{PDOC50179}
{PS50179; VHS}
{BEGIN}
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* VHS domain profile *
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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 gamma-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.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: December 2001 / First entry.

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

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