E3 ubiquitin-protein ligase that mediates ubiquitination oF target proteins. Depending on the associated E2 ligase, mediates 'Lys-48'- and 'Lys-63'-linked polyubiquitination of substrates. Part of a BAG6-dependent quality control process ensuring that proteins of the secretory pathway that are mislocalized to the cytosol are degraded by the proteasome. Probably acts by providing the ubiquitin ligase activity associated with the BAG6 complex and be responsible for ubiquitination of the hydrophobic mislocalized proteins and their targeting to the proteasome. May also play a role in the endosomal recycling of IGF2R, the cation-independent mannose-6-phosphate receptor. May play a role in the endosomal sorting and degradation of several membrane receptors including EGFR, FLT3, MET and CXCR4, by mediating their ubiquitination. By ubiquitinating CDKN1A/p21 and targeting it for degradation, may also promote cell proliferation. May monoubiquitinate AICDA.
