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VHS Domain
Class:Ubiquitin processes

No Image The three dimensional structure of the VHS domains from Drosophila Hrs and the human Target of Myb1, Tom1, have been solved. The VHS domain is comprised of eight alpha helices that fold into a right handed superhelical structure. The core of the VHS domain consists almost exclusively of hydrophobic residues with polar, acidic, and basic residues restricted to the surface of the domain. In the case of Hrs1, the protein forms a pyramid-like structure for which the VHS superhelical structure forms the base while the FYVE domain sits on top, forming the upper portion of the pyramid. Interestingly, comparison of the VHS domain with other known structures reveals structural similarity with HEAT and ARM repeats, two known protein-protein interaction motifs. Furthermore, the VHS domain shares structural similarity the ENTH domain, a domain involved in vesicle trafficking that is found in a variety of proteins (ie. Epsins, CALM, and AP-180).

Structure Reference:

Misra et al. (2000) Biochemistry. 39(37):11282-11290. PDB: 1ELK.

Domain binding and function:
 structure The approximately 150 amino acid VHS (Vps27p, Hrs and STAM) domain has been identified in over 40 different eukaryotic proteins. VHS domains can be found in the context of other modular domains such as the SH3 domain and the FYVE domain in EAST and Hrs proteins, respectively. This domain is also found at the amino-terminus of several proteins that have been implicated in signaling from receptor tyrosine kinases (RTKs). VHS domains are found in proteins such as STAM, EAST, and Hrs that have been linked to RTK-mediated endocytosis. The VHS domain of GGA proteins binds to an acidic di-leucine motif in the cytoplasmic domain of sorting receptors including the mannose 6-phosphate receptor. GGA proteins are required for the targeting of mannose 6-phosphate receptor to the lysosome, where the receptor functions to mediate lysosomal enzyme sorting.
Examples of Proteins: 
VHS proteins
Binding partner
GGA di-leucine motif in the cytoplasmic tail of mannose-6-phosphate receptor
Hrs Hrs FYVE domain

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