Two distinct genes for ADP/ATP translocase are expressed at the mRNA level in adult human liver

Several clones hybridizing with a bovine ADP/ATP translocase cDNA were isolated from an adult human liver cDNA library in the vector pEX1. DNA sequence analysis revealed that these clones encode two distinct forms of translocase. In particular, two clones specifying the COOH-end-proximal five-sixths of the protein exhibit a 9% amino acid sequence divergence and totally dissimilar 3' untranslated regions. One of these cDNAs is nearly identical in sequence to an ADP/ATP translocase clone (hp2F1) recently isolated from a human fibroblast cDNA library [Battini, R., Ferrari, S., Kaczmarek, L., Calabretta, B., Chen, S. & Baserga, R. (1987) J. Biol. Chem. 262, 4355-4359], with three amino acid changes and a few differences in the 3' untranslated region. Another clone isolated from the pEX1 library contains a reading frame encoding the remaining, NH2-end-proximal, 37 amino acids of the translocase. This sequence differs significantly (14% amino acid sequence divergence) from the corresponding segment of hp2F1, and the 5' untranslated regions of the two clones are totally dissimilar. RNA transfer hybridization experiments utilizing the clones isolated from the pEX1 library revealed the presence in HeLa cells of three distinct mRNA species. The pattern of hybridization and the sizes of these mRNAs suggest a greater complexity of organization and expression of the ADP/ATP translocase genes in human cells than indicated by the analysis of the cDNA clones. ; © 1988 by the National Academy of Sciences. Contributed by Giuseppe Attardi, September 25, 1987. We are greatly indebted to Keith Stanley for providing us with the human cDNA library in the vector pEX1 and to John Walker for the bovine ADP/ATP translocase clone T10.1BE9. The technical assistance of Ms. Arger Drew is gratefully acknowledged. These investigations were supported by National Institutes of Health Grant GM-11726 to G.A. and a Damon Runyon-Walter Winchell Cancer Fund Fellowship to J.H. The publication costs of this article were defrayed in part by page ...