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, contributing 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:phosphoinositide binding site [chemical binding site]
Evidence:
Structure:1H0A; Rattus norvegicus Epsin ENTH domain binds inositol 1,4,5-trisphosphate or Ins(1,4,5)p3; contacts at 4.0A - View structure with Cn3D
Comment:ENTH domains bind phosphoinositides (PtdInsPs), usually with a preference for PdtIns(4,5)P2, although not all ENTH domains show this preference.
Jiyao W et al.(2023). "The conserved domain database in 2023.",