Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.5 (cathepsin D)
 4,130 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have isolated and characterized a human genomic clone for a lysosomal enzyme gene. The start point of transcription was identified using primer extension of poly(A)+ mRNA. This genomic clone is specific for human alpha-galactosidase A, and it includes sequences for the promoter, complete signal peptide, first exon, and part of the first intron. Direct and inverted repeat elements of 10, 11, 16, 19, and 22 nucleotides (nt) flank the promoter site. A (GA)n repeat element of approx. 60 nt with strong homology to similar elements identified in several species is located upstream from the promoter. A GGGCGG site specific for DNA-binding protein Sp1 is located near a CAAT box, and the CCGCCC inverted repeat of the Sp1 binding sequence is located by the TATA box. The sequence immediately flanking the ATG start codon of the human alpha-galactosidase A is highly homologous to sequences flanking the ATG start codons of the other human lysosomal hydrolases for which sequence information is available (beta-glucocerebrosidase, cathepsin B, cathepsin D, and beta-hexosaminidase alpha chain), but not for any of the other 133 human signal peptides examined. Our analysis also reveals that conversion of the propeptide to the mature enzyme involves cleavage of a C-terminal rather than an N-terminal fragment. This information about the normal alpha-galactosidase A gene will be useful for comparison to data obtained from patients with Fabry disease, who are characterized by a deficiency of this enzyme. This is the first genomic clone described to date for any lysosomal enzyme, and it establishes a reference for future analyses of the molecular events that mediate the expression of this important class of enzymes.
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PMID:A genomic clone containing the promoter for the gene encoding the human lysosomal enzyme, alpha-galactosidase A. 289 62

In the fat body of insects with cyclic egg maturation, lysosomes play a critical role in the termination of vitellogenesis by selectively degrading the secretory machinery involved in the massive production of yolk protein precursors. To investigate this fat body-specific lysosomal activity in the mosquito, a cathepsin D-like aspartic protease (LAP) was previously purified and its cDNA cloned. Here we report the isolation of the AaLAP gene from an Aedes aegypti genomic library. The transcribed region of the gene is comprised of five exons, spanning 1904 base pairs. Restriction fragment length polymorphism (RFLP) and genomic clone analyses show this gene to be single copy and polymorphic. Primer extension analysis revealed two putative transcription start sites (TSS). The extension products corresponding to the distal and proximal TSSs were present in both pre- and vitellogenic fat bodies, suggesting that both TSSs are involved in housekeeping as well as tissue-specific expression of this gene. TATA box-like and arthropod initiator sequences, hallmarks of regulated genes, were present near each putative TSS. Several sequences resembling binding sites for liver- and fat body-specific transcription factors were identified within 1 kb upstream and downstream of the gene. Significantly, direct binding for the C/EBP and GATA families of transcription factors was demonstrated in vitro by electrophoretic mobility shift assays (EMSA). Three sequences located upstream of AaLAP resembled the Drosophila melanogaster yolk protein fat body enhancer (Dm Yp FBE). Potential hormone-response elements were also recognized in the gene; however, they did not bind the mosquito ecdysteroid receptor/Ultraspiracle heterodimer in EMSA experiments, indicating that these sequences may interact with different nuclear receptors.
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PMID:Analysis of the mosquito lysosomal aspartic protease gene: an insect housekeeping gene with fat body-enhanced expression. 913 12