Figure 9

Functional analysis. Potential binding sites and post-translational modifications predicted by ELM [46, 47], NetPhos [46], and O-glycosylation [48] for the cytoplasmic tail of human Notch ligands. Prediction of ubiquitination sites is based on the preference for acidic residues adjacent to the target lysine [49]. 14-3-3, 14-3-3 proteins interacting motif (Ser/Thr phosphorylation required); Cyc, cyclin binding site; FHA, forkhead-associated domain interaction motif 1 (Thr phosphorylation required); PDZ, class I, II, or III PDZ binding motif; SH2, Src Homology 2 (SH2) domains interaction motif (tyrosine phosphorylation required; subtypes include GRB2, SH-PTP2, SRC, STAT3, STAT5, STAT6); SH3, SH3 domains binding motif (subtypes include class I, class II, and other non-canonical motifs); TRAF2, tumor necrosis factor receptor associated protein binding motif; Ub, ubiquitination site; WW, WW domain binding motif (subtypes include Group I (PPXY), Group II (PPLP), Group III, and Group IV, which requires Ser/Thr phosphorylation). Tyrosine-based sorting signals responsible for the interaction with the μ subunit of the AP (Adaptor Protein) complex are shown as doughnuts. Potential phosphorylation sites are in red; kinases are abbreviated as follows: CDK, Ser/Thr cyclin dependent kinase; CK1, casein kinase 1; CK2, casein kinase 2; GSK3, glycogen synthase kinase 3; PKA, protein kinase A; PKB, protein kinase B; PDK, Proline-Directed Kinase; PLK, Polo-like-kinase. ITIM, immunoreceptor tyrosine-based inhibitory motif (tyrosine phosphorylation required); ITSM, immunoreceptor tyrosine-based switch motif (tyrosine phosphorylation required). Sites that are candidates for O-glycosylation with β-N-acetylglucosamine are shown as grey diamonds; sites that are predicted to be both glycosylated and phosphorylated are shown as black diamonds.