Gene Symbol: VPH1
Description: H(+)-transporting V0 sector ATPase subunit a
Alias: H(+)-transporting V0 sector ATPase subunit a
Species: Saccharomyces cerevisiae S288c

Top Publications

  1. Diepholz M, Venzke D, Prinz S, Batisse C, Flörchinger B, Rössle M, et al. A different conformation for EGC stator subcomplex in solution and in the assembled yeast V-ATPase: possible implications for regulatory disassembly. Structure. 2008;16:1789-98 pubmed publisher
    ..However, the relative arrangement of the EG and C subunits in solution is more open than that in the holoenzyme, suggesting a conformational change of EGC during regulatory assembly and disassembly. ..
  2. Ochotny N, Van Vliet A, Chan N, Yao Y, Morel M, Kartner N, et al. Effects of human a3 and a4 mutations that result in osteopetrosis and distal renal tubular acidosis on yeast V-ATPase expression and activity. J Biol Chem. 2006;281:26102-11 pubmed
    ..That a4 W520L affects both Vo and V1 subunits is a unique phenotype for any V-ATPase subunit mutation and supports the concerted pathway for V-ATPase assembly in vivo. ..
  3. Kawasaki Nishi S, Bowers K, Nishi T, Forgac M, Stevens T. The amino-terminal domain of the vacuolar proton-translocating ATPase a subunit controls targeting and in vivo dissociation, and the carboxyl-terminal domain affects coupling of proton transport and ATP hydrolysis. J Biol Chem. 2001;276:47411-20 pubmed
    ..quot;a" subunit of the vacuolar proton-translocating ATPase (V-ATPase) is encoded by two genes in yeast, VPH1 and STV1...
  4. Manolson M, Wu B, Proteau D, Taillon B, Roberts B, Hoyt M, et al. STV1 gene encodes functional homologue of 95-kDa yeast vacuolar H(+)-ATPase subunit Vph1p. J Biol Chem. 1994;269:14064-74 pubmed
    The Saccharomyces cerevisiae gene, VPH1 (Vacuolar pH 1), encodes a 95-kDa integral membrane subunit of the vacuolar-type H(+)-ATPase (V-ATPase) that is required for enzyme assembly; disruption of the VPH1 gene impairs vacuolar ..
  5. Diab H, Ohira M, Liu M, Cobb E, Kane P. Subunit interactions and requirements for inhibition of the yeast V1-ATPase. J Biol Chem. 2009;284:13316-25 pubmed publisher
    ..We propose that upon disassembly, the H subunit undergoes a conformational change that inhibits V(1)-ATPase activity and precludes V(0) interactions. ..
  6. Landolt Marticorena C, Williams K, Correa J, Chen W, Manolson M. Evidence that the NH2 terminus of vph1p, an integral subunit of the V0 sector of the yeast V-ATPase, interacts directly with the Vma1p and Vma13p subunits of the V1 sector. J Biol Chem. 2000;275:15449-57 pubmed
    ..These results suggest that Vph1p may function as a component of a fixed structural link, or stator, coupling V(1) ATP hydrolysis to V(0) proton translocation. ..
  7. Oot R, Wilkens S. Subunit interactions at the V1-Vo interface in yeast vacuolar ATPase. J Biol Chem. 2012;287:13396-406 pubmed publisher
  8. Manolson M, Proteau D, Preston R, Stenbit A, Roberts B, Hoyt M, et al. The VPH1 gene encodes a 95-kDa integral membrane polypeptide required for in vivo assembly and activity of the yeast vacuolar H(+)-ATPase. J Biol Chem. 1992;267:14294-303 pubmed
    ..F., and Jones, E. W. (1989) Proc. Natl. Acad. Sci. U.S.A. 86, 7027-7031). Vacuoles purified from yeast bearing the vph1-1 mutation had no detectable bafilomycin-sensitive ATPase activity or ATP-dependent proton pumping...
  9. Benlekbir S, Bueler S, Rubinstein J. Structure of the vacuolar-type ATPase from Saccharomyces cerevisiae at 11-Å resolution. Nat Struct Mol Biol. 2012;19:1356-62 pubmed publisher
    ..We provide support for this model by demonstrating that mutation of subunit H to increase the rigidity of the linker between its two domains decreases its ability to inhibit ATPase activity. ..

