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 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.
Shi
G P
GP
Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts 02115.
Webb
A C
AC
Foster
K E
KE
Knoll
J H
JH
Lemere
C A
CA
Munger
J S
JS
Chapman
H A
HA
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
D002403:Cathepsins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; C534281:CTSL protein, human; D056668:Cathepsin L; C028217:cathepsin S