P100, a transcriptional coactivator, is a human homologue of staphylococcal nuclease.
Staphylococcus aureus nuclease (SNase) homologues, previously thought to be restricted to bacteria and archaea, are demonstrated by sequence analysis to be present also in eukaryotes. The human cellular coactivator p100 is shown to contain four repeats, each of which is a SNase homologue. Surprisingly, these repeats are unlikely to possess SNase-like activities as each lacks equivalent SNase catalytic residues, yet they may mediate p100's single-stranded DNA-binding function. Products of Corydalis sempervirens and Saccharomyces cerevisiae open reading frames are predicted to adopt the same fold and possess similar functions as SNase. Five additional hypothetical proteins of bacterial origin are also predicted to be active SNase-like nucleases, including one that appears to be C-terminally truncated in a manner analogous to an engineered active SNase variant. Conservation of Asp-19 and Asp-83 among these homologues suggests a re-evaluation of the roles of these residues in Ca(2+)-binding and/or catalysis.
Ponting
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CP
Fibrinolysis Research Unit, University of Oxford, United Kingdom. Ponting@Molbiol.ox.ac.uk
D000595:Amino Acid Sequence; D002118:Calcium / Q000378:metabolism; D002384:Catalysis; D006801:Humans; D008836:Micrococcal Nuclease / Q000378:metabolism*; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D015534:Trans-Activators / Q000378:metabolism*
D015534:Trans-Activators; D008836:Micrococcal Nuclease; D002118:Calcium