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As the largest group in the ubiquitination process, E3 ligases have different E2-binding structures and catalytic mechanisms of Ub transfer, and they are generally divided into three major categories: RING (really interesting new gene) domain E3 (~600 members), HECT (homologous to E6AP carboxyl terminus) domain E3 (28 members), RBR (RING-between-RING) domain E3 (14 members) (Fig

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