FCY1_YEAST
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 03-AUG-2022, entry version 182.
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}.
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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; 61.
DR DIP; DIP-1662N; -.
DR IntAct; Q12178; 2.
DR MINT; Q12178; -.
DR STRING; 4932.YPR062W; -.
DR iPTMnet; Q12178; -.
DR MaxQB; Q12178; -.
DR PaxDb; Q12178; -.
DR PRIDE; Q12178; -.
DR EnsemblFungi; YPR062W_mRNA; YPR062W; YPR062W.
DR GeneID; 856175; -.
DR KEGG; sce:YPR062W; -.
DR SGD; S000006266; FCY1.
DR VEuPathDB; FungiDB:YPR062W; -.
DR eggNOG; KOG1018; Eukaryota.
DR HOGENOM; CLU_025810_7_2_1; -.
DR InParanoid; Q12178; -.
DR OMA; AILHAEM; -.
DR BioCyc; MetaCyc:YPR062W-MON; -.
DR BioCyc; YEAST:YPR062W-MON; -.
DR BRENDA; 3.5.4.1; 984.
DR UniPathway; UPA00574; UER00635.
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: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 InterPro; IPR016192; APOBEC/CMP_deaminase_Zn-bd.
DR InterPro; IPR002125; CMP_dCMP_dom.
DR InterPro; IPR016193; Cytidine_deaminase-like.
DR Pfam; PF00383; dCMP_cyt_deam_1; 1.
DR SUPFAM; SSF53927; SSF53927; 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
