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. 1987 Jun;84(12):4039–4043. doi: 10.1073/pnas.84.12.4039

Multiple genes encode the human Na+,K+-ATPase catalytic subunit.

M M Shull, J B Lingrel
PMCID: PMC305017  PMID: 3035563

Abstract

A human genomic library was constructed and screened with hybridization probes derived from sheep and rat cDNAs encoding the alpha and alpha(+) isoforms, respectively, of the Na+,K+-ATPase catalytic subunit. Genomic sequences spanning 150 kilobases were isolated. Four genes, designated alpha A, alpha B, alpha C, and alpha D, each 20-25 kilobases in length, were identified by restriction mapping, Southern blot hybridization analysis, and limited DNA sequencing. We present evidence that two of these genes, alpha A and alpha B, encode the alpha and alpha(+) isoforms, respectively. The other genes, alpha C and alpha D, one of which is physically linked to the alpha(+) gene, exhibit nucleotide and amino acid homology to Na+,K+-ATPase catalytic subunit cDNA sequences but do not correspond to any previously identified isoforms.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bell G. I., Karam J. H., Rutter W. J. Polymorphic DNA region adjacent to the 5' end of the human insulin gene. Proc Natl Acad Sci U S A. 1981 Sep;78(9):5759–5763. doi: 10.1073/pnas.78.9.5759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Benton W. D., Davis R. W. Screening lambdagt recombinant clones by hybridization to single plaques in situ. Science. 1977 Apr 8;196(4286):180–182. doi: 10.1126/science.322279. [DOI] [PubMed] [Google Scholar]
  3. Brandl C. J., Green N. M., Korczak B., MacLennan D. H. Two Ca2+ ATPase genes: homologies and mechanistic implications of deduced amino acid sequences. Cell. 1986 Feb 28;44(4):597–607. doi: 10.1016/0092-8674(86)90269-2. [DOI] [PubMed] [Google Scholar]
  4. Chaudhury S., Ismail-Beigi F., Gick G. G., Levenson R., Edelman I. S. Effect of thyroid hormone on the abundance of Na,K-adenosine triphosphatase alpha-subunit messenger ribonucleic acid. Mol Endocrinol. 1987 Jan;1(1):83–89. doi: 10.1210/mend-1-1-83. [DOI] [PubMed] [Google Scholar]
  5. Feinberg A. P., Vogelstein B. A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem. 1983 Jul 1;132(1):6–13. doi: 10.1016/0003-2697(83)90418-9. [DOI] [PubMed] [Google Scholar]
  6. Frischauf A. M., Lehrach H., Poustka A., Murray N. Lambda replacement vectors carrying polylinker sequences. J Mol Biol. 1983 Nov 15;170(4):827–842. doi: 10.1016/s0022-2836(83)80190-9. [DOI] [PubMed] [Google Scholar]
  7. Garg L. C., Knepper M. A., Burg M. B. Mineralocorticoid effects on Na-K-ATPase in individual nephron segments. Am J Physiol. 1981 Jun;240(6):F536–F544. doi: 10.1152/ajprenal.1981.240.6.F536. [DOI] [PubMed] [Google Scholar]
  8. Geering K., Girardet M., Bron C., Kraehenbühl J. P., Rossier B. C. Hormonal regulation of (Na+,K+)-ATPase biosynthesis in the toad bladder. Effect of aldosterone and 3,5,3'-triiodo-L-thyronine. J Biol Chem. 1982 Sep 10;257(17):10338–10343. [PubMed] [Google Scholar]
  9. Harik S. I. Blood--brain barrier sodium/potassium pump: modulation by central noradrenergic innervation. Proc Natl Acad Sci U S A. 1986 Jun;83(11):4067–4070. doi: 10.1073/pnas.83.11.4067. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kawakami K., Noguchi S., Noda M., Takahashi H., Ohta T., Kawamura M., Nojima H., Nagano K., Hirose T., Inayama S. Primary structure of the alpha-subunit of Torpedo californica (Na+ + K+)ATPase deduced from cDNA sequence. Nature. 1985 Aug 22;316(6030):733–736. doi: 10.1038/316733a0. [DOI] [PubMed] [Google Scholar]
  11. Kawakami K., Ohta T., Nojima H., Nagano K. Primary structure of the alpha-subunit of human Na,K-ATPase deduced from cDNA sequence. J Biochem. 1986 Aug;100(2):389–397. doi: 10.1093/oxfordjournals.jbchem.a121726. [DOI] [PubMed] [Google Scholar]
  12. Keller E. B., Noon W. A. Intron splicing: a conserved internal signal in introns of animal pre-mRNAs. Proc Natl Acad Sci U S A. 1984 Dec;81(23):7417–7420. doi: 10.1073/pnas.81.23.7417. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kim D., Marsh J. D., Barry W. H., Smith T. W. Effects of growth in low potassium medium or ouabain on membrane Na,K-ATPase, cation transport, and contractility in cultured chick heart cells. Circ Res. 1984 Jul;55(1):39–48. doi: 10.1161/01.res.55.1.39. [DOI] [PubMed] [Google Scholar]
