Carbamoyl-phosphate synthase small subunit, GATase1 domain (IPR035686)

Short name: CPSase_GATase1

Overlapping homologous superfamilies

Domain relationships


Glutamine amidotransferase (GATase) enzymes catalyse the removal of the ammonia group from glutamine and then transfer this group to a substrate to form a new carbon-nitrogen group [PMID: 4355768]. The GATase domain exists either as a separate polypeptidic subunit or as part of a larger polypeptide fused in different ways to a synthase domain. Two classes of GATase domains have been identified [PMID: 3298209, PMID: 6086650]: class-I (also known as trpG-type or triad) and class-II (also known as purF-type or Ntn). In class I glutamine amidotransferases, a triad of conserved Cys-His-Glu forms the active site, wherein the catalytic cysteine is essential for the amidotransferase activity [PMID: 8548458, PMID: 9575335]. Different structures show that the active site Cys of type 1 GATase is located at the tip of a nucleophile elbow.

The E.coli carbamoyl phosphate synthase (CPSase) is a heterodimeric enzyme composed of a small and a large subunit (with the exception of CPSase III). CPSase catalyses the synthesis of carbamoyl phosphate from biocarbonate, ATP and glutamine or ammonia, and represents the first committed step in pyrimidine and arginine biosynthesis in prokaryotes and eukaryotes, and in the urea cycle in most terrestrial vertebrates [PMID: 10387030, PMID: 11212301]. The small subunit catalyses the hydrolysis of glutamine to ammonia, which in turn used by the large chain to synthesize carbamoyl phosphate. The C-terminal domain of the small subunit of CPSase has glutamine amidotransferase activity.

In animals CPSase small subunit is part of a fusion protein, CAD, which combines enzymatic activities of the pyrimidine pathway (glutamine-dependent carbamyl phosphate synthetase (GLN-CPSase), aspartate transcarbamylase (ATCase), and dihydroorotase (DHOase)) [PMID: 24332717]. In fungi, the CAD-like protein Ura2 is a fusion protein with CPSase and ATCase activity, but without DHOase activity, which is provided by a separate protein [PMID: 24332717].

This entry represents the class-I GATase domain of the CPSase small subunit.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.