General structure of Notch proteins, showing conserved functional domains and proteins that interact with different regions. Inset shows the Notch heterodimeric receptor, which is generated by proteolytic processing and reassociation of the extracellular and intracellular fragments before reaching the cell surface. The putative cleavage site is indicated in the main figure by the black arrow. The extracellular domain consists of 29-36 tandem EGF-like repeats and 3 Lin/Notch repeats (LNR) involved in DSL ligand binding and Notch activation. The ligand-induced proteolytic cleavage site is indicated by the white arrow. The intracellular domain includes 6 cdc10 repeats, which mediate protein interactions essential for Notch function; the RAM domain, which binds CSL effector molecules; and the NCR region associated with cytokine-specific effects of Notch1 and 2. See text for discussion of the various proteins that interact with Notch.