InterPro domain: IPR044924

This family of proteins includes uncharacterised sequences from eukaryotes, cyanobacteria and Leptospira as well as the DREG-2 protein from Drosophila melanogaster (Fruit fly) which has been identified as a rhythmically (diurnally) regulated gene [ 1 ]. This family is a member of the Haloacid Dehalogenase (HAD) superfamily of aspartate-nucleophile hydrolases. The superfamily is defined by the presence of three short catalytic motifs [ 2 ]. The subfamilies are defined [ 3 ] based on the location and the observed or predicted fold of a so-called, capping domain, [ 4 ], or the absence of such a domain. This family is a member of subfamily 1A in which the cap domain consists of a predicted alpha helical bundle found in between the first and second catalytic motifs. A distinctive feature of this family is a conserved tandem pair of tryptophan residues in the cap domain. The most divergent sequences included within the scope of this entry are from plants and have "FW" at this position instead. Most likely, these sequences, like the vast majority of HAD sequences, represent phosphatase enzymes.

This superfamily represents the inserted capping domain between the first and second catalytic domains.

1. Extent and character of circadian gene expression in Drosophila melanogaster: identification of twenty oscillating mRNAs in the fly head. Curr. Biol. 5, 1424-36
2. Computer analysis of bacterial haloacid dehalogenases defines a large superfamily of hydrolases with diverse specificity. Application of an iterative approach to database search. J. Mol. Biol. 244, 125-32
3. The crystal structure of bacillus cereus phosphonoacetaldehyde hydrolase: insight into catalysis of phosphorus bond cleavage and catalytic diversification within the HAD enzyme superfamily. Biochemistry 39, 10385-96