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Gene Review

ATP2A1  -  ATPase, Ca++ transporting, cardiac muscle,...

Homo sapiens

Synonyms: ATP2A, Calcium pump 1, Calcium-transporting ATPase sarcoplasmic reticulum type, fast twitch skeletal muscle isoform, Endoplasmic reticulum class 1/2 Ca(2+) ATPase, SERCA1, ...
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Disease relevance of ATP2A1

  • Exclusion of linkage of the RYR1, CACNA1S, and ATP2A1 genes to recurrent exertional rhabdomyolysis in Thoroughbreds [1].
  • Dissection of the functional differences between sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) 1 and 2 isoforms and characterization of Darier disease (SERCA2) mutants by steady-state and transient kinetic analyses [2].
  • To study the involvement of SERCA enzymes in differentiation, in this work differentiation of colon and gastric cancer cell lines was initiated, and the change in the expression of SERCA isoenzymes as well as intracellular calcium levels were investigated [3].
  • Collectively, these findings provide the first survey on phenotypic consequences of depleted SERCA-gated stores for epidermal homeostasis that explain how depleted SERCA2 calcium stores provoke focal lesions rather than generalized dermatoses, a phenotype highly reminiscent of the human genodermatosis Darier disease [4].
  • In primary as well as in secondary hypertrophied human myocardium, the expression of SR Ca(2+)-ATPase is reduced and inversely related to the degree of the hypertrophy [5].

High impact information on ATP2A1


Chemical compound and disease context of ATP2A1


Biological context of ATP2A1


Anatomical context of ATP2A1


Associations of ATP2A1 with chemical compounds

  • In the SERCA1a structure with bound Ca(2+), this groove is closed, accounting for the ability of Ca(2+) to disrupt PLN-SERCA interactions [19].
  • The further addition of vanadate and thapsigargin, both of which stabilize the E(2) conformation, did not diminish binding of PLN to SERCA [20].
  • SERCA overexpression reduces hydroxyl radical injury in murine myocardium [21].
  • Inositol 1,4,5-trisphosphate released 11% of the Ca(2+) accumulated in permeabilized A7r5 cells pretreated with tg with an EC(50) that was 5 times higher than for the SERCA-containing Ca(2+) store but failed to release Ca(2+) in 16HBE14o- cells [22].
  • The effects of the phenylalanine 256 to valine mutation on the sensitivity of sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA) Ca2+ pump isoforms 1, 2, and 3 to thapsigargin and other inhibitors [23].

