Chromosomal localization of human Na +,K +-ATPase α- and β-subunit genes

Abstract

Na +,K +-ATPase is a heterodimeric enzyme responsible for the active maintenance of sodium and potassium gradients across the plasma membrane. Recently, cDNAs for several tissue-specific isoforms of the larger catalytic α-subunit and the smaller β-subunit have been cloned. We have hybridized rat brain and human kidney cDNA probes, as well as human genomic isoform-specific DNA fragments, to Southern filters containing panels of rodent × human somatic cell hybrid lines. The results obtained have allowed us to assign the loci for the ubiquitously expressed α-chain ( ATP1A1) to human chromosome 1, region 1p21→cen, and for the α2 isoform that predominates in neural and muscle tissues ( ATP1A2) to chromosome 1, region cen→q32. A common PstI RFLP was detected with the ATP1A2 probe. The α3 gene, which is expressed primarily in neural tissues ( ATP1A3), was assigned to human chromosome 19. A fourth α gene of unknown function (αD) that was isolated by molecular cloning ( ATP1AL1) was mapped to chromosome 13. Although evidence to date had suggested a single gene for the β-subunit, we found hybridizing restriction fragments derived from two different human chromosomes. On the basis of knowledge of conserved linkage goups on human and murine chromosomes, we propose that the coding gene ATP1B is located on the long arm of human chromosome 1 and that the sequence on human chromosome 4 ( ATP1BL1) is either a related gene or a pseudogene.