VHS protein domain
{{Infobox protein family
| Symbol = VHS
| Name = VHS
| image = PDB 1dvp EBI.jpg
| width =
| caption = crystal structure of the vhs and fyve tandem domains of hrs, a protein involved in membrane trafficking and signal transduction
| Pfam = PF00790
| Pfam_clan = CL0009
| InterPro = IPR002014
| SMART = VHS
| PROSITE =
| MEROPS =
| SCOP = 1elk
| TCDB =
| OPM family =
| OPM protein =
| CAZy =
| CDD =
}}
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.{{cite journal|vauthors=Lohi O, Poussu A, Mao Y, Quiocho F, Lehto VP | title=VHS domain -- a longshoreman of vesicle lines. | journal=FEBS Lett | year= 2002 | volume= 513 | issue= 1 | pages= 19–23 | pmid=11911875 | doi= 10.1016/s0014-5793(01)03287-2| bibcode=2002FEBSL.513...19L | s2cid=10894998 }}
Function
Structure
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.{{cite journal |vauthors=Mao Y, Nickitenko A, Duan X, Lloyd TE, Wu MN, Bellen H, Quiocho FA | title = Crystal structure of the VHS and FYVE tandem domains of Hrs, a protein involved in membrane trafficking and signal transduction | journal = Cell | volume = 100 | issue = 4 | pages = 447–56 |date=February 2000 | pmid = 10693761 | doi = 10.1016/S0092-8674(00)80680-7| s2cid = 4979735 | doi-access = free }} 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
Based on regions surrounding the domain, VHS-proteins can be divided into 4 groups:
- 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 ([http://www.ebi.ac.uk/interpro/IEntry?ac=IPR000306 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.{{cite journal |vauthors=Misra S, Beach BM, Hurley JH | title = Structure of the VHS domain of human Tom1 (target of myb 1): insights into interactions with proteins and membranes | journal = Biochemistry | volume = 39 | issue = 37 | pages = 11282–90 |date=September 2000 | pmid = 10985773 | doi = 10.1021/bi0013546}}