Figure 1.

General structure of Notch family of receptors. Notch receptors are proteolytically processed into two separate sub-parts that remain non-covalently associated. The N-terminus of the protein, located outside the cell, contains a series of EGF-like repeats (dark green) involved in ligand binding. The numbers of EGF-like repeats differ between different Notch family members. The extracellular portion of the Notch receptors also contains the negative regulatory region (NRR, blue), which prevents Notch signaling until ligand binds. The site of ADAM protease cleavage (Site 2 or S2) is located close to transmembrane domain. The transmembrane domain contains the site of γ-secretase cleavage (Site 3 or S3). The intracellular region of the Notch receptors contains an RBP-J associated molecular domain (RAM, pink), a series of ankyrin repeats (ANK, gray), a transactivation domain (TAD, aqua) and a proline-serine-threonine rich domain (PEST, orange). Note, that Notch3 and Notch4 lack the TAD domain, but contain the other domains indicated in the figure.