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InterPro: IPR006131 Aspartate/ornithine carbamoyltransferase, Asp/Orn-binding domain

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UniProtKB

Matches:

4165 proteins

Overview:	sorted by AC,	sorted by name,	of known structure,	proteins with splice variants
Detailed:	sorted by AC,	sorted by name,	of known structure	proteins with splice variants
Table:	For all matching proteins,	of known structure
Architectures
Accession List
Matches in BioMart

Accession

IPR006131 Asp_carbamoyltransf_Asp/Orn_bd

Secondary

IPR002029

Type

Domain

Signatures Help

Database	ID	Name	Proteins
Pfam	PF00185	OTCace	4165
Signatures in BioMart

InterPro Relationships Help

Found in

IPR006130 Aspartate/ornithine carbamoyltransferase
IPR017702 Probable carbamoyltransferase YgeW

GO Term annotation Help

Process

GO:0006520 cellular amino acid metabolic process

Function

GO:0016597 amino acid binding
GO:0016743 carboxyl- or carbamoyltransferase activity

InterPro annotation

Entry Details in BioMart

Abstract

This family contains two related enzymes:

Aspartate carbamoyltransferase (EC:2.1.3.2) (ATCase) catalyzes the conversion of aspartate and carbamoyl phosphate to carbamoylaspartate, the second step in the de novo biosynthesis of pyrimidine nucleotides [1]. In prokaryotes ATCase consists of two subunits: a catalytic chain (gene pyrB) and a regulatory chain (gene pyrI), while in eukaryotes it is a domain in a multi- functional enzyme (called URA2 in yeast, rudimentary in Drosophila, and CAD in mammals [2]) that also catalyzes other steps of the biosynthesis of pyrimidines.
Ornithine carbamoyltransferase (EC:2.1.3.3) (OTCase) catalyzes the conversion of ornithine and carbamoyl phosphate to citrulline. In mammals this enzyme participates in the urea cycle [3] and is located in the mitochondrial matrix. In prokaryotes and eukaryotic microorganisms it is involved in the biosynthesis of arginine. In some bacterial species it is also involved in the degradation of arginine [4] (the arginine deaminase pathway).

It has been shown [5] that these two enzymes are evolutionary related. The predicted secondary structure of both enzymes are similar and there are some regions of sequence similarities. One of these regions includes three residues which have been shown, by crystallographic studies [6], to be implicated in binding the phosphoryl group of carbamoyl phosphate and is described by IPR006132. The carboxyl-terminal, aspartate/ornithine-binding domain is connected to the amino-terminal domain by two alpha-helices, which comprise a hinge between domains [7].

Structural links Help

PDB - click here

SCOP: c.78.1.1

CATH: 3.40.50.1370

Database links Help

Enzyme: EC:2.1.3

PANDIT: PF00185

Blocks: IPB006131

Taxonomic coverage Help

Overlapping InterPro entries Help

IPR006131

Numbers of overlapping proteins

Average numbers of overlapping amino acids

Example proteins Help

O50039 Ornithine carbamoyltransferase, chloroplastic

P00480 Ornithine carbamoyltransferase, mitochondrial

P05150 Ornithine carbamoyltransferase

P05990 CAD protein

P11725 Ornithine carbamoyltransferase, mitochondrial

More proteins

Example Proteins Key

InterPro entry accession number/name and structure databases		Colour code
IPR011702	Glutamine amidotransferase superfamily
IPR002195	Dihydroorotase, conserved site
IPR005479	Carbamoyl phosphate synthetase, large subunit, ATP-binding
IPR011761	ATP-grasp fold
IPR011059	Metal-dependent hydrolase, composite domain
IPR006680	Amidohydrolase 1
IPR000991	Glutamine amidotransferase class-I, C-terminal
IPR002292	Ornithine carbamoyltransferase
IPR005481	Carbamoyl phosphate synthase, large subunit, N-terminal
IPR005480	Carbamoyl phosphate synthetase, large subunit, oligomerisation
IPR013816	ATP-grasp fold, subdomain 2
IPR002082	Aspartate carbamoyltransferase, eukaryotic
IPR013817	Pre-ATP-grasp fold
IPR005483	Carbamoyl phosphate synthase, large subunit
IPR017926	Glutamine amidotransferase type 1
IPR016185	PreATP-grasp-like fold
IPR006130	Aspartate/ornithine carbamoyltransferase
IPR004722	Dihydroorotase multifunctional complex type
IPR002474	Carbamoyl phosphate synthase, small subunit, N-terminal
IPR006132	Aspartate/ornithine carbamoyltransferase, carbamoyl-P binding
IPR006131	Aspartate/ornithine carbamoyltransferase, Asp/Orn-binding domain
IPR011607	MGS-like
IPR006275	Carbamoyl phosphate synthase, large subunit, glutamine-dependent
IPR006274	Carbamoyl phosphate synthase, small subunit
IPR001317	Carbamoyl phosphate synthase, GATase domain
	ModBase
	SWISS-MODEL
	PDB Chain
	CATH Domain
	SCOP Domain

