The human genome encodes at least three non-allellic G proteins with alpha i-type subunits.

The amino acid sequence and composition of alpha-subunits of signal transducing G proteins of the same kind appear to vary by no more than 2% from species to species. Here we isolated a human liver cDNA using an oligonucleotide complementary to the sequences encoding the pertussis toxin (PTX) ADP-ribosylation site of the alpha-subunit of the rat brain G protein called Gi. Its open reading frame characterizes it as an alpha i-type cDNA--as opposed to alpha o-type--but predicts an amino acid composition that differs by 7% and 14%, respectively, from two other human alpha i-type molecules. Together with human brain alpha i (type-1) and human monocyte alpha i (type-2), the new human liver alpha i cDNA (type-3) forms parts of a family of alpha i molecules. Type-3 alpha i cDNA hybridizes to a approximately 3.6 kilobase long mRNA and type-2 alpha i cDNA hybridizes to an mRNA species of approximately 2.7 kilobases. This indicates that the human genome has at least three non-allellic genes encoding non-alpha o-type PTX substrates and provides structural evidence for the hypothesis that distinct effector systems are regulated by similar but nevertheless distinct PTX substrates.