STV1 is one of two yeast genes encoding isoforms of the a subunit of the yeast V-ATPase V₀ domain (1, 2). Vacuolar (H )-ATPases (V-ATPases) are ATP-dependent proton pumps that acidify intracellular vacuolar compartments. Vacuolar acidification is important for many cellular processes, including endocytosis, targeting of newly synthesized lysosomal enzymes, and other molecular targeting processes. The V-ATPase consists of two separable domains. The V₁ domain has eight known subunits, is peripherally associated with the vacuolar membrane, and catalyzes ATP hydrolysis. The V₀ domain is an integral membrane structure of five subunits, and transports protons across the membrane. The structure, function, and assembly of V-ATPases are reviewed in references 5, 3, 6 and 7.

Deletion of STV1 has little effect on cell growth, but deletion of both STV1 and VPH1, which encodes the second a subunit isoform, causes a more severe growth defect at neutral pH or in the presence of excess calcium (1). Overproduction of Stv1p partially complements a defect in vacuolar acidification in the vph1 null mutant (1). Stv1p and Vph1p show different localization patterns in indirect immunofluorescence assays, suggesting that they may be equivalent subunits for V-ATPases located on different organelles (1).

Stv1p and Vph1p are 55% identical and proteins similar to Vph1p have also been identified in rat, mouse, C. elegans and humans (8). Mutations in the isoforms of human V-ATPase most similar to Vph1p, a3 and a4, result in osteopetrosis and distal renal tubular acidosis, respectively (9, 10).

Last updated: 2000-05-17