The HD domain is found in a superfamily of enzymes with a predicted or known phosphohydrolase activity. These enzymes appear to be involved in the nucleic acid metabolism, signal transduction and possibly other functions in bacteria, archaea and eukaryotes.The fact that all the highly conserved residues in the HD superfamily are histidines or aspartates suggests that coordination of divalent cations is essential for the activity of these proteins [<cite idref="PUB00005837"/>]. This domain is also found in eukaryotic 3',5'-cGMP phosphodiesterase (<db_xref db="EC" dbkey="3.1.4.17"/>) (PDE), which is located in photoreceptor outer segments and it is light activated, playing a pivotal role insignal transduction. This profile/HMM does not detect HD homologues in bacterial glycine aminoacyl-tRNA synthetases (beta subunit).