More Information


  1. Couoh Cardel S, Milgrom E, Wilkens S. Affinity Purification and Structural Features of the Yeast Vacuolar ATPase Vo Membrane Sector. J Biol Chem. 2015;290:27959-71 pubmed publisher
  2. Dechant R, Saad S, Ibáñez A, Peter M. Cytosolic pH regulates cell growth through distinct GTPases, Arf1 and Gtr1, to promote Ras/PKA and TORC1 activity. Mol Cell. 2014;55:409-21 pubmed publisher
    ..Together, these data provide a molecular mechanism for how cytosolic pH links C-source availability to the activity of signaling networks promoting cell growth. ..
  3. Tarsio M, Zheng H, Smardon A, Martínez Muñoz G, Kane P. Consequences of loss of Vph1 protein-containing vacuolar ATPases (V-ATPases) for overall cellular pH homeostasis. J Biol Chem. 2011;286:28089-96 pubmed publisher
    In yeast cells, subunit a of the vacuolar proton pump (V-ATPase) is encoded by two organelle-specific isoforms, VPH1 and STV1...
  4. Ryan M, Graham L, Stevens T. Voa1p functions in V-ATPase assembly in the yeast endoplasmic reticulum. Mol Biol Cell. 2008;19:5131-42 pubmed publisher
    ..Our results suggest Voa1p functions with Vma21p early in V(0) assembly in the ER, but then it dissociates before exit of the V(0)-Vma21p complex from the ER for transport to the Golgi compartment. ..
  5. Parsons L, Wilkens S. Probing subunit-subunit interactions in the yeast vacuolar ATPase by peptide arrays. PLoS ONE. 2012;7:e46960 pubmed publisher
    ..The subunit-subunit interaction data are discussed in context of our current model of reversible enzyme dissociation. ..
  6. Ayciriex S, Le Guedard M, Camougrand N, Velours G, Schoene M, Leone S, et al. YPR139c/LOA1 encodes a novel lysophosphatidic acid acyltransferase associated with lipid droplets and involved in TAG homeostasis. Mol Biol Cell. 2012;23:233-46 pubmed publisher
    ..Our results from purification of subcellular compartments and proteomic studies show that Loa1p is associated with LD and active in this compartment. Loa1p is therefore a novel LPA AT and plays a role in LD formation. ..
  7. Keenan Curtis K, Kane P. Novel vacuolar H+-ATPase complexes resulting from overproduction of Vma5p and Vma13p. J Biol Chem. 2002;277:2716-24 pubmed
    ..Overproduced Vma5p associated with cytosolic V(1) complexes; this association may cause the lethality. ..
  8. Su Y, Blake Palmer K, Sorrell S, Javid B, Bowers K, Zhou A, et al. Human H+ATPase a4 subunit mutations causing renal tubular acidosis reveal a role for interaction with phosphofructokinase-1. Am J Physiol Renal Physiol. 2008;295:F950-8 pubmed publisher
    ..Thus in the context of dRTA, stability and function of the metabolon composed of H+ATPase and glycolytic components can be compromised by either loss of required PFK-1 binding (G820R) or loss of pump protein (R807Q). ..
  9. Banerjee S, Kane P. Direct interaction of the Golgi V-ATPase a-subunit isoform with PI(4)P drives localization of Golgi V-ATPases in yeast. Mol Biol Cell. 2017;28:2518-2530 pubmed publisher
    ..We propose that NT domains of Vo a-subunit isoforms interact specifically with PI lipids in their organelles of residence. These interactions can transmit organelle-specific targeting or regulation information to V-ATPases. ..
  10. Bueler S, Rubinstein J. Vma9p need not be associated with the yeast V-ATPase for fully-coupled proton pumping activity in vitro. Biochemistry. 2015;54:853-8 pubmed publisher
    ..This observation shows that Vma9p is not necessary in vitro for this principal activity of the V-ATPase. ..
