The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

ATP2C1  -  ATPase, Ca++ transporting, type 2C, member 1

Homo sapiens

Synonyms: ATP-dependent Ca(2+) pump PMR1, ATP2C1A, ATPase 2C1, BCPM, Calcium-transporting ATPase type 2C member 1, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of ATP2C1

  • Mutations in ATP2C1, encoding a calcium pump, cause Hailey-Hailey disease [1].
  • This study demonstrates that defects in ATP2C1 cause HHD and together with the recent identification of ATP2A2 as the defective gene in Darier's disease, provide further evidence of the critical role of Ca(2+)signaling in maintaining epidermal integrity [2].
  • This finding suggests that mutation of the ATP2C1 gene may give rise to an extracutaneous phenotype, such as the liver dysfunction observed in severe cases, including our own [3].
  • Consequently, infected HHD, H-2Db-/- beta2m-/- mice generate only HLA-A2.1-restricted CD8(+) CTL responses against influenza A and vaccinia viruses [4].
  • We demonstrate that expression of hSPCA1 in yeast fully complements pmr1 phenotypes of hypersensitivity to Ca(2+) chelators and Mn(2+) toxicity [5].

Psychiatry related information on ATP2C1


High impact information on ATP2C1

  • Regulation of cytoplasmic calcium is impaired in cultured keratinocytes from HHD patients, and the normal epidermal calcium gradient is attenuated in vivo in HHD patients [1].
  • The current study examined whether endonuclease-mediated mRNA decay involved the selective binding of PMR1 to substrate mRNA on polysomes [8].
  • Endonuclease-mediated mRNA decay involves the selective targeting of PMR1 to polyribosome-bound substrate mRNA [8].
  • Deletion mutagenesis identified polysome-targeting domains in the N and C termini of PMR1, either of which could target GFP to polysomes [8].
  • The availability of purified PMR-1 and recombinant vigilin made it possible to test the hypothesis that RNA-binding proteins interact with cis-acting elements to stabilize target mRNAs by blocking cleavage by site-specific mRNA endonucleases [9].

Chemical compound and disease context of ATP2C1


Biological context of ATP2C1


Anatomical context of ATP2C1


Associations of ATP2C1 with chemical compounds

  • Recently, functional analysis of a series of site-specific mutants, designed to mimic missense mutations found in ATP2C1, uncovered specific defects in Ca(2+) and/or Mn(2+) transport and protein expression in mutant hSPCA1 polypeptides [18].
  • The addition of retinoids or corticosteroids to the cell culture inhibited the UVB-induced suppression of both ATP2A2 and ATP2C1 mRNA levels, and UVB-induced suppression of ATP2C1 mRNA was also inhibited by the addition of ciclosporin, tacrolimus and vitamin D(3) [19].
  • CONCLUSION: Our results suggest that ATP2C1 plays an essential role for basal keratinocytes to keep in the undifferentiated state and that its reduction evokes differentiation and up-localization to suprabasal layers most likely via the manganese starvation in the Golgi apparatus of keratinocytes [20].
  • Neither detachment of keratinocyte from culture dish nor treatment with high concentrations of calcium suppressed ATP2C1 expression, while both procedures induced differentiation markers, K10 keratin and involucrin [20].
  • Recent studies have revealed that HHD is caused by mutations in the ATP2C1 gene encoding a novel Ca(2+) pump [21].

Regulatory relationships of ATP2C1

  • The catalytic turnover rate of SPCA2 was found enhanced relative to SPCA1 pumps [22].

Other interactions of ATP2C1


Analytical, diagnostic and therapeutic context of ATP2C1

  • In order to investigate the molecular and physiological basis of HHD in the patient carrying missense mutation A528P, located in the putative nucleotide binding domain of the molecule, site-directed mutagenesis was employed to introduce this mutation into the wild-type ATP2C1 (hSPCA1) sequence [18].
  • In this study, we used denaturing high-performance liquid chromatography to screen all 28 exons and flanking intron boundaries of ATP2C1 for mutations in 9 HHD patients [18].
  • The transient reporter assay demonstrated that region +21/+57 was necessary for activation of the ATP2C1 promoter, and the electrophoretic mobility shift assay demonstrated that the region was recognized by the transcription factors, Sp1 and YY1 [15].
  • The addition of anti-interleukin (IL)-6 antibody to the cell culture prevented the UVB-induced suppression of ATP2A2 and ATP2C1 mRNA; in contrast, the addition of anti-IL-8 antibody slightly accelerated the suppression [19].
  • Mutation of ATP2C1 gene was detected by polymerase chain reaction (PCR) and DNA sequencing [26].


