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. S-ubiquitinyl-[E1 ubiquitin-activating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E1 ubiquitin-activating enzyme]-L-cysteine + N(6)-monoubiquitinyl-[acceptor protein]-L-lysine. Inhibited by inorganic arsenite such as phenylarsenoxides. Protein modification; protein ubiquitination. Interacts with CPNE1 (via VWFA domain) and CPNE4 (via VWFA domain) (PubMed:12522145). Interacts with UBR2 (PubMed:31268597). Mainly localizes to the cytoplasm. Highly expressed in reticulocytes. By EPO/Erythropoietin which induces erythroid differentiation. Phosphorylated. Phosphorylation affects subcellular location. Ubiquitinated: autoubiquitinates, possibly affecting its subcellular location. Belongs to the ubiquitin-conjugating enzyme family. Truncated N-terminus. Truncated N-terminus. Extended N-terminus.