Regulatory relationships of ATP2A1


Other interactions of ATP2A1


Analytical, diagnostic and therapeutic context of ATP2A1


  1. Exclusion of linkage of the RYR1, CACNA1S, and ATP2A1 genes to recurrent exertional rhabdomyolysis in Thoroughbreds. Dranchak, P.K., Valberg, S.J., Onan, G.W., Gallant, E.M., Binns, M.M., Swinburne, J.E., Mickelson, J.R. Am. J. Vet. Res. (2006) [Pubmed]
  2. Dissection of the functional differences between sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) 1 and 2 isoforms and characterization of Darier disease (SERCA2) mutants by steady-state and transient kinetic analyses. Dode, L., Andersen, J.P., Leslie, N., Dhitavat, J., Vilsen, B., Hovnanian, A. J. Biol. Chem. (2003) [Pubmed]
  3. Expression of endomembrane calcium pumps in colon and gastric cancer cells. Induction of SERCA3 expression during differentiation. Gélébart, P., Kovács, T., Brouland, J.P., van Gorp, R., Grossmann, J., Rivard, N., Panis, Y., Martin, V., Bredoux, R., Enouf, J., Papp, B. J. Biol. Chem. (2002) [Pubmed]
  4. Consequences of depleted SERCA2-gated calcium stores in the skin. Müller, E.J., Caldelari, R., Kolly, C., Williamson, L., Baumann, D., Richard, G., Jensen, P., Girling, P., Delprincipe, F., Wyder, M., Balmer, V., Suter, M.M. J. Invest. Dermatol. (2006) [Pubmed]
  5. Reduced myocardial sarcoplasmic reticulum Ca(2+)-ATPase protein expression in compensated primary and secondary human cardiac hypertrophy. Schotten, U., Koenigs, B., Rueppel, M., Schoendube, F., Boknik, P., Schmitz, W., Hanrath, P. J. Mol. Cell. Cardiol. (1999) [Pubmed]
  6. Calcium pump of the plasma membrane. Carafoli, E. Physiol. Rev. (1991) [Pubmed]
  7. Mutations in the gene-encoding SERCA1, the fast-twitch skeletal muscle sarcoplasmic reticulum Ca2+ ATPase, are associated with Brody disease. Odermatt, A., Taschner, P.E., Khanna, V.K., Busch, H.F., Karpati, G., Jablecki, C.K., Breuning, M.H., MacLennan, D.H. Nat. Genet. (1996) [Pubmed]
  8. Pharmacological modulation of sarcoplasmic reticulum function in smooth muscle. Laporte, R., Hui, A., Laher, I. Pharmacol. Rev. (2004) [Pubmed]
  9. Ca2+ homeostasis in Brody's disease. A study in skeletal muscle and cultured muscle cells and the effects of dantrolene an verapamil. Benders, A.A., Veerkamp, J.H., Oosterhof, A., Jongen, P.J., Bindels, R.J., Smit, L.M., Busch, H.F., Wevers, R.A. J. Clin. Invest. (1994) [Pubmed]
  10. Inhibition of sarcoplasmic Ca2+-ATPase increases caffeine- and halothane-induced contractures in muscle bundles of malignant hyperthermia susceptible and healthy individuals. Schuster, F., Müller, R., Hartung, E., Roewer, N., Anetseder, M. BMC anesthesiology [electronic resource]. (2005) [Pubmed]
  11. Sarcoplasmic reticulum Ca2+ pumps in heart and diaphragm of cardiomyopathic hamster: effects of perindopril. Anger, M., Lambert, F., Chemla, D., Desche, P., Scalbert, E., Lompre, A.M., Lecarpentier, Y. Am. J. Physiol. (1995) [Pubmed]
  12. Phospholamban domain IB forms an interaction site with the loop between transmembrane helices M6 and M7 of sarco(endo)plasmic reticulum Ca2+ ATPases. Asahi, M., Green, N.M., Kurzydlowski, K., Tada, M., MacLennan, D.H. Proc. Natl. Acad. Sci. U.S.A. (2001) [Pubmed]
  13. Insulin receptor substrate proteins create a link between the tyrosine phosphorylation cascade and the Ca2+-ATPases in muscle and heart. Algenstaedt, P., Antonetti, D.A., Yaffe, M.B., Kahn, C.R. J. Biol. Chem. (1997) [Pubmed]
  14. Regulation of sarco/endoplasmic and plasma membrane calcium ATPase gene expression by calcium in cultured human lens epithelial cells. Marian, M.J., Mukhopadhyay, P., Borchman, D., Tang, D., Paterson, C.A. Cell Calcium (2007) [Pubmed]
  15. Skeletal muscle sarcoplasmic reticulum phenotype in myotonic dystrophy. Damiani, E., Angelini, C., Pelosi, M., Sacchetto, R., Bortoloso, E., Margreth, A. Neuromuscul. Disord. (1996) [Pubmed]
  16. Sarcolipin regulates sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) by binding to transmembrane helices alone or in association with phospholamban. Asahi, M., Sugita, Y., Kurzydlowski, K., De Leon, S., Tada, M., Toyoshima, C., MacLennan, D.H. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  17. Sarcolipin regulates the activity of SERCA1, the fast-twitch skeletal muscle sarcoplasmic reticulum Ca2+-ATPase. Odermatt, A., Becker, S., Khanna, V.K., Kurzydlowski, K., Leisner, E., Pette, D., MacLennan, D.H. J. Biol. Chem. (1998) [Pubmed]
