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Gene Review

Atp6v0d2  -  ATPase, H+ transporting, lysosomal V0...

Mus musculus

Synonyms: 1620401A02Rik, AI324824, Osteoclast-specific vacuolar ATP synthase, V-ATPase, V-ATPase subunit d 2, ...
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Disease relevance of Atp6v0d2

  • Our results further indicate that blocking the expression of CA II and V-ATPase with antisense RNA or DNA leads to decreased bone resorption [1].
  • The results suggest that the inhibition of V-ATPase function via knockdown of ATP6L expression using RNA interfering technology can effectively retard the cancer growth and suppress the cancer metastasis by the decrease of proton extrusion and the down-regulation of gelatinase activity [2].
  • Introduction: The TCIRG1 gene encodes the a3 isoform of the V-ATPase a subunit, and mutations at this locus account for approximately 60% of infantile malignant osteopetrosis cases [3].
  • Although these anticancer effects of bafilomycin are considered to be attributable to the intracellular acidosis by V-ATPase inhibition, the exact mechanism remains unclear [4].
  • Bafilomycin A1, a macrolide antibiotic isolated from Streptomyces species, has been used as an inhibitor of vacuolar H(+) ATPase (V-ATPase) [4].

High impact information on Atp6v0d2

  • In osteoclast cultures treated with the 16-kD V-ATPase antisense RNA, acidification of an unknown population of intracellular vesicles was highly stimulated [1].
  • Instead, the E5-induced pH differential was attributed to impairment of V-ATPase activity, even though the amount of ATPase present in the Golgi complex was unaltered [5].
  • Since E5 also interacts with the 16-kD pore-forming subunit of the vacuolar H(+)-ATPase (V-ATPase), the oncoprotein could conceivably interfere with the pH homeostasis of the Golgi complex [5].
  • While the precise mechanism of receptor activation is unknown, E5 associates with several cellular proteins, including PDGF-R and the 16K V-ATPase protein, and induces the preferential phosphorylation of immature, Endo H-sensitive forms of the receptor [6].
  • Cn and V-ATPase modulate effector gene expression at the mRNA level by inhibiting transcription factor NF-kappaB [7].

Chemical compound and disease context of Atp6v0d2


Biological context of Atp6v0d2


Anatomical context of Atp6v0d2


Associations of Atp6v0d2 with chemical compounds

  • Here, we reported the molecular cloning and characterization of three novel subunit isoforms, C2, d2 and G3, of mouse V-ATPase [12].
  • V-ATPase, which overly functions in some cancers with metastatic potential, plays an important role in maintaining neutral cytosolic pH, very acidic luminal pH, and acidic extracellular pH [2].
  • To test for possible physiologic functions of the actin binding activity of V-ATPase, early responses of resorbing osteoclasts to inhibition of phosphatidylinositol 3-kinase activity by wortmannin and LY294002 were examined [17].
  • Unique cysteine residues were introduced into a Cys-less form of subunit B, and the V-ATPase complex in isolated vacuolar membranes from each mutant strain was reacted with the bifunctional, photoactivable maleimide reagent 4-(N-maleimido)benzophenone [18].
  • The direct binding interaction between V-ATPase and aldolase may be a new mechanism for the regulation of the V-ATPase and may underlie the proximal tubule acidification defect in hereditary fructose intolerance [19].

Physical interactions of Atp6v0d2


Co-localisations of Atp6v0d2

  • In immunocytochemical assays, aldolase was found to colocalize with V-ATPase in the renal proximal tubule [19].
  • After stimulation, the V-ATPase with the a3 isoform was immunochemically colocalized with lysosome marker lamp2 and was detected in acidic organelles [15].
  • In contrast, Rab11 colocalized with V-ATPase in apical regions of proximal tubule, and Rab20 colocalized with the enzyme in intercalated cells [21].

Regulatory relationships of Atp6v0d2

  • CONCLUSIONS: The immunohistochemical data in combination with the membrane fractionation studies are consistent with a potential role for Rab11 and Rab20 in regulating V-ATPase traffic in specific segments of the nephron [21].
  • Immunopurified V-ATPase from 1,25(OH)2D3-stimulated cultures exhibited 20-fold greater ATPase activity than the enzyme from unstimulated cultures, which do not contain osteoclasts [22].

