The rabbit muscle phosphofructokinase gene. Implications for protein structure, function, and tissue specificity.

Sequence homologies between bacterial and rabbit muscle phosphofructokinases and between the amino- and carboxyl-terminal halves of the latter suggest that the mammalian enzyme evolved from a prokaryotic progenitor by gene duplication and divergence (Poorman, R. A., Randolph, A., Kemp, R. G., and Heinrikson, R. L. (1984) Nature 309, 467-469). We have isolated the gene for the rabbit enzyme and determined the nucleotide sequence for all the exons and most of the introns. This represents the first eukaryotic phosphofructokinase gene ever sequenced. The cloned gene is 17 kilobase pairs long. The coding sequence for 780 amino acids is split into 22 exons ranging in size from 15 to 63 codons. Sequence analysis shows that 75% of the bases at the third position of the codons in these exons are either G or C. Exons XV and XVI code for the 30 amino acid residues which were left unidentified in the published primary structure for this enzyme. When overlaid on the structure of the protein, most of the introns are located between or near the ends of the secondary structural elements but not at analogous positions in the two protein-coding halves of the gene.