PROSITE documentation PDOC50179VHS 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.
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PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Schultz J. Milpetz F. Bork P. Ponting C.P. |
| Title | SMART, a simple modular architecture research tool: identification of signaling domains. | |
| Source | Proc. Natl. Acad. Sci. U.S.A. 95:5857-5864(1998). | |
| PubMed ID | 9600884 |
| 2 | Authors | Lohi O. Lehto V.-P. |
| Title | VHS domain marks a group of proteins involved in endocytosis and vesicular trafficking. | |
| Source | FEBS Lett. 440:255-257(1998). | |
| PubMed ID | 9872381 |
| 3 | Authors | Mao Y. Nickitenko A. Duan X. Lloyd T.E. Wu M.N. Bellen H. Quiocho F.A. |
| Title | Crystal structure of the VHS and FYVE tandem domains of Hrs, a protein involved in membrane trafficking and signal transduction. | |
| Source | Cell 100:447-456(2000). | |
| PubMed ID | 10693761 |
| 4 | Authors | Misra S. Beach B.M. Hurley J.H. |
| Title | Structure of the VHS domain of human Tom1 (target of myb 1): insights into interactions with proteins and membranes. | |
| Source | Biochemistry 39:11282-11290(2000). | |
| PubMed ID | 10985773 | |
| DOI | 10.1021/bi0013546 |
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