{PDOC00676}
{PS00866; CPSASE_1}
{PS00867; CPSASE_2}
{BEGIN}
*****************************************************
* Carbamoyl-phosphate synthase subdomain signatures *
*****************************************************

Carbamoyl-phosphate synthase (CPSase) catalyzes the ATP-dependent synthesis of
carbamyl-phosphate from  glutamine  (EC  6.3.5.5) or ammonia (EC 6.3.4.16) and
bicarbonate [1].   This important enzyme initiates both the urea cycle and the
biosynthesis of arginine and pyrimidines.

Glutamine-dependent CPSase  (CPSase  II)  is  involved  in the biosynthesis of
pyrimidines and purines. In bacteria such as Escherichia coli, a single enzyme
is involved  in  both biosynthetic pathways while other bacteria have separate
enzymes. The bacterial enzymes are formed of two subunits. A small chain (gene
carA) that provides glutamine amidotransferase activity (GATase) necessary for
removal of  the  ammonia  group  from glutamine, and a large chain (gene carB)
that provides  CPSase  activity. Such a structure is also present in fungi for
arginine biosynthesis  (genes  CPA1  and CPA2). In most  eukaryotes, the first
three steps   of   pyrimidine   biosynthesis   are   catalyzed   by   a  large
multifunctional enzyme  -  called URA2 in yeast, rudimentary in Drosophila and
CAD in  mammals [2]. The CPSase domain is located between an N-terminal GATase
domain and   the  C-terminal  part  which  encompass  the  dihydroorotase  and
aspartate transcarbamylase activities.

Ammonia-dependent CPSase (CPSase I) is involved in the urea cycle in ureolytic
vertebrates; it  is  a  monofunctional  protein  located  in the mitochondrial
matrix.

The CPSase  domain  is  typically  120  Kd  in  size  and  has arisen from the
duplication of an ancestral subdomain of about 500 amino acids. Each subdomain
independently binds to  ATP and it is suggested that the two homologous halves
act separately, one  to catalyze the phosphorylation of bicarbonate to carboxy
phosphate and the other that of carbamate to carbamyl phosphate.

The CPSase  subdomain is also present in a single copy in the biotin-dependent
enzymes acetyl-CoA  carboxylase  (EC 6.4.1.2) (ACC), propionyl-CoA carboxylase
(EC 6.4.1.3)  (PCCase),  pyruvate  carboxylase  (EC  6.4.1.1)  (PC)  and  urea
carboxylase (EC 6.3.4.6).

As signatures for  the  subdomain, we selected two conserved regions which are
probably important for binding ATP and/or catalytic activity.

-Consensus pattern: [FYV]-[PS]-[LIVMC]-[LIVMA]-[LIVM]-[KR]-[PSA]-[STA]-x(3)-
                    [SG]-G-x-[AG]
-Sequences known to belong to this class detected by the pattern: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Consensus pattern: [LIVMF]-[LIMN]-E-[LIVMCA]-N-[PATLIVM]-[KR]-[LIVMSTAC]
-Sequences known to belong to this class detected by the pattern: ALL.
-Other sequence(s) detected in Swiss-Prot: 35.

-Last update: July 1998 / Patterns and text revised.

[ 1] Simmer J.P., Kelly R.E., Rinker A.G. Jr., Scully J.L., Evans D.R.
     "Mammalian carbamyl phosphate synthetase (CPS). DNA sequence and
     evolution of the CPS domain of the Syrian hamster multifunctional
     protein CAD."
     J. Biol. Chem. 265:10395-10402(1990).
     PubMed=1972379
[ 2] Davidson J.N., Chen K.C., Jamison R.S., Musmanno L.A., Kern C.B.
     "The evolutionary history of the first three enzymes in pyrimidine
     biosynthesis."
     BioEssays 15:157-164(1993).
     PubMed=8098212

--------------------------------------------------------------------------------
PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and
distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives
(CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html
--------------------------------------------------------------------------------

{END}