Dihydroorotase (IPR004722)

Short name: DHOase

Overlapping homologous superfamilies

Family relationships


Dihydroorotase belongs to MEROPS peptidase family M38 (clan MJ), and includes peptides classified as a non-peptidase homologues. DHOase catalyses 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 [PMID: 1671037].

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 melanogaster and CAD in mammals and which catalyzes the first three steps of pyrimidine biosynthesis [PMID: 8098212]. 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 [PMID: 2570735] 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 [PMID: 2897615] that there are two highly conserved regions. The first located in the N-terminal extremity contains two histidine residues suggested [PMID: 2570735] to be involved in binding the zinc ion. The second is found in the C-terminal part. Members of this family of proteins are predicted to adopt a TIM barrel fold [PMID: 9144792].

Dihydroorotase 'multifunctional complex type' EC:, in contrast to the homodimeric type of dihydroorotase found in Escherichia coli, tends to appear in a large multifunctional complex with aspartate transcarbamoylase. Homologous domains appear in multifunctional proteins of higher eukaryotes. In some species, including Pseudomonas putida and Pseudomonas aeruginosa, this protein is inactive but is required as a non-catalytic subunit of aspartate transcarbamoylase (ATCase). In these species, a second, active dihydroorotase is also present.

GO terms

Biological Process

GO:0006221 pyrimidine nucleotide biosynthetic process

Molecular Function

GO:0004151 dihydroorotase activity
GO:0046872 metal ion binding

Cellular Component

No terms assigned in this category.

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.