{PDOC00135}
{PS01053; ARGINASE_1}
{PS51409; ARGINASE_2}
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* Arginase family signature and profile *
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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
[3-6].  Each monomer forms a conserved alpha/beta fold with a central parallel
beta-sheet flanked on both sides by several alpha-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 beta-sheet [3-6]. We have used one of these regions
for  a  signature pattern and we have also developed a profile that covers the
entire arginase structure.

-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.

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

-Expert(s) to contact by email:
           Ouzounis C.; ouzounis@ebi.ac.uk

-Last update: November 2008 / Text revised; profile added; patterns deleted.

[ 1] Ouzounis C.A., Kyrpides N.C.
     "On the evolution of arginases and related enzymes."
     J. Mol. Evol. 39:101-104(1994).
     PubMed=8064866
[ 2] Jenkinson C.P., Grody W.W., Cederbaum S.D.
     "Comparative properties of arginases."
     Comp. Biochem. Physiol. 114B:107-132(1996).
     PubMed=8759304
[ 3] Kanyo Z.F., Scolnick L.R., Ash D.E., Christianson D.W.
     "Structure of a unique binuclear manganese cluster in arginase."
     Nature 383:554-557(1996).
     PubMed=8849731
[ 4] Elkins J.M., Clifton I.J., Hernandez H., Doan L.X., Robinson C.V.,
     Schofield C.J., Hewitson K.S.
     "Oligomeric structure of proclavaminic acid amidino hydrolase:
     evolution of a hydrolytic enzyme in clavulanic acid biosynthesis."
     Biochem. J. 366:423-434(2002).
     PubMed=12020346; DOI=10.1042/BJ20020125
[ 5] 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.
     "Crystal structure of agmatinase reveals structural conservation and
     inhibition mechanism of the ureohydrolase superfamily."
     J. Biol. Chem. 279:50505-50513(2004).
     PubMed=15355972; DOI=10.1074/jbc.M409246200
[ 6] Dowling D.P., Di Costanzo L., Gennadios H.A., Christianson D.W.
     "Evolution of the arginase fold and functional diversity."
     Cell. Mol. Life Sci. 65:2039-2055(2008).
     PubMed=18360740; DOI=10.1007/s00018-008-7554-z

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