Domain present in VPS-27, Hrs and STAM
SMART accession number:SM00288
Description: Unpublished observations. Domain of unknown function.
Interpro abstract (IPR018205):

The VHS domain is a ~140 residues long domain, whose name is derived from its occurrence in VPS-27, Hrs and STAM. Based on regions surrounding the domain, VHS-proteins can be divided into 4 groups [(PUBMED:11911875)]:

  • STAM/EAST/Hbp which all share the domain composition VHS-SH3-ITAM and carry one or two ubiquitin-interacting motifs
  • Proteins with a FYVE domain (IPR000306) C-terminal to VHS which also carry one or two ubiquitin-interacting motifs
  • GGA proteins with a domain composition VHS-GAT (GGA and Tom1) homology domain
  • VHS domain alone or in combination with domains other than those listed above
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 [(PUBMED:10985773)].

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 double-layer superhelix [(PUBMED:10693761)]. 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. In this entry, the domain is found in ADP-ribosylation factor-binding proteins and Hepatocyte growth factor-regulated tyrosine kinase substrates as well as vacuolar protein-sorting machinery proteins, amongst others.

Family alignment:
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There are 1933 VHS domains in 1933 proteins in SMART's nrdb database.

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