  11. Liu C, van Dyk D, Li Y, Andrews B, Rao H. A genome-wide synthetic dosage lethality screen reveals multiple pathways that require the functioning of ubiquitin-binding proteins Rad23 and Dsk2. BMC Biol. 2009;7:75 pubmed publisher
  12. Hoffman Sommer M, Kucharczyk R, Piekarska I, Kozlowska E, Rytka J. Mutations in the Saccharomyces cerevisiae vacuolar fusion proteins Ccz1, Mon1 and Ypt7 cause defects in cell cycle progression in a num1Delta background. Eur J Cell Biol. 2009;88:639-52 pubmed publisher
    ..Together, these results indicate that deregulation of the cell cycle in these mutants results from two separate mechanisms, one of which is related to calcium homeostasis. ..
  13. Tabke K, Albertmelcher A, Vitavska O, Huss M, Schmitz H, Wieczorek H. Reversible disassembly of the yeast V-ATPase revisited under in vivo conditions. Biochem J. 2014;462:185-97 pubmed publisher
    ..Results from overlay blots, pull-down assays and bimolecular fluorescence complementation support the assumption that subunit C interacts directly with microtubules without involvement of linker proteins...
  14. Ediger B, Melman S, Pappas D, Finch M, Applen J, Parra K. The tether connecting cytosolic (N terminus) and membrane (C terminus) domains of yeast V-ATPase subunit a (Vph1) is required for assembly of V0 subunit d. J Biol Chem. 2009;284:19522-32 pubmed publisher
    ..Deletions were made at residues securing the N terminus of subunit a (yeast isoform Vph1) to its membrane-bound C-terminal domain in order to understand the role of this conserved region for V-ATPase ..
  15. Davis Kaplan S, Compton M, Flannery A, Ward D, Kaplan J, Stevens T, et al. PKR1 encodes an assembly factor for the yeast V-type ATPase. J Biol Chem. 2006;281:32025-35 pubmed
    ..Our data indicate that Pkr1p functions together with the other V-ATPase assembly factors in the ER to efficiently assemble the V-ATPase membrane sector. ..
  16. Hayashi K, Sun Wada G, Wada Y, Nakanishi Matsui M, Futai M. Defective assembly of a hybrid vacuolar H(+)-ATPase containing the mouse testis-specific E1 isoform and yeast subunits. Biochim Biophys Acta. 2008;1777:1370-7 pubmed publisher
    ..These results suggest that subunit E, especially its amino-terminal domain, plays a pertinent role in the assembly of V-ATPase subunits in vacuolar membranes. ..
  17. Chan C, Prudom C, Raines S, Charkhzarrin S, Melman S, De Haro L, et al. Inhibitors of V-ATPase proton transport reveal uncoupling functions of tether linking cytosolic and membrane domains of V0 subunit a (Vph1p). J Biol Chem. 2012;287:10236-50 pubmed publisher
    ..The consequences of uncoupling V-ATPases in vivo as potential drug targets are discussed. ..
  18. Takahashi H, McCaffery J, Irizarry R, Boeke J. Nucleocytosolic acetyl-coenzyme a synthetase is required for histone acetylation and global transcription. Mol Cell. 2006;23:207-17 pubmed
    ..Thus, acetyl-CoA metabolism is directly linked to chromatin regulation and may affect diverse cellular processes in which acetylation and metabolism intersect, such as disease states and aging. ..
  19. Kota Z, Pali T, Dixon N, Kee T, Harrison M, Findlay J, et al. Incorporation of transmembrane peptides from the vacuolar H(+)-ATPase in phospholipid membranes: spin-label electron paramagnetic resonance and polarized infrared spectroscopy. Biochemistry. 2008;47:3937-49 pubmed publisher
    ..Comparison of the peptide behavior in lipid bilayers is made with membranous subunit c assemblies of the 16-kDa proteolipid from Nephrops norvegicus, which can substitute functionally for Vma3p in S. cerevisiae. ..
