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Arginase family proteins are ureohydrolases with important roles in arginine/agmatine metabolism, the urea cycle, histidine degradation, and other pathways. The family includes arginase and evolutionary related [1] enzymes of about 300 amino acids that typically contain two manganese ions in the active site.

Some proteins that belong to the arginase family are listed below:

• Arginase (EC 3.5.3.1), a ubiquitous enzyme which catalyzes the degradation of arginine to ornithine and urea [2]. Two isoenzymes are found in mammals. Arginase-1 catalyzes the final cytosolic step of the urea cycle in liver, but it is also found in non-hepatic tissues. Arginase-2 is a mitochondrial enzyme that functions in arginine homeostasis in nonhepatic tissues. Deficiency of arginase can lead to diseases related to the accumulation of arginine or ammonia.
• Agmatinase (EC 3.5.3.11) (agmatine ureohydrolase), a prokaryotic enzyme (gene speB) that catalyzes the hydrolysis of agmatine into putrescine and urea.
• Formiminoglutamase (EC 3.5.3.8) (formiminoglutamate hydrolase), a prokaryotic enzyme (gene hutG) that hydrolyzes N-formimino-glutamate into glutamate and formamide.
• Proclavaminate amidinohydrolase (EC 3.5.3.22) from Streptomyces clavuligerus (gene pah), an enzyme involved in antibiotic clavulanic acid biosynthesis.
• Guanidinobutyrase (EC 3.5.3.7) from Arthrobacter sp. (gene gbh), an enzyme that hydrolyzes guanidinobutanoate into aminobutanoate and urea and that requires one zinc ion instead of manganese.
• Hypothetical proteins from methanogenic archaebacteria.

Known 3-D structures of such enzymes show trimeric or hexameric structures [3,4,5,6]. Each monomer forms a conserved α/β fold with a central parallel β-sheet flanked on both sides by several α-helices (see <PDB:1RLA; B>). Three conserved regions that contain charged residues which are involved in the binding of the two manganese ions in the active site are located in loop segments of the central β-sheet [3,4,5,6]. We have used one of these regions for a signature pattern and we have also developed a profile that covers the entire arginase structure.

Ouzounis C.

November 2008 / Text revised; profile added; patterns deleted.

PROSITE methods (with tools and information) covered by this documentation:

ARGINASE_2, PS51409; Arginase family profile  (MATRIX)

Sequences known to belong to this class detected by the profile: ALL Other sequence(s) detected in Swiss-Prot: NONE.

• Domain architecture view of Swiss-Prot proteins matching PS51409 • Retrieve an alignment of Swiss-Prot true positive hits:   Clustal format, color, condensed view  / Clustal format, color  / Clustal format, plain text  / Fasta format • Retrieve the sequence logo from the alignment • Taxonomic tree view of all Swiss-Prot/TrEMBL entries matching PS51409 • Retrieve a list of all Swiss-Prot/TrEMBL entries matching PS51409 • Scan Swiss-Prot/TrEMBL entries against PS51409 • view ligand binding statistics

Matching PDB structures: 1CEV 1D3V 1GQ6 1GQ7 ... [ALL]

ARGINASE_1, PS01053; Arginase family signature  (PATTERN)

Consensus pattern: [ST]-[LIVMFY]-D-[LIVM]-D-x(3)-[PAQ]-x(3)-P-[GSA]-x(7)-G The 2 D's bind manganese Sequences known to belong to this class detected by the pattern: ALL Other sequence(s) detected in Swiss-Prot: NONE.

• Retrieve an alignment of Swiss-Prot true positive hits:   Clustal format, color, condensed view  / Clustal format, color  / Clustal format, plain text  / Fasta format • Retrieve the sequence logo from the alignment • Taxonomic tree view of all Swiss-Prot/TrEMBL entries matching PS01053 • Retrieve a list of all Swiss-Prot/TrEMBL entries matching PS01053 • Scan Swiss-Prot/TrEMBL entries against PS01053 • view ligand binding statistics

Matching PDB structures: 1CEV 1D3V 1GQ6 1GQ7 ... [ALL]

1	Authors	Ouzounis C.A., Kyrpides N.C.
	Title	On the evolution of arginases and related enzymes.
	Source	J. Mol. Evol. 39:101-104(1994).
	PubMed ID	8064866

2	Authors	Jenkinson C.P., Grody W.W., Cederbaum S.D.
	Title	Comparative properties of arginases.
	Source	Comp. Biochem. Physiol. 114B:107-132(1996).
	PubMed ID	8759304

3	Authors	Kanyo Z.F., Scolnick L.R., Ash D.E., Christianson D.W.
	Title	Structure of a unique binuclear manganese cluster in arginase.
	Source	Nature 383:554-557(1996).
	PubMed ID	8849731

4	Authors	Elkins J.M., Clifton I.J., Hernandez H., Doan L.X., Robinson C.V., Schofield C.J., Hewitson K.S.
	Title	Oligomeric structure of proclavaminic acid amidino hydrolase: evolution of a hydrolytic enzyme in clavulanic acid biosynthesis.
	Source	Biochem. J. 366:423-434(2002).
	PubMed ID	12020346
	DOI	10.1042/BJ20020125

5	Authors	Ahn H.J., Kim K.H., Lee J., Ha J.Y., Lee H.H., Kim D., Yoon H.J., Kwon A.R., Suh S.W.
	Title	Crystal structure of agmatinase reveals structural conservation and inhibition mechanism of the ureohydrolase superfamily.
	Source	J. Biol. Chem. 279:50505-50513(2004).
	PubMed ID	15355972
	DOI	10.1074/jbc.M409246200

6	Authors	Dowling D.P., Di Costanzo L., Gennadios H.A., Christianson D.W.
	Title	Evolution of the arginase fold and functional diversity.
	Source	Cell. Mol. Life Sci. 65:2039-2055(2008).
	PubMed ID	18360740
	DOI	10.1007/s00018-008-7554-z

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