CAD protein; includes: glutamine-dependent carbamoyl-phosphate synthase; aspartate carbamoyltransferase; dihydroorotase (CAD)

Function

• fusion protein encoding four enzymatic activities of the pyrimidine pathway (GATase, CPSase, ATCase & DHOase)
• allosterically regulated & controlled by phosphorylation
• 5-phosphoribose 1-diphosphate is an activator
• UMP is an inhibitor of the CPSase reaction
• pyrimidine metabolism; UMP biosynthesis via de novo pathway

2 ATP + L-glutamine + HCO3- + H2O = 2 ADP + phosphate + L-glutamate + carbamoyl phosphate

carbamoyl phosphate + L-aspartate = phosphate + N-carbamoyl-L-aspartate

(S)-dihydroorotate + H2O = N-carbamoyl-L-aspartate

Cofactor:

• binds 1 Zn+2 per subunit (for dihydroorotase activity) (putative)

Structure

• homohexamer
• in the central section; belongs to the DHOase family
• contains 2 ATP-grasp domains
• contains 1 glutamine amidotransferase type-1 domain

Compartment

cytoplasm

Comparative biology

• in mammalian cells carbamoyl phosphate synthase (glutamine), aspartate transcarbamoylase, & dihydroorotase are combined on a single polypeptide chain

Notes

• GATase (glutamine amidotransferase) & CPSase (carbamoyl phosphate synthase) form together the glutamine-dependent CPSase (GD-CPSase)

More general terms

• carbamoyl phosphate synthase
• amidohydrolase
• transferase
• phosphoprotein

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=790
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:790
• OMIM: https://mirror.omim.org/entry/114010
• UniProt: http://www.uniprot.org/uniprot/P27708.html