 The E3 ubiquitin-protein ligases SMURF1 and SMURF2 regulate the levels of SMADs.They accept ubiquitin from an E2 conjugating enzyme where they transfer ubiquitin to the RSMADs which causes their ubiquitination and subsequent proteosomal degradation.SMURF1 binds to SMAD1 and SMAD5 while SMURF2 binds SMAD1, SMAD2, SMAD3, SMAD6 and SMAD7.