PROSITE documentation PDOC50179
VHS domain profile


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.

Last update:

December 2001 / First entry.


Technical section

PROSITE method (with tools and information) covered by this documentation:

VHS, PS50179; VHS domain profile  (MATRIX)


1AuthorsSchultz J. Milpetz F. Bork P. Ponting C.P.
TitleSMART, a simple modular architecture research tool: identification of signaling domains.
SourceProc. Natl. Acad. Sci. U.S.A. 95:5857-5864(1998).
PubMed ID9600884

2AuthorsLohi O. Lehto V.-P.
TitleVHS domain marks a group of proteins involved in endocytosis and vesicular trafficking.
SourceFEBS Lett. 440:255-257(1998).
PubMed ID9872381

3AuthorsMao Y. Nickitenko A. Duan X. Lloyd T.E. Wu M.N. Bellen H. Quiocho F.A.
TitleCrystal structure of the VHS and FYVE tandem domains of Hrs, a protein involved in membrane trafficking and signal transduction.
SourceCell 100:447-456(2000).
PubMed ID10693761

4AuthorsMisra S. Beach B.M. Hurley J.H.
TitleStructure of the VHS domain of human Tom1 (target of myb 1): insights into interactions with proteins and membranes.
SourceBiochemistry 39:11282-11290(2000).
PubMed ID10985773

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