This protein is a 'fusion' protein encoding four enzymatic activities of the pyrimidine pathway (GATase, CPSase, ATCase and DHOase). 2 ATP + H2O + hydrogencarbonate + L-glutamine = 2 ADP + carbamoyl phosphate + 2 H(+) + L-glutamate + phosphate carbamoyl phosphate + L-aspartate = H(+) + N-carbamoyl-L-aspartate + phosphate (S)-dihydroorotate + H2O = H(+) + N-carbamoyl-L-aspartate Binds 3 Zn(2+) ions per subunit (for dihydroorotase activity). Binds 4 magnesium or manganese ions per subunit. Allosterically regulated and controlled by phosphorylation. 5-phosphoribose 1-diphosphate (PRPP) is an activator while UMP and UTP are inhibitors of the CPSase reaction (By similarity). Pyrimidine metabolism; UMP biosynthesis via de novo pathway; (S)-dihydroorotate from bicarbonate: step 1/3. Pyrimidine metabolism; UMP biosynthesis via de novo pathway; (S)-dihydroorotate from bicarbonate: step 2/3. Pyrimidine metabolism; UMP biosynthesis via de novo pathway; (S)-dihydroorotate from bicarbonate: step 3/3. Homohexamer. Interacts with CIPC. Cytosolic and unphosphorylated in resting cells, translocates to the nucleus in response to EGF stimulation, nuclear import promotes optimal cell growth. Activated by MAP kinase (Erk1/2) phosphorylation just prior to the S phase of the cell cycle, when the demand for pyrimidine nucleotides is greatest, and down-regulated as the cells emerge from S phase by protein kinase A (PKA) phosphorylation. Phosphorylation at Ser-1859 by RPS6KB1 downstream of MTOR promotes oligomerization and stimulates dihydroorotase activity. Phosphorylation at Ser-1406 reduces sensitivity to feedback inhibition by UTP (By similarity). GATase (glutamine amidotransferase) and CPSase (carbamoyl phosphate synthase) form together the glutamine-dependent CPSase (GD-CPSase) (EC 6.3.5.5). In the central section; belongs to the metallo-dependent hydrolases superfamily. DHOase family. CAD subfamily.