Mouse proton pump ATPase C subunit isoforms (C2-a and C2-b) specifically expressed in kidney and lung

J Biol Chem. 2003 Nov 7;278(45):44843-51. doi: 10.1074/jbc.M307197200. Epub 2003 Aug 28.


The vacuolar-type H+-ATPases (V-ATPases) are multimeric proton pumps involved in a wide variety of physiological processes. We have identified two alternative splicing variants of C2 subunit isoforms: C2-a, a lung-specific isoform containing a 46-amino acid insertion, and C2-b, a kidney-specific isoform without the insert. Immunohistochemistry with isoform-specific antibodies revealed that V-ATPase with C2-a is localized specifically in lamellar bodies of type II alveolar cells, whereas the C2-b isoform is found in the plasma membranes of renal alpha and beta intercalated cells. Immunoprecipitation combined with immunohistological analysis revealed that C2-b together with other kidney-specific isoforms was selectively assembled to form a unique proton pump in intercalated cells. Furthermore, a chimeric yeast V-ATPase with mouse the C2-a or C2-b isoform showed a lower Km(ATP) and lower proton transport activity than that with C1 or Vma5p (yeast C subunit). These results suggest that V-ATPases with the C2-a and C2-b isoform are involved in luminal acidification of lamellar bodies and regulation of the renal acid-base balance, respectively.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid-Base Equilibrium
  • Alternative Splicing
  • Amino Acid Sequence
  • Blotting, Northern
  • Cell Membrane / enzymology
  • Conserved Sequence
  • Gene Expression*
  • Humans
  • Immunohistochemistry
  • Immunosorbent Techniques
  • In Situ Hybridization
  • Isoenzymes / chemistry
  • Isoenzymes / genetics
  • Isoenzymes / physiology
  • Kidney / enzymology*
  • Kidney / physiology
  • Kinetics
  • Lung / enzymology*
  • Microscopy, Immunoelectron
  • Molecular Sequence Data
  • Organ Specificity
  • Proton Pumps / chemistry
  • Proton Pumps / genetics*
  • Proton Pumps / physiology
  • Pulmonary Alveoli / enzymology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Alignment
  • Vacuolar Proton-Translocating ATPases / chemistry
  • Vacuolar Proton-Translocating ATPases / genetics*
  • Vacuolar Proton-Translocating ATPases / physiology


  • Isoenzymes
  • Proton Pumps
  • Atp6v1c1 protein, mouse
  • Atp6v1c2 protein, mouse
  • Vacuolar Proton-Translocating ATPases