The activity of RING finger ubiquitin ligases (E3) is dependent on their ability to facilitate transfer of ubiquitin from ubiquitin-conjugating enzymes (E2) to substrates. The G2BR domain within the E3 ubiquitin-protein ligase AMFR (also known as gp78) binds selectively and with high affinity to the E2 Ube2g2. Binding to the G2BR results in conformational changes in Ube2g2 that affect ubiquitin loading. The Ube2g2-G2BR interaction also causes a 50-fold increase in affinity between the E2 and RING finger. Hence, the Ube2g2-binding region (G2BR) is required for the function of gp78. In yeast, Ubc7p, the ortholog of Ube2g2, is recruited by Cue1p to the ER membrane. Cue1p directly binds Ubc7p through a stretch of 50 aa domain analogous to G2BR, i.e. suggesting that this domain which activates ERAD and Hrd1p stimulating ubiquitylation, might be the yeast equivalent of the G2BR domain [, , ].
