Smoothened

Smoothened is a G protein-coupled receptor protein encoded by the gene of the hedgehog pathway conserved from flies to humans. It is the molecular target of the teratogen cyclopamine.

Cellular localization plays an essential role in the function of SMO. Stimulation of the Patched receptor by Sonic hedgehog leads to translocation of SMO to the primary cilium. Furthermore, SMO that is mutated in the domain required for ciliary localisation cannot contribute to pathway activation. SMO has also been shown to bind Costal-2 and play a role in the localization of the Ci cytoplasmic complex.

SMO can function as an oncogene. Activating SMO mutations can lead to unregulated activation of the hedgehog pathway and cancer.