title: Molecular cloning and structural and functional characterization of human cathepsin F, a new cysteine proteinase of the papain family with a long propeptide domain.
abstract: A cDNA encoding a new cysteine proteinase belonging to the papain family and called cathepsin F has been cloned from a human prostate cDNA library. This cDNA encodes a polypeptide of 484 amino acids, with the same domain organization as other cysteine proteinases, including a hydrophobic signal sequence, a prodomain, and a catalytic region. However, this propeptide domain is unusually long and distinguishes cathepsin F from other proteinases of the papain family. Cathepsin F also shows all structural motifs characteristic of these proteinases, including the essential cysteine residue of the active site. Consistent with these structural features, cathepsin F produced in Escherichia coli as a fusion protein with glutathione S-transferase degrades the synthetic peptide benzyloxycarbonyl-Phe-Arg-7-amido-4-methylcoumarin, a substrate commonly used for functional characterization of cysteine proteinases. Furthermore, this proteolytic activity is blocked by trans-epoxysuccinyl-L-leucylamido-(4-guanidino)butane, an inhibitor of cysteine proteinases. The gene encoding cathepsin F maps to chromosome 11q13, close to that encoding cathepsin W. Cathepsin F is widely expressed in human tissues, suggesting a role in normal protein catabolism. Northern blot analysis also revealed a significant level of expression in some cancer cell lines opening the possibility that this enzyme could be involved in degradative processes occurring during tumor progression.
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D056646:Cathepsin F; D002403:Cathepsins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D004926:Escherichia coli; D015698:Genomic Library; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D011467:Prostate / Q000737:chemistry; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000096:biosynthesis; D016415:Sequence Alignment; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured