E3 ubiquitin ligase catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins. Involved in the TLR and IL-1 signaling pathways via interaction with the complex containing IRAK kinases and TRAF6. Mediates Lys-63-linked polyubiquitination of IRAK1 allowing subsequent NF-kappa-B activation (PubMed:12496252, PubMed:17675297). Mediates Lys-48-linked polyubiquitination of RIPK3 leading to its subsequent proteasome-dependent degradation, preferentially recognizes and mediates the degradation of the Thr-182 phosphorylated form of RIPK3 (PubMed:29883609). Negatively regulates necroptosis by reducing RIPK3 expression (PubMed:29883609). Mediates Lys-63-linked ubiquitination of RIPK1 (PubMed:29883609).
