RNF213

Atypical E3 ubiquitin ligase that can catalyse 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 catalysing 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. Also functions as an intracellular sensor for ISGylated proteins: upon type I interferon stimulation, undergoes ISGylation and oligomerises on lipid droplets to form a binding platform for ISG15-modified substrate proteins, thereby acting as a broad-spectrum antimicrobial effector. Restricts intracellular bacterial pathogens, such as Listeria monocytogenes, in an ISG15-dependent manner by decorating the bacterial surface with ubiquitin to promote autophagic clearance. Location: Cytoplasm, cytosol; Lipid droplet (UniProt). Locus 17q25.3 (HGNC).