Other interactions of Atp6v0d2

  • NM9.2 is a putative neuronal isoform of the 9.2 kDa subunit in V-ATPase [11].
  • A novel putative M9.2 isoform of V-ATPase expressed in the nervous system [11].
  • A putative role of Ac39/physophilin in the inactivation of the V-ATPase by disassembly of its V1 sector is also discussed [23].
  • Ac39 has recently been shown to be present in a synaptosomal complex which, in addition to synaptophysin, includes the bulk of synaptobrevin II, and subunits c and Ac115 of the V0 sector of the V-ATPase [23].
  • These results suggest that the V-ATPase, with the a4 isoform, is important for renal acid/base homeostasis [16].

Analytical, diagnostic and therapeutic context of Atp6v0d2


  1. Inhibition of bone resorption in vitro by antisense RNA and DNA molecules targeted against carbonic anhydrase II or two subunits of vacuolar H(+)-ATPase. Laitala, T., Väänänen, H.K. J. Clin. Invest. (1994) [Pubmed]
  2. The growth and metastasis of human hepatocellular carcinoma xenografts are inhibited by small interfering RNA targeting to the subunit ATP6L of proton pump. Lu, X., Qin, W., Li, J., Tan, N., Pan, D., Zhang, H., Xie, L., Yao, G., Shu, H., Yao, M., Wan, D., Gu, J., Yang, S. Cancer Res. (2005) [Pubmed]
  3. RANKL Treatment Releases the Negative Regulation of the Poly(ADP-Ribose) Polymerase-1 on Tcirg1 Gene Expression During Osteoclastogenesis. Beranger, G.E., Momier, D., Rochet, N., Quincey, D., Guigonis, J.M., Samson, M., Carle, G.F., Scimeca, J.C. J. Bone Miner. Res. (2006) [Pubmed]
  4. Bafilomycin Induces the p21-Mediated Growth Inhibition of Cancer Cells under Hypoxic Conditions by Expressing Hypoxia-Inducible Factor-1{alpha}. Lim, J.H., Park, J.W., Kim, M.S., Park, S.K., Johnson, R.S., Chun, Y.S. Mol. Pharmacol. (2006) [Pubmed]
  5. Golgi alkalinization by the papillomavirus E5 oncoprotein. Schapiro, F., Sparkowski, J., Adduci, A., Suprynowicz, F., Schlegel, R., Grinstein, S. J. Cell Biol. (2000) [Pubmed]
  6. E5 oncoprotein retained in the endoplasmic reticulum/cis Golgi still induces PDGF receptor autophosphorylation but does not transform cells. Sparkowski, J., Anders, J., Schlegel, R. EMBO J. (1995) [Pubmed]
  7. Calcineurin and vacuolar-type H+-ATPase modulate macrophage effector functions. Conboy, I.M., Manoli, D., Mhaiskar, V., Jones, P.P. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  8. Specific inhibitors of vacuolar H(+)-ATPase trigger apoptotic cell death of osteoclasts. Okahashi, N., Nakamura, I., Jimi, E., Koide, M., Suda, T., Nishihara, T. J. Bone Miner. Res. (1997) [Pubmed]
  9. Comparative analysis of the effects of a novel vacuolar adenosine 5'-triphosphatase inhibitor, FR202126, and doxycycline on bone loss caused by experimental periodontitis in rats. Niikura, K. J. Periodontol. (2006) [Pubmed]
  10. Expression and function of the mouse V-ATPase d subunit isoforms. Nishi, T., Kawasaki-Nishi, S., Forgac, M. J. Biol. Chem. (2003) [Pubmed]
  11. A novel putative M9.2 isoform of V-ATPase expressed in the nervous system. Ueda, T., Ugawa, S., Shimada, S. Neuroreport (2003) [Pubmed]
