The VHS domain is an about 150 residues long domain, whose name is derived from its occurrence in VPS-27, Hrs and STAM. The VHS domain is found at the N-termini of proteins associated with endocytocis and/or vesicular trafficking, often in association with other domains like FYVE (see <PDOC50178>), SH3 (see <PDOC50002>) or TAM [1,2]. The VHS domain of Hrs makes both intra- and intermolecular interactions with FYVE domains and it has been proposed that it might as well interact with other domains. The VHS domain might function as a multipurpose docking adapter that localizes proteins to the membrane through interactions with the membrane and/or the endocytic machinery [3,4].

Resolution of the crystal structure of the VHS domain of Drosophila Hrs and human Tom1 revealed that it consists of eight helices arranged in a superhelix [3,4].

Some proteins known to contain a VHS domain are listed below:

• Yeast VPS27, which controls membrane trafficking through the prevacuolar/ endosomal compartment.
• Animal Hrs (hepatocyte growth factor regulated tyrosine kinase substrate) is found on the surface of early endosome and may play a role in vesicular transport.
• Mammalian Hrs-2, which modulates vesicle trafficking in neurotransmission.
• Animal STAM (signal-transducing adaptor molecule), which interacts with Hrs and may therefore be involved in endocytosis/vesicular transport.
• Avian EAST (epidermal growth factor receptor-associated protein with SH3 and TAM domains), which colocalizes with clathrin in vesicular structure.
• Vertebrate Tom1 and Tom1-like. Tom1 may help to regulate membrane trafficking in response to c-Myb activity during cellular differentiation or transformation.
• Avian Tom-1b.
• Human Golgi localized γ-ear containing ARF binding (GGA) proteins. GGAs are localized to the trans-Golgi network and late Golgi membranes.

The profile we developed covers the entire VHS domain.