Protein O-Glucosyltransferases Rumi (RUMI)

Abstract

Protein O-glucosylation involves the addition of a β-linked glucose to the hydroxyl group of a serine residue within an epidermal growth factor-like (EGF) repeat. EGF repeats are small protein modules found in many cell surfaces and secreted proteins, defined by the presence of six conserved cysteine residues forming three disulfide bonds (Campbell and Bork 1993). O-Glucose was originally identified on EGF repeats from bovine clotting factors VII and IX in 1988 (Hase et al. 1988). Comparison of sequences surrounding the modified serine on these and other proteins led to the proposal of a consensus sequence for O-glucosylation, C1-X-S-X-P-C2, where C1 and C2 are the first and second conserved cysteines of the EGF repeat (Harris and Spellman 1993). Database searches using this consensus sequence reveal more than 40 proteins in mammals are predicted to be O-glucosylated (Fernandez-Valdivia et al. 2011;Rana et al. 2011), including all members of the Notch receptor family. Recent glycoproteomic site mapping data on mouse Notch1 reveal that all 16 of the predicted sites are modified, most at high stoichiometries, indicating that the consensus sequence accurately predicts modification (Rana et al. 2011). An additional site was found with alanine in place of proline (C1ASAAC2), suggesting that the consensus sequence can be expanded to C1-X-S-X-P/A-C2, adding a few additional predicted sites from database searches (Rana et al. 2011). The O-glucose is typically extended by two α3-linked xyloses to the trisaccharide, Xylα1-3Xylα1-3Glcβ1-O-Ser in mammals, although mono and disaccharide forms have also been seen (Moloney et al. 2000; Rana et al. 2011; Whitworth et al. 2010).