E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates (By similarity). Required for prevention of apoptotic death in early embryogenesis. 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. Shuttles between the nucleus and the cytoplasm. In the nucleus, delocalizes from the nucleolus to the nucleoplasm in response to DNA damage. In the developing embryo, expressed predominantly in the central nervous system and early limb bud. In the adult, highest expression in Purkinje cell bodies and cells lining the ductus deferens. Ubiquitin ligase activity is mediated by two distinct domains, PHD-type zinc fingers 2 and 3. The use of these distinct domains may allow ubiquitination of different targets by each domain. The HECT domain is catalytically inactive and does not contribute to this activity. Embryos die prior to implantation due to massive apoptosis resulting in blastocyst involution. Extended N-terminus.