VHS protein domain

Protein family

VHS

crystal structure of the vhs and fyve tandem domains of hrs, a protein involved in membrane trafficking and signal transduction

Identifiers
Symbol| VHS
Pfam| PF00790
Pfam clan| CL0009
InterPro| IPR002014
SMART| VHS
SCOP2| 1elk / SCOPe / SUPFAM
| Available protein structures:

Pfam  | structures / ECOD
PDB| RCSB PDB; PDBe; PDBj
PDBsum| structure summary

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]

## Function

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

## Structure

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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.

## Classification

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

* STAM/EAST/STAM2(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]

## References

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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\. Bibcode:2002FEBSL.513...19L. doi:10.1016/s0014-5793(01)03287-2. PMID 11911875. S2CID 10894998.
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. S2CID 4979735.
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