RING E3 ubiquitin transferases serve as mediators bringing the ubiquitin-charged E2 ubiquitin-conjugating enzyme (EC 188.8.131.52
) and an acceptor protein together to enable the direct transfer of ubiquitin through the formation of an isopeptide bond between the C-terminal glycine residue of ubiquitin and the epsilon-amino group of an L-lysine residue of the acceptor protein. Unlike EC 184.108.40.206
, HECT-type E3 ubiquitin transferase, the RING-E3 domain does not form a catalytic thioester intermediate with ubiquitin. Many members of the RING-type E3 ubiquitin transferase family are not able to bind a substrate directly, and form a complex with a cullin scaffold protein and a substrate recognition module (the complexes are named CRL for Cullin-RING-Ligase). In these complexes, the RING-type E3 ubiquitin transferase provides an additional function, mediating the transfer of a NEDD8 protein from a dedicated E2 carrier to the cullin protein (see EC 220.127.116.11
, cullin-RING-type E3 NEDD8 transferase). cf. EC 18.104.22.168
, RBR-type E3 ubiquitin transferase.