VHS protein domain

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PDB 1dvp EBI.jpg
crystal structure of the vhs and fyve tandem domains of hrs, a protein involved in membrane trafficking and signal transduction
Symbol VHS
Pfam PF00790
Pfam clan CL0009
InterPro IPR002014
SCOP 1elk

In molecular biology, the VHS protein domain is approximately 140 residues long. Its name is an acronym derived from its occurrence in VPS-27, Hrs and STAM. It is a domain commonly found in the N-terminus of many proteins.[1]


VHS domains thought to be very important in vesicular trafficking, in particular, aiding membrane targeting and cargo recognition role.[1]


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.[2] 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.


Based on regions surrounding the domain, VHS-proteins can be divided into 4 groups:[1]

  • 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 (INTERPRO) 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.[3]


  1. ^ a b c Lohi O, Poussu A, Mao Y, Quiocho F, Lehto VP (2002). "VHS domain -- a longshoreman of vesicle lines". FEBS Lett. 513 (1): 19–23. doi:10.1016/s0014-5793(01)03287-2. PMID 11911875. 
  2. ^ Mao Y, Nickitenko A, Duan X, Lloyd TE, Wu MN, Bellen H, Quiocho FA (February 2000). "Crystal structure of the VHS and FYVE tandem domains of Hrs, a protein involved in membrane trafficking and signal transduction". Cell. 100 (4): 447–56. doi:10.1016/S0092-8674(00)80680-7. PMID 10693761. 
  3. ^ Misra S, Beach BM, Hurley JH (September 2000). "Structure of the VHS domain of human Tom1 (target of myb 1): insights into interactions with proteins and membranes". Biochemistry. 39 (37): 11282–90. doi:10.1021/bi0013546. PMID 10985773. 

This article incorporates text from the public domain Pfam and InterPro IPR002014