Regulation of Na+,K(+)-ATPases. I. Cloning and analysis of the 5'-flanking region of the rat NKAA2 gene encoding the alpha 2 subunit.

The nucleotide (nt) sequence of the genomic clone, spanning at least the first two exons of the rat Na+,K(+)-ATPase alpha 2 subunit-encoding gene and 6.5 kb of the 5'-flanking region, has been determined. S1 nuclease mapping analysis of the 5' end of the Na+,K(+)-ATPase mRNA indicated that the transcription start point (tsp) is located 105 bp upstream from the start codon. The tsp was identical among three adult-rat tissues (brain, skeletal muscle and heart) which produce the alpha 2 isoform. A TATA-like sequence was found 33 bp upstream from the tsp. In addition, multiple consensus binding sites for a wide variety of regulatory proteins were present throughout the upstream and downstream tsp-flanking regions. A remarkable conservation in the nt sequence of the 5'-flanking region was confirmed between the rat and human genes.