E3 ubiquitin-protein ligase that have both tumor-promoting and tumor-suppressing activities and functions in several biological processes including innate immunity, regulation of ferroptosis as well as cell proliferation and migration ( ). Acts as an antiviral effector against multiple viruses by targeting specific viral proteins for ubiquitination and degradation including norovirus NTPase protein or SARS-CoV-2 NSP5 and NSP8 proteins (, ). Mechanistically, recognizes the C-terminal glutamine-containing motif usually generated by viral proteases that process the polyproteins and trigger their ubiquitination and subsequent degradation ( ). Mediates 'Lys-63'-linked polyubiquitination and stabilization of the JUN coactivator RNF187 in response to growth factor signaling via the MEK/ERK pathway, thereby regulating JUN transactivation and cellular proliferation . Promotes the TLR4-mediated signaling activation through its E3 ligase domain leading to production of pro-inflammatory cytokines and type I interferon (By similarity). Also plays a negative role in the regulation of exogenous cytosolic DNA virus-triggered immune response. Mechanistically, enhances the 'Lys-48'-linked ubiquitination of STING1 leading to its proteasome-dependent degradation . Mediates the ubiquitination of the SIN3-HDAC chromatin remodeling complex component BRMS1 . Modulates NCOA4-mediated ferritinophagy and ferroptosis in glioblastoma cells by ubiquitinating NCOA4, leading to its degradation .
(Microbial infection) Promotes Zika virus replication by mediating envelope protein E ubiquitination.
Subcellular locations: Nucleus, Cytoplasm, Golgi apparatus
Skeletal muscle and placenta, at lower levels in heart, brain and pancreas. Isoform 1 is widely expressed with high level in testis, kidney and heart.