  12. Diversity of mouse proton-translocating ATPase: presence of multiple isoforms of the C, d and G subunits. Sun-Wada, G.H., Yoshimizu, T., Imai-Senga, Y., Wada, Y., Futai, M. Gene (2003) [Pubmed]
  13. The amino-terminal domain of the B subunit of vacuolar H+-ATPase contains a filamentous actin binding site. Holliday, L.S., Lu, M., Lee, B.S., Nelson, R.D., Solivan, S., Zhang, L., Gluck, S.L. J. Biol. Chem. (2000) [Pubmed]
  14. Selective expression of vacuolar H+-ATPase subunit d2 by particular subsets of dendritic cells among leukocytes. Sato, K., Shikano, S., Xia, G., Takao, J., Chung, J.S., Cruz, P.D., Xie, X.S., Ariizumi, K. Mol. Immunol. (2006) [Pubmed]
  15. From lysosomes to the plasma membrane: localization of vacuolar-type H+ -ATPase with the a3 isoform during osteoclast differentiation. Toyomura, T., Murata, Y., Yamamoto, A., Oka, T., Sun-Wada, G.H., Wada, Y., Futai, M. J. Biol. Chem. (2003) [Pubmed]
  16. a4, a unique kidney-specific isoform of mouse vacuolar H+-ATPase subunit a. Oka, T., Murata, Y., Namba, M., Yoshimizu, T., Toyomura, T., Yamamoto, A., Sun-Wada, G.H., Hamasaki, N., Wada, Y., Futai, M. J. Biol. Chem. (2001) [Pubmed]
  17. Vacuolar H+-ATPase binding to microfilaments: regulation in response to phosphatidylinositol 3-kinase activity and detailed characterization of the actin-binding site in subunit B. Chen, S.H., Bubb, M.R., Yarmola, E.G., Zuo, J., Jiang, J., Lee, B.S., Lu, M., Gluck, S.L., Hurst, I.R., Holliday, L.S. J. Biol. Chem. (2004) [Pubmed]
  18. Cysteine-directed cross-linking to subunit B suggests that subunit E forms part of the peripheral stalk of the vacuolar H+-ATPase. Arata, Y., Baleja, J.D., Forgac, M. J. Biol. Chem. (2002) [Pubmed]
  19. Interaction between aldolase and vacuolar H+-ATPase: evidence for direct coupling of glycolysis to the ATP-hydrolyzing proton pump. Lu, M., Holliday, L.S., Zhang, L., Dunn, W.A., Gluck, S.L. J. Biol. Chem. (2001) [Pubmed]
  20. Interaction between vacuolar H(+)-ATPase and microfilaments during osteoclast activation. Lee, B.S., Gluck, S.L., Holliday, L.S. J. Biol. Chem. (1999) [Pubmed]
  21. Distribution of Rab GTPases in mouse kidney and comparison with vacuolar H+-ATPase. Curtis, L.M., Gluck, S. Nephron. Physiology [electronic resource]. (2005) [Pubmed]
  22. Vacuolar H+-ATPase activity and expression in mouse bone marrow cultures. Lee, B.S., Holliday, L.S., Krits, I., Gluck, S.L. J. Bone Miner. Res. (1999) [Pubmed]
  23. Brain Ac39/physophilin: cloning, coexpression and colocalization with synaptophysin. Carrión-Vázquez, M., Fernández, A.M., Chowen, J., Nieto-Sampedro, M. Eur. J. Neurosci. (1998) [Pubmed]
  24. Mouse proton pump ATPase C subunit isoforms (C2-a and C2-b) specifically expressed in kidney and lung. Sun-Wada, G.H., Murata, Y., Namba, M., Yamamoto, A., Wada, Y., Futai, M. J. Biol. Chem. (2003) [Pubmed]
  25. The Sos1-Rac1 signaling. Possible involvement of a vacuolar H(+)-ATPase E subunit. Miura, K., Miyazawa, S., Furuta, S., Mitsushita, J., Kamijo, K., Ishida, H., Miki, T., Suzukawa, K., Resau, J., Copeland, T.D., Kamata, T. J. Biol. Chem. (2001) [Pubmed]
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