The ENTH domain

Abstract

The epsin NH2-terminal homology (ENTH) domain is a membrane interacting module composed by a superhelix of alpha-helices. It is present at the NH2-terminus of proteins that often contain consensus sequences for binding to clathrin coat components and their accessory factors, and therefore function as endocytic adaptors. ENTH domain containing proteins have additional roles in signaling and actin regulation and may have yet other actions in the nucleus. The ENTH domain is structurally similar to the VHS domain. These domains define two families of adaptor proteins which function in membrane traffic and whose interaction with membranes is regulated, in part, by phosphoinositides.

Phosphoinositides in Constitutive Membrane Traffic

“…Binding of PtdIns(4,5)P 2 by the ENTH domain causes the NH 2 -terminal helix of the domain to penetrate into the lipid bilayer, slowing membrane dissociation of the domain and inducing membrane curvature (103,336). Proteins that contain ENTH/ANTH domains also contain multiple recognition motifs for other types of protein-protein interaction modules and probably function as scaffold proteins that assemble protein complexes on membranes (73). The ANTH domain proteins AP180 and CALM bind to clathrin and AP2 adaptors and are proposed to nucleate the polymerization of the clathrin coat (172).…”

EpsinR2 Interacts with Clathrin, Adaptor Protein-3, AtVTI12, and Phosphatidylinositol-3-Phosphate. Implications for EpsinR2 Function in Protein Trafficking in Plant Cells

“…Epsin 1 was originally identified as a protein that plays a critical role in endocytosis (Chen et al, 1998). Subsequently, a large number of epsin-related proteins were identified in a variety of organisms (De Camilli et al, 2002;Wendland, 2002;Overstreet et al, 2003;LegendreGuillemin et al, 2004;Song et al, 2006). A common feature of all epsin-related APs is the presence of a highly conserved epsin N-terminal homology (ENTH) domain.…”

“…A common feature of all epsin-related APs is the presence of a highly conserved epsin N-terminal homology (ENTH) domain. Epsin-related proteins can be divided into two functional categories: group one is involved in endocytosis from the plasma membrane and includes animal epsin1 and Lqf, and yeast (Saccharomyces cerevisiae) Ent1p and Ent2p (Chen et al, 1998;De Camilli et al, 2002;Wendland, 2002); group two is involved in lysosomal/ vacuolar trafficking pathways from the TGN or endosomes and includes animal EpsinR/clint/enthoprotin, yeast Ent3p and Ent4p, and Arabidopsis (Arabidopsis thaliana) EPSIN1 (Kalthoff et al, 2002;Wasiak et al, 2002;Hirst et al, 2003;Chidambaram et al, 2004;Eugster et al, 2004;Saint-Pol et al, 2004;Song et al, 2006). Although the epsin proteins are divided into two functional groups, they may play essentially the same role in different pathways, that is, facilitation of CCV formation at donor membrane compartments.…”

A Role for Epsin N-terminal Homology/AP180 N-terminal Homology (ENTH/ANTH) Domains in Tubulin Binding

“…However, recent structural studies have refined our understanding such that ENTH-like domains from these proteins have been re-designated ANTH domaincontaining proteins in accordance with their higher structural similarity to AP180 rather than epsin (14). In an effort to simplify the nomenclature applied in this study, we refer to these homologous structures as E/ANTH domains when collectively discussing proteins bearing either domain, but maintain the ENTH or ANTH nomenclature when discussing individual proteins.A common feature among many E/ANTH domain-bearing proteins is that their C termini contain peptide motifs, indicative of a functional role in clathrin-mediated membrane budding including clathrin and clathrin adaptor protein-binding elements (1,15). In addition to their interactions with multiple endocytic components, many of the currently characterized E/ANTH proteins, including epsin, AP180, and HIP1/12, are localized to clathrin-coated pits where they function in clathrin-mediated endocytosis (2, 16 -25).…”

“…A common feature among many E/ANTH domain-bearing proteins is that their C termini contain peptide motifs, indicative of a functional role in clathrin-mediated membrane budding including clathrin and clathrin adaptor protein-binding elements (1,15). In addition to their interactions with multiple endocytic components, many of the currently characterized E/ANTH proteins, including epsin, AP180, and HIP1/12, are localized to clathrin-coated pits where they function in clathrin-mediated endocytosis (2, 16 -25).…”