E3 (ubiquitin) ligases interact with ubiquitin-E2 (ubiquitin-conjugating) enzymes and the target protein, transferring the ubiquitin from the E2 to the substrate. RING-between-RING (RBR) E3 ligases are characterised by three closely spaced domains: RING1 (a classical RING finger domain), a In-Betweeen-RING (IBR) domain and a RING2 domain. The mechanism of action is described as RING/HECT-like, with the RING1 domain facilitating E2-transfer (E3 RING-like) to form a thioester intermediate with a cysteine in RING2 which then modifies the substrate protein (HECT-like). (Adapted from PMID:24469331).