Gene Symbol: ENA1
Description: Na(+)/Li(+)-exporting P-type ATPase ENA1
Alias: HOR6, PMR2, Na(+)/Li(+)-exporting P-type ATPase ENA1
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. Cagnac O, Leterrier M, Yeager M, Blumwald E. Identification and characterization of Vnx1p, a novel type of vacuolar monovalent cation/H+ antiporter of Saccharomyces cerevisiae. J Biol Chem. 2007;282:24284-93 pubmed
    ..Similar to Nhx1p, the prevacuolar compartment-bound Na+/H+ antiporter, the vacuole-bound Vnx1p appears to play roles in the regulation of ion homeostasis and cellular pH. ..
  2. Benito B, Quintero F, Rodriguez Navarro A. Overexpression of the sodium ATPase of Saccharomyces cerevisiae: conditions for phosphorylation from ATP and Pi. Biochim Biophys Acta. 1997;1328:214-26 pubmed
    The ENA1 gene of Saccharomyces cerevisiae encodes a putative ATPase necessary for Na+ efflux. Plasma membranes and intracellular membranes of a yeast strain overexpressing the ENA1 gene contain significant amounts of ENA1 protein...
  3. Mulet J, Leube M, Kron S, Rios G, Fink G, Serrano R. A novel mechanism of ion homeostasis and salt tolerance in yeast: the Hal4 and Hal5 protein kinases modulate the Trk1-Trk2 potassium transporter. Mol Cell Biol. 1999;19:3328-37 pubmed
    ..Our data support a role for regulation of membrane potential in adaptation to salt stress that is mediated by the Hal4 and Hal5 kinases. ..
  4. Siniossoglou S, Hurt E, Pelham H. Psr1p/Psr2p, two plasma membrane phosphatases with an essential DXDX(T/V) motif required for sodium stress response in yeast. J Biol Chem. 2000;275:19352-60 pubmed
    ..This growth defect is due to the inability of the psr1psr2 mutant to properly induce transcription of ENA1/PMR2, the major sodium extrusion pump of yeast cells...
  5. Merchan S, Pedelini L, Hueso G, Calzada A, Serrano R, Yenush L. Genetic alterations leading to increases in internal potassium concentrations are detrimental for DNA integrity in Saccharomyces cerevisiae. Genes Cells. 2011;16:152-65 pubmed publisher
  6. Ye T, García Salcedo R, Ramos J, Hohmann S. Gis4, a new component of the ion homeostasis system in the yeast Saccharomyces cerevisiae. Eukaryot Cell. 2006;5:1611-21 pubmed
    ..This defect is due to diminished expression of the ENA1 gene, which encodes the Na(+) and Li(+) export pump...
  7. Ye T, Elbing K, Hohmann S. The pathway by which the yeast protein kinase Snf1p controls acquisition of sodium tolerance is different from that mediating glucose regulation. Microbiology. 2008;154:2814-26 pubmed publisher
    ..We have previously reported that Snf1p together with Gis4p controls ion homeostasis by regulating expression of ENA1, which encodes the Ena1p Na(+) extrusion system...
  8. Haro R, Garciadeblas B, Rodriguez Navarro A. A novel P-type ATPase from yeast involved in sodium transport. FEBS Lett. 1991;291:189-91 pubmed
    The gene ENA1 was cloned by its ability to complement the Li+ sensitivity of a low Li(+)-efflux strain...
  9. Merchan S, Bernal D, Serrano R, Yenush L. Response of the Saccharomyces cerevisiae Mpk1 mitogen-activated protein kinase pathway to increases in internal turgor pressure caused by loss of Ppz protein phosphatases. Eukaryot Cell. 2004;3:100-7 pubmed
    ..Finally, despite its role in G1/S transition, increased levels of activated Mpk1 do not appear to be responsible for the cell cycle phenotype observed in Ppz-deficient strains. ..

More Information


  1. Navarre C, Goffeau A. Membrane hyperpolarization and salt sensitivity induced by deletion of PMP3, a highly conserved small protein of yeast plasma membrane. EMBO J. 2000;19:2515-24 pubmed
    ..Expression of plant RCI2A in yeast could substitute for the loss of Pmp3p, indicating a common role for Pmp3p and the plant homologue. ..
