UBE2O

E2/E3 hybrid ubiquitin-protein ligase that displays both E2 and E3 ligase activities and mediates monoubiquitination of target proteins. Negatively regulates TRAF6-mediated NF-kappa-B activation independently of its E2 activity. Acts as a positive regulator of BMP7 signaling by mediating monoubiquitination of SMAD6, thereby regulating adipogenesis. Mediates monoubiquitination at different sites of the nuclear localization signal (NLS) of BAP1, leading to cytoplasmic retention of BAP1. Also able to monoubiquitinate the NLS of other chromatin-associated proteins, such as INO80 and CXXC1, affecting their subcellular location. Acts as a regulator of retrograde transport by assisting the TRIM27:MAGEL2 E3 ubiquitin ligase complex to mediate 'Lys-63'-linked ubiquitination of WASHC1, leading to promote endosomal F-actin assembly. Mediates the monoubiquitination of cytoplasmic CTNNA1 to promote cell-to-extracellular matrix adhesions. Mechanistically, ubiquitination of CTNNA1 triggers a binding switch from beta- catenin/CTNNB1 to vinculin/VCL that directs CTNNA1 to mediate matrix adhesion..

Function from UniProtKB (Q9C0C9), read 2026-09-23. CC BY 4.0.