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Simplified model of HECT E3-mediated protein ubiquitination. E2 ~ Ub thioester binds HECT E3 domain, followed by transthiolation reaction producing HECT E3 ~ Ub thioester. Subsequently, HECT E3 ~ Ub ligates Ub onto the lysine of the substrate, followed by polyUb chain growth. C- and N-lobes of HECT domain rotate relative to each other during the catalytic cycle.
