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EPS15 and EPS15R are substrates of the epidermal growth factor (EGF) receptor kinase that are characterized by the presence of a protein:protein interaction domain, the EH domain, and by their ability to bind to the clathrin adaptor protein complex adaptor protein 2. Evidence suggests that eps15 and eps15R are involved in endocytosis (1). The most striking difference between these two related proteins is that Eps15R is also found in the nucleus, whereas Eps15 is excluded from this compartment at steady state (2). Eps15R plays a key role in clathrin-mediated endocytosis of transmembrane receptors. Using a mutational approach, it has been found that the second ubiquitin-interacting motif (UIM) of Eps15 and Eps15R is essential for their ubiquitination (3)
