E3 ubiquitin-protein ligase RNF217 (RNF217)

E3 ubiquitin-protein ligase RNF217 is a member of the RBR (RING-in-between-RING) E3 ligase family. It codes for a protein of 284 amino acids carrying two RING finger domains, separated by an IBR (in-between-RING) motif. RNF217 functions as an E3 ubiquitin ligase mediating the polyubiquitination and degradation of the iron exporter ferroportin (FPN), thereby regulating cellular and systemic iron homeostasis. RNF217’s expression is epigenetically regulated by Tet1-mediated demethylation, making it responsive to iron status. The protein also interacts with the antiapoptotic protein HAX1, which suggests a secondary role in apoptosis and cell death signaling. Deregulation or mutation of RNF217 has been implicated in certain cancers (especially myeloid leukemia), though no drugs currently target RNF217 directly. Disruption or altered activity of RNF217 can significantly affect iron metabolism, leading to phenotypes reminiscent of hemochromatosis or iron overload, and makes it a putative therapeutic target for iron-related disorders.

Other names

RNF217Ring finger protein 217C6orf172IBRDC1OSTLMGC26996dJ84N20.1IBR domain-containing protein 1Opposite STLIBR domain containing 1Probable E3 ubiquitin-protein ligase RNF217

For hypothetical drugs: Inhibition of RNF217 could stabilize ferroportin, increasing iron export and reducing iron overload; activation would promote ferroportin degradation, reducing iron export