Endophilin B1/Bif-1: Proteins and Enzymes

Endophilin B1/Bax-interacting Factor 1 (Bif-1), also known as SH3-domain GRB2-like Endophilin B1 (SH3GLB1), is a 365 amino acid (aa) member of the endophilin protein family with a predicted molecular weight of approximately 43 kDa. The human protein shares 96% and 95% aa sequence identity with the mouse and rat orthologs, respectively. Endophilin B1/Bif-1 contains an N-terminal N-BAR domain and a C-terminal SH3 domain that are important for its roles in apoptosis and autophagy. The N-BAR domain is required for the ability of Endophilin B1/Bif-1 to interact with Bax and promote mitochrondrial outer membrane permeabilization. This domain within Endophilin B1/Bif-1 is also required for the promotion of ATG9 trafficking from the Golgi to phagophores. Both the N-BAR and SH3 domains are required for stimulation of the autophagy-promoting Beclin 1 complex and subsequent autophagosome formation. The autophagy-promoting activities of Endophilin B1/Bif-1 can be positively regulated by CDK5 and negatively regulated by GSK-3 beta. Endophilin B1/Bif-1 also has a potentially complex role in cancer. It has been reported to act as a tumor suppressor in several cancer types, including lymphoma and pancreatic and breast cancers. In contrast, overexpression of Endophilin B1/Bif-1 may contribute to a decrease in overall survival rate in patients with hepatocellular carcinoma.