Fig. 1. E/ANTH proteins and their domains. A series of ENTH- and ANTH-bearing proteins from human and yeast are depicted. Within their C-terminal region, these proteins contain short peptide motifs and protein domains that predominantly mediate protein interactions. The I/LWEQ domain, also called the talin-like domain, can bind to actin. The ubiquitin-interacting motif (UIM) is a consensus motif (EDExLxxAxxxSxxE/D) that mediates interactions with ubiquitylated proteins. The methionine-rich domain, found within the C-terminal region of enthoprotin, contains 17% methionine residues but its function is unknown. NPF motifs bind to Eps15 homology (EH) domain-containing proteins. A -ear/GAE-domain-binding motif with the consensus sequence [D/E][G/A]_(0-1)F[G/A][D/E], where is any hydrophobic amino acid, has been recently identified in enthoprotin and other proteins (Duncan and Payne, 2003). Clathrin-binding motifs encompass multiple sequences that bind to the terminal domain of the clathrin heavy chain including DLL motifs and type I and II clathrin boxes. For HIP1 and HIP12/HIP1R, the C-terminal most clathrin-binding motif represents a putative new binding site for clathrin light chains present within an extended -helical segment of the proteins (V.L.-G. et al., unpublished). The -ear-binding motif includes DPW, DPF and FxDxF motifs that bind to the ear of the -adaptin subunit of AP-2. Hypothetical E/ANTH proteins from S. pombe are denoted by their GenBank accession numbers.