  1. Mutations in ATP2C1, encoding a calcium pump, cause Hailey-Hailey disease. Hu, Z., Bonifas, J.M., Beech, J., Bench, G., Shigihara, T., Ogawa, H., Ikeda, S., Mauro, T., Epstein, E.H. Nat. Genet. (2000) [Pubmed]
  2. Hailey-Hailey disease is caused by mutations in ATP2C1 encoding a novel Ca(2+) pump. Sudbrak, R., Brown, J., Dobson-Stone, C., Carter, S., Ramser, J., White, J., Healy, E., Dissanayake, M., Larrègue, M., Perrussel, M., Lehrach, H., Munro, C.S., Strachan, T., Burge, S., Hovnanian, A., Monaco, A.P. Hum. Mol. Genet. (2000) [Pubmed]
  3. A case of generalized Hailey-Hailey disease with fatal liver injury. Amagai, M., Kobayashi, M., Wakabayashi, K., Hakuno, M., Hashiguchi, A., Nishikawa, T., Hata, J. The Keio journal of medicine. (2001) [Pubmed]
  4. HLA-A2.1-restricted education and cytolytic activity of CD8(+) T lymphocytes from beta2 microglobulin (beta2m) HLA-A2.1 monochain transgenic H-2Db beta2m double knockout mice. Pascolo, S., Bervas, N., Ure, J.M., Smith, A.G., Lemonnier, F.A., Pérarnau, B. J. Exp. Med. (1997) [Pubmed]
  5. Functional expression in yeast of the human secretory pathway Ca(2+), Mn(2+)-ATPase defective in Hailey-Hailey disease. Ton, V.K., Mandal, D., Vahadji, C., Rao, R. J. Biol. Chem. (2002) [Pubmed]
  6. Hailey-Hailey disease with affective disorder: report of a case with novel ATP2C1 gene mutation. Yokota, K., Sawamura, D. J. Dermatol. Sci. (2006) [Pubmed]
  7. Psychological etiology in cardiovascular disorders. Basic findings and new trends. Mertens, C. Acta psychiatrica Belgica. (1986) [Pubmed]
  8. Endonuclease-mediated mRNA decay involves the selective targeting of PMR1 to polyribosome-bound substrate mRNA. Yang, F., Schoenberg, D.R. Mol. Cell (2004) [Pubmed]
  9. Vigilin binding selectively inhibits cleavage of the vitellogenin mRNA 3'-untranslated region by the mRNA endonuclease polysomal ribonuclease 1. Cunningham, K.S., Dodson, R.E., Nagel, M.A., Shapiro, D.J., Schoenberg, D.R. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  10. Caenorhabditis elegans PMR1, a P-type calcium ATPase, is important for calcium/manganese homeostasis and oxidative stress response. Cho, J.H., Ko, K.M., Singaravelu, G., Ahnn, J. FEBS Lett. (2005) [Pubmed]
  11. Bacterial infection-induced generalized Hailey-Hailey disease successfully treated by etretinate. Mashiko, M., Akiyama, M., Tsuji-Abe, Y., Shimizu, H. Clin. Exp. Dermatol. (2006) [Pubmed]
  12. 5-fluorouracil-based chemotherapy enhances the antitumor activity of a thymidylate synthase-directed polyepitopic peptide vaccine. Correale, P., Del Vecchio, M.T., Di Genova, G., Savellini, G.G., La Placa, M., Terrosi, C., Vestri, M., Urso, R., Lemonnier, F., Aquino, A., Bonmassar, E., Giorgi, G., Francini, G., Cusi, M.G. J. Natl. Cancer Inst. (2005) [Pubmed]
  13. Activity of the hSPCA1 Golgi Ca2+ pump is essential for Ca2+-mediated Ca2+ response and cell viability in Darier disease. Foggia, L., Aronchik, I., Aberg, K., Brown, B., Hovnanian, A., Mauro, T.M. J. Cell. Sci. (2006) [Pubmed]
