Supplementary Figure 10: Model for UBE3A localization. | Nature Neuroscience

Supplementary Figure 10: Model for UBE3A localization.

From: Loss of nuclear UBE3A causes electrophysiological and behavioral deficits in mice and is associated with Angelman syndrome

Supplementary Figure 10: Model for UBE3A localization.The alternative text for this image may have been generated using AI.

Nuclear localization of UBE3A is controlled by two steps: (1) PSMD4 mediated import into the nucleus of both isoforms (mediated by the AZUL domain, as well as sequences in the HECT domain which may be required for proper folding) and (2) selective retention of the mUBE3A-Iso3 isoform in the nucleus by means of a functional Zn-finger. The N-terminal extension of mUBE3A-Iso2 interferes with nuclear retention. The AS-associated p.G20V, p.C21Y and p.G593R mutations (human UBE3A isoform 1 numbering; mouse UBE3A-Iso3 p.G590R) cause mislocalization of UBE3A by either affecting import in the nucleus (p.G593R) or by affecting nuclear retention (p.G20V, p.C21Y). See discussion for more details about this model. TF: transcription factor.

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