Advances in Na+,K+-ATPase studies: from protein to gene and back to protein.

Complete primary structures of both subunits of Na+,K+-ATPase from various sources have been established by a combination of the methods for molecular cloning and protein chemistry. The gene family homologous to the alpha-subunit cDNA of animal Na+,K+-ATPases has been found in the human genome. Some genes of this family encode the known isoforms (alpha I and alpha II) of the Na+,K+-ATPase catalytic subunit. The proteins coded by other genes can be either new isoforms of the Na+,K+-ATPase catalytic subunit or other ion-transporting ATPases. Expression of the genes of this family proceeds in a tissue-specific manner and changes during the postnatal development and neoplastic transformation. The complete exon-intron structure of one of the genes of this family has been established. This gene codes for the form of the catalytic subunit, the existence of which has been unknown. Apparently, all the genes of the discovered family have a similar intron-exon structure. There is certain correlation between the gene structure and the proposed domain arrangement of the alpha-subunit. The results obtained have become the basis for the experiments which prove the existence of the earlier unknown alpha III isoform of the Na+,K+-ATPase catalytic subunit and have made possible the study of its function.