Polyserase-I, a human polyprotease with the ability to generate independent serine protease domains from a single translation product.
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.
Cal
Santiago
S
Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Instituto Universitario de Oncología, Universidad de Oviedo, 33006-Oviedo, Spain.
Quesada
Victor
V
Garabaya
Cecilia
C
Lopez-Otin
Carlos
C
D020413:3' Untranslated Regions; D020816:Amino Acid Motifs; D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D019556:COS Cells; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002888:Chromosomes, Human, Pair 19; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000378:metabolism; D000939:Epitopes; D005091:Exons; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000378:metabolism; D008969:Molecular Sequence Data; D014176:Protein Biosynthesis; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D012697:Serine Endopeptidases / Q000737:chemistry* / Q000378:metabolism*; D014018:Tissue Distribution
D020413:3' Untranslated Regions; D018076:DNA, Complementary; D000939:Epitopes; D012333:RNA, Messenger; D011994:Recombinant Proteins; D005982:Glutathione Transferase; D012697:Serine Endopeptidases; C477599:polyserase I, human