269|PubMed:15879217, FT ECO:0007744|PDB:1OX7, ECO:0007744|PDB:1P6O, FT ECO:0007744|PDB:1RB7, ECO:0007744|PDB:1UAQ, FT ECO:0007744|PDB:1YSB, ECO:0007744|PDB:1YSD" FT BINDING 91 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:12637534, FT ECO:0000269|PubMed:12906827, ECO:0000269|PubMed:15879217, FT ECO:0007744|PDB:1OX7, ECO:0007744|PDB:1P6O, FT ECO:0007744|PDB:1RB7, ECO:0007744|PDB:1UAQ, FT ECO:0007744|PDB:1YSB, ECO:0007744|PDB:1YSD" FT BINDING 94 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:12637534, FT ECO:0000269|PubMed:12906827, ECO:0000269|PubMed:15879217, FT ECO:0007744|PDB:1OX7, ECO:0007744|PDB:1P6O, FT ECO:0007744|PDB:1RB7, ECO:0007744|PDB:1UAQ, FT ECO:0007744|PDB:1YSB, ECO:0007744|PDB:1YSD" FT BINDING 155 FT /ligand="substrate" FT /evidence="ECO:0000269|PubMed:12637534, FT ECO:0000269|PubMed:12906827, ECO:0007744|PDB:1P6O, FT ECO:0007744|PDB:1UAQ" FT HELIX 11..27 FT /evidence="ECO:0007829|PDB:1P6O" FT STRAND 34..39 FT /evidence="ECO:0007829|PDB:1P6O" FT TURN 40..42 FT /evidence="ECO:0007829|PDB:1P6O" FT STRAND 45..50 FT /evidence="ECO:0007829|PDB:1P6O" FT HELIX 53..56 FT /evidence="ECO:0007829|PDB:1P6O" FT HELIX 63..71 FT /evidence="ECO:0007829|PDB:1P6O" FT HELIX 76..79 FT /evidence="ECO:0007829|PDB:1P6O" FT STRAND 82..88 FT /evidence="ECO:0007829|PDB:1P6O" FT HELIX 92..101 FT /evidence="ECO:0007829|PDB:1P6O" FT STRAND 105..113 FT /evidence="ECO:0007829|PDB:1P6O" FT HELIX 118..124 FT /evidence="ECO:0007829|PDB:1P6O" FT STRAND 128..131 FT /evidence="ECO:0007829|PDB:1P6O" FT HELIX 135..147 FT /evidence="ECO:0007829|PDB:1P6O" FT HELIX 149..155 FT /evidence="ECO:0007829|PDB:1P6O" SQ SEQUENCE 158 AA; 17507 MW; 19DB41E9AF26ADDC CRC64; MVTGGMASKW DQKGMDIAYE EAALGYKEGG VPIGGCLINN KDGSVLGRGH NMRFQKGSAT LHGEISTLEN CGRLEGKVYK DTTLYTTLSP CDMCTGAIIM YGIPRCVVGE NVNFKSKGEK YLQTRGHEVV VVDDERCKKI MKQFIDERPQ DWFEDIGE //