Identification of a region in G protein γ subunits conserved across species but hypervariable among subunit isoforms

The heterotrimeric GTP binding proteins, G proteins, consist of three distinct subunits: α, β, and γ. There are 12 known mammalian γ subunit genes whose products are the smallest and most variable of the G protein subunits. Sequencing of the bovine brain γ10 protein by electrospray mass spectrometry revealed that it differs from the human protein by an Ala to Val substitution near the N‐terminus. Comparison of γ isoform subunit sequences indicated that they vary substantially more at the N‐terminus than at other parts of the protein. Thus, species variation of this region might reflect the lack of conservation of a functionally unimportant part of the protein. Analysis of 38 γ subunit sequences from four different species shows that the N‐terminus of a given γ subunit isoform is as conserved between different species as any other part of the protein, including highly conserved regions. These data suggest that the N‐terminus of γ is a functionally important part of the protein exhibiting substantial isoform‐specific variation.