Even if the role of UBE3A in the proteasomal degradation has been well-established [10,12,49,50], involvement of Nef in regulation of proteasomal degradation of viral and cellular proteins is poorly explained, though it is reported that Nef is mono-ubiquitinated [14], degrades a key transcription factor of HIV-1, Tat [38], and excludes SERINC5 for the virus infection [8,40] and UbcH7, the E2 Ub-conjugating enzyme, from the Nef mediated lipid raft to inhibit c-Clb, a Ub ligase [15]. Here, UBE3A is linked to viral infectious disease.