InterPro domain: IPR004908

V-ATPases (also known as V1V0-ATPase or vacuolar ATPase) are found in the eukaryotic endomembrane system, and in the plasma membrane of prokaryotes and certain specialised eukaryotic cells. V-ATPases hydrolyse ATP to drive a proton pump, and are involved in a variety of vital intra- and inter-cellular processes such as receptor mediated endocytosis, protein trafficking, active transport of metabolites, homeostasis and neurotransmitter release [ 1 ]. V-ATPases are composed of two linked complexes: the V1 complex (subunits A-H) contains the catalytic core that hydrolyses ATP, while the V0 complex (subunits a, c, c', c'', d) forms the membrane-spanning pore. V-ATPases may have an additional role in membrane fusion through binding to t-SNARE proteins [ 2 ].

Transmembrane ATPases are membrane-bound enzyme complexes/ion transporters that use ATP hydrolysis to drive the transport of protons across a membrane. Some transmembrane ATPases also work in reverse, harnessing the energy from a proton gradient, using the flux of ions across the membrane via the ATPase proton channel to drive the synthesis of ATP.

There are several different types of transmembrane ATPases, which can differ in function (ATP hydrolysis and/or synthesis), structure (e.g., F-, V- and A-ATPases, which contain rotary motors) and in the type of ions they transport [ 3 , 4 ]. The different types include:

• F-ATPases (ATP synthases, F1F0-ATPases), which are found in mitochondria, chloroplasts and bacterial plasma membranes where they are the prime producers of ATP, using the proton gradient generated by oxidative phosphorylation (mitochondria) or photosynthesis (chloroplasts).
• V-ATPases (V1V0-ATPases), which are primarily found in eukaryotes and they function as proton pumps that acidify intracellular compartments and, in some cases, transport protons across the plasma membrane [ 5 ]. They are also found in bacteria [ 6 ].
• A-ATPases (A1A0-ATPases), which are found in Archaea and function like F-ATPases, though with respect to their structure and some inhibitor responses, A-ATPases are more closely related to the V-ATPases [ 7 , 8 ].
• P-ATPases (E1E2-ATPases), which are found in bacteria and in eukaryotic plasma membranes and organelles, and function to transport a variety of different ions across membranes.
• E-ATPases, which are cell-surface enzymes that hydrolyse a range of NTPs, including extracellular ATP.

This entry represents subunit H (also known as Vma13p) found in the V1 complex of V-ATPases. This subunit has a regulatory function, being responsible for activating ATPase activity and coupling ATPase activity to proton flow [ 9 ]. The yeast enzyme contains five motifs similar to the HEAT or Armadillo repeats seen in the importins, and can be divided into two distinct domains: a large N-terminal domain consisting of stacked alpha helices, and a smaller C-terminal alpha-helical domain with a similar superhelical topology to an armadillo repeat [ 10 ].

1. A structural model of the vacuolar ATPase from transmission electron microscopy. Micron 36, 109-26
2. A new view of an old pore. Cell 121, 496-7
3. The evolution of A-, F-, and V-type ATP synthases and ATPases: reversals in function and changes in the H+/ATP coupling ratio. FEBS Lett. 576, 1-4
4. Mechanisms of ATPases--a multi-disciplinary approach. Curr. Protein Pept. Sci. 5, 89-105
5. Regulation and isoform function of the V-ATPases. Biochemistry 49, 4715-23
6. F-and V-ATPases in the genus Thermus and related species. Syst. Appl. Microbiol. 21, 12-22
7. New insights into structure-function relationships between archeal ATP synthase (A1A0) and vacuolar type ATPase (V1V0). Bioessays 30, 1096-109
8. F-type or V-type? The chimeric nature of the archaebacterial ATP synthase. Biochim. Biophys. Acta 1101, 232-5
9. Structure and assembly of the yeast V-ATPase. J. Bioenerg. Biomembr. 35, 301-12
10. Crystal structure of the regulatory subunit H of the V-type ATPase of Saccharomyces cerevisiae. Proc. Natl. Acad. Sci. U.S.A. 98, 7134-9