Protein ubiquitination and deubiquitination is a reversible process catalyzed by ubiquitinating enzymes and deubiquitinating enzymes. Deubiquitinating enzymes function as ubiquitin-specific proteases and can be divided into five subfamilies based on catalytic domain structure. At least 14 members of the JAMM ubiquitin protease subfamily have been identified, including signal transducing adaptor molecule binding protein. STAM-binding protein is an endosomal DUB that preferentially displays ubiquitin isopeptidase activity toward K63-linked chains, which is critically dependent upon its interaction with STAM. STAMBP interacts with the STAM adaptor protein and becomes integrated into the multivesicular body sorting machinery to help regulate endosomal trafficking and receptor tyrosine kinase stability by deubiquitining target proteins. Evidence indicates that endosomal STAMBP antagonizes the ubiquitin-dependent trafficking of EGFR to the lysosomal compartment. Nijman, S.M. et al. Cell 123, 773-86.
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