Ubiquitin is transferred from E1 to E2 and finally to one of three types of E3 ubiquitin ligases. The RING-type ligase binds to E2 and directly transfers the ubiquitin from E2 to the substrate. The RBR type has a RING1, RING2 and in-between RING (IBR) domain. The RING1 domain binds to E2-ubiquitin complex and the ubiquitin is transferred to RING2. Finally, the ligase transfers the ubiquitin from RING2 to the substrate. HECT type ligase, similar to RBR, first transfers the ubiquitin from the E2-ubiquitin complex to itself and then to substrate. Ubi, Ubiquitin.