RNF220

E3 ubiquitin-protein ligase that promotes the ubiquitination and proteasomal degradation of multiple substrates including GRIA1, GRIA2, PHOX2A and PHOX2B, STAT1, STAT3 and SIN3B. Independently of its E3 ligase activity, acts as a CTNNB1 stabilizer through USP7-mediated deubiquitination of CTNNB1 promoting Wnt signaling. Plays a critical role in the regulation of nuclear lamina. Modulates synaptic activity and brain functions by promoting degradation of AMPA receptor subunits GRIA1 and GRIA2. The RNF220/ZC4H2 complex monoubiquitinates PHOX2A and PHOX2B to enhance their DNA-binding ability and transactivity (By similarity). Promotes 'Lys-63'-linked polyubiquitination of Gli transcriptional activators and repressors, facilitating their nuclear export by CRM1 to fine-tune the sonic hedgehog/Gli signaling (By similarity). Regulates type I and type II interferon responses upon viral or bacterial infection by mediating 'Lys-63'-linked polyubiquitination of STAT1. Also regulates STAT3 phosphorylation, nuclear translocation, and transcriptional activity via ubiquitination. Promotes OLIG1 and OLIG2 'Lys-63'-linked polyubiquitination and stabilization, two master regulatory transcription factors involved in oligodendroglial development..

Function from UniProtKB (Q5VTB9), read 2026-09-23. CC BY 4.0.