Molecular cloning and structural and functional characterization of human cathepsin F, a new cysteine proteinase of the papain family with a long propeptide domain

J Biol Chem. 1999 May 14;274(20):13800-9. doi: 10.1074/jbc.274.20.13800.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cathepsin F
  • Cathepsins / chemistry
  • Cathepsins / genetics*
  • Cathepsins / physiology*
  • Chromosome Mapping
  • Cloning, Molecular
  • Escherichia coli
  • Genomic Library
  • Humans
  • Male
  • Mice
  • Molecular Sequence Data
  • Prostate / chemistry
  • Protein Conformation
  • Recombinant Proteins / biosynthesis
  • Sequence Alignment
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Recombinant Proteins
  • Cathepsins
  • CTSF protein, human
  • Cathepsin F
  • Ctsf protein, mouse

Associated data

  • GENBANK/AJ007331
  • GENBANK/AJ131851
  • GENBANK/H39591