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48  structures 1374  species 0  interactions 9626  sequences 166  architectures

Family: VHS (PF00790)

Summary: VHS domain

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This is the Wikipedia entry entitled "VHS protein domain". More...

VHS protein domain Edit Wikipedia article

PDB 1dvp EBI.jpg
crystal structure of the vhs and fyve tandem domains of hrs, a protein involved in membrane trafficking and signal transduction
Pfam clanCL0009

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

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VHS domain Provide feedback

Domain present in VPS-27, Hrs and STAM.

Literature references

  1. Mao Y, Nickitenko A, Duan X, Lloyd TE, Wu MN, Bellen H, Quiocho FA; , Cell 2000;100:447-456.: Crystal structure of the VHS and FYVE tandem domains of Hrs, a protein involved in membrane trafficking and signal transduction. PUBMED:10693761 EPMC:10693761

  2. Lohi O, Lehto VP; , FEBS Lett 1998;440:255-257.: VHS domain marks a group of proteins involved in endocytosis and vesicular trafficking. PUBMED:9872381 EPMC:9872381

Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR002014

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, SH3 or TAM [ PUBMED:9600884 , PUBMED:9872381 ]. 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 [ PUBMED:10693761 , 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 superhelix [ PUBMED:10693761 , PUBMED:10985773 ].

Gene Ontology

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Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan ENTH_VHS (CL0009), which has the following description:

This clan includes the related ENTH and ANTH domains as well as the VHS domain. The ENTH domain is approximately 150 residues in length and is a solenoid of alpha-helices. The various ENTH domains have various lipid specificities but the key feature that distinguishes it functionally from ANTH domains is its ability to bend membranes. It does this by folding an additional N-terminal helix on lipid binding. The ANTH domain is approximately 300 residues in length and is a PtdIns(4,5)P2 binding domain. It has no membrane bending properties. The VHS (Vps-27, Hrs and STAM) domain is a 140 residue long domain present in the very NH2-terminus of at least 60 proteins. Based on their functional characteristics and on recent data on the involvement of VHS in cargo recognition in trans-Golgi, VHS domains are considered to have a general membrane targeting/cargo recognition role in vesicular trafficking [5].

The clan contains the following 3 members:



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Seed source: Alignment kindly provided by SMART
Previous IDs: none
Type: Domain
Sequence Ontology: SO:0000417
Author: SMART
Number in seed: 15
Number in full: 9626
Average length of the domain: 131.20 aa
Average identity of full alignment: 29 %
Average coverage of the sequence by the domain: 23.50 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 29.8 29.8
Trusted cut-off 29.8 29.8
Noise cut-off 29.7 29.7
Model length: 141
Family (HMM) version: 21
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Species distribution

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Archea Archea Eukaryota Eukaryota
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Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence


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For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the VHS domain has been found. There are 48 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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