  2. Alepuz P, Cunningham K, Estruch F. Glucose repression affects ion homeostasis in yeast through the regulation of the stress-activated ENA1 gene. Mol Microbiol. 1997;26:91-8 pubmed
    In this report we show that the ENA1/PMR2A gene is under glucose repression. The SNF1 protein kinase, acting independently from the HOG and calcineurin pathways, is essential to release ENA1 from glucose repression...
  3. Marqués M, Zamarbide Forés S, Pedelini L, Llopis Torregrosa V, Yenush L. A functional Rim101 complex is required for proper accumulation of the Ena1 Na+-ATPase protein in response to salt stress in Saccharomyces cerevisiae. FEMS Yeast Res. 2015;15:fov017 pubmed publisher
    ..We show here that the salt sensitivity phenotype of the rim8/art9 mutant is due to severe defects in Ena1 protein accumulation, which is not attributable to transcriptional defects...
  4. Goossens A, de La Fuente N, Forment J, Serrano R, Portillo F. Regulation of yeast H(+)-ATPase by protein kinases belonging to a family dedicated to activation of plasma membrane transporters. Mol Cell Biol. 2000;20:7654-61 pubmed
  5. Yenush L, Mulet J, Arino J, Serrano R. The Ppz protein phosphatases are key regulators of K+ and pH homeostasis: implications for salt tolerance, cell wall integrity and cell cycle progression. EMBO J. 2002;21:920-9 pubmed
    ..In addition to providing a coherent explanation for all Ppz-dependent phenotypes, our results provide evidence for a causal relationship between intracellular cation homeostasis and a potential cell cycle checkpoint. ..
  6. Cagnac O, Aranda Sicilia M, Leterrier M, Rodriguez Rosales M, Venema K. Vacuolar cation/H+ antiporters of Saccharomyces cerevisiae. J Biol Chem. 2010;285:33914-22 pubmed publisher
    ..The relative importance of Nhx1p, Vnx1p, and Vcx1p in the vacuolar accumulation of monovalent cations will be discussed. ..
  7. Masson J, Ramotar D. The transcriptional activator Imp2p maintains ion homeostasis in Saccharomyces cerevisiae. Genetics. 1998;149:893-901 pubmed
    ..Two genes that independently restored normal salt-resistance to the imp2Delta mutant, ENA1 and HAL3, were isolated...
  8. Munson A, Love S, Shu J, Palanivel V, Rosenwald A. ARL1 participates with ATC1/LIC4 to regulate responses of yeast cells to ions. Biochem Biophys Res Commun. 2004;315:617-23 pubmed
    ..Additionally, expression of ENA1, the Na(+)/Li(+) efflux ATPase, and activated calcineurin, but not normal calcineurin, suppressed the Li(+)-..
  9. Liu X, Yang H, Zhang X, Liu L, Lei M, Zhang Z, et al. Bdf1p deletion affects mitochondrial function and causes apoptotic cell death under salt stress. FEMS Yeast Res. 2009;9:240-6 pubmed publisher
    ..These results indicate that the bromodomain-containing protein, Bdf1p, is involved in the regulation of apoptosis in yeast cells. ..
  10. Zahradka J, Van Heusden G, Sychrova H. Yeast 14-3-3 proteins participate in the regulation of cell cation homeostasis via interaction with Nha1 alkali-metal-cation/proton antiporter. Biochim Biophys Acta. 2012;1820:849-58 pubmed publisher
    ..Our results showed for the first time that the yeast 14-3-3 proteins and an alkali-metal-cation efflux system interact and that this interaction enhances the cell survival upon salt stress. ..
  11. Wieland J, Nitsche A, Strayle J, Steiner H, Rudolph H. The PMR2 gene cluster encodes functionally distinct isoforms of a putative Na+ pump in the yeast plasma membrane. EMBO J. 1995;14:3870-82 pubmed
    We report a structural and functional analysis of the PMR2 gene cluster in yeast...
