Epsin N-Terminal Homology (ENTH) domain of Epsin family
Members of the epsin family play an important role as accessory proteins in clathrin-mediated endocytosis. They are important factors in clathrin-coated vesicle (CCV) generation. They contribute to membrane deformation and play a key function as adaptor proteins, coupling various components of clathrin-mediated uptake. They also have an important role in selecting and recognizing cargo. Three isoforms have been identified in mammals, epsin-1 to -3, and these are conserved in vertebrates. Epsin-1 is highly enriched and represents the dominant isoform in the brain. It is required for proper synaptic vesicle retrieval and modulates the endocytic capacity of synaptic vesicles. Epsins contain an Epsin N-Terminal Homology (ENTH) domain, an evolutionarily conserved protein module found primarily in proteins that participate in clathrin-mediated endocytosis. The 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 CCVs. 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 binds Ins(1,4,5)p3; contacts at 4.0A - View structure with Cn3D
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.
Jiyao W et al.(2023). "The conserved domain database in 2023.",