InterPro: IPR006439 HAD-superfamily hydrolase, subfamily IA, variant 1

This family represents part of one structural subfamily of the Haloacid Dehalogenase (HAD) superfamily of aspartate-nucleophile hydrolases. The superfamily is defined by the presence of three short catalytic motifs [1]. The subfamilies are defined [2] based on the location and the observed or predicted fold of a so-called capping domain [3], or the absence of such a domain. Subfamily I consists of sequences in which the capping domain is found in between the first and second catalytic motifs. Subfamily II consists of sequences in which the capping domain is found between the second and third motifs. Subfamily III sequences have no capping domain in either of these positions. The Subfamily IA and IB capping domains are predicted by PSI-PRED to consist of an alpha helical bundle. Subfamily I encompasses such a wide region of sequence space (the sequences are highly divergent) that modelling it with a single HMM is impossible, resulting in an overly broad description which allows in many unrelated sequences. Subfamily IA and IB are separated based on an apparent phylogenetic bifurcation. Subfamily IA is still too broad to model, but can be further subdivided into large chunks based on phylogenetic trees. Of the three motifs defining the HAD superfamily, the third has three variant forms [2]: (1) hhhhsDxxx(x)(D/E), (2) hhhhssxxx(x)D and (3) hhhhDDxxx(x)s where _s_ refers to a small amino acid and _h_ to a hydrophobic one. All three of these variants are found in subfamily 1A.