Figure 1.

Diagram of UBE3A substrate cascade to Angelman syndrome. Angelman syndrome is caused by the pathological loss of maternal UBE3A protein expression, resulting in the loss of regulation of its pool of downstream substrates. UBE3A direct interactors/substrates are labeled as a 1° inside a circle. Indirect substrates/changes are labeled as 2° inside a circle. Gene products associated with neurodevelopment are in tan colored circles and associated with Autism spectrum disorders are colored. Following the loss of UBE3A changes to these 1°substrates are the initiators of cascade of events which lead to 2° changes. These 2° changes can be in the form of protein-protein interactions, cell biological, electrophysiological, etc. The convergence of these 2° and downstream changes produce phenotypes characteristic of Angelman syndrome. Given some proteins known to be misregulated in ASDs are primary or secondary interactors in this UBE3A-dependent pathway, as indicated by the colored substrates, the phenotypic overlap between Angelman Syndrome and autism spectrum disorders it is not surprising. Through the study of UBE3A substrates, more overlapping molecular changes underlying shared phenotypes may become apparent.