Molecular cloning and characterization of a novel form of the human vacuolar H+-ATPase e-subunit: an essential proton pump component

Gene. 2007 May 15;393(1-2):94-100. doi: 10.1016/j.gene.2007.01.020. Epub 2007 Feb 7.

Abstract

Several of the 13 subunits comprising mammalian H(+)-ATPases have multiple alternative forms, encoded by separate genes and with differing tissue expression patterns. These may play an important role in the intracellular localization and activity of H(+)-ATPases. Here we report the cloning of a previously uncharacterized human gene, ATP6V0E2, encoding a novel H(+)-ATPase e-subunit designated e2. We demonstrate that in contrast to the ubiquitously expressed gene encoding the e1 subunit (previously called e), this novel gene is expressed in a more restricted tissue distribution, particularly kidney and brain. We show by complementation studies in a yeast strain deficient for the ortholog of this subunit, that either form of the e-subunit is essential for proper proton pump function. The identification of this novel form of the e-subunit lends further support to the hypothesis that subunit differences may play a key role in the structure, site and function of H(+)-ATPases within the cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acidosis, Renal Tubular / enzymology
  • Acidosis, Renal Tubular / genetics
  • Alternative Splicing / genetics
  • Amino Acid Sequence
  • Cloning, Molecular
  • DNA, Complementary / genetics
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Genetic Complementation Test
  • Humans
  • Molecular Sequence Data
  • Protein Subunits / chemistry
  • Protein Subunits / genetics*
  • Protein Subunits / metabolism
  • Proton Pumps / genetics*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Vacuolar Proton-Translocating ATPases / chemistry
  • Vacuolar Proton-Translocating ATPases / genetics*
  • Vacuolar Proton-Translocating ATPases / metabolism
  • Yeasts / growth & development

Substances

  • DNA, Complementary
  • Protein Subunits
  • Proton Pumps
  • RNA, Messenger
  • Vacuolar Proton-Translocating ATPases

Associated data

  • GENBANK/DQ989009
  • GENBANK/DQ995344