  14. Lin M. H., Akera T. Increased (Na+,K+)-ATPase concentrations in various tissues of rats caused by thyroid hormone treatment. J Biol Chem. 1978 Feb 10;253(3):723–726. [PubMed] [Google Scholar]
  15. Lo S. C., August T. R., Liberman U. A., Edelman I. S. Dependence of renal (Na+ + k+)-adenosine triphosphatase activity on thyroid status. J Biol Chem. 1976 Dec 25;251(24):7826–7833. [PubMed] [Google Scholar]
  16. Lytton J. Insulin affects the sodium affinity of the rat adipocyte (Na+,K+)-ATPase. J Biol Chem. 1985 Aug 25;260(18):10075–10080. [PubMed] [Google Scholar]
  17. Lytton J., Lin J. C., Guidotti G. Identification of two molecular forms of (Na+,K+)-ATPase in rat adipocytes. Relation to insulin stimulation of the enzyme. J Biol Chem. 1985 Jan 25;260(2):1177–1184. [PubMed] [Google Scholar]
  18. MacLennan D. H., Brandl C. J., Korczak B., Green N. M. Amino-acid sequence of a Ca2+ + Mg2+-dependent ATPase from rabbit muscle sarcoplasmic reticulum, deduced from its complementary DNA sequence. Nature. 1985 Aug 22;316(6030):696–700. doi: 10.1038/316696a0. [DOI] [PubMed] [Google Scholar]
  19. Matsuda T., Iwata H., Cooper J. R. Specific inactivation of alpha (+) molecular form of (Na+ + K+)-ATPase by pyrithiamin. J Biol Chem. 1984 Mar 25;259(6):3858–3863. [PubMed] [Google Scholar]
  20. Mount S. M. A catalogue of splice junction sequences. Nucleic Acids Res. 1982 Jan 22;10(2):459–472. doi: 10.1093/nar/10.2.459. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Norrander J., Kempe T., Messing J. Construction of improved M13 vectors using oligodeoxynucleotide-directed mutagenesis. Gene. 1983 Dec;26(1):101–106. doi: 10.1016/0378-1119(83)90040-9. [DOI] [PubMed] [Google Scholar]
  22. Ovchinnikov YuA, Modyanov N. N., Broude N. E., Petrukhin K. E., Grishin A. V., Arzamazova N. M., Aldanova N. A., Monastyrskaya G. S., Sverdlov E. D. Pig kidney Na+,K+-ATPase. Primary structure and spatial organization. FEBS Lett. 1986 Jun 9;201(2):237–245. doi: 10.1016/0014-5793(86)80616-0. [DOI] [PubMed] [Google Scholar]
  23. Proverbio F., Proverbio T., Marín R. Na+-ATPase is a different entity from the (Na+ + K+)-ATPase in rat kidney basolateral plasma membranes. Biochim Biophys Acta. 1986 Jun 13;858(1):202–205. doi: 10.1016/0005-2736(86)90307-x. [DOI] [PubMed] [Google Scholar]
  24. Rigby P. W., Dieckmann M., Rhodes C., Berg P. Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J Mol Biol. 1977 Jun 15;113(1):237–251. doi: 10.1016/0022-2836(77)90052-3. [DOI] [PubMed] [Google Scholar]
  25. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Schmitt C. A., McDonough A. A. Developmental and thyroid hormone regulation of two molecular forms of Na+-K+-ATPase in brain. J Biol Chem. 1986 Aug 5;261(22):10439–10444. [PubMed] [Google Scholar]
  27. Schneider J. W., Mercer R. W., Caplan M., Emanuel J. R., Sweadner K. J., Benz E. J., Jr, Levenson R. Molecular cloning of rat brain Na,K-ATPase alpha-subunit cDNA. Proc Natl Acad Sci U S A. 1985 Sep;82(18):6357–6361. doi: 10.1073/pnas.82.18.6357. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Shull G. E., Greeb J., Lingrel J. B. Molecular cloning of three distinct forms of the Na+,K+-ATPase alpha-subunit from rat brain. Biochemistry. 1986 Dec 16;25(25):8125–8132. doi: 10.1021/bi00373a001. [DOI] [PubMed] [Google Scholar]
  29. Shull G. E., Lingrel J. B. Molecular cloning of the rat stomach (H+ + K+)-ATPase. J Biol Chem. 1986 Dec 25;261(36):16788–16791. [PubMed] [Google Scholar]
  30. Shull G. E., Schwartz A., Lingrel J. B. Amino-acid sequence of the catalytic subunit of the (Na+ + K+)ATPase deduced from a complementary DNA. Nature. 1985 Aug 22;316(6030):691–695. doi: 10.1038/316691a0. [DOI] [PubMed] [Google Scholar]
  31. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  32. Sweadner K. J. Two molecular forms of (Na+ + K+)-stimulated ATPase in brain. Separation, and difference in affinity for strophanthidin. J Biol Chem. 1979 Jul 10;254(13):6060–6067. [PubMed] [Google Scholar]
  33. Vigne P., Frelin C., Lazdunski M. Ontogeny of the (Na+,K+)-ATPase during chick skeletal myogenesis. J Biol Chem. 1982 May 25;257(10):5380–5384. [PubMed] [Google Scholar]
  34. Wolitzky B. A., Fambrough D. M. Regulation of the (Na+ + K+)-ATPase in cultured chick skeletal muscle. Modulation of expression by the demand for ion transport. J Biol Chem. 1986 Jul 25;261(21):9990–9999. [PubMed] [Google Scholar]

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