The mammalian Notch receptor and ligand families. (A) The mammalian Notch receptor family comprises 4 members: Notch1, Notch2, Notch3, and Notch4. Notch proteins contain several conserved structural motifs. The extracellular domain contains a variable number of epidermal growth factor (EGF)–like repeats involved in ligand binding, and 3 Lin-12/Notch repeats involved in Notch heterodimerization. The intracellular domain contains a RAM23 motif involved in binding Notch downstream signaling proteins, 7 cdc10/ankyrin repeats also involved in mediating downstream signaling, and a PEST domain involved in Notch protein degradation. (B) The mammalian Notch ligand family consists of 5 members: Jagged1, Jagged2,Dll1, Dll3, and Dll4. Within the extracellular domain, Jagged family members contain a cysteine-rich region likely involved in the control of Notch receptor binding specificity, as well as a von Willebrand factor type C domain likely involved in ligand dimerization. These motifs are not present in Dll family members. Extracellular motifs common to all Notch ligands include a single Delta/Serrate/Lag-2 (DSL) domain involved in receptor binding, as well as a variable number of EGF-like repeats that may stabilize receptor binding.