The N-terminal domain of GPR61, an orphan G-protein-coupled receptor, is essential for its constitutive activity.

G-protein-coupled receptor 61 (GPR61) is an orphan receptor that is abundantly expressed in the brain, which suggests its involvement in various physiological functions in the central nervous system. It couples with Gs and shows constitutive activity. To investigate the role of the N-terminal segment in the constitutive activity of GPR61, we measured [(35)S]GTPgammaS binding using a GPR61-Gs fusion protein and derivatives that had a deletion or alanine mutation in the N-terminal segment.