Epsin N-Terminal Homology (ENTH)-like domain of AP-4 complex accessory subunit Tepsin and similar domains
This family is composed of proteins containing an ENTH-like domain including vertebrate AP-4 complex accessory subunit Tepsin and Arabidopsis thaliana VHS domain-containing protein At3g16270. Tepsin is also called ENTH Domain-containing protein 2 (ENTHD2), Epsin for AP-4, or Tetra-epsin. It associates with the adapter-like complex 4 (AP-4), a heterotetramer composed of two large adaptins (epsilon and beta), a medium adaptin (mu) and a small adaptin (sigma), which forms a non-clathrin coat on vesicles departing the Trans-Golgi Network. The Epsin N-Terminal Homology (ENTH) domain is an evolutionarily conserved protein module found primarily in proteins that participate in clathrin-mediated endocytosis. ENTH domain is highly similar to the N-terminal region of the AP180 N-Terminal Homology (ANTH_N) domain. ENTH and ANTH_N domains are structurally similar to the VHS domain and are composed of a superhelix of eight alpha helices. ENTH domains bind both, inositol phospholipids with preference for PtdIns(4,5)P2, and proteins, and contribute to the nucleation and formation of clathrin coats on membranes. ENTH domains also function in the development of membrane curvature through lipid remodeling during the formation of clathrin-coated vesicles. ENTH and ANTH (E/ANTH)-containing proteins have recently been shown to function with adaptor protein-1 and GGA adaptors at the Trans-Golgi Network, which suggests that E/ANTH domains are universal components of the machinery for clathrin-mediated membrane budding.
Feature 1:putative phosphoinositide binding site [chemical binding site]
Evidence:
Comment:based on the binding of Rattus norvegicus Epsin ENTH domain to inositol 1,4,5-trisphosphate
Comment:ENTH domains bind phosphoinositides (PtdInsPs), usually with a preference for PdtIns(4,5)P2, although not all ENTH domains show this preference.