Considering more broadly the cellular turnover of RNF20 and the role of additional factors, the HECT-domain E3 ubiquitin ligase Smad ubiquitin regulatory factor 2 (Smurf2) that itself has tumour suppressive roles, polyubiquitinates RNF20, marking it for proteasomal degradation, and in this way is linked in with the regulation of H2Bub1 [125]. The gene discussed is RNF20; the disease is neoplasm.