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  2. E3 ubiquitin-protein ligase RNF213

E3 ubiquitin-protein ligase RNF213

Definition:

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.

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