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.