VMA3 encodes the c subunit of the yeast V-ATPase V₀ domain (1). 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 6, 7, 8 and 9.

The V₀ c, c' (Vma11p), and c'' (Vma16p) subunits are highly hydrophobic integral membrane proteolipids, and have similar amino acid sequences; all three are required for V-ATPase activity (6, 9). Vma3p is also involved in copper and iron homeostasis (5, 4). The vma3 null mutant is viable but lacks vacuolar (H )-ATPase activity, and is defective in vacuolar acidification, vacuole biogenesis, vacuolar protein targeting, and endocytosis (1). The a and b V₀ subunits do not assemble in the absence of Vma3p (1).

V-ATPases have been identified in numerous eukaryotes; c subunit homologs have been identified in Drosophila, Manduca sexta, and Nephrops norvegicus, and the Drosophila and Nephrops genes can rescue the vma3 null phenotype (10, 11).

Last updated: 2000-05-18