Zinc metalloprotease that specifically cleaves 'Lys-63'-linked polyubiquitin chains (PubMed:15314065, PubMed:23542699, PubMed:34425109). Does not cleave 'Lys-48'-linked polyubiquitin chains (PubMed:15314065). Plays a role in signal transduction for cell growth and MYC induction mediated by IL-2 and GM-CSF (PubMed:10383417). Potentiates BMP (bone morphogenetic protein) signaling by antagonizing the inhibitory action of SMAD6 and SMAD7 (PubMed:11483516). Has a key role in regulation of cell surface receptor-mediated endocytosis and ubiquitin-dependent sorting of receptors to lysosomes (PubMed:15314065, PubMed:17261583). Endosomal localization of STAMBP is required for efficient EGFR degradation but not for its internalization (PubMed:15314065, PubMed:17261583). Involved in the negative regulation of PI3K-AKT-mTOR and RAS-MAP signaling pathways (PubMed:23542699). Binds 2 Zn(2+) ions per subunit. Inhibited by N-ethylmaleimide (PubMed:15314065). Strongly and specifically inhibited by ubiquitin variants UbV(SP.2) and UbV(SP.3) (PubMed:34425109). Also inhibited by UbV(SP.1); an ubiquitin variant that also inhibits STAMBPL1 (PubMed:34425109). Interacts with STAM (PubMed:10383417, PubMed:15314065). Interacts with SMAD6 and SMAD7 (PubMed:11483516). Interacts with CHMP3; the interaction appears to relieve the autoinhibition of CHMP3 (PubMed:17146056, PubMed:17261583). Interacts with SMURF2 and RNF11; this interaction promotes ubiquitination (PubMed:14755250). Ubiquitously expressed. The JAMM motif is essential for the protease activity. Phosphorylated after BMP type I receptor activation. Ubiquitinated by SMURF2 in the presence of RNF11. The disease is caused by variants affecting the gene represented in this entry. X-ray crystallography studies of STAMBPL1, another member of the peptidase M67C family, has shown that Glu-280 binds zinc indirectly via a water molecule. Nevertheless, this residue is essential for catalytic activity. Belongs to the peptidase M67C family.