Structure of the human lysosomal acid phosphatase gene.
We have isolated a 12-kb genomic clone, which encodes human lysosomal acid phosphatase (LAP), a lysosomal membrane glycoprotein. The human LAP gene has a size of about 9 kb and contains 11 exons (83-947 bp in size). The signal sequence and the first eight amino acids of the LAP protein are encoded by exon 1, the remaining luminal domain by exons 2-10 and the transmembrane and cytoplasmic domains, as well as the 3'-untranslated region, by exon 11. The sequence of the LAP gene confirmed the sequence deduced from the cDNA clone except for nucleotide 1917 in the 3'-untranslated region, where T is changed to C. The 5'-flanking sequence shows promoter activity, as analysed by coupling to bacterial chloramphenicol acetyltransferase. S1-nuclease-protection and primer-extension analysis demonstrate transcription initiation at multiple sites clustering within 23 bp upstream of the translation-initiation codon. Sequences characteristic for promoter regions like TATA-box and CAAT-box sequences could not be identified at typical positions. The absence of these sequences, the high GC content (63.5%), two GC boxes and a region complying with the properties of a CpG island, indicate that LAP is a housekeeping gene.
Georg-August-Universität Göttingen, Biochemie II, Federal Republic of Germany.
C
C
Geier
K
K
von Figura
R
R
Pohlmann
D000135:Acid Phosphatase / Q000097:blood / Q000235:genetics*; D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D004247:DNA / Q000097:blood / Q000235:genetics; D005091:Exons; D005796:Genes; D006801:Humans; D007438:Introns; D007962:Leukocytes / Q000201:enzymology; D008247:Lysosomes / Q000201:enzymology*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D015183:Restriction Mapping
D004247:DNA; D000135:Acid Phosphatase