The epsins define a family of proteins that interact with components of the clathrin coat and contain a new protein module

Epsin (epsin 1) is an interacting partner for the EH domain-containing regi on of Eps15 and has been implicated in conjunction with Eps15 in clathrin-m ediated endocytosis, We report here the characterization of a similar prote in (epsin 2), which we have cloned from human and rat brain libraries, Epsi n 1 and 2 are most similar in their NH2-terminal region, which represents a module (epsin NH2 terminal homology domain, ENTH domain) found in a variet y of other proteins of the data base. The multiple DPW motifs, typical of t he central region of epsin 1, are only partially conserved in epsin 2, Both proteins, however, interact through this central region with the clathrin adaptor AP-2, In addition, we show here that both epsin 1 and 2 interact wi th clathrin, The three NPF motifs of the COOH-terminal region of epsin 1 ar e conserved in the corresponding region of epsin 2, consistent with the bin ding of both proteins to Eps15, Epsin 2, like epsin 1, is enriched in brain , is present in a brain-derived clathrin-coated vesicle fraction, is concen trated in the peri-Golgi region and at the cell periphery of transfected ce lls, and partially colocalizes with clathrin, High overexpression of green fluorescent protein-epsin 2 mislocalizes components of the clathrin coat an d inhibits clathrin-mediated endocytosis. The epsins define a new protein f amily implicated in membrane dynamics at the cell surface.