Genomic organization of the human ATP1AL1 gene encoding a ouabain-sensitive H,K-ATPase

The human ATP1AL1 gene belongs to the family of Na,K-ATPase and H,K-ATPase (X,K-ATPases) genes. It encodes a catalytic subunit of hitherto unknown human ouabain-sensitive H,K-ATPase that represents a novel third group of X,K-ATPases distinct from the known Na,K-ATPase and gastric H,K-ATPase. Cloning of the ATP1AL1 gene is described in this report. The exon-intron structure of ATP1AL1 was found to be very similar to that of related genes. It contains 23 exons and spans approximately 32 kb of genomic DNA. All ATP1AL1 exons and 12 of its 22 introns were entirely sequenced. A total of nine Alu repeats were identified in introns. The transcription initiation site was mapped 187 bp upstream of the ATG initiation codon by primer extension and S1 nuclease protection analyses of RNA from human skin and colon. Sequence analysis of the 5'-flanking region (1.48 kb) revealed numerous potential binding sites for transcription factors Sp1 and AP2 and one putative NF-kappa B binding site. The 0.85-kb region from position -484 (5'-flanking region) to position +369 (intron 1) meets the structural criteria of a CpG island. It is suggested that the ATP1AL1 gene contains two poly(A) addition sites that may function in a tissue-specific manner.