期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2003
卷号：100
期号：16
页码：9185-9190
DOI：10.1073/pnas.1633392100
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：We have identified and cloned a human liver cDNA encoding an unusual mosaic polyprotein, called polyserase-I (polyserine protease-I). This protein exhibits a complex domain organization including a type II transmembrane motif, a low-density lipoprotein receptor A module, and three tandem serine protease domains. This unusual modular architecture is also present in the sequences predicted for mouse and rat polyserase-I. Human polyserase-I gene maps to 19p13, and its last exon overlaps with that corresponding to the 3' UTR of the gene encoding translocase of mitochondrial inner membrane 13. Northern blot analysis showed the presence of a major polyserase-I transcript of 5.4 kb in human fetal and adult tissues and in tumor cell lines. Analysis of processing mechanisms of polyserase-I revealed that it is synthesized as a membrane-associated polyprotein that is further processed to generate three independent serine protease units. Two of these domains are proteolytically active against synthetic peptides commonly used for assaying serine proteases. These proteolytic activities of the polyserase-I units are blocked by serine protease inhibitors. We show an example of generation of separate serine protease domains from a single translation product in human tissues and illustrate an additional mechanism for expanding the complexity of the human degradome, the entire protease complement of human cells and tissues.
