E3 ubiquitin-protein ligase that promotes the degradation of insoluble ubiquitinated proteins, including insoluble PAX6, poly-Gln repeat expanded HTT and poly-Ala repeat expanded ARX (By similarity). Mediates PAX6 ubiquitination leading to proteasomal degradation, thereby modulating cortical neurogenesis (By similarity). May also inhibit PAX6 transcriptional activity, possibly in part by preventing the binding of PAX6 to its consensus sequences (By similarity). May contribute to the regulation of the intracellular level of HN (humanin) or HN-containing proteins through the proteasomal degradation pathway (By similarity). Mediates MED15 ubiquitination leading to proteasomal degradation (PubMed:16904669). May contribute to the innate restriction of retroviruses (PubMed:18248090). Upon overexpression, reduces HIV-1 and murine leukemia virus infectivity, by suppressing viral gene expression (PubMed:18248090). Antiviral activity depends on a functional E3 ubiquitin-protein ligase domain (PubMed:18248090). May regulate TRIM5 turnover via the proteasome pathway, thus counteracting the TRIM5-mediated cross-species restriction of retroviral infection at early stages of the retroviral life cycle (PubMed:18248090). Acts as an inhibitor of the AIM2 inflammasome by promoting autophagy-dependent degradation of AIM2 (PubMed:27498865). Mechanistically, undergoes autoubiquitination upon DNA stimulation, promoting interaction with AIM2 and SQSTM1/p62, leading to AIM2 recruitment to autophagosomes (PubMed:27498865).
