To reach the lysosomes, down-regulated receptors such as the epidermal growth factor receptor (EGFR) must first be sorted into internal vesicles of late endosomes (multivesicular bodies), a ubiquitin-dependent event that requires the coordinated function of the endosome sorting complex required for transport (ESCRT) proteins.
The JAMM domain containing zinc metalloprotease AMSH (Associated Molecule with the SH3-domain of STAM) acts as a deubiquitinylating enzyme during the sorting process to regulate receptor trafficking by specifically cleaving Lys63-linked polyubiquitin chains from internalized receptors. The amino-terminal half of AMSH proteins interacts with clathrin and ESCRT proteins on the endosome, whereas the C-terminal half is engaged in Lys63-linkage-specific deubiquitination. AMSH mediated cleavage of K63 linked ubiquitin chains is enhanced in the presence of its binding partner STAM.
Recombinant protein expressed with N-terminal His-tag. Exhibits K63-polyubiuqitin chain linkage specificity in vitro.
