Distribution of EGF-like repeats with consensus O-fucosylation and/or O-glucosylation motifs in Notch receptors and their ligands. Alignment of extracellular domains of Drosophila Notch (dNotch), its human homologs (hNotch1–4) and their ligands are shown. Jag is Jagged; Dll is Delta-like. Blue and yellow boxes indicate EGF-like repeats with a consensus motif for O-glucosylation and O-fucosylation, respectively. The red lines denote Ca+//0-binding EGF-like repeats. hNotch3 and hNotch4 have 34 and 29 EGF-like repeats, respectively. The dotted lines in the schematic of these two proteins show the EGF-like repeats missing compared to dNotch, hNotch1 and hNotch2 (Uyttendaele et al. 1996). Note that the distribution of O-glucosylation, O-fucosylation and Ca+//0-binding EGF-like repeats is well conserved in Notch receptors. dSerrate and hDll3 do not have a predicted O-glucosylation motif. We note that mouse and rat Dll3 have a single predicted O-glucosylation motif (not shown). LNR, Lin12-Notch repeat; HD, heterodimerization; TM, transmembrane; DSL, Delta-Serrate-Lag2; CR, cysteine-rich. S1–S4 show the position of Notch cleavage sites