The enzymes of the ubiquitylation pathway play a pivotal role in a number of cellular processes including the regulated and targeted proteasome-dependent degradation of substrate proteins. Three classes of enzymes are involved in the process of ubiquitylation; activating enzymes (E1s), conjugating enzymes (E2s) and protein ligases (E3s). Ring Finger Protein 11 (RNF11) is a member of the E3 protein ligase family and cloning of the human gene was first described by Seki et al. (1999). The intrinsic E3 ligase activity of RNF11 is conferred through a RING domain at the C-terminus of the protein. RNF11 has been shown to interact with the HECT-type E3 ubiquitin ligases Nedd4, AIP4, SMURF1 and SMURF2, as well as with Cullin1, the core protein of the multi-subunit SCF E3 ubiquitin ligase complex (Santonico, Belleudi et al., 2010; Kitching et al., 2003). RNF11 has been found to mediate the ubiquitylation of AMSH by the E3 ligase SMURF2. It is thought that RNF11 recruits AMSH to SMURF2 for ubiquitylation, leading to its degradation by the 26S proteasome (Li and Seth 2004).
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