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CTSF  -  cathepsin F

Homo sapiens

Synonyms: CATSF, CLN13, Cathepsin F
 
 
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Disease relevance of CTSF

 

High impact information on CTSF

 

Biological context of CTSF

  • Here, we describe the complete human cathepsin F (CTSF) gene which is composed of 13 exons [5].
  • To investigate the evolutionary relatedness to other human cathepsins, we determined the genomic organization and the chromosomal localization of cathepsin F and isolated its putative promoter region [6].
  • However, contrary to all known cathepsins, the open reading frame of the cathepsin F cDNA did not encode a signal sequence, thus suggesting that the protease is targeted to the lysosomal compartment via an N-terminal signal peptide-independent lysosomal targeting pathway [4].
  • A cDNA for a novel human papain-like cysteine protease, designated cathepsin F, has been cloned from a lambdagt10-skeletal muscle cDNA library [4].
  • A comparison of the genomic structures between this novel part of the cathepsin F gene and those of several cystatin genes revealed striking similarities, supporting the hypothesis that the cathepsin F gene resulted from a gene fusion between an ancestral cystatin and cathepsin gene [5].
 

Anatomical context of CTSF

  • Transient expression