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J. Biol. Chem., Vol. 265, Issue 16, 9027-9032, Jun, 1990
Human gastric (H+ + K+)-ATPase gene. Similarity to (Na+ + K+)-ATPase genes in exon/intron organization but difference in control region
M Maeda, K Oshiman, S Tamura and M Futai
Department of Organic Chemistry and Biochemistry, Osaka University, Japan.
The human gastric (H+ + K+)-ATPase gene (15 kilobases) was cloned, and its
nucleotide sequence was determined. The gene has 22 exons and codes a
protein of 1,035 residues including the initiator methionine (Mr =
114,047). A conserved lysine-rich sequence with inserted glycine residues
was found near the amino terminus of the enzyme. The phosphorylation site
and pyridoxal 5'-phosphate- and fluorescein isothiocyanate-binding residues
found in the rat and pig enzymes are also conserved in the human enzyme.
The positions of introns in the human (H+ + K+)-ATPase gene are essentially
the same as those in the human (Na+ + K+)-ATPase alpha and alpha III
subunits; but the first introns of the two enzymes are difficult to align,
and unlike in the (Na+ + K+)-ATPase gene, the sixth exon in the (H+ +
K+)-ATPase gene is not separated by an intron. Furthermore, the ninth
intron is located two bases upstream of the position for the corresponding
intron of the (Na+ + K+)-ATPase alpha III subunit. The similarity in
organization of these two ATPase genes and the homology in the primary
structures of their proteins (approximately 60%) suggest that these two
genes were derived from a common ancestral gene. However, the 5'-flanking
regions of the genes for (H+ + K+)-ATPase and the (Na+ + K+)-ATPase alpha
(+) subunit show no apparent sequence homology, indicating that their
transcriptions are regulated differently. The control region of the
fast-twitch sarcoplasmic reticulum Ca2(+)-ATPase gene also showed no
sequence homology to that of (H+ + K+)-ATPase. The 5'-flanking region of
the (H+ + K+)-ATPase gene contains potential binding sites for RNA
polymerase II and various transcriptional regulation factors and several
direct and inverted repeat sequences which may be important for specific
and controlled expression of the gene in gastric parietal cells. There are
two polyadenylation signals in the 3'-flanking region of the (H+ +
K+)-ATPase gene, but the sequence of this region shows no homology to those
of the corresponding regions of the genes for the (Na+ + K+)-ATPase alpha
and alpha III subunits.

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