%0 Journal Article %T Phylogenomic analysis of the GIY-YIG nuclease superfamily %A Stanislaw Dunin-Horkawicz %A Marcin Feder %A Janusz M Bujnicki %J BMC Genomics %D 2006 %I BioMed Central %R 10.1186/1471-2164-7-98 %X We carried out database searches to identify all members of known GIY-YIG nuclease families. Multiple sequence alignments together with predicted secondary structures of identified families were represented as Hidden Markov Models (HMM) and compared by the HHsearch method to the uncharacterized protein families gathered in the COG, KOG, and PFAM databases. This analysis allowed for extending the GIY-YIG superfamily to include members of COG3680 and a number of proteins not classified in COGs and to predict that these proteins may function as nucleases, potentially involved in DNA recombination and/or repair. Finally, all old and new members of the GIY-YIG superfamily were compared and analyzed to infer the phylogenetic tree.An evolutionary classification of the GIY-YIG superfamily is presented for the very first time, along with the structural annotation of all (sub)families. It provides a comprehensive picture of sequence-structure-function relationships in this superfamily of nucleases, which will help to design experiments to study the mechanism of action of known members (especially the uncharacterized ones) and will facilitate the prediction of function for the newly discovered ones.The GIY-YIG superfamily groups together nucleases characterized by the presence of a domain of typically ~100 aa, with two short motifs "GIY" and "YIG" in the N-terminal part, followed by an Arg residue in the center and a Glu residue in the C-terminal part [1]. The GIY-YIG domain has been originally identified in a group of homing endonucleases (HEases). 'Homing' is a gene conversion process that occurs in Eukaryota, Archaea, Bacteria, and viruses, where a mobile sequence (a group I, group II, or archaeal intron or an intein) is copied and inserted into a cognate allele. It is initiated by a double-strand cut in the target allele, catalyzed by a HEase encoded within the mobile element (reviews: [2,3]). Unlike transposases, HEases do not recognize their mobile DNA, only recognize an %U http://www.biomedcentral.com/1471-2164/7/98