Pathways & interactions
Short name: ENTH_VHS
- VHS domain (IPR002014)
- CID domain (IPR006569)
- RNA polymerase II-binding domain (IPR006903)
- AP180 N-terminal homology (ANTH) domain (IPR011417)
- ENTH domain (IPR013809)
- Target of Myb protein 1 (IPR014645)
- Ubiquitin binding protein, Hrs/VPS27 (IPR017073)
- CTD kinase subunit gamma CTK3 (IPR024638)
- Epsin-3, metazoa (IPR027318)
- Epsin-2, metazoa (IPR027319)
- ADP-ribosylation factor-binding protein GGA3 (IPR027422)
- TOM1-like protein 1 (IPR027428)
- Target of Myb1-like 2 (IPR027429)
- Sla2 family (IPR030224)
- Phosphatidylinositol-binding clathrin assembly protein (IPR030412)
- Clathrin interactor 1 (IPR030544)
- Clathrin interactor EPSIN 1 (IPR033521)
- Tepsin, ENTH/VHS domain (IPR035802)
- Calcium homeostasis endoplasmic reticulum protein (IPR039037)
- AP-4 complex accessory subunit Tepsin (IPR039273)
- Epsin, ENTH domain (IPR039416)
This superfamily represents domains with a multi-helical, alpha-alpha 2-layered structural fold as found in: the ENTH domain of Epsin; the VHS domain of Hrs, Tom1, and ADP-ribosylation factors; the RPR domain of PCF11 protein; and the N-terminal domain of phosphoinositide-binding clathrin adaptor.
The epsin NH2-terminal homology (ENTH) domain is a membrane interacting module composed of 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 signalling and actin regulation and may have yet other actions in the nucleus. The ENTH domain is structurally similar to the VHS domain.
The ENTH domain is approximately 150 amino acids long. The ENTH domain forms a compact globular structure, composed of eight alpha-helices connected by loops of varying length. Three helical hairpins that are stacked consecutively with a right-handed twist determine the general topology of the domain. This stacking gives the ENTH domain a rectangular appearance when viewed face on. The most highly conserved amino acids fall roughly into two classes: internal residues that are involved in packing and therefore are necessary for structural integrity, and solvent accessible residues that may be involved in protein-protein interactions [PMID: 11911874].
VHS domains are found at the N-termini of select proteins involved in intracellular membrane trafficking. The domain consists of eight helices arranged in a superhelix. The surface of the domain has two main features: a basic patch on one side due to several conserved positively charged residues on helix 3 and a negatively charged ridge on the opposite side, formed by residues on helix 2. Comparison of the two VHS domains and the ENTH domain reveals a conserved surface, composed of helices 2 and 4, that is utilised for protein-protein interactions. In addition, VHS domain-containing proteins are also often localized to membranes. It has therefore been suggested that the conserved positively charged surface of helix 3 in VHS and ENTH domains plays a role in membrane binding [PMID: 10985773].