Binding of RhoA by the C2 domain of E3 ligase Smurf1 is essential for Smurf1-regulated RhoA ubiquitination and cell protrusive activity

► The C2 domain of Smurf1 plays key role in substrate selection. ► Smurf1 C2 domain is important for binding of RhoA but not Smad1. ► The C2 domain is essential for Smurf1-regulated cell protrusive activity. ► The C2 domain is dispensable for Smurf1down-regulating BMP signaling.