  12. Marquina M, González A, Barreto L, Gelis S, Munoz I, Ruiz A, et al. Modulation of yeast alkaline cation tolerance by Ypi1 requires calcineurin. Genetics. 2012;190:1355-64 pubmed publisher
    ..by a combination of increased efflux of lithium, mediated by augmented expression of the alkaline cation ATPase ENA1, and decreased lithium influx through the Trk1,2 high-affinity potassium transporters...
  13. Wadskog I, Forsmark A, Rossi G, Konopka C, Oyen M, Goksör M, et al. The yeast tumor suppressor homologue Sro7p is required for targeting of the sodium pumping ATPase to the cell surface. Mol Biol Cell. 2006;17:4988-5003 pubmed
    ..We propose a model in which blocked exocytic sorting in sro7Delta mutants, gives rise to quality control-mediated routing of Ena1p to the vacuole. ..
  14. Hoeberichts F, Perez Valle J, Montesinos C, Mulet J, Planes M, Hueso G, et al. The role of K(+) and H(+) transport systems during glucose- and H(2)O(2)-induced cell death in Saccharomyces cerevisiae. Yeast. 2010;27:713-25 pubmed publisher
    ..A triple mutant ena1-4 tok1 nha1, devoid of K(+) efflux systems, is more tolerant to both glucose- and H(2)O(2)-induced cell death...
  15. Sant Ana G, Paes L, Paiva A, Fietto L, Totola A, Trópia M, et al. Protective effect of ions against cell death induced by acid stress in Saccharomyces. FEMS Yeast Res. 2009;9:701-12 pubmed publisher
    ..cerevisiae Na(+)-ATPases (ena1-4), Na(+)/H(+) antiporter (nha1Delta) and Na(+)/H(+) antiporter prevacuolar (nhx1Delta) null mutants, respectively...
  16. Ruiz A, Arino J. Function and regulation of the Saccharomyces cerevisiae ENA sodium ATPase system. Eukaryot Cell. 2007;6:2175-83 pubmed
  17. Benito B, Garciadeblas B, Rodríguez Navarro A. Potassium- or sodium-efflux ATPase, a key enzyme in the evolution of fungi. Microbiology. 2002;148:933-41 pubmed
    ..The parasites Leishmania and Trypanosoma have ATPases phylogenetically related to fungal K(+)-ATPases, which are probably functional homologues of the fungal enzymes. ..
  18. de Nadal E, Calero F, Ramos J, Arino J. Biochemical and genetic analyses of the role of yeast casein kinase 2 in salt tolerance. J Bacteriol. 1999;181:6456-62 pubmed
    ..Deletion of CKB1 increased the salt sensitivity of a strain lacking Ena1 ATPase, the major determinant for sodium efflux, suggesting that the function of the kinase is not mediated by Ena1...
  19. Maresova L, Sychrova H. Physiological characterization of Saccharomyces cerevisiae kha1 deletion mutants. Mol Microbiol. 2005;55:588-600 pubmed
    ..One of the transporters formerly believed to extrude K+ from the yeast cells (besides Ena1-4p and Nha1p) was named Kha1p and presumed as a putative plasma membrane K+/H+ antiporter...
  20. Serrano R, Ruiz A, Bernal D, Chambers J, Arino J. The transcriptional response to alkaline pH in Saccharomyces cerevisiae: evidence for calcium-mediated signalling. Mol Microbiol. 2002;46:1319-33 pubmed
    ..Alkalinization resulted in the repression of 232 genes. The response of four upregulated genes, ENA1 (encoding a Na+-ATPase also induced by saline stress) and PHO84, PHO89 and PHO12 (encoding genes upregulated by ..
  21. Maresova L, Sychrova H. Genetic interactions among the Arl1 GTPase and intracellular Na(+) /H(+) antiporters in pH homeostasis and cation detoxification. FEMS Yeast Res. 2010;10:802-11 pubmed publisher
    ..We conclude that Arl1p, Kha1p and Nhx1p collaborate in survival strategies at nonoptimal pH, temperatures and cation concentrations, but work independent of each other. ..
