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Information on EC 6.3.5.5 - carbamoyl-phosphate synthase (glutamine-hydrolysing) and Organism(s) Homo sapiens and UniProt Accession P27708

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EC Tree
IUBMB Comments
The product carbamoyl phosphate is an intermediate in the biosynthesis of arginine and the pyrimidine nucleotides . The enzyme from Escherichia coli has three separate active sites, which are connected by a molecular tunnel that is almost 100 A in length . The amidotransferase domain within the small subunit of the enzyme hydrolyses glutamine to ammonia via a thioester intermediate. The ammonia migrates through the interior of the protein, where it reacts with carboxyphosphate to produce the carbamate intermediate. The carboxyphosphate intermediate is formed by the phosphorylation of hydrogencarbonate by ATP at a site contained within the N-terminal half of the large subunit. The carbamate intermediate is transported through the interior of the protein to a second site within the C-terminal half of the large subunit, where it is phosphorylated by another ATP to yield the final product, carbamoyl phosphate . cf. EC 6.3.4.16, carbamoyl-phosphate synthase (ammonia).
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Homo sapiens
UNIPROT: P27708
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The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
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2
ATP
+
L-glutamine
+
hydrogencarbonate
+
H2O
=
2
ADP
+
phosphate
+
L-glutamate
+
carbamoyl phosphate
2
+
+
+
=
2
+
+
+
Synonyms
cps iii, cad protein, carbamoyl phosphate synthetase iii, carbamoyl phosphate synthetase ii, cpsii, carbamoyl-phosphate synthetase 2, glutamine-dependent carbamyl phosphate synthetase, carbamoyl phosphate synthetase (glutamine-hydrolyzing), cpsase type ii, carbamylphosphate synthetase - aspartate transcarbamylase, more
SYNONYM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
CAD protein
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Carbamoyl phosphate synthase (glutamine)
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Carbamoyl phosphate synthetase (glutamine-hydrolyzing)
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Carbamoyl-phosphate synthetase (glutamine-hydrolysing)
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Carbamoylphosphate synthase
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Carbamoylphosphate synthetase
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Carbamoylphosphate synthetase II
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Carbamyl phosphate synthetase (glutamine)
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Carbamyl phosphate sythetase II
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CPS
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CPS1
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CPSase
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CPSase type II
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CPSase-A
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CPSase-P
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Glutamine-dependent carbamyl phosphate synthetase
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Synthase, carbamoylphosphate (glutamine)
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Synthetase, carbamoylphosphate (glutamine-hydrolyzing)
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REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
Phosphorylation
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amination
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amide group transfer
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PATHWAY SOURCE
PATHWAYS
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-, -, -, -, -, -, -
SYSTEMATIC NAME
IUBMB Comments
hydrogen-carbonate:L-glutamine amido-ligase (ADP-forming, carbamate-phosphorylating)
The product carbamoyl phosphate is an intermediate in the biosynthesis of arginine and the pyrimidine nucleotides [4]. The enzyme from Escherichia coli has three separate active sites, which are connected by a molecular tunnel that is almost 100 A in length [8]. The amidotransferase domain within the small subunit of the enzyme hydrolyses glutamine to ammonia via a thioester intermediate. The ammonia migrates through the interior of the protein, where it reacts with carboxyphosphate to produce the carbamate intermediate. The carboxyphosphate intermediate is formed by the phosphorylation of hydrogencarbonate by ATP at a site contained within the N-terminal half of the large subunit. The carbamate intermediate is transported through the interior of the protein to a second site within the C-terminal half of the large subunit, where it is phosphorylated by another ATP to yield the final product, carbamoyl phosphate [6]. cf. EC 6.3.4.16, carbamoyl-phosphate synthase (ammonia).
