VMA2 encodes the B subunit of the yeast V-ATPase V₁ domain (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 1, 5, 6 and 7.

The B subunit (Vma2p) of the V-ATPase contains nucleotide binding sites, but does not catalyze ATP hydrolysis (1). Some vma2 point mutations reduce the ATPase and proton transport activities of the V-ATPase holoenzyme, suggesting that ATP binding to the noncatalytic sites may regulate V-ATPase activity (8, 9).26 PH,PR,CC, The vma2 null mutation is synthetically lethal with mutations that cause defects in endocytosis (10, 11).

V-ATPases have been identified in numerous eukaryotes (1, 7); the vma2 null phenotype can be fully complemented by expression of the Candida tropicalis V-ATPase B subunit, and partially complemented by the bovine B subunit (12).

Last updated: 2000-05-11