MGP Database

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MGP000391

UniProt Annotations

Entry Information
Gene Namecarbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase
Protein EntryPYR1_HUMAN
UniProt IDP27708
SpeciesHuman
Comments
Comment typeDescription
Biophysicochemical PropertiesKinetic parameters: KM=28 uM for dihydroorotate {ECO:0000269|PubMed:24332717}; KM=241 uM for N-carbamoyl-L-aspartate {ECO:0000269|PubMed:24332717};
Catalytic Activity2 ATP + L-glutamine + HCO(3)(-) + H(2)O = 2 ADP + phosphate + L-glutamate + carbamoyl phosphate. {ECO:0000269|PubMed:24332717}.
Catalytic ActivityCarbamoyl phosphate + L-aspartate = phosphate + N-carbamoyl-L-aspartate. {ECO:0000269|PubMed:24332717}.
Catalytic Activity(S)-dihydroorotate + H(2)O = N-carbamoyl-L- aspartate. {ECO:0000269|PubMed:24332717}.
CofactorName=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000269|PubMed:24332717, ECO:0000269|PubMed:7766613}; Note=Binds 3 Zn(2+) ions per subunit (for dihydroorotase activity). {ECO:0000269|PubMed:24332717, ECO:0000269|PubMed:7766613};
Enzyme RegulationAllosterically regulated and controlled by phosphorylation. 5-phosphoribose 1-diphosphate (PRPP) is an activator while UMP and UTP are inhibitors of the CPSase reaction. {ECO:0000269|PubMed:11872754}.
FunctionThis protein is a "fusion" protein encoding four enzymatic activities of the pyrimidine pathway (GATase, CPSase, ATCase and DHOase). {ECO:0000269|PubMed:24332717}.
InductionTranscriptionally repressed following hypoxia by HIF1A. {ECO:0000269|PubMed:16155188}.
MiscellaneousGATase (glutamine amidotransferase) and CPSase (carbamoyl phosphate synthase) form together the glutamine- dependent CPSase (GD-CPSase) (EC 6.3.5.5).
PathwayPyrimidine metabolism; UMP biosynthesis via de novo pathway; (S)-dihydroorotate from bicarbonate: step 1/3.
PathwayPyrimidine metabolism; UMP biosynthesis via de novo pathway; (S)-dihydroorotate from bicarbonate: step 2/3.
PathwayPyrimidine metabolism; UMP biosynthesis via de novo pathway; (S)-dihydroorotate from bicarbonate: step 3/3.
PtmActivated 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. {ECO:0000269|PubMed:16964243, ECO:0000269|PubMed:17081983, ECO:0000269|PubMed:17485345, ECO:0000269|PubMed:18669648, ECO:0000269|PubMed:18691976, ECO:0000269|PubMed:20068231, ECO:0000269|PubMed:21406692, ECO:0000269|PubMed:23429703, ECO:0000269|PubMed:23429704}.
SimilarityContains 1 glutamine amidotransferase type-1 domain. {ECO:0000305}.
SimilarityContains 2 ATP-grasp domains. {ECO:0000305}.
SimilarityIn the central section; belongs to the DHOase family. {ECO:0000305}.
Subcellular LocationCytoplasm {ECO:0000269|PubMed:15890648}. Nucleus {ECO:0000269|PubMed:15890648}. Note=Cytosolic and unphosphorylated in resting cells, translocates to the nucleus in response to EGF stimulation, nuclear import promotes optimal cell growth.
SubunitHomohexamer. {ECO:0000269|PubMed:24332717}.
Web ResourceName=Wikipedia; Note=Aspartate carbamoyltransferase entry; URL="http://en.wikipedia.org/wiki/Aspartate_carbamoyltransferase";
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