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. 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 (PubMed:2995985). Interacts with CIPC (By similarity). 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 (By similarity). Phosphorylation at Ser-1406 reduces sensitivity to feedback inhibition by UTP. 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.