HECT E3 ligases. (a) Smurf2. I is the schematic representation of the assembly of the Smurf2 E3 ligase: ubiquitin (Ub) in purple, E2 ligase (E2) in dark blue, HECT domain (HECT) in pink, WW3 domain in light blue, WW2 domain in orange, WW1 in yellow, C2 domain in green, and substrate protein in grey. Protein assembly II is the 3D representation of the C2 domain as found in PDB code 2JQZ. Protein assembly III is the 3D representation of the WW2 and WW3 domains in complex with a fragment of the substrate protein Smad7 as found in PDB code 2KXQ. Protein assembly IV is the 3D representation of the HECT domain as found in PDB code 1ZVD. (b) HUWE1. Schematic representation of the assembly of the Smurf2 E3 ligase adapted from Hunkeler M. et al. [162]: HECT domain (HECT) in pink, armadillo repeated as domain 1–4 (ARLD1–4) in shades of lilac, ubiquitin associated domain (UBA) in yellow, tryptophan and glutamic acid-rich domain (WWE) in orange, HUWE1 WWE module associated domain (HWA) in salmon pink, tower domain in dark blue, Bcl-2 homology region 3 (BH3) in light blue, and ubiquitin binding motif 1 (UBM1) in green. The 3D representation of the individually crystalized fragments of this assembly are represented next to their position in the scheme (UBA (PDB code 2EKK) yellow, HECT (PDB code 3H1D) pink, WWE (PDB code 6MIW) orange, and UBM1 (PDB code 2MUL) green).