Molecular cloning and characterization of novel tissue-specific isoforms of the human vacuolar H(+)-ATPase C, G and d subunits, and their evaluation in autosomal recessive distal renal tubular acidosis
Autor: | Katherine J. Borthwick, Annabel N. Smith, Fiona E. Karet |
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Rok vydání: | 2002 |
Předmět: |
Gene isoform
Vacuolar Proton-Translocating ATPases DNA Complementary Protein subunit Molecular Sequence Data Locus (genetics) Genes Recessive Biology Molecular cloning Kidney Gene Expression Regulation Enzymologic Distal renal tubular acidosis Genetics medicine Humans Amino Acid Sequence Cloning Molecular Gene Family Health Sequence Homology Amino Acid General Medicine Acidosis Renal Tubular Sequence Analysis DNA medicine.disease Molecular biology Isoenzymes Alternative Splicing Protein Subunits medicine.anatomical_structure ATP6V1G3 Mutation Hydrophobic and Hydrophilic Interactions Sequence Alignment |
Zdroj: | Gene. 297(1-2) |
ISSN: | 0378-1119 |
Popis: | Several of the 13 subunits comprising mammalian H+-ATPases have multiple isoforms, encoded by separate genes and with differing tissue expression patterns, which may play an important role in the intracellular localization and activity of H+-ATPases. Here we report the cloning of three previously uncharacterized human genes, ATP6V1C2, ATP6V1G3 and ATP6V0D2, encoding novel H+-ATPase subunit isoforms C2, G3 and d2, respectively. We demonstrate that these novel genes are expressed in kidney and few other tissues, and confirm previous reports that the C1, G1 and d1 isoforms are ubiquitously expressed, while G2 is brain-specific. Previously we have shown that mutations in two kidney-specific genes, ATP6V1B1 and ATP6V0A4, encoding the H+-ATPase B1 and a4 subunit isoforms, cause recessive distal renal tubular acidosis (dRTA). As the genes reported here are expressed mainly in kidney, we assessed their candidacy as causative genes for recessive dRTA in eight kindreds unlinked to either known disease locus. Although no potential disease-causing mutations were seen in this cohort, this does not rule out a role for these genes in other families. The identification of these three novel tissue-specific isoforms supports the hypothesis that subunit differences may play a key role in the structure, site and function of H+-ATPases within the cell. |
Databáze: | OpenAIRE |
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