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Description

Smurf1 is a member of the Nedd4-like family of E3 ligases. It contains an amino terminal C2 domain and 2 WW domains that are responsible for cellular localization and substrate recognition, and a catalytic carboxyl terminal HECT domain.Smurf1 was originally identified as a negative regulator of the TGF-beta/BMP (bone morphogenetic proteins) signalling pathway by degrading SMAD proteins and TGF-beta /BMP receptors. To date, over a dozen substrates have been identified, including Runx2, MEKK2, RhoA, Par6, JunB, Talin head, Prickle1, TRAF family proteins, and STAT1. This suggests a pleiotropic role for Smurf1 in various cellular functions such as bone homeostasis, embryonic development, cell movement and polarity control, and immune response. Aberrant expression of Smurfs has been shown to occur in several types of cancers, including breast, oesophageal, pancreatic and renal cell carcinomas.