  20. Wilms T, Swinnen E, Eskes E, Dolz Edo L, Uwineza A, Van Essche R, et al. The yeast protein kinase Sch9 adjusts V-ATPase assembly/disassembly to control pH homeostasis and longevity in response to glucose availability. PLoS Genet. 2017;13:e1006835 pubmed publisher
    ..As both Sch9 and the V-ATPase are highly conserved in higher eukaryotes, it will be interesting to further clarify their cooperative action on the cellular processes that influence growth and ageing. ..
  21. Wang L, Seeley E, Wickner W, Merz A. Vacuole fusion at a ring of vertex docking sites leaves membrane fragments within the organelle. Cell. 2002;108:357-69 pubmed
    ..Their vertex enrichment requires cis-SNARE complex disassembly and is thus part of the normal fusion pathway. ..
  22. Smardon A, Nasab N, Tarsio M, Diakov T, Kane P. Molecular Interactions and Cellular Itinerary of the Yeast RAVE (Regulator of the H+-ATPase of Vacuolar and Endosomal Membranes) Complex. J Biol Chem. 2015;290:27511-23 pubmed publisher
    ..subunit, and it binds Rav2 and Skp1 of RAVE; the E, G, and C subunits of the V-ATPase peripheral V1 sector; and Vph1 of the membrane Vo sector...
  23. Numrich J, Péli Gulli M, Arlt H, Sardu A, Griffith J, Levine T, et al. The I-BAR protein Ivy1 is an effector of the Rab7 GTPase Ypt7 involved in vacuole membrane homeostasis. J Cell Sci. 2015;128:2278-92 pubmed publisher
    ..Our data, thus, reveal that Ivy1 is a novel regulator of vacuole membrane homeostasis with connections to TORC1 signaling. ..
  24. Nakatogawa H, Ishii J, Asai E, Ohsumi Y. Atg4 recycles inappropriately lipidated Atg8 to promote autophagosome biogenesis. Autophagy. 2012;8:177-86 pubmed publisher
  25. Graham L, Hill K, Stevens T. Assembly of the yeast vacuolar H+-ATPase occurs in the endoplasmic reticulum and requires a Vma12p/Vma22p assembly complex. J Cell Biol. 1998;142:39-49 pubmed
    ..This is the first evidence for a dedicated assembly complex in the ER required for the assembly of an integral membrane protein complex (V-ATPase) as it is transported through the secretory pathway. ..
  26. Compton M, Graham L, Stevens T. Vma9p (subunit e) is an integral membrane V0 subunit of the yeast V-ATPase. J Biol Chem. 2006;281:15312-9 pubmed
    ..These results demonstrate that Vma9p is an integral membrane subunit of the yeast V-ATPase V0 subcomplex and suggest a model for the arrangement of polypeptides within the V0 subcomplex. ..
  27. Oluwatosin Y, Kane P. Mutations in the yeast KEX2 gene cause a Vma(-)-like phenotype: a possible role for the Kex2 endoprotease in vacuolar acidification. Mol Cell Biol. 1998;18:1534-43 pubmed
    ..This is the first time a mutation of this type has been identified. ..
  28. Corbacho I, Teixidó F, Olivero I, Hernández L. Dependence of Saccharomyces cerevisiae Golgi functions on V-ATPase activity. FEMS Yeast Res. 2012;12:341-50 pubmed publisher
    ..0, which supports the existence of a mechanism that, in the absence of a functional V-ATPase, could contribute to pH regulation at least in the late Golgi. ..
  29. Muller O, Bayer M, Peters C, Andersen J, Mann M, Mayer A. The Vtc proteins in vacuole fusion: coupling NSF activity to V(0) trans-complex formation. EMBO J. 2002;21:259-69 pubmed
    ..We propose that Vtc proteins may couple ATP-dependent NSF activity to a subset of V(0) sectors in order to activate them for V(0) trans-complex formation and/or control fusion pore opening. ..
  30. Thaker Y, Hunke C, Yau Y, Shochat S, Li Y, Gruber G. Association of the eukaryotic V1VO ATPase subunits a with d and d with A. FEBS Lett. 2009;583:1090-5 pubmed publisher
    ..The data are discussed in light of subunit a and d forming a peripheral stalk, connecting the catalytic A(3)B(3) hexamer with V(O). ..