  22. Petrezselyova S, Kinclova Zimmermannova O, Sychrova H. Vhc1, a novel transporter belonging to the family of electroneutral cation-Cl(-) cotransporters, participates in the regulation of cation content and morphology of Saccharomyces cerevisiae vacuoles. Biochim Biophys Acta. 2013;1828:623-31 pubmed publisher
    ..Considering its identified function, we propose to refer to the yeast YBR235w gene as VHC1 (vacuolar protein homologous to CCC family 1). ..
  23. Serra Cardona A, Petrezsélyová S, Canadell D, Ramos J, Ariño J. Coregulated expression of the Na+/phosphate Pho89 transporter and Ena1 Na+-ATPase allows their functional coupling under high-pH stress. Mol Cell Biol. 2014;34:4420-35 pubmed publisher
    ..This network mimics the one regulating expression of the Na(+)-ATPase gene ENA1, encoding a major determinant for Na(+) detoxification...
  24. Marquez J, Serrano R. Multiple transduction pathways regulate the sodium-extrusion gene PMR2/ENA1 during salt stress in yeast. FEBS Lett. 1996;382:89-92 pubmed
    The yeast PMR2/ENA1 gene encodes an ATPase involved in sodium extrusion and induced by NaCl. At low salt concentrations (0.3 M) induction is mediated by the HOG-MAP kinase pathway, a system activated by non-specific osmotic stress...
  25. Petrezselyova S, López Malo M, Canadell D, Roque A, Serra Cardona A, Marques M, et al. Regulation of the Na+/K+-ATPase Ena1 Expression by Calcineurin/Crz1 under High pH Stress: A Quantitative Study. PLoS ONE. 2016;11:e0158424 pubmed publisher
    Regulated expression of the Ena1 Na+-ATPase is a crucial event for adaptation to high salt and/or alkaline pH stress in the budding yeast Saccharomyces cerevisiae...
  26. Logg K, Warringer J, Hashemi S, Käll M, Blomberg A. The sodium pump Ena1p provides mechanistic insight into the salt sensitivity of vacuolar protein sorting mutants. Biochim Biophys Acta. 2008;1783:974-84 pubmed publisher
    ..This paper discusses potential mechanistic hypotheses, like Ena1p transporter activity or localization kinetics, or ESCRT component's influence on signaling, for linking endosomal sorting functions to cellular salt sensitivity. ..
  27. Platara M, Ruiz A, Serrano R, Palomino A, Moreno F, Arino J. The transcriptional response of the yeast Na(+)-ATPase ENA1 gene to alkaline stress involves three main signaling pathways. J Biol Chem. 2006;281:36632-42 pubmed
    ..A key target is the gene ENA1, encoding a Na(+)-ATPase, whose induction by alkaline pH has been shown to involve calcineurin and the Rim101/Nrg1 ..
  28. Mulet J, Alejandro S, Romero C, Serrano R. The trehalose pathway and intracellular glucose phosphates as modulators of potassium transport and general cation homeostasis in yeast. Yeast. 2004;21:569-82 pubmed
    ..These results indicate that Tps1, like Pgm2 and Hxk2, increases the levels of glucose phosphates and suggest that these metabolites, directly or indirectly, activate Trk. ..
  29. Crespo J, Daicho K, Ushimaru T, Hall M. The GATA transcription factors GLN3 and GAT1 link TOR to salt stress in Saccharomyces cerevisiae. J Biol Chem. 2001;276:34441-4 pubmed
    ..Here we show that transcription of ENA1, a gene encoding a lithium and sodium ion transporter essential for salt tolerance in yeast, is controlled by the ..
  30. Zahradka J, Sychrova H. Plasma-membrane hyperpolarization diminishes the cation efflux via Nha1 antiporter and Ena ATPase under potassium-limiting conditions. FEMS Yeast Res. 2012;12:439-46 pubmed publisher
    ..In trk1? trk2? mutants, the potassium efflux via potassium exporters Nha1 and Ena1 is diminished and can be restored either by the expression of TRK1 or deletion of TOK1...
  31. Rios G, Ferrando A, Serrano R. Mechanisms of salt tolerance conferred by overexpression of the HAL1 gene in Saccharomyces cerevisiae. Yeast. 1997;13:515-28 pubmed
    ..The effect of HAL1 on intracellular Na+ was mediated by the PMR2/ENA1 gene, corresponding to a major Na+ efflux system...