Structure of the Human Gastric H,K-ATPase Gene and Comparison of the 5′-Flanking Sequences of the Human and Rat Genes

We have isolated and analyzed the genes encoding the human and rat gastric H,K-ATPase catalytic subunits. The complete sequence of the human gene, including 2.2 kb of 5'-flanking sequence, and the 5' end of the rat gene, including exons 1-4 and 2.5 kb of 5'-flanking sequence, have been determined. The human gene contains 22 exons. Its intron-exon organization is identical to that of the Na,K-ATPase gene, except that exon 6 corresponds to a fusion of exons 6 and 7 of the Na,K-ATPase gene. The transcription initiation sites of both the human and rat genes were determined by primer extension and S1 nuclease protection analyses. Comparison of the 5'-flanking regions of the human and rat genes revealed three extended regions of high sequence similarity, one of which includes a potential TATA box and other basic promoter elements beginning about 30 nucleotides upstream of the transcription start site. Other conserved sequences, including possible response elements for Ca2+ and cAMP, which are known intracellular mediators of acid secretion, are located up to 2 kb 5' to the transcription initiation site.