Atypical E3 ubiquitin ligase that can catalyze ubiquitination of both proteins and lipids, and which is involved in various processes, such as lipid metabolism, angiogenesis and cell-autonomous immunity (   ). Acts as a key immune sensor by catalyzing ubiquitination of the lipid A moiety of bacterial lipopolysaccharide (LPS) via its RZ-type zinc-finger: restricts the proliferation of cytosolic bacteria, such as Salmonella, by generating the bacterial ubiquitin coat through the ubiquitination of LPS . Also acts indirectly by mediating the recruitment of the LUBAC complex, which conjugates linear polyubiquitin chains . Ubiquitination of LPS triggers cell-autonomous immunity, such as antibacterial autophagy, leading to degradation of the microbial invader . Involved in lipid metabolism by regulating fat storage and lipid droplet formation; act by inhibiting the lipolytic process . Also regulates lipotoxicity by inhibiting desaturation of fatty acids . Also acts as an E3 ubiquitin-protein ligase via its RING-type zinc finger: mediates 'Lys-63'-linked ubiquitination of target proteins (, ). Involved in the non-canonical Wnt signaling pathway in vascular development: acts by mediating ubiquitination and degradation of FLNA and NFATC2 downstream of RSPO3, leading to inhibit the non-canonical Wnt signaling pathway and promoting vessel regression . Also has ATPase activity; ATPase activity is required for ubiquitination of LPS .
Subcellular locations: Cytoplasm, Cytosol, Lipid droplet
Widely expressed (at protein level).
Major isoform detected in all tissues examined.
Minor isoform with restricted expression.