E3 ubiquitin-protein ligase SMURF2 (SMURF2)

E3 ubiquitin-protein ligase SMURF2 is a member of the HECT-type E3 ubiquitin ligase family, localized to human chromosome 17q23.3-q24.1. It acts as a negative regulator of TGF-β signaling by ubiquitinating and targeting for proteasomal degradation specific components such as TGF-β receptors and Smad proteins, as well as other substrates. SMURF2 consists of a C2 domain, WW domains for substrate/adaptor recognition, and a C-terminal HECT catalytic domain. Through these molecular interactions, SMURF2 controls cellular functions such as signal transduction, protein stability, cell proliferation, and homeostasis. Abnormal regulation or mutation of SMURF2 has been associated with several disease states, most notably cancer. Therapeutic targeting is being explored, though currently only experimental protein-based inhibitors such as UbV S2.4 have been reported to specifically inhibit SMURF2 in vitro

Other names

SMAD specific E3 ubiquitin protein ligase 2Smad ubiquitination regulatory factor 2hSMURF2HECT-type E3 ubiquitin transferase SMURF2

Inhibition of E3 ubiquitin ligase activity (by protein-based inhibitor UbV S2.4, which targets the E2 binding site and disrupts E2-E3 interaction)