STRUCTURE OF THE GENE ENCODING THE HUMAN PLASMA-MEMBRANE CALCIUM-PUMPISOFORM-1

The complete structure of the gene for the human plasma membrane calci um ATPase isoform 1 (hPMCA1) has been elucidated. The protein is encod ed by 21 exons present on overlapping clones covering more than 100 ki lobases (kb) of DNA. An intron of over 35 kb separates the 5'-untransl ated exon 1 from the exon containing the translational start codon. Th e entire putative promoter and 5'-flanking region is embedded in a CpG island and is characterized by the presence of numerous Sp1 factor-bi nding sequences and by the absence of a TATA box. In accordance with t he ubiquitous tissue distribution of its mRNA these results suggest th at the hPMCA1 gene is of the housekeeping type. No alternative splicin g comparable to that identified in PMCA2 RNAs at site ''A'' and in PMC A3 RNAs close to site ''C'' seems to occur in hPMCA1 transcripts; howe ver, a region in intron 6 shows significant resemblance to the site '' A'' alternatively spliced exons in PMCA2 and may represent a pseudoexo n or a functional exon not yet detected in any PMCA1 mRNA. At six posi tions, intron interruptions in the hPMCA1 gene correlate with the boun daries of putative transmembrane domains in the protein, whereas most of the remaining intron positions do not show an obvious correlation w ith the proposed pump domain structure. The limited conservation of in tron positions in different P-type pump genes indicates their early se paration from a common ancestor.