Active, Recombinant Human AMSH*

Background: Human AMSH (also known as STAMBP) is a zinc-dependent JAMM/MPN⁺ deubiquitylase (DUB) whose ordered Ins-2 loop enforces K63-linked chain specificity. AMSH is only active when allosterically activated by its binding partners STAM1 or STAM2. Binding the SH3 domain of STAM within ESCRT-0 recruits AMSH to early endosomes. There it trims K63 ubiquitin signals just before multivesicular-body scission, thereby modulating ESCRT-regulated trafficking events. Loss-of-function mutations in AMSH cause autosomal-recessive microcephaly–capillary malformation syndrome, whereas pharmacologic or genetic inhibition of STAMBP dampens NLRP7/NALP7 inflammasome activation.