Scientific background: |
SERCA1(SARCOPLASMIC RETICULUM Ca(2+)-ATPase 1), also called ATP2A1, is an enzyme that in humans is encoded by the ATP2A1 gene. This gene encodes one of the SERCA Ca(2+)-ATPases, which are intracellular pumps located in the sarcoplasmic or endoplasmic reticula of muscle cells. The SERCA1 gene is mapped on 16p11.2. This enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen, and is involved in muscular excitation and contraction. Zhang et al. (1995)determined that the human ATP2A1 gene is 26 kb long and contains 23 exons, 1 of which can be alternatively spliced.Overexpression of S1T, but not full-length SERCA1, induced ER stress in HeLa cells and amplified ER stress through the PERK (EIF2AK3)-EIF2A -ATF4 -CHOP (DDIT3) pathway. Mutations in this gene cause some autosomal recessive forms of Brody disease, characterized by increasing impairment of muscular relaxation during exercise. |
References: |
1.Brandl, C. J., Green, N. M., Korczak, B., MacLennan, D. H. Two Ca(2+) ATPase genes: homologies and mechanistic implications of deduced amino acid sequences. Cell 44: 597-607, 1986.
2.Karpati, G., Charuk, J., Carpenter, S., Jablecki, C., Holland, P. Myopathy caused by a deficiency of Ca(2+)-adenosine triphosphatase in sarcoplasmic reticulum (Brody's disease). Ann. Neurol. 20: 38-49, 1986.
3.Zhang, Y., Fujii, J., Phillips, M. S., Chen, H.-S., Karpati, G., Yee, W.-C., Schrank, B., Cornblath, D. R., Boyland, K. B., MacLennan, D. H. Characterization of cDNA and genomic DNA encoding SERCA1, the Ca(2+)-ATPase of human fast-twitch skeletal muscle sarcoplasmic reticulum, and its elimination as a candidate gene for Brody disease. Gemomics 30: 415-424, 1995.
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