7oik

Structural highlights

Function

RN213_MOUSE 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 (PubMed:32573437). 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 (PubMed:34012115). Also acts indirectly by mediating the recruitment of the LUBAC complex, which conjugates linear polyubiquitin chains (By similarity). Ubiquitination of LPS triggers cell-autonomous immunity, such as antibacterial autophagy, leading to degradation of the microbial invader (By similarity). Involved in lipid metabolism by regulating fat storage and lipid droplet formation; act by inhibiting the lipolytic process (By similarity). Also regulates lipotoxicity by inhibiting desaturation of fatty acids (By similarity). Also acts as an E3 ubiquitin-protein ligase via its RING-type zinc finger: mediates 'Lys-63'-linked ubiquitination of target proteins (By similarity). 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 (By similarity). Also has ATPase activity; ATPase activity is required for ubiquitination of LPS (PubMed:32573437).[UniProtKB:Q63HN8]^{[1] [2]}

See Also

• Ubiquitin protein ligase 3D structures
• 3D structures of ubiquitin conjugating enzyme

References

1. ↑ Ahel J, Lehner A, Vogel A, Schleiffer A, Meinhart A, Haselbach D, Clausen T. Moyamoya disease factor RNF213 is a giant E3 ligase with a dynein-like core and a distinct ubiquitin-transfer mechanism. Elife. 2020 Jun 23;9:e56185. PMID:32573437 doi:10.7554/eLife.56185
2. ↑ Otten EG, Werner E, Crespillo-Casado A, Boyle KB, Dharamdasani V, Pathe C, Santhanam B, Randow F. Ubiquitylation of lipopolysaccharide by RNF213 during bacterial infection. Nature. 2021 Jun;594(7861):111-116. PMID:34012115 doi:10.1038/s41586-021-03566-4