E3 ubiquitin-protein ligase which accepts ubiquitin from E2 ubiquitin-conjugating enzymes UBE2L3 and UBE2L6 in the form of a thioester and then directly transfers the ubiquitin to targeted substrates, such as UCKL1 (PubMed:16709802, PubMed:27485036). Involved in the cytolytic activity of natural killer cells and cytotoxic T-cells (PubMed:10438909). Protects against staurosporin-induced cell death (PubMed:27485036). [E2 ubiquitin-conjugating enzyme]-S-ubiquitinyl-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-N(6)-ubiquitinyl-L-lysine. Protein modification; protein ubiquitination. Interacts with UBE2L3, UBE2L6 and UCKL1. Expressed specifically in natural killer cells, activated macrophages and cytotoxic T-cells (PubMed:10438909). Present in natural killer cells (at protein level) (PubMed:10912506). Ubiquitously expressed with high expression in testis (PubMed:27485036). In natural killer cells, by IFNB1/IFN-beta and IL2/interleukin-2 (at protein level) (PubMed:10438909). Up-regulated by endoplasmic reticulum (ER) stress triggered by thapsigargin or tunicamycin (PubMed:27485036). The first IBR-type zinc finger is the most crucial for interaction with UBE2L3, UBE2L6 and UCKL1. Members of the RBR family are atypical E3 ligases. They interact with the E2 conjugating enzyme UBE2L3 and function like HECT-type E3 enzymes: they bind E2s via the first RING domain, but require an obligate trans-thiolation step during the ubiquitin transfer, requiring a conserved cysteine residue in the second RING domain. Belongs to the RBR family. RNF19 subfamily. Truncated N-terminus. Truncated N-terminus. Truncated N-terminus.