Differences in structure, dynamics, and zinc coordination between isoforms of human ubiquitin ligase UBE3A.

ABSTRACT: Abnormalities in the expression of the ubiquitin ligase UBE3A (ubiquitin-protein ligase E3A)/E6AP (human papillomavirus E6-associated protein) are implicated in neurological disorders including Angelman syndrome and autism. Human UBE3A is expressed as three protein isoforms that differ in their abundance and subcellular localization. While previous studies indicate isoform-specific functions, the distinct roles of each isoform in human development remain unknown. The isoforms differ only by an extension at the N-terminal end of the AZUL (N-terminal zinc [Zn]-binding domain Amino-terminal Zn finger of the UBE3A Ligase) domain, which tethers UBE3A to the proteasome by interaction with proteasomal subunit Rpn10. Differences in the structure and biophysical properties of UBE3A isoforms likely

SUBMITTER: Bregnard TA 

PROVIDER: S-EPMC11795592 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature