Evolutionary and functional relationships within the DJ1 superfamily.
BACKGROUND
Inferences about protein function are often made based on sequence homology to other gene products of known activities. This approach is valuable for small families of conserved proteins but can be difficult to apply to large superfamilies of proteins with diverse function. In this study we looked at sequence homology between members of the DJ-1/ThiJ/PfpI superfamily, which includes a human protein of unclear function, DJ-1, associated with inherited Parkinson's disease.


RESULTS
DJ-1 orthologs in a variety of eukaryotic species cluster together in a single group. The most closely related group is the bacterial ThiJ genes. These are kinases involved in the biosynthesis of thiamine, a function that has been dispensed with evolutionarily in most eukaryotes where thiamine is an essential nutrient. The similarity with other characterized members of the superfamily, including proteases, is more remote. This is congruent with the recently solved crystal structures that fail to demonstrate the presence of a catalytic triad required for protease activity.


CONCLUSIONS
DJ-1 may have evolved from the bacterial gene encoding ThiJ kinase. However, as this function has been dispensed with in eukaryotes it appears that the gene has been co-opted for another function.
Bandyopadhyay
Sourav
S
Laboratory of Neurogenetics, National Institute on Aging, 9000 Rockville Pike, Bethesda, MD 20892, USA. bandys@mail.nih.gov
Cookson
Mark R
MR
D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D030161:Avian Proteins / Q000235:genetics / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology; D002645:Chickens / Q000235:genetics; D002522:Chlorocebus aethiops / Q000235:genetics; D017124:Conserved Sequence / Q000235:genetics; D006224:Cricetinae; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology; D019143:Evolution, Molecular; D029941:Fish Proteins / Q000235:genetics / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008647:Mesocricetus / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics / Q000502:physiology*; D015513:Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D010802:Phylogeny; D000071617:Protein Deglycase DJ-1; D051381:Rats; D020317:Salmo salar / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D029867:Xenopus Proteins / Q000235:genetics / Q000502:physiology
D030161:Avian Proteins; D029742:Caenorhabditis elegans Proteins; D029721:Drosophila Proteins; D029941:Fish Proteins; D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; D029867:Xenopus Proteins; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1