CAS REGISTRY NUMBER
COMMENTARY hide
37233-48-0
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SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
2 ATP + L-Gln + HCO3-
2 ADP + phosphate + L-Glu + carbamoyl phosphate
show the reaction diagram
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?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
human Rad9 checkpoint protein
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stimulates the carbamoyl phosphate synthetase activity of the multifunctional protein CAD. Rad9 binds to the Cpsase domain, and, moreover, this binding results in a 2fold stimulation of the CPSase activity of CAD
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ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
gene encodes four enzymatic activities of the pyrimidine pathway, i.e. GATase, CPSase, ATCase and DHOase
SwissProt
Manually annotated by BRENDA team
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
SOURCE
-
serum samples from patients with acute liver failure due to acetaminophen, Wilson disease, or ischemia show readily detectable CPS1 that i not observed in patients with chronic viral hepatitis or in control donors. CPS1 rapidly decreases to undetectable levels in sera of patients with acetaminophen-related acute liver failure who ultimately recover
Manually annotated by BRENDA team
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY hide
GeneOntology No.
LITERATURE
SOURCE
presence in the cytosol surrounding the nucleus, plus partial localization in the lysosome
Manually annotated by BRENDA team
coexpression of small GTPase Rheb with CAD leads to increased accumulation of CAD on lysosomes
Manually annotated by BRENDA team
both a farnesyltransferase inhibitor that blocks membrane association of Rheb and knockdown of Rheb mislocalize CAD to the nucleus
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
small GTPases Rheb1 and Rheb2 bind to CAD. Binding is more pronounced with Rheb2 than with Rheb1. Rheb binds CAD in a GTP- and effector domain-dependent manner. Rheb binds at the C-terminal region of the carbamoyl-phosphate synthetase domain and not in the dihydroorotase and aspartate transcarbamoylase domains. Rheb stimulates carbamoyl-phosphate synthetase activity of CAD in vitro. Expression of Rheb leads to increased accumulation of CAD on lysosomes
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION?
PYR1_HUMAN
2225
0
242984
Swiss-Prot
other Location (Reliability: 2)
APPLICATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
medicine
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serum samples from patients with acute liver failure due to acetaminophen, Wilson disease, or ischemia show readily detectable CPS1 that i not observed in patients with chronic viral hepatitis or in control donors. CPS1 rapidly decreases to undetectable levels in sera of patients with acetaminophen-related acute liver failure who ultimately recover
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Lindsey-Boltz, L.A.; Wauson, E.M.; Graves, L.M.; Sancar, A.
The human Rad9 checkpoint protein stimulates the carbamoyl phosphate synthetase activity of the multifunctional protein CAD
Nucleic Acids Res.
32
4524-4530
2004
Homo sapiens
Manually annotated by BRENDA team
Lindley, T.E.; Laberge, T.; Hall, A.; Hewett-Emmett, D.; Walsh, P.J.; Anderson, P.M.
Sequence, expression and evolutionary relationships of carbamoyl phosphate synthetase I in the toad Xenopus laevis
J. Exp. Zool. A
307
163-175
2007
Homo sapiens
Manually annotated by BRENDA team
Weerasinghe, S.V.; Jang, Y.J.; Fontana, R.J.; Omary, M.B.
Carbamoyl phosphate synthetase-1 is a rapid turnover biomarker in mouse and human acute liver injury
Am. J. Physiol. Gastrointest. Liver Physiol.
307
G355-G364
2014
Homo sapiens, Mus musculus
Manually annotated by BRENDA team
Sato, T.; Akasu, H.; Shimono, W.; Matsu, C.; Fujiwara, Y.; Shibagaki, Y.; Heard, J.J.; Tamanoi, F.; Hattori, S.
Rheb protein binds CAD (carbamoyl-phosphate synthetase 2, aspartate transcarbamoylase, and dihydroorotase) protein in a GTP- and effector domain-dependent manner and influences its cellular localization and carbamoyl-phosphate synthetase (CPSase) activity
J. Biol. Chem.
290
1096-1105
2015
Homo sapiens (P27708)
Manually annotated by BRENDA team