HUMAN CATHEPSIN-S - CHROMOSOMAL LOCALIZATION, GENE STRUCTURE, AND TISSUE DISTRIBUTION

The human lysosomal cysteine proteinases, cathepsins H, L, and B, have been mapped to chromosomes 15, 9, and 8, respectively, and the genomi c structures of cathepsins L and B have been determined. We report her e the chromosomal localization and partial gene structure for a recent ly sequenced human cysteine proteinase, cathepsin S. A 20-kilobase pai r genomic clone of the human cathepsin S gene was isolated from a huma n fibroblast genomic library and used to map the human cathepsin S gen e to chromosome 1q21 by fluorescence in situ hybridization. This clone contains exons 1 through 5, introns 1 through 4, part of intron 5, an d >7 kilobase pairs of the 5'-flanking sequence. The gene structure of human cathepsin S is similar to that of cathepsin L through the first 5 exons, except that cathepsin S introns are substantially larger. Se quencing of the 5'-flanking region revealed, similar to human cathepsi n B, no classical TATA or CAAT box. In contrast to cathepsin B, cathep sin S contains only two SP1 and at least 18 AP1 binding sites that pot entially could be involved in regulation of the gene. This 5'-flanking region also contains CA microsatellites. The presence of AP1 sites an d CA microsatellites suggest that cathepsin S can be specifically regu lated. Results of Northern blotting using probes for human cathepsins B, L, and S are consistent with this hypothesis; only cathepsin S show s a restricted tissue distribution, with highest levels in spleen, hea rt, and lung. In addition, immunostaining of lung tissue demonstrated detectable cathepsin S only in lung macrophages. The high level of exp ression in the spleen and in phagocytes suggests that cathepsin S may have a specific function in immunity, perhaps related to antigen proce ssing.