Homing endonucleases are encoded by mobile DNA elements that are found inserted within host genes in all domains of life. The crystal structure of the homing nuclease PI-Sce [<cite idref="PUB00010172"/>] revealed two domains: an endonucleolytic centre resembling the C-terminal domain of <taxon tax_id="7227">Drosophila melanogaster</taxon> Hedgehog protein, and a second domain containing the protein-splicing active site. This domain corresponds to the C-terminal domain, which has structural similarity to <db_xref db="INTERPRO" dbkey="IPR001767"/>.