InterPro : IPR005483

Name  Carbamoyl-phosphate synthase large subunit, CPSase domain Short Name  CbamoylP_synth_lsu_CPSase_dom
Type  Domain Description  Carbamoyl phosphate synthase (CPSase) is a heterodimeric enzyme composed of a small and a large subunit (with the exception of CPSase III, see below). 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 [, ]. CPSase has three active sites, one in the small subunit and two in the large subunit. The small subunit contains the glutamine binding site and catalyses the hydrolysis of glutamine to glutamate and ammonia. The large subunit has two homologous carboxy phosphate domains, both of which have ATP-binding sites; however, the N-terminal carboxy phosphate domain catalyses the phosphorylation of biocarbonate, while the C-terminal domain catalyses the phosphorylation of the carbamate intermediate []. The carboxy phosphate domain found duplicated in the large subunit of CPSase is also present as a single copy in the biotin-dependent enzymes acetyl-CoA carboxylase () (ACC), propionyl-CoA carboxylase () (PCCase), pyruvate carboxylase () (PC) and urea carboxylase ().Most prokaryotes carry one form of CPSase that participates in both arginine and pyrimidine biosynthesis, however certain bacteria can have separate forms. The large subunit in bacterial CPSase has four structural domains: the carboxy phosphate domain 1, the oligomerisation domain, the carbamoyl phosphate domain 2 and the allosteric domain []. CPSase heterodimers from Escherichiacolicontain two molecular tunnels: an ammonia tunnel and a carbamate tunnel. These inter-domain tunnels connect the three distinct active sites, and function as conduits for the transport of unstable reaction intermediates (ammonia and carbamate) between successive active sites []. The catalytic mechanism of CPSase involves the diffusion of carbamate through the interior of the enzyme from the site of synthesis within the N-terminal domain of the large subunit to the site of phosphorylation within the C-terminal domain.Eukaryotes have two distinct forms of CPSase: a mitochondrial enzyme (CPSase I) that participates in both arginine biosynthesis and the urea cycle; and a cytosolic enzyme (CPSase II) involved in pyrimidine biosynthesis. CPSase II occurs as part of a multi-enzyme complex along with aspartate transcarbamoylase and dihydroorotase; this complex is referred to as the CAD protein []. The hepatic expression of CPSase is transcriptionally regulated by glucocorticoids and/or cAMP []. There is a third form of the enzyme, CPSase III, found in fish, which uses glutamine as a nitrogen source instead of ammonia []. CPSase III is closely related to CPSase I, and is composed of a single polypeptide that may have arisen from gene fusion of the glutaminase and synthetase domains []. This entry represents the CPSase domain of the large subunit of carbamoyl phosphate synthase.

Sequence Features

GO Displayer


InterPro protein domain ID --> Contigs



0 Child Features

2 Contains

Id Name Short Name Type
IPR005481 Carbamoyl-phosphate synthase, large subunit, N-terminal CarbamoylP_synth_lsu_N Domain
IPR013816 ATP-grasp fold, subdomain 2 ATP_grasp_subdomain_2 Domain

1 Found In

Id Name Short Name Type
IPR006275 Carbamoyl-phosphate synthase, large subunit CarbamoylP_synth_lsu Family

1 Parent Features

Id Name Short Name Type
IPR005479 Carbamoyl-phosphate synthetase large subunit-like, ATP-binding domain CbamoylP_synth_lsu-like_ATP-bd Domain

9 Publications

First Author Title Year Journal Volume Pages
Raushel FM The amidotransferase family of enzymes: molecular machines for the production and delivery of ammonia. 1999 Biochemistry 38 7891-9
Thoden JB The structure of carbamoyl phosphate synthetase determined to 2.1 A resolution. 1999 Acta Crystallogr D Biol Crystallogr 55 8-24
Schoneveld OJ cyclicAMP and glucocorticoid responsiveness of the rat carbamoylphosphate synthetase gene requires the interplay of upstream regulatory units. 2007 Biochimie 89 574-80
Holden HM Carbamoyl phosphate synthetase: an amazing biochemical odyssey from substrate to product. 1999 Cell Mol Life Sci 56 507-22
Stapleton MA Role of conserved residues within the carboxy phosphate domain of carbamoyl phosphate synthetase. 1996 Biochemistry 35 14352-61
Kim J Structural defects within the carbamate tunnel of carbamoyl phosphate synthetase. 2002 Biochemistry 41 12575-81
Guy HI Cloning, expression, and functional interactions of the amidotransferase domain of mammalian CAD carbamyl phosphate synthetase. 1994 J Biol Chem 269 7702-8
Saha N Air-breathing catfish, Clarias batrachus upregulates glutamine synthetase and carbamyl phosphate synthetase III during exposure to high external ammonia. 2007 Comp Biochem Physiol B Biochem Mol Biol 147 520-30
Hong J Carbamyl phosphate synthetase III, an evolutionary intermediate in the transition between glutamine-dependent and ammonia-dependent carbamyl phosphate synthetases. 1994 J Mol Biol 243 131-40

To cite PlanMine, please refer to the following publication:

Rozanski, A., Moon, H., Brandl, H., Martín-Durán, J. M., Grohme, M., Hüttner, K., Bartscherer, K., Henry, I., & Rink, J. C.
PlanMine 3.0—improvements to a mineable resource of flatworm biology and biodiversity
Nucleic Acids Research, gky1070. doi:10.1093/nar/gky1070 (2018)