VHS Domain

Domain Binding and Function

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.

Structure Reference

1. Misra, S. et al. (2000) Biochemistry 39(37), 11282–11290.

Examples of Domain Proteins

Binding Examples

VHS Domain Proteins	Binding Partners
Hrs	Hrs FYVE domain