Summary
Human α-galactosidase (EC 3.2.1.22) is a lysosomal hydrolase encoded by a single gene located in the chromosomal region Xq21.33-q22. The deficient activity of this enzyme results in Fabry disease, an X-linked recessive disorder which leads to premature death in affected males. For studies of the structure and function of α-galactosidase and for characterization of the genetic lesions in families with Fabry disease, the full-length cDNA was isolated, sequenced and used to obtain the human chromosomal gene. The 1393 bp full-length cDNA had a 60 nt 5’ untranslated region and encoded a precursor peptide of 429 amino acids including a signal peptide of 31 residues. The functional integrity of this cDNA was demonstrated by transient expression in COS-1 cells. The entire ~12 kb chromosomal gene, including ~9 and ~11 kb of 5’ and 3’ flanking sequence, was isolated. The gene had seven exons whose sequences were identical to those in the full-length cDNA. The 5’ flanking region of this housekeeping gene contained Spl and CCAAT box promoter elements as well as sequences corresponding to the AP-1, “OCTA” and “core” enhancer elements. Four direct repeats of the “chorion box” enhancer were preceded by an upstream “HTF” island. All intron-exon splice junctions conformed to the GT/AG consensus sequence. The novel lack of a 3’ untranslated sequence in the α-galactosidase cDNA was confirmed by sequencing the genomic 3’ region.
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Bishop, D.F., Kornreich, R., Eng, C.M., Ioannou, Y.A., Fitzmaurice, T.F., Desnick, R.J. (1988). Human α-Galactosidase: Characterization and Eukaryotic Expression of the Full-Length cDNA and Structural Organization of the Gene. In: Salvayre, R., Douste-Blazy, L., Gatt, S. (eds) Lipid Storage Disorders. NATO ASI Series, vol 150. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-1029-7_102
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DOI: https://doi.org/10.1007/978-1-4613-1029-7_102
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