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Protein Domain : 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 Escherichia colicontain 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.

Publication Counts Displayer

0 Child Features

2 Contains

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

1 Cross References

Identifier
Source . Name

Subject . Primary Identifier
PR00098 PRINTS IPR005483

3 Data Sets

Name URL
TrEMBL data set http://www.ebi.ac.uk/trembl/
InterPro data set  
InterPro GO Annotation data set  

1 Found In

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

1 GO Annotation


Subject . Secondary Identifier

Subject . Name

Subject . Symbol

Ontology Term . Identifier

Ontology Term . Name
Carbamoyl-phosphate synthase large subunit, CPSase domain   GO:0006807 nitrogen compound metabolic process

1 Ontology Annotations


Subject . Secondary Identifier

Subject . Name

Subject . Symbol

Ontology Term . Identifier

Ontology Term . Name
Carbamoyl-phosphate synthase large subunit, CPSase domain   GO:0006807 nitrogen compound metabolic process

1 Parent Features

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

13 Proteins

DB identifier Primary Accession
Organism . Name
FBpp0088675 P05990 Drosophila melanogaster
FBpp0283274 Q29HK5 Drosophila pseudoobscura
FBpp0164447 B4L1V5 Drosophila mojavensis
FBpp0233106 B4M2B0 Drosophila virilis
FBpp0262297 B4PXW0 Drosophila yakuba
A8WNQ4_CAEBR A8WNQ4 Caenorhabditis briggsae
H2WCA3_CAEJA H2WCA3 Caenorhabditis japonica
G0N3L4_CAEBE G0N3L4 Caenorhabditis brenneri
G0P6A6_CAEBE G0P6A6 Caenorhabditis brenneri
Q18990_CAEEL Q18990 Caenorhabditis elegans
PYR1_DROME-2 P05990-2 Drosophila melanogaster
E3LGA7_CAERE E3LGA7 Caenorhabditis remanei
E3NWU9_CAERE E3NWU9 Caenorhabditis remanei