Phosphatidylinositol Binding Clathrin Assembly Protein (PICALM)

Dreyling et al. (1996) identified a breakpoint on chromosome 11 involving the previously unknown gene, CALM. CALM has a very high homology to the murine clathrin assembly protein ap3. Mao et al. (2001) determined the crystal structure of the N-terminal domain (the NAP domain) of the Drosophila Lap protein, which is homologous to human PICALM. The structure revealed a novel fold consisting of a large double layer of sheets of 10 alpha helices and a unique site for binding phosphoinositides.This motif is found in other proteins predicted to have domains of similar structure (e.g., Huntingtin-interacting protein-1). The structure is in part similar to the epsin N-terminal (ENTH) domain, but epsin lacks the phosphatidylinositol-4,5-bisphosphate-binding site.