<p>The VHS domain is a ~140 residues long domain, whose name is derivedfrom its occurrence in VPS-27, Hrs and STAM. Based on regions surrounding the domain, VHS-proteins can be divided into 4 groups [<cite idref="PUB00007169"/>]: <ul> <li>STAM/EAST/Hbp which all share the domain composition VHS-SH3-ITAM and carry one or two ubiquitin-interacting motifs</li> </ul> <ul> <li>Proteins with a FYVE domain (<db_xref db="INTERPRO" dbkey="IPR000306"/>) C-terminal to VHS which also carry one or two ubiquitin-interacting motifs</li> </ul> <ul> <li>GGA proteins with a domain composition VHS-GAT (GGA and Tom1) homology domain</li> </ul> <ul> <li>VHS domain alone or in combination with domains other than those listed above</li> </ul>The VHS domain is always found at the N-terminus of proteins suggesting that such topology is important for function. The domain is considered to have a general membrane targeting/cargo recognition role in vesicular trafficking [<cite idref="PUB00008037"/>].</p><p>Resolution of the crystal structure of the VHS domain of Drosophila Hrs andhuman Tom1 revealed that it consists of eight helices arranged in a double-layer superhelix[<cite idref="PUB00008038"/>]. The existence of conserved patches of residues on the domain surface suggests that VHS domains may be involved in protein-protein recognition and docking. Overall, sequence similarity is low (approx 25%) amongst domain family members.</p> VHS