Superfamily of UvrA-related NTP-binding proteins. Implications for rational classification of recombination/repair systems.

A superfamily of proteins encoded by bacterial, phage and eukaryotic genomes and performing a wide range of NTP-dependent functions was delineated by amino acid sequence comparison. The new superfamily brought together bacterial proteins UvrA, RecF, RecN, MutH and HexA, T4 phage gp46, T5 phage D13 protein, lambda phage EA59 protein and yeast Rad50 protein, all involved in recombination, repair and, in some cases, also in replication of respective genomes, and a family of bacterial and eukaryotic proteins implicated in active transport of various compounds, cell division and nodulation whose relationship to UvrA had been recognized previously. For some of the members of the new superfamily, NTPase activity or NTP-binding capacity have been demonstrated. All these proteins encompassed four distinct conserved sequence motifs, of which two constituted the NTP-binding pattern typical of a vast class of ATP and GTP-binding proteins, whereas the other two were unique for the new superfamily. The new superfamily was characterized by an unusually large span of length variation of polypeptide segments separating the two conserved motifs of the NTP-binding pattern. Sequence similarity was revealed, on the one hand, between the N-terminal NTP-binding domain of UvrA, recN, gp46 and D13, and on the other hand, between the C-terminal NTP-binding domain of UvrA, recF and EA59. Possible relationships between different pathways of DNA repair and recombination are briefly analyzed from the viewpoint of involvement of NTPases of different groups.