The four human EH domain-containing proteins (EHD1-4) are a distinct highly-homologous subfamily of the Eps15-homology (EH) domain family. They are distinct from most other EH family members in having the EH-domain at the C-terminus (Naslavsky & Caplan 2005). EH domains interact with other proteins; peptides containing Asp-Pro-Phe (NPF) motifs are major targets for EH-domain binding (Salcini et al. 1997).
EH domain family proteins have regulatory roles in endocytic membrane transport events (Naslavsky & Caplan 2005); the EHD subfamily is believed to regulate endocytic recycling (George et al. 2007). All four human EHD proteins can rescue the vacuolated intestinal phenotype observed when the C. elegans orthologue rme-1 is mutated (George et al. 2007).
Over 20 interaction partners have been reported for the C-terminal EHD proteins including clathirin, syndaptins and Arp2/3 (see Naslavsky & Caplan 2005). EHD1-3 all interact with Rabenosyn-5 (Rab5), a Rab5 effector (Naslavsky et al. 2004).