VHS protein domain explained

Symbol:	VHS
VHS
Pfam:	PF00790
Pfam Clan:	CL0009
Interpro:	IPR002014
Smart:	VHS
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]

Function

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

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.^[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

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]

Notes and References

1. Lohi O, Poussu A, Mao Y, Quiocho F, Lehto VP . VHS domain -- a longshoreman of vesicle lines. . FEBS Lett . 2002 . 513 . 1 . 19–23 . 11911875 . 10.1016/s0014-5793(01)03287-2. 10894998 .
2. Mao Y, Nickitenko A, Duan X, Lloyd TE, Wu MN, Bellen H, Quiocho FA . 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 . February 2000 . 10693761 . 10.1016/S0092-8674(00)80680-7. 4979735 . free .
3. Misra S, Beach BM, Hurley JH . Structure of the VHS domain of human Tom1 (target of myb 1): insights into interactions with proteins and membranes . Biochemistry . 39 . 37 . 11282–90 . September 2000 . 10985773 . 10.1021/bi0013546.