E3 ubiquitin-protein ligase which may specifically enhance the E2 activity of HIP2. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfer the ubiquitin to targeted substrates (By similarity). May be involved in T-cell proliferation by regulating LIF secretion (PubMed:15670816). May play a role in lysosome homeostasis (By similarity). S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine. Protein modification; protein ubiquitination. Expressed in brain, thymus, muscle and kidney. Highly expressed in most tissues up to 15.5 dpc. Thereafter, expressed at highest levels in the nervous system. The RING-CH-type zinc finger domain is required for E3 ligase activity. Mice have defects in formation of corpus callosum and show degeneration of substantia gelatinosa lamina II axons in adulthood. They have normal lymphoid development but show hyperproliferation of T-cells in response to mitogens.