Gαi2 is a 40-41 kDa alpha-subunit of heterotrimeric protein that shares sequence homology with Gαi3 and Gαi1. All these G proteins can be ADP-ribosylated at the carboxy terminal Cys of the CAAX sequence, interfering with receptor coupling. Gαi2 is expressed widely in tissues and cell lines. Activation of PLC-β by Gαi-coupled receptors is the result of release of Gβg subunits from Gαi. Gαi2 regulates potassium channel activation. Mutation at Arg179 has been identified in tumors. This and the Q205L mutant inhibit adenylyl cyclase.