Publications Open in usermanual
1.	Lerner CG, Switzer RL. Cloning and structure of the Bacillus subtilis aspartate transcarbamylase gene (pyrB). J. Biol. Chem. 261 11156-65 1986 [PubMed: 3015959] http://intl.jbc.org/cgi/reprint/261/24/11156.pdf
2.	Davidson JN, Chen KC, Jamison RS, Musmanno LA, Kern CB. The evolutionary history of the first three enzymes in pyrimidine biosynthesis. Bioessays 15 157-64 1993 [PubMed: 8098212] http://dx.doi.org/10.1002/bies.950150303
3.	Takiguchi M, Matsubasa T, Amaya Y, Mori M. Evolutionary aspects of urea cycle enzyme genes. Bioessays 10 163-6 1989 [PubMed: 2662961] http://dx.doi.org/10.1002/bies.950100506
4.	Baur H, Stalon V, Falmagne P, Luethi E, Haas D. Primary and quaternary structure of the catabolic ornithine carbamoyltransferase from Pseudomonas aeruginosa. Extensive sequence homology with the anabolic ornithine carbamoyltransferases of Escherichia coli. Eur. J. Biochem. 166 111-7 1987 [PubMed: 3109911] http://dx.doi.org/10.1111/j.1432-1033.1987.tb13489.x
5.	Houghton JE, Bencini DA, O'Donovan GA, Wild JR. Protein differentiation: a comparison of aspartate transcarbamoylase and ornithine transcarbamoylase from Escherichia coli K-12. Proc. Natl. Acad. Sci. U.S.A. 81 4864-8 1984 [PubMed: 6379651] http://ukpmc.ac.uk/picrender.cgi?tool=EBI&pubmedid=6379651&action=stream&blobtype=pdf
6.	Ke HM, Honzatko RB, Lipscomb WN. Structure of unligated aspartate carbamoyltransferase of Escherichia coli at 2.6-A resolution. Proc. Natl. Acad. Sci. U.S.A. 81 4037-40 1984 [PubMed: 6377306] http://ukpmc.ac.uk/articlerender.cgi?tool=EBI&pubmedid=6377306
7.	Beernink PT, Endrizzi JA, Alber T, Schachman HK. Assessment of the allosteric mechanism of aspartate transcarbamoylase based on the crystalline structure of the unregulated catalytic subunit. Proc. Natl. Acad. Sci. U.S.A. 96 5388-93 1999 [PubMed: 10318893] http://dx.doi.org/10.1073/pnas.96.10.5388

Additional Reading Open in usermanual
	Sankaranarayanan R, Cherney MM, Cherney LT, Garen CR, Moradian F, James MN. The crystal structures of ornithine carbamoyltransferase from Mycobacterium tuberculosis and its ternary complex with carbamoyl phosphate and L-norvaline reveal the enzyme's catalytic mechanism. J. Mol. Biol. 375 2008 1052-63 [PubMed: 18062991] http://dx.doi.org/10.1016/j.jmb.2007.11.025
	De Vos D, Xu Y, Hulpiau P, Vergauwen B, Van Beeumen JJ. Structural investigation of cold activity and regulation of aspartate carbamoyltransferase from the extreme psychrophilic bacterium Moritella profunda. J. Mol. Biol. 365 2007 379-95 [PubMed: 17070547] http://dx.doi.org/10.1016/j.jmb.2006.09.064
	Cardia JP, Eldo J, Xia J, O'Day EM, Tsuruta H, Gryncel KR, Kantrowitz ER. Use of L-asparagine and N-phosphonacetyl-L-asparagine to investigate the linkage of catalysis and homotropic cooperativity in E. coli aspartate transcarbomoylase. Proteins 71 2008 1088-96 [PubMed: 18004787] http://dx.doi.org/10.1002/prot.21760
	De Vos D, Xu Y, Aerts T, Van Petegem F, Van Beeumen JJ. Crystal structure of Sulfolobus acidocaldarius aspartate carbamoyltransferase in complex with its allosteric activator CTP. Biochem. Biophys. Res. Commun. 372 2008 40-4 [PubMed: 18477471] http://dx.doi.org/10.1016/j.bbrc.2008.04.173
	Stieglitz KA, Xia J, Kantrowitz ER. The first high pH structure of Escherichia coli aspartate transcarbamoylase. Proteins 74 2009 318-27 [PubMed: 18618694] http://dx.doi.org/10.1002/prot.22162

InterPro 23.1