Fig. 7. Conservation of cis-acting determinants of LIN-12 trafficking in vertebrate Notch proteins. The relevant portion of LIN-12 region 1 was aligned with the equivalent region from Dm Notch, Danio rerio (Dr) Notch1-3, Mm Notch 1-3, Rattus norvegicus (Rn) Notch1-3 and Hs Notch 1-3. The requirement for the leucines and upstream serine/threonines in internalization has been verified experimentally for the LIN-12 DTS. We have marked the conserved di-leucine and serine residues in red, with shading. The conserved di-leucine in Dr Notch2 and Dr Notch3 and the di-leucine-like `LM' in other Notch3 proteins are shaded, but not marked in red to emphasize the lack of upstream negative or phospho-accepting amino acids that may be important for function as an internalization signal. Most vertebrate Notch proteins also have a canonical (D/E)XXXLL consensus motif (Bonifacino and Traub, 2003); the key residues are marked in red without shading. Conserved lysines that have been verified experimentally as being involved in degradation of LIN-12 are marked in blue.