E3 ubiquitin-protein ligase that participates in multiple biological processes including cell survival, differentiation, apoptosis, and in particular, the innate immune response (PubMed:27981609, PubMed:28747347). Participates in the activation of interferon-gamma signaling by promoting proteasomal degradation of the repressor SOCS1 (PubMed:12163497). Plays a positive role in the TNFalpha and IL-1beta signaling pathways. Mechanistically, induces the ‘Lys-63’-linked polyubiquitination of MAP3K7/TAK1 component leading to the activation of NF-kappa-B (PubMed:22084099, PubMed:23152791, PubMed:27981609, PubMed:34871740). Modulates also STAT3 activity through negative regulation of PIAS3, either by degradation of PIAS3 through the ubiquitin-proteasome pathway or exclusion of PIAS3 from the nucleus (PubMed:20516148). Negatively regulates TLR3/4-mediated innate immune response by catalyzing ‘Lys-6’- and ‘Lys-33’-linked polyubiquitination of TICAM1 and thereby disrupting the TICAM1-TBK1 interaction (PubMed:28747347).