  31. Malkus P, Graham L, Stevens T, Schekman R. Role of Vma21p in assembly and transport of the yeast vacuolar ATPase. Mol Biol Cell. 2004;15:5075-91 pubmed
  32. Castrol C, Koretsky A, Domach M. NMR-Observed phosphate trafficking and polyphosphate dynamics in wild-type and vph1-1 mutant Saccharomyces cerevisae in response to stresses. Biotechnol Prog. 1999;15:65-73 pubmed
    ..Wild-type yeast and a vacuolar vph1-1 mutant, which lacks polyphosphate, were subjected to different stimuli...
  33. Makrantoni V, Dennison P, Stark M, Coote P. A novel role for the yeast protein kinase Dbf2p in vacuolar H+-ATPase function and sorbic acid stress tolerance. Microbiology. 2007;153:4016-26 pubmed
    ..The yeast V-ATPase is therefore involved in mediating sorbic acid stress tolerance, and we have shown a novel and unexpected role for the cell cycle-regulated protein kinase Dbf2p in promoting V-ATPase function. ..
  34. Mizuta M, Satoh E, Katoh C, Tanaka K, Moriguchi K, Suzuki K. Screening for yeast mutants defective in recipient ability for transkingdom conjugation with Escherichia coli revealed importance of vacuolar ATPase activity in the horizontal DNA transfer phenomenon. Microbiol Res. 2012;167:311-6 pubmed publisher
    ..Lack of either ZUO1 gene or SSZ1 gene, each of which encodes a component of the ribosome-associated cytoplasmic molecular chaperone, also strongly affected transkingdom conjugation. ..
  35. Gibson L, Cadwallader G, Finbow M. Evidence that there are two copies of subunit c" in V0 complexes in the vacuolar H+-ATPase. Biochem J. 2002;366:911-9 pubmed
    ..On the basis of the mutational and binding studies, it seems likely that two copies of subunit c" are next to each other. ..
  36. Hesselink R, Fedorov A, Hemminga M, Prieto M. Membrane-bound peptides from V-ATPase subunit a do not interact with an indole-type inhibitor. J Pept Sci. 2008;14:383-8 pubmed
    ..SB 242784, which is a highly potent inhibitor of V-ATPase, does not show any interaction with the peptides, indicating that TM7 alone is not sufficient for inhibitor binding. ..
  37. Finnigan G, Cronan G, Park H, Srinivasan S, Quiocho F, Stevens T. Sorting of the yeast vacuolar-type, proton-translocating ATPase enzyme complex (V-ATPase): identification of a necessary and sufficient Golgi/endosomal retention signal in Stv1p. J Biol Chem. 2012;287:19487-500 pubmed publisher
    ..These data define a novel sorting signal that is both necessary and sufficient for trafficking of the V-ATPase within the Golgi/endosomal network. ..
  38. Hesselink R, Koehorst R, Nazarov P, Hemminga M. Membrane-bound peptides mimicking transmembrane Vph1p helix 7 of yeast V-ATPase: a spectroscopic and polarity mismatch study. Biochim Biophys Acta. 2005;1716:137-45 pubmed
    ..This large flexibility of R735 might be important for its function in proton translocation in the V-ATPase enzyme. ..
  39. Leng X, Manolson M, Liu Q, Forgac M. Site-directed mutagenesis of the 100-kDa subunit (Vph1p) of the yeast vacuolar (H+)-ATPase. J Biol Chem. 1996;271:22487-93 pubmed
    ..To test whether the 100-kDa subunit plays a role in proton transport, site-directed mutagenesis of the VPH1 gene, which is one of two genes that encodes this subunit in yeast, has been carried out in a strain lacking both ..
  40. Qi J, Forgac M. Cellular environment is important in controlling V-ATPase dissociation and its dependence on activity. J Biol Chem. 2007;282:24743-51 pubmed
    ..Moreover, catalytic activity is not absolutely required for V-ATPase dissociation. ..
  41. Mattie S, McNally E, Karim M, Vali H, Brett C. How and why intralumenal membrane fragments form during vacuolar lysosome fusion. Mol Biol Cell. 2017;28:309-321 pubmed publisher