進化的分類によるO-GIcNAc修飾タンパク質の解析

Abstract

O-GlcNAcylation, the attachment of a single N-acetylglucosamine to serine/threonine residues of proteins by O-GlcNAc transferase (OGT), is essential for protein function in eukaryotes. OGT was shown to be essential for the viability of embryonic stem cells. In spite of these important roles, no consensus sequence for O-GlcNAcylation had been found so far. There are many parallels between phosphorylation and O-GlcNAcylation; attachment occurs to serine/threonine residues, half- life is short, occurrence is infrequent in structured regions, whereas dominant in intrinsically disordered regions (IDRs). In this study, we clustered O-GlcNAcylated proteins to investigate the relation between their evolutionary conservation and function for proteins. We used the experimental data of human O-GlcNAcylated proteins. Firstly, KEGG ortholog cluster was used for homology search in eukaryotes with genomes completely sequenced. Secondly, O-GlcNAcylated residues in orthologous proteins were checked for conservation using multiple sequence alignment. Finally, O-GlcNAcylated proteins were clustered by the degree of their conservation. In the clustering result, O-GlcNAcylated proteins clustered into 3 clusters, Classes 1 to 3. In addition, each cluster further clustered into 3 subclusters, like subclasses 1-1 to 1-3. Both ratios of O-GlcNAcylation within IDRs and cooccurrence of O-GlcNAcylation/phosphorylation at identical region were high in evolutionarily young clusters. Comparison of the degree of conservation in OGT and O-GlcNAcase (OGA), the degrading enzyme of O-GlcNAc, showed that OGT was more widely conserved than OGA. In addition, approximately half of O-GlcNAcylated proteins were as conserved as OGA. These results suggest that a lot of O-GlcNAcylated proteins were acquired along with OGA.