title: Human cathepsin S: chromosomal localization, gene structure, and tissue distribution.
abstract: The human lysosomal cysteine proteinases, cathepsins H, L, and B, have been mapped to chromosomes 15, 9, and 8, respectively, and the genomic structures of cathepsins L and B have been determined. We report here the chromosomal localization and partial gene structure for a recently sequenced human cysteine proteinase, cathepsin S. A 20-kilobase pair genomic clone of the human cathepsin S gene was isolated from a human fibroblast genomic library and used to map the human cathepsin S gene to chromosome 1q21 by fluorescence in situ hybridization. This clone contains exons 1 through 5, introns 1 through 4, part of intron 5, and > 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. Sequencing of the 5'-flanking region revealed, similar to human cathepsin B, no classical TATA or CAAT box. In contrast to cathepsin B, cathepsin S contains only two SP1 and at least 18 AP1 binding sites that potentially could be involved in regulation of the gene. This 5'-flanking region also contains CA microsatellites. The presence of AP1 sites and CA microsatellites suggest that cathepsin S can be specifically regulated. Results of Northern blotting using probes for human cathepsins B, L, and S are consistent with this hypothesis; only cathepsin S shows a restricted tissue distribution, with highest levels in spleen, heart, and lung. In addition, immunostaining of lung tissue demonstrated detectable cathepsin S only in lung macrophages. The high level of expression in the spleen and in phagocytes suggests that cathepsin S may have a specific function in immunity, perhaps related to antigen processing.
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts 02115.
authors.forename: G P
authors.initials: GP
authors.lastname: Shi
authors.forename: A C
authors.initials: AC
authors.lastname: Webb
authors.forename: K E
authors.initials: KE
authors.lastname: Foster
authors.forename: J H
authors.initials: JH
authors.lastname: Knoll
authors.forename: C A
authors.initials: CA
authors.lastname: Lemere
authors.forename: J S
authors.initials: JS
authors.lastname: Munger
authors.forename: H A
authors.initials: HA
authors.lastname: Chapman
mesh_terms: D000818:Animals; D001483:Base Sequence; D056668:Cathepsin L; D002403:Cathepsins / Q000096:biosynthesis* / Q000235:genetics*; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D002884:Chromosomes, Human, Pair 15; D002898:Chromosomes, Human, Pair 8; D002899:Chromosomes, Human, Pair 9; D003546:Cysteine Endopeptidases; D010450:Endopeptidases; D005091:Exons; D015698:Genomic Library; D015186:Hominidae / Q000235:genetics*; D006801:Humans; D007438:Introns; D007621:Karyotyping; D008168:Lung / Q000201:enzymology*; D008969:Molecular Sequence Data; D009928:Organ Specificity; D011401:Promoter Regions, Genetic
chemical_list: D002403:Cathepsins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; C534281:CTSL protein, human; D056668:Cathepsin L; C028217:cathepsin S