E3 ubiquitin-protein ligase RNF213 (RNF213)

E3 ubiquitin-protein ligase RNF213, also known as Mysterin, is a massive 591 kDa enzyme that functions as both an E3 ubiquitin ligase and a dynein-like AAA+ ATPase. It is historically recognized as the primary susceptibility gene for Moyamoya disease, a rare cerebrovascular disorder characterized by progressive stenosis of the internal carotid arteries. Recent landmark studies have identified RNF213 as the first known enzyme to ubiquitylate a non-protein substrate, specifically the lipid A moiety of bacterial lipopolysaccharide (LPS). This LPS ubiquitylation acts as a critical 'eat-me' signal that recruits autophagy adapters and the LUBAC complex, triggering xenophagy to clear cytosol-invading Gram-negative bacteria like Salmonella. Beyond its role in infection, RNF213 is involved in vascular development, lipid droplet regulation, and inflammatory signaling, making it a significant target for both anti-infective strategies and cerebrovascular therapies.

Other names

MysterinRing finger protein 213MYMY2ALOMYSTR