Molecular cloning of β3 subunit, a third form of the G protein β-subunit polypeptide

The signal-transducing guanine nucleotide-binding regulatory (G) proteins are heterotrimers composed of three subunits - α, β, and γ. Although multiple distinctive forms of the α subunit have been described, only two forms of the β subunits of the G proteins have been identified. To investigate further the structural diversity of the β subunits, we screened bovine and human retina cDNA libraries and isolated clones encoding three distinct types of G protein β subunit. One form was identical to previously isolated β1-subunit cDNA clones that encode the 36-kDa form of the β subunit, whereas a second form was identical to previously described β2 cDNAs that encode the 35-kDa β isoform. In addition, we identified another species, designated β3 subunit, which encodes a third distinct form of the β subunit. The β3-subunit cDNA corresponds to a 2.0-kilobase mRNA expressed in all tissues and clonal cell lines examined. Nucleotide sequence analysis indicates that the encoded peptide consists of 340-amino acid residues with a M_r of 37,221. The amino acid sequences of the three β subunits are closely related: 83% identity between β1 and β3 subunits and 81% identity between β2 and β3 subunits. By contrast, the 3′-untranslated regions of the three cDNAs show no significant homology. Our data support the hypothesis that a family of β-subunit polypeptides exists and extend understanding of β-subunit structure.