Dihydroorotase (EC 126.96.36.199) (DHOase) catalyzes the third step in the de novo
biosynthesis of pyrimidine, the conversion of ureidosuccinic acid (N-carbamoyl-L-aspartate) into dihydroorotate. Dihydroorotase binds a zinc ion
which is required for its catalytic activity .
In bacteria, DHOase is a dimer of identical chains of about 400 amino-acid
residues (gene pyrC). In higher eukaryotes, DHOase is part of a large multi-functional protein known as 'rudimentary' in Drosophila and CAD in mammals and
which catalyzes the first three steps of pyrimidine biosynthesis . The
DHOase domain is located in the central part of this polyprotein. In yeasts,
DHOase is encoded by a monofunctional protein (gene URA4). However, a
defective DHOase domain  is found in a multifunctional protein (gene URA2)
that catalyzes the first two steps of pyrimidine biosynthesis.
The comparison of DHOase sequences from various sources shows  that there
are two highly conserved regions. The first located in the N-terminal
extremity contains two histidine residues suggested  to be involved in
binding the zinc ion. The second is found in the C-terminal part. We developed
signature patterns for both regions.
Allantoinase (EC 188.8.131.52) is the enzyme that hydrolyzes allantoin into
allantoate. In yeast (gene DAL1) , it is the first enzyme in the allantoin
degradation pathway; in amphibians  and fishs it catalyzes the second step
in the degradation of uric acid. The sequence of allantoinase is evolutionary
related to that of DHOases.
December 2004 / Pattern and text revised.
PROSITE methods (with tools and information) covered by this documentation:
Brown D.C., Collins K.D.
Dihydroorotase from Escherichia coli. Substitution of Co(II) for the active site Zn(II).
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