Characterization of the EFC/F-BAR domain protein, FCHO2

We have previously shown that SGIP1 alpha is an endocytic protein specifically expressed in neural tissues. SGIP1 alpha has a lipid-binding domain called the MP domain, which shows no significant homology to any other domains. In this study, we characterized FCHO2, a protein with a high level of homology to SGIP1 alpha. FCHO2 lacks the MP domain but has another lipid-binding domain, the EFC/F-BAR domain. FCHO2 was ubiquitously expressed. The FCHO2 EFC domain bound to phosphatidylserine and phosphoinositides and deformed the plasma membrane and liposomes into narrow tubes. FCHO2 localized to clathrin-coated pits at the plasma membrane and bound to Eps15, an important adaptor protein in clathrin-mediated endocytosis. FCHO2 knockdown reduced transferrin endocytosis. These results suggest that FCHO2 regulates clathrin-mediated endocytosis through its interactions with membranes and Eps15. These properties of FCHO2 are similar to those of SGIP1 alpha. FCHO2 is likely to be a ubiquitous homologue of SGIP1 alpha. We furthermore found that FCHO2 was subjected to monoubiquitination, and gel filtration analysis showed that FCHO2 formed an oligomer. These new properties might also contribute to the role of FCHO2 in clathrin-mediated endocytosis.