A 16-kb fragment of human DNA containing the cathepsin D (CATD) gene was isolated. Nucleotide sequencing, primer extension, protection from mung bean nuclease, and promoter activity assays were used to characterize the gene. The transcribed portion of the gene is about 11,000 bp and is organized into 9 exons analogous with the human pepsinogen A gene. Human pepsinogen A and CATD proteins have 42% sequence identity, while the two cDNAs are 55.7% identical. The positions of the splice junctions are fully conserved in these two genes. The noncoding sequences of the two genes are dissimilar. We report the nucleotide sequence of an Eco RI-Bam HI fragment that contains the transcription initiation site. The promoter region contains no TATA and CCAAT boxes, but five potential Sp1 binding sites (one of them in the first intron) and four AP-2 binding sites (two of them in the first intron). In COS-1 cells, the region containing the three proximal Sp1 sites possesses the bulk of the promoter activity of the 5'-flanking sequence. The transcription start site of the CATD gene is localized within a CpG cluster. In the interval -390 through +450, the content of CpG is 5.8 times above the average throughout the human genome.
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