The heterotrimeric G protein Gz, is a member of the Gi family. Unlike other Gi family members it lacks an ADP ribosylation site cysteine four residues from the carboxyl terminus and is thus pertussis toxin-insensitive. It inhibits adenylyl cyclase types I, V and VI. G alpha (z) interacts with the Rap1 GTPase activating protein (Rap1GAP) to attenuate Rap1 signaling. Like all G-proteins Gz has an intrinsic GTPase activity, but this activity tends to be lower for the pertussis toxin insensitive G-proteins, most strikingly so for Gz, whose kcat value for GTP hydrolysis is 200-fold lower than those of Gs or Gi (Grazziano et al. 1989). Gz knockout mice have disrupted platelet aggregation at physiological concentrations of epinephrine and responses to several neuroactive drugs are altered (Yang et al. 2000).