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Gene Review

ATP6AP1  -  ATPase, H+ transporting, lysosomal...

Homo sapiens

Synonyms: 16A, ATP6IP1, ATP6S1, Ac45, CF2, ...
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Disease relevance of ATP6AP1

  • Moreover, a chronic myelogenous leukemia patient who experienced a complete remission after CD4(+) donor lymphocyte infusions also developed high-titer antibodies to ATP6S1 [1].
  • Three additional vaccinated melanoma patients and three metastatic non-small cell lung carcinoma patients vaccinated with autologous GM-CSF-secreting tumor cells similarly showed a correlation between humoral responses to ATP6S1 and tumor destruction [1].
  • A fraction of DNA from the human fetal lung fibroblast line IMR-90, 30-fold enriched for ribosomal DNA, was cloned in the lambda phage vector Charon 16A [2].
  • Streptococcus pneumoniae type 16A, a hitherto undescribed pneumococcal type [3].
  • Human placental DNA, enriched for ribosomal sequences, was cloned in the phage vector lambda Charon 16A [4].

Psychiatry related information on ATP6AP1

  • An extended region of the greater mustached bat's cochlea, the sparsely innervated (SI) zone, is located just basally to the frequency place of the dominant 61-kHz component of the echolocation signal (CF2) [5].

High impact information on ATP6AP1

  • A chimeric promoter containing six copies of the -181 to -171 region of Rab 16A fused to a minimal promoter conferred ABA-responsive expression on the reporter gene [6].
  • Overexpression of XAP3 enhanced X transactivation activity [7].
  • One of the activation domains of X (amino acids 90-122) is required for binding to XAP3, while the NH2-terminal part of XAP3 is necessary for binding to X [7].
  • Both X and XAP3 bound specifically to the eta PKC isoenzyme synthesized in rabbit reticulocyte lysates [7].
  • Hence, the cDNA encoding the protein Ac45 was cloned from a bovine adrenal medulla library [8].

Chemical compound and disease context of ATP6AP1

  • Carbon dioxide absorbents, such as soda lime and Baralyme brand absorbent, convert sevoflurane to CF2 = C(CF3)OCH2F, a vinyl ether called "Compound A," whose toxicity raises concerns regarding the safety of sevoflurane in rebreathing circuits [9].
  • Forty-four patients affected by nasal polyps were admitted to the Department of Otolaryngology, Lublin University School of Medicine, Lublin, Poland, and screened for the most-commonly identified CFTR mutations [DeltaF508, G542X, N1303 K, 1717-1 (G to A), W1282X, G551D, R553X and DeltaI507] by applying the INNO-LIPA CF2 test strips [10].

Biological context of ATP6AP1

  • Furthermore, the overall degree of amino acid sequence identity between the mammalian and invertebrate Ac45 proteins is very low (<18%), except for a surprisingly highly conserved putative targeting motif in the carboxy-terminal region [11].
  • Primer extension analysis revealed that the mouse Ac45 gene contains two major transcription initiation sites [11].
  • The 26-residue cytoplasmic tail of Ac45 was intrinsically capable of mediating endocytosis of the cell surface protein Tac, indicating that the tail contains an autonomous internalization signal [12].
  • Southern hybridization, PCR amplification, and DNA sequence analyses were performed on the toxin A (tcdA) and toxin B (tcdB) genes of type CF2 isolate 5340 [13].
  • Type CF2 5340 tcdA exhibited a 1,821-bp truncation, due to three deletions in the 3' end of the gene, and a point mutation in the 5' end of the gene, resulting in a premature stop codon at tcdA position 139 [13].

Anatomical context of ATP6AP1

  • We conclude that the regionally conserved Xenopus Ac45 protein is synthesized as an N-glycosylated approximately 60-kDa precursor that is intracellularly cleaved to an approximately 40-kDa product and speculate that it may assist in the V-ATPase-mediated acidification of neuroendocrine secretory granules [14].
  • Experiments with a specific antibody against Ac45 demonstrated that it is copurifying with the V-ATPase from chromaffin granules [8].
  • Steady state immunolabeling showed that Ac45 is located on the plasma membrane and in a vacuolar compartment in the juxtanuclear region [12].
  • Ac45 is a type I transmembrane protein associated with vacuolar H+-ATPase, a proton pump mediating the acidification of multiple intracellular organelles [12].
  • RESULTS: Significant enhancement of fluorescence for 16AP and NBD C(6)-HPC was evident in solutions incubated with whole tears and purified TL but not with tears depleted of TL for fixed and unfixed corneas [15].

Associations of ATP6AP1 with chemical compounds


Analytical, diagnostic and therapeutic context of ATP6AP1

  • Western blot analysis showed that immunoreactive Ac45 represents a approximately 40-kDa product that is expressed predominantly in neuroendocrine tissues; deglycosylation resulted in a approximately 27-kDa immunoreactive Ac45 product which is smaller than predicted for the intact protein [14].
  • REA type CF2 is a toxin variant strain of C. difficile that retains the ability to cause disease in humans but is not detected in clinical immunoassays for toxin A [13].
  • This strain, identified by restriction endonuclease analysis (REA) as type CF2, was not detected by an immunoassay for C. difficile toxin A. Culture supernatants of CF2 failed to elicit significant enterotoxic activity in the rabbit ileal loop assay but did produce atypical cytopathic effects in cell culture assay [13].
  • Bedside-inoculated 16A media is superior to the routine method for the recovery of microorganisms causing peritonitis in CAPD patients [20].
  • Since targeted prolong release was observed in formulation CF2 and CF5, these formulations were further subjected to in vivo drug release study using rabbits as an animal model [21].


  1. ATP6S1 elicits potent humoral responses associated with immune-mediated tumor destruction. Hodi, F.S., Schmollinger, J.C., Soiffer, R.J., Salgia, R., Lynch, T., Ritz, J., Alyea, E.P., Yang, J., Neuberg, D., Mihm, M., Dranoff, G. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  2. Molecular analysis of cloned human 18S ribosomal DNA segments. Wilson, G.N., Hollar, B.A., Waterson, J.R., Schmickel, R.D. Proc. Natl. Acad. Sci. U.S.A. (1978) [Pubmed]
  3. Streptococcus pneumoniae type 16A, a hitherto undescribed pneumococcal type. Austrian, R., Boettger, C., Dole, M., Fairly, L., Freid, M. J. Clin. Microbiol. (1985) [Pubmed]
  4. Molecular analysis of rearrangements in human ribosomal RNA gene clones. Respess, J., Erickson, J., Rushford, C., Jackson, D., Schmickel, R. Gene (1983) [Pubmed]
  5. Micromechanical responses to tones in the auditory fovea of the greater mustached bat's cochlea. Russell, I.J., Kössl, M. J. Neurophysiol. (1999) [Pubmed]
  6. cis-acting DNA elements responsive to gibberellin and its antagonist abscisic acid. Skriver, K., Olsen, F.L., Rogers, J.C., Mundy, J. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  7. The hepatitis B virus X-associated protein, XAP3, is a protein kinase C-binding protein. Cong, Y.S., Yao, Y.L., Yang, W.M., Kuzhandaivelu, N., Seto, E. J. Biol. Chem. (1997) [Pubmed]
  8. A novel accessory subunit for vacuolar H(+)-ATPase from chromaffin granules. Supek, F., Supekova, L., Mandiyan, S., Pan, Y.C., Nelson, H., Nelson, N. J. Biol. Chem. (1994) [Pubmed]
  9. Factors affecting the concentration of compound A resulting from the degradation of sevoflurane by soda lime and Baralyme in a standard anesthetic circuit. Fang, Z.X., Eger, E.I. Anesth. Analg. (1995) [Pubmed]
  10. Analysis of most common CFTR mutations in patients affected by nasal polyps. Kostuch, M., Klatka, J., Semczuk, A., Wojcierowski, J., Kulczycki, L., Oleszczuk, J. European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery. (2005) [Pubmed]
  11. Structural gene organization and evolutionary aspects of the V-ATPase accessory subunit Ac45. Schoonderwoert, V.T., Martens, G.J. Biochim. Biophys. Acta (2002) [Pubmed]
  12. Intracellular trafficking of the vacuolar H+-ATPase accessory subunit Ac45. Jansen, E.J., Holthuis, J.C., McGrouther, C., Burbach, J.P., Martens, G.J. J. Cell. Sci. (1998) [Pubmed]
  13. Toxin gene analysis of a variant strain of Clostridium difficile that causes human clinical disease. Sambol, S.P., Merrigan, M.M., Lyerly, D., Gerding, D.N., Johnson, S. Infect. Immun. (2000) [Pubmed]
  14. Biosynthesis of the vacuolar H+-ATPase accessory subunit Ac45 in Xenopus pituitary. Holthuis, J.C., Jansen, E.J., Schoonderwoert, V.T., Burbach, J.P., Martens, G.J. Eur. J. Biochem. (1999) [Pubmed]
  15. Tear lipocalin: evidence for a scavenging function to remove lipids from the human corneal surface. Gasymov, O.K., Abduragimov, A.R., Prasher, P., Yusifov, T.N., Glasgow, B.J. Invest. Ophthalmol. Vis. Sci. (2005) [Pubmed]
  16. Interstrand loops CD and EF act as pH-dependent gates to regulate fatty acid ligand binding in tear lipocalin. Gasymov, O.K., Abduragimov, A.R., Yusifov, T.N., Glasgow, B.J. Biochemistry (2004) [Pubmed]
  17. Long-duration, low-flow sevoflurane anesthesia using two carbon dioxide absorbents. Quantification of degradation products in the circuit. Bito, H., Ikeda, K. Anesthesiology (1994) [Pubmed]
  18. Closed-circuit anesthesia with sevoflurane in humans. Effects on renal and hepatic function and concentrations of breakdown products with soda lime in the circuit. Bito, H., Ikeda, K. Anesthesiology (1994) [Pubmed]
  19. Toxicity of compound A in rats. Effect of increasing duration of administration. Gonsowski, C.T., Laster, M.J., Eger, E.I., Ferrell, L.D., Kerschmann, R.L. Anesthesiology (1994) [Pubmed]
  20. Evaluation of aerobic Bactec 6A non-resin- and 16A resin-containing media for the recovery of microorganisms causing peritonitis. Blondeau, J.M., Pylypchuk, G.B., Kappel, J.E., Baltzan, R.B., Yaschuk, Y., Adolph, A.J. Diagn. Microbiol. Infect. Dis. (1995) [Pubmed]
  21. Design and evaluation of soluble ocular drug insert for controlled release of ciprofloxacin hydrochloride. Mundada, A.S., Shrikhande, B.K. Drug development and industrial pharmacy. (2006) [Pubmed]
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