  18. Functional comparison between secretory pathway Ca2+/Mn2+-ATPase (SPCA) 1 and sarcoplasmic reticulum Ca2+-ATPase (SERCA) 1 isoforms by steady-state and transient kinetic analyses. Dode, L., Andersen, J.P., Raeymaekers, L., Missiaen, L., Vilsen, B., Wuytack, F. J. Biol. Chem. (2005) [Pubmed]
  19. Modeling of the inhibitory interaction of phospholamban with the Ca2+ ATPase. Toyoshima, C., Asahi, M., Sugita, Y., Khanna, R., Tsuda, T., MacLennan, D.H. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  20. Physical interactions between phospholamban and sarco(endo)plasmic reticulum Ca2+-ATPases are dissociated by elevated Ca2+, but not by phospholamban phosphorylation, vanadate, or thapsigargin, and are enhanced by ATP. Asahi, M., McKenna, E., Kurzydlowski, K., Tada, M., MacLennan, D.H. J. Biol. Chem. (2000) [Pubmed]
  21. SERCA overexpression reduces hydroxyl radical injury in murine myocardium. Hiranandani, N., Bupha-Intr, T., Janssen, P.M. Am. J. Physiol. Heart Circ. Physiol. (2006) [Pubmed]
  22. 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]
  23. The effects of the phenylalanine 256 to valine mutation on the sensitivity of sarcoplasmic/endoplasmic reticulum Ca2+ ATPase (SERCA) Ca2+ pump isoforms 1, 2, and 3 to thapsigargin and other inhibitors. Wootton, L.L., Michelangeli, F. J. Biol. Chem. (2006) [Pubmed]
  24. Ser16-, but not Thr17-phosphorylation of phospholamban influences frequency-dependent force generation in human myocardium. Brixius, K., Wollmer, A., Bölck, B., Mehlhorn, U., Schwinger, R.H. Pflugers Arch. (2003) [Pubmed]
  25. Depletion of intracellular calcium stores is toxic to SH-SY5Y neuronal cells. Nguyen, H.N., Wang, C., Perry, D.C. Brain Res. (2002) [Pubmed]
  26. Interferon-gamma induces a decrease in the intracellular calcium pump in a human salivary gland cell line. Meehan, S., Wu, A.J., Kang, E.C., Sakai, T., Ambudkar, I.S. Am. J. Physiol. (1997) [Pubmed]
  27. A mathematical model predicts that calreticulin interacts with the endoplasmic reticulum Ca(2+)-ATPase. Baker, H.L., Errington, R.J., Davies, S.C., Campbell, A.K. Biophys. J. (2002) [Pubmed]
  28. Prolactin stimulates prostate cell proliferation by increasing endoplasmic reticulum content due to SERCA 2b over-expression. Cr??pin, A., Bidaux, G., Vanden-Abeele, F., Dewailly, E., Goffin, V., Prevarskaya, N., Slomianny, C. Biochem. J. (2007) [Pubmed]
  29. SPCA1 pumps and Hailey-Hailey disease. Missiaen, L., Raeymaekers, L., Dode, L., Vanoevelen, J., Van Baelen, K., Parys, J.B., Callewaert, G., De Smedt, H., Segaert, S., Wuytack, F. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  30. Phosphorylation and regulation of the Ca(2+)-pumping ATPase in cardiac sarcoplasmic reticulum by calcium/calmodulin-dependent protein kinase. Narayanan, N., Xu, A. Basic Res. Cardiol. (1997) [Pubmed]
  31. SR Ca(2+)-ATPase/phospholamban in cardiomyocyte function. Tada, M., Toyofuku, T. J. Card. Fail. (1996) [Pubmed]
  32. Regional expression of phospholamban in the human heart. Bokník, P., Unkel, C., Kirchhefer, U., Kleideiter, U., Klein-Wiele, O., Knapp, J., Linck, B., Lüss, H., Müller, F.U., Schmitz, W., Vahlensieck, U., Zimmermann, N., Jones, L.R., Neumann, J. Cardiovasc. Res. (1999) [Pubmed]
  33. Phospholamban: a protein coming of age. Kadambi, V.J., Kranias, E.G. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
  34. Method-related effects of adenovirus-mediated LacZ and SERCA1 gene transfer on contractile behavior of cultured failing human cardiomyocytes. Weisser-Thomas, J., Dieterich, E., Janssen, P.M., Schmidt-Schweda, S., Maier, L.S., Sumbilla, C., Pieske, B. Journal of pharmacological and toxicological methods. (2005) [Pubmed]
  35. Sequence variants of the sarco(endo)plasmic reticulum Ca(2+)-transport ATPase 3 gene (SERCA3) in Caucasian type II diabetic patients (UK Prospective Diabetes Study 48). Varadi, A., Lebel, L., Hashim, Y., Mehta, Z., Ashcroft, S.J., Turner, R. Diabetologia (1999) [Pubmed]
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