Figure 5. Mechanisms of paralogue specificity.

(A) The predominant modification by SUMO-1 of RanGAP1 has been reported to be due to the protection of RanGAP1–SUMO-1 from SENP-mediated deSUMOylation through binding of this complex to RanBP2, an interaction which only occurs weakly for RanGAP–SUMO-2, leaving it susceptible to deSUMOylation. (B) Alternatively, a growing number of SUMO substrates have been shown to contain paralogue-specific SIMs, which can mediate their paralogue-specific SUMOylation through non-covalent binding to the SUMO protein, or to SUMO-loaded Ubc9. (C) Paralogue specificity may arise through the paralogue-specific actions of E3 enzymes, such as RanBP2, which appears to preferentially conjugate SUMO-2 to substrate proteins.