SMURF2

E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfers the ubiquitin to targeted substrates. Interacts with SMAD7 to trigger SMAD7-mediated transforming growth factor beta/TGF-beta receptor ubiquitin-dependent degradation, thereby down-regulating TGF-beta signaling. In addition, interaction with SMAD7 activates autocatalytic degradation, which is prevented by interaction with AIMP1. Also forms a stable complex with TGF-beta receptor-mediated phosphorylated SMAD1, SMAD2 and SMAD3, and targets SMAD1 and SMAD2 for ubiquitination and proteasome-mediated degradation. SMAD2 may recruit substrates, such as SNON, for ubiquitin-dependent degradation. Negatively regulates TGFB1-induced epithelial-mesenchymal transition and myofibroblast differentiation. Acts as an activator of ferroptosis by mediating ubiquitination and degradation of GSTP1, thereby preventing detoxification of 4-hydroxynonenal (4-HNE) reactive aldehyde. Acts as a positive regulator of smoothened signaling pathway by mediating ubiquitination of PTCH1, leading to endocytosis and lysosomal degradation of PTCH1 (By similarity)..

Function from UniProtKB (Q9HAU4), read 2026-09-23. CC BY 4.0.