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Gene Review

ATP12A  -  ATPase, H+/K+ transporting, nongastric,...

Homo sapiens

Synonyms: ATP1AL1, Non-gastric H(+)/K(+) ATPase subunit alpha, Potassium-transporting ATPase alpha chain 2, Proton pump
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Disease relevance of ATP12A


Psychiatry related information on ATP12A

  • Proton-pump inhibitor treatment resulted in an absolute risk reduction of peptic ulcer by 36.6% in acute and 34.6% in chronic non-steroidal anti-inflammatory drugs/aspirin users; indeed, the number needed to treat to avoid one peptic ulcer in elderly non-steroidal anti-inflammatory drugs/aspirin users was three both in acute and chronic users [6].
  • Proton pump inhibitor-based triple therapies have shown more consistent and higher eradication rates with a short duration of treatment, good patient compliance, fewer side effects, prompt symptom relief and fast ulcer healing [7].
  • Once we have the correct diagnosis stabilized, life style modification should be the first step in the management of GERD, aided with antacids, H2 receptors antagonists and/or Proton pump inhibitors [8].

High impact information on ATP12A

  • Proton-pump inhibition of gastric chloride secretion in congenital chloridorrhea [9].
  • In this study we find that the intracellular Na+ content in cells expressing ATP1AL1 and gH,Kbeta is two times lower than that in control HEK 293 cells in response to incubation for 3 h in the presence of 1 microM ouabain [10].
  • Proton pump activity is not measurable in the plasma membrane of unstimulated neutrophils but becomes readily detectable upon activation by soluble agonists [11].
  • Proton pump inhibitors do not reduce atazanavir concentrations in HIV-infected patients treated with ritonavir-boosted atazanavir [12].
  • Proton pump inhibitors are the mainstay of therapy for symptom relief, healing of erosive esophagitis, resolution of peptic ulceration, reduction of the risk for NSAID-induced mucosal damage, and prevention of disease recurrence [13].

Chemical compound and disease context of ATP12A


Biological context of ATP12A


Anatomical context of ATP12A


Associations of ATP12A with chemical compounds

  • Genomic organization of the human ATP1AL1 gene encoding a ouabain-sensitive H,K-ATPase [21].
  • Proton pump inhibitors (PPIs), drugs that are widely used for treatment of acid related diseases, are either substituted pyridylmethylsulfinyl benzimidazole or imidazopyridine derivatives [28].
  • BACKGROUND: Proton pump inhibitors such as omeprazole and lansoprazole are mainly metabolized by CYP2C19 in the liver [29].
  • BACKGROUND: Proton pump inhibitors such as omeprazole produce a long-lasting inhibition of gastric acid secretion associated with significant increases in plasma gastrin [30].
  • Proton pump inhibitors play an important role in increasing the bioavailability of antibiotics in the gastric mucus by altering gastric volumes and increasing the stability of some antibiotics, e.g., clarithromycin [31].

Physical interactions of ATP12A


Regulatory relationships of ATP12A


Other interactions of ATP12A


Analytical, diagnostic and therapeutic context of ATP12A

  • We constructed primers specific for ATP1AL1 and performed RT-PCR on RNA isolated from human placenta and human kidney [39].
  • The ATP1AL1 protein was identified as a 114 kD band in both MVM and BM by Western blot, however, the protein was more abundant in the MVM [39].
  • A series of Northern blot hybridization experiments using probes derived from the rat gastric H+,K(+)-ATPase cDNA and the human ATP1AL1 gene revealed the presence of a 4.3-kilobase mRNA in colon that seemed likely to encode the distal colon H+,K(+)-ATPase, the enzyme responsible for K+ absorption in mammalian colon [40].
  • Stable interaction of ATP1AL1 with either the endogenous Na(+)-K(+)-ATPase beta-subunit or the gastric H(+)-K(+)-ATPase beta-subunit was tested by confocal immunofluorescence microscopy and surface biotinylation [41].
  • CONCLUSIONS: Proton-pump inhibitor treatment for ulcer bleeding produces small, but potentially important, reductions in transfusion requirements and length of hospitalization [42].


