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 (, ). 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 . Negatively regulates necroptosis by reducing RIPK3 expression . Mediates 'Lys-63'-linked ubiquitination of RIPK1 .
Expressed at high levels in normal skin but decreased in keratinocytes from toxic epidermal necrolysis (TEN) patients (at protein level).