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Description

E3 ubiquitin-protein ligase RNF213 (UniProt: Q63HN8, also known as ALK lymphoma oligomerization partner on chromosome 17, Mysterin, RING finger protein 213, RING-type E3 ubiquitin transferase RNF21) is encoded by the RNF213 (also known as ALO17, C17orf27, KIAA1554, KIAA1618, MYSTR) gene (Gene ID: 57674) in human. RNF213 is a widely expressed, homooligomeric, cytoplasmic protein that has E3 ubiquitin-protein ligase and AAA+ ATPase activity. It contains a zinc-finger domain (aa 3997-4036) that is required for its ubiquitin-protein ligase activity. RNF213 is shown to be involved in angiogenesis and in non-canonical Wnt signaling pathway in vascular development. Four isoforms of RNF213 have been described that are produced by alternative splicing. RNF213 ligase activity is negatively regulated by PTP1B in HER2+ breast cancer cells and RNF213 knockdown is shown to reverse the effects of PTP1B deficiency on alpha-keto-dependent dehydrogenases, non-mitochondrial oxygen consumption, and hypoxia-induced death of HER2+ BC cells. RNF213 activity is down-regulated by let-7c miRNA, which binds to the 3'-UTR transcript of RNF213. Microbial infection leading to induction of pro-inflammatory cytokines are shown to up-regulate its activity. Defects in RNF213 gene are known to cause Moyamoya disease 2, a progressive cerebral angiopathy characterized by bilateral intracranial carotid artery stenosis and telangiectatic vessels in the region of the basal ganglia, which can lead to transient ischemia and/or rupture of the collateral vessel. (Ref.: Banh, RS et al (2016). Nat. Cell Biol. 18(7), 803-813).