  1. Vacuolar H+-ATPase B1 Subunit Mutations that Cause Inherited Distal Renal Tubular Acidosis Affect Proton Pump Assembly and Trafficking in Inner Medullary Collecting Duct Cells. Yang, Q., Li, G., Singh, S.K., Alexander, E.A., Schwartz, J.H. J. Am. Soc. Nephrol. (2006) [Pubmed]
  2. Expression of ATP1AL1, a non-gastric proton pump, in human colorectum. Takahashi, Y., Sakai, H., Kuragari, M., Suzuki, T., Tauchi, K., Minamimura, T., Tsukada, K., Asano, S., Takeguchi, N. Jpn. J. Physiol. (2002) [Pubmed]
  3. Proton pump inhibitors in acute peptic ulcer bleeding. Rockey, D.C. Gastroenterology (2005) [Pubmed]
  4. Proton-pump inhibitors or H2-receptor antagonists for Helicobacter pylori eradication-a meta-analysis. Holtmann, G., Layer, P., Goebell, H. Lancet (1996) [Pubmed]
  5. Proton pump inhibitor-therapy refractory gastro-oesophageal reflux disease patients, who are they? Bredenoord, A.J., Dent, J. Gut (2007) [Pubmed]
  6. Proton-pump inhibitors reduce the risk of uncomplicated peptic ulcer in elderly either acute or chronic users of aspirin/non-steroidal anti-inflammatory drugs. Pilotto, A., Franceschi, M., Leandro, G., Paris, F., Cascavilla, L., Longo, M.G., Niro, V., Andriulli, A., Scarcelli, C., Di Mario, F. Aliment. Pharmacol. Ther. (2004) [Pubmed]
  7. Review: eradication of Helicobacter pylori. Problems and recommendations. Huang, J.Q., Hunt, R.H. J. Gastroenterol. Hepatol. (1997) [Pubmed]
  8. Typical and atypical presentations of gastroesophageal reflux disease and its management. Gómez, J.E. Boletín de la Asociación Médica de Puerto Rico. (2004) [Pubmed]
  9. Proton-pump inhibition of gastric chloride secretion in congenital chloridorrhea. Aichbichler, B.W., Zerr, C.H., Santa Ana, C.A., Porter, J.L., Fordtran, J.S. N. Engl. J. Med. (1997) [Pubmed]
  10. ATP1AL1, a member of the non-gastric H,K-ATPase family, functions as a sodium pump. Grishin, A.V., Caplan, M.J. J. Biol. Chem. (1998) [Pubmed]
  11. Activation of proton pumping in human neutrophils occurs by exocytosis of vesicles bearing vacuolar-type H+-ATPases. Nanda, A., Brumell, J.H., Nordström, T., Kjeldsen, L., Sengelov, H., Borregaard, N., Rotstein, O.D., Grinstein, S. J. Biol. Chem. (1996) [Pubmed]
  12. Proton pump inhibitors do not reduce atazanavir concentrations in HIV-infected patients treated with ritonavir-boosted atazanavir. Guiard-Schmid, J.B., Poirier, J.M., Bonnard, P., Meynard, J.L., Slama, L., Lukiana, T., Jaillon, P., Pialoux, G. AIDS (2005) [Pubmed]
  13. Aging, the gastrointestinal tract, and risk of acid-related disease. Greenwald, D.A. Am. J. Med. (2004) [Pubmed]
  14. Clinical pharmacology of proton pump inhibitors: what the practising physician needs to know. Robinson, M., Horn, J. Drugs (2003) [Pubmed]
  15. Pharmacokinetics of clarithromycin in Helicobacter pylori eradication therapy in patients with liver cirrhosis. Azuma, T., Ito, S., Suto, H., Ito, Y., Miyaji, H., Yamazaki, Y., Kato, T., Kuriyama, M. Aliment. Pharmacol. Ther. (2000) [Pubmed]
  16. Proton pump inhibitor, clarithromycin and either amoxycillin or nitroimidazole: a meta-analysis of eradication of Helicobacter pylori. Gisbert, J.P., González, L., Calvet, X., García, N., López, T., Roqué, M., Gabriel, R., Pajares, J.M. Aliment. Pharmacol. Ther. (2000) [Pubmed]
