Angelman syndrome-associated point mutations in the Zn-binding N-terminal (AZUL) domain of UBE3A ubiquitin ligase inhibit binding to the proteasome.

Deregulation of the HECT ubiquitin ligase UBE3A/E6AP has been implicated in Angelman syndrome as well as autism spectrum disorders. We and others have previously identified the 26S proteasome as one of the major UBE3A-interacting protein complexes. Here, we characterize the interaction of UBE3A and the proteasomal subunit PSMD4 (Rpn10/S5a).