title: Molecular cloning and characterization of a novel form of the human vacuolar H+-ATPase e-subunit: an essential proton pump component.
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.
authors.affiliation: Department of Medical Genetics, University of Cambridge, Cambridge Institute for Medical Research, Cambridge, UK.
authors.forename: Katherine G
authors.initials: KG
authors.lastname: Blake-Palmer
authors.forename: Ya
authors.initials: Y
authors.lastname: Su
authors.forename: Annabel N
authors.initials: AN
authors.lastname: Smith
authors.forename: Fiona E
authors.initials: FE
authors.lastname: Karet
mesh_terms: D000141:Acidosis, Renal Tubular / Q000201:enzymology / Q000235:genetics; D017398:Alternative Splicing / Q000235:genetics; D000595:Amino Acid Sequence; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005816:Genetic Complementation Test; D006801:Humans; D008969:Molecular Sequence Data; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D017494:Proton Pumps / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D025262:Vacuolar Proton-Translocating ATPases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015003:Yeasts / Q000254:growth & development
chemical_list: D018076:DNA, Complementary; D021122:Protein Subunits; D017494:Proton Pumps; D012333:RNA, Messenger; D025262:Vacuolar Proton-Translocating ATPases