Ubiquitin-protein ligase that probably functions as an E3 ligase in conjunction with specific E1 and E2 ligases. May also function as an E4 ligase mediating the assembly of polyubiquitin chains on substrates ubiquitinated by another E3 ubiquitin ligase. Mediates 'Lys-48'-linked polyubiquitination of substrates. Protein modification; protein ubiquitination. Expressed in liver, heart, brain, kidney and testis. The U-box domain is required for the ubiquitin protein ligase activity. Belongs to the ubiquitin conjugation factor E4 family.