  17. Proton-pump inhibitor therapy for acetylsalicylic acid associated upper gastrointestinal symptoms: a randomized placebo-controlled trial. Laheij, R.J., Van Rossum, L.G., Jansen, J.B., Verheugt, F.W. Aliment. Pharmacol. Ther. (2003) [Pubmed]
  18. Gastroprotective therapy and risk of gastrointestinal ulcers: risk reduction by COX-2 therapy. Wolfe, F., Anderson, J., Burke, T.A., Arguelles, L.M., Pettitt, D. J. Rheumatol. (2002) [Pubmed]
  19. Chromosomal localization of human Na+, K+-ATPase alpha- and beta-subunit genes. Yang-Feng, T.L., Schneider, J.W., Lindgren, V., Shull, M.M., Benz, E.J., Lingrel, J.B., Francke, U. Genomics (1988) [Pubmed]
  20. Stimulation of protein kinase C pathway mediates endocytosis of human nongastric H+-K+-ATPase, ATP1AL1. Reinhardt, J., Kosch, M., Lerner, M., Bertram, H., Lemke, D., Oberleithner, H. Am. J. Physiol. Renal Physiol. (2002) [Pubmed]
  21. Genomic organization of the human ATP1AL1 gene encoding a ouabain-sensitive H,K-ATPase. Sverdlov, V.E., Kostina, M.B., Modyanov, N.N. Genomics (1996) [Pubmed]
  22. The family of human Na,K-ATPase genes. ATP1AL1 gene is transcriptionally competent and probably encodes the related ion transport ATPase. Modyanov, N.N., Petrukhin, K.E., Sverdlov, V.E., Grishin, A.V., Orlova, M.Y., Kostina, M.B., Makarevich, O.I., Broude, N.E., Monastyrskaya, G.S., Sverdlov, E.D. FEBS Lett. (1991) [Pubmed]
  23. Ouabain-sensitive H,K-ATPase: tissue-specific expression of the mammalian genes encoding the catalytic alpha subunit. Pestov, N.B., Romanova, L.G., Korneenko, T.V., Egorov, M.V., Kostina, M.B., Sverdlov, V.E., Askari, A., Shakhparonov, M.I., Modyanov, N.N. FEBS Lett. (1998) [Pubmed]
  24. pH effects on cystine transport in lysosome-rich leucocyte granular fractions. Gahl, W.A., Tietze, F. Biochem. J. (1985) [Pubmed]
  25. Elevated expression of vacuolar proton pump genes and cellular PH in cisplatin resistance. Murakami, T., Shibuya, I., Ise, T., Chen, Z.S., Akiyama, S., Nakagawa, M., Izumi, H., Nakamura, T., Matsuo , K., Yamada, Y., Kohno, K. Int. J. Cancer (2001) [Pubmed]
  26. Proton pump inhibitors and gastric acid secretion. Wolfe, M.M., Welage, L.S., Sachs, G. Am. J. Gastroenterol. (2001) [Pubmed]
  27. Human nongastric H+-K+-ATPase: transport properties of ATP1al1 assembled with different beta-subunits. Crambert, G., Horisberger, J.D., Modyanov, N.N., Geering, K. Am. J. Physiol., Cell Physiol. (2002) [Pubmed]
  28. Chemistry of covalent inhibition of the gastric (H+, K+)-ATPase by proton pump inhibitors. Shin, J.M., Cho, Y.M., Sachs, G. J. Am. Chem. Soc. (2004) [Pubmed]
  29. Effect of genotypic differences in CYP2C19 on cure rates for Helicobacter pylori infection by triple therapy with a proton pump inhibitor, amoxicillin, and clarithromycin. Furuta, T., Shirai, N., Takashima, M., Xiao, F., Hanai, H., Sugimura, H., Ohashi, K., Ishizaki, T., Kaneko, E. Clin. Pharmacol. Ther. (2001) [Pubmed]
  30. An ascending single-dose safety and tolerance study of an oral formulation of rabeprazole (E3810). Lew, E.A., Barbuti, R.C., Kovacs, T.O., Sytnic, B., Humphries, T.J., Walsh, J.H. Aliment. Pharmacol. Ther. (1998) [Pubmed]
  31. Helicobacter pylori: factors affecting eradication and recurrence. Vakil, N. Am. J. Gastroenterol. (2005) [Pubmed]
  32. Metabolic interactions of the proton-pump inhibitors lansoprazole, omeprazole and pantoprazole with other drugs. Meyer, U.A. European journal of gastroenterology & hepatology. (1996) [Pubmed]
  33. Treatment of reflux oesophagitis of moderate and severe grade with ranitidine or pantoprazole--comparison of 24-hour intragastric and oesophageal pH. Armbrecht, U., Abucar, A., Hameeteman, W., Schneider, A., Stockbrügger, R.W. Aliment. Pharmacol. Ther. (1997) [Pubmed]
  34. A YAC contig and an EST map in the pericentromeric region of chromosome 13 surrounding the loci for neurosensory nonsyndromic deafness (DFNB1 and DFNA3) and limb-girdle muscular dystrophy type 2C (LGMD2C). Guilford, P., Dodé, C., Crozet, F., Blanchard, S., Chaïb, H., Levilliers, J., Levi-Acobas, F., Weil, D., Weissenbach, J., Cohen, D. Genomics (1995) [Pubmed]
  35. Concomitant dosing of famotidine with a triple therapy increases the cure rates of Helicobacter pylori infections in patients with the homozygous extensive metabolizer genotype of CYP2C19. Okudaira, K., Furuta, T., Shirai, N., Sugimoto, M., Miura, S. Aliment. Pharmacol. Ther. (2005) [Pubmed]
  36. The human cationic amino acid transporter (ATRC1): physical and genetic mapping to 13q12-q14. Albritton, L.M., Bowcock, A.M., Eddy, R.L., Morton, C.C., Tseng, L., Farrer, L.A., Cavalli-Sforza, L.L., Shows, T.B., Cunningham, J.M. Genomics (1992) [Pubmed]
  37. Lansoprazole and omeprazole in the prevention of relapse of reflux oesophagitis: a long-term comparative study. Carling, L., Axelsson, C.K., Forssell, H., Stubberöd, A., Kraglund, K., Bonnevie, O., Ekström, P. Aliment. Pharmacol. Ther. (1998) [Pubmed]
  38. Proton pump inhibitor treatment of patients with gastroesophageal reflux-related chronic cough: a comparison between two different daily doses of lansoprazole. Baldi, F., Cappiello, R., Cavoli, C., Ghersi, S., Torresan, F., Roda, E. World J. Gastroenterol. (2006) [Pubmed]
  39. Non-gastric H+/K+ ATPase is present in the microvillous membrane of the human placental syncytiotrophoblast. Johansson, M., Jansson, T., Pestov, N.B., Powell, T.L. Placenta (2004) [Pubmed]
  40. Isolation and characterization of a cDNA encoding the putative distal colon H+,K(+)-ATPase. Similarity of deduced amino acid sequence to gastric H+,K(+)-ATPase and Na+,K(+)-ATPase and mRNA expression in distal colon, kidney, and uterus. Crowson, M.S., Shull, G.E. J. Biol. Chem. (1992) [Pubmed]
  41. Differential localization of human nongastric H(+)-K(+)-ATPase ATP1AL1 in polarized renal epithelial cells. Reinhardt, J., Grishin, A.V., Oberleithner, H., Caplan, M.J. Am. J. Physiol. Renal Physiol. (2000) [Pubmed]
  42. Systematic review and meta-analysis: proton-pump inhibitor treatment for ulcer bleeding reduces transfusion requirements and hospital stay--results from the Cochrane Collaboration. Leontiadis, G.I., Sharma, V.K., Howden, C.W. Aliment. Pharmacol. Ther. (2005) [Pubmed]
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