  14. Hailey-Hailey disease: molecular and clinical characterization of novel mutations in the ATP2C1 gene. Dobson-Stone, C., Fairclough, R., Dunne, E., Brown, J., Dissanayake, M., Munro, C.S., Strachan, T., Burge, S., Sudbrak, R., Monaco, A.P., Hovnanian, A. J. Invest. Dermatol. (2002) [Pubmed]
  15. Transcriptional regulation of ATP2C1 gene by Sp1 and YY1 and reduced function of its promoter in Hailey-Hailey disease keratinocytes. Kawada, H., Nishiyama, C., Takagi, A., Tokura, T., Nakano, N., Maeda, K., Mayuzumi, N., Ikeda, S., Okumura, K., Ogawa, H. J. Invest. Dermatol. (2005) [Pubmed]
  16. Deficiency of ATP2C1, a Golgi ion pump, induces secretory pathway defects in endoplasmic reticulum (ER)-associated degradation and sensitivity to ER stress. Ramos-Castañeda, J., Park, Y.N., Liu, M., Hauser, K., Rudolph, H., Shull, G.E., Jonkman, M.F., Mori, K., Ikeda, S., Ogawa, H., Arvan, P. J. Biol. Chem. (2005) [Pubmed]
  17. Role for plasma membrane-related Ca2+-ATPase-1 (ATP2C1) in pancreatic beta-cell Ca2+ homeostasis revealed by RNA silencing. Mitchell, K.J., Tsuboi, T., Rutter, G.A. Diabetes (2004) [Pubmed]
  18. Hailey-Hailey disease: identification of novel mutations in ATP2C1 and effect of missense mutation A528P on protein expression levels. Fairclough, R.J., Lonie, L., Van Baelen, K., Haftek, M., Munro, C.S., Burge, S.M., Hovnanian, A. J. Invest. Dermatol. (2004) [Pubmed]
  19. Effects of drugs and anticytokine antibodies on expression of ATP2A2 and ATP2C1 in cultured normal human keratinocytes. Mayuzumi, N., Ikeda, S., Kawada, H., Ogawa, H. Br. J. Dermatol. (2005) [Pubmed]
  20. ATP2C1 is specifically localized in the basal layer of normal epidermis and its depletion triggers keratinocyte differentiation. Yoshida, M., Yamasaki, K., Daiho, T., Iizuka, H., Suzuki, H. J. Dermatol. Sci. (2006) [Pubmed]
  21. Novel mutation in ATP2C1 gene in a Japanese patient with Hailey-Hailey disease. Ohtsuka, T., Okita, H., Hama, N., Yamazaki, S. Dermatology (Basel) (2006) [Pubmed]
  22. Dissection of the functional differences between human secretory pathway Ca2+/Mn2+-ATPase (SPCA) 1 and 2 isoenzymes by steady-state and transient kinetic analyses. Dode, L., Andersen, J.P., Vanoevelen, J., Raeymaekers, L., Missiaen, L., Vilsen, B., Wuytack, F. J. Biol. Chem. (2006) [Pubmed]
  23. Human keratinocyte ATP2C1 localizes to the Golgi and controls Golgi Ca2+ stores. Behne, M.J., Tu, C.L., Aronchik, I., Epstein, E., Bench, G., Bikle, D.D., Pozzan, T., Mauro, T.M. J. Invest. Dermatol. (2003) [Pubmed]
  24. Ca2+ uptake and release properties of a thapsigargin-insensitive nonmitochondrial Ca2+ store in A7r5 and 16HBE14o- cells. Missiaen, L., Vanoevelen, J., Parys, J.B., Raeymaekers, L., De Smedt, H., Callewaert, G., Erneux, C., Wuytack, F. J. Biol. Chem. (2002) [Pubmed]
  25. Evidence for a secretory pathway Ca2+-ATPase in sea urchin spermatozoa. Gunaratne, H.J., Vacquier, V.D. FEBS Lett. (2006) [Pubmed]
  26. Detection of ATP2C1 gene mutation in familial benign chronic pemphigus. Chen, S., Huang, C., Li, J. Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban. (2005) [Pubmed]
WikiGenes - Universities