Comparison of the roles of each secretin residue in binding and biological activity with that of other family B GPCR ligands. Top, role in binding affinity. Bottom, role in biological activity. Open circles, little importance (Ki or EC50 values are less than 10-fold of that of natural ligand). Grey circles, important (Ki or EC50 values are more than 10-fold but less than 100-fold of that of natural ligand). Black circles, critical (Ki or EC50 values are more than 100-fold of that of natural ligand). Sec, secretin; SecR, secretin receptor; GLP1R, GLP1 receptor.