Catalyzes the hydrolytic deamination of cytosine to uracil or 5-methylcytosine to thymine. Is involved in the pyrimidine salvage pathway, which allows the cell to utilize cytosine for pyrimidine nucleotide synthesis. cytosine + H(+) + H2O = NH4(+) + uracil kcat is 91 sec(-1) with cytosine as substrate and 17 sec(-1) with 5-fluorocytosine as substrate. Pyrimidine metabolism; UMP biosynthesis via salvage pathway; uracil from cytosine: step 1/1. Homodimer. Also catalyzes the conversion of 5-fluorocytosine (5FC) to 5-fluorouracil (5FU); this activity allows the formation of a cytotoxic chemotherapeutic agent from a non-cytotoxic precursor. yCD/5FC is one of the most widely used enzyme/prodrug combinations for gene-directed enzyme prodrug therapy (GDEPT) for the treatment of cancers. 5FU is an anticancer drug used to treat breast, colon, rectal, stomach, and pancreatic cancers, and is the drug of choice for treating colorectal carcinoma. However, the drug has high gastrointestinal and hematological toxicities. In contrast, the prodrug 5FC is fairly non-toxic to human, because of the lack of CD activity in human cells. By producing 5FU in the tumor, the CD/5FC system minimizes the undesired toxic effects of 5FU. Present with 5180 molecules/cell in log phase SD medium. Belongs to the cytidine and deoxycytidylate deaminase family.