PROSITE documentation PDOC00135Arginase family signature and profile
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.
Expert(s) to contact by email: Last update:November 2008 / Text revised; profile added; patterns deleted.
-------------------------------------------------------------------------------
PROSITE methods (with tools and information) covered by this documentation:
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 |
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 prosite_license.html.
View entry in original PROSITE document format
View entry in raw text format (no links)