CAD protein
This protein is a "fusion" protein encoding four enzymatic activities of the pyrimidine pathway (GATase, CPSase, ATCase and DHOase).
Including the following 3 domains:
Glutamine-dependent carbamoyl-phosphate synthase
EC=6.3.5.5
2 ATP + L-glutamine + HCO3- + H2O = 2 ADP + phosphate + L-glutamate + carbamoyl phosphate.
Aspartate carbamoyltransferase
EC=2.1.3.2
Carbamoyl phosphate + L-aspartate = phosphate + N-carbamoyl-L-aspartate.
Dihydroorotase
EC=3.5.2.3
(S)-dihydroorotate + H2O = N-carbamoyl-L-aspartate.
Enzyme regulation
Allosterically regulated and controlled by phosphorylation. 5-phosphoribose 1-diphosphate (PRPP) is an activator while UMP and UTP are inhibitors of the CPSase reaction.
Post-translational modification
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 sensitivy to feedback inhibition by UTP.
Dihydroorotate dehydrogenase (quinone), mitochondrial
Short name=DHOdehase
EC=1.3.5.2
Alternative name(s):
Dihydroorotate oxidase
- Catalyzes the conversion of dihydroorotate to orotate with quinone as electron acceptor.
- Binds 1 FMN per subunit.
- Mitochondrion inner membrane; Single-pass membrane protein.
- MILLER SYNDROME OMIN #263750
Uridine 5'-monophosphate synthase
Short name=UMP synthase
Including the following 2 domains:
Orotate phosphoribosyltransferase
Short name=OPRT
Short name=OPRTase
EC=2.4.2.10
Orotidine 5'-phosphate decarboxylase
Short name=ODC
EC=4.1.1.23
Alternative name(s):
OMPdecase
CTP synthase 1
EC=6.3.4.2
Alternative name(s):
CTP synthetase 1
UTP--ammonia ligase 1
- Catalyzes the ATP-dependent amination of UTP to CTP with either L-glutamine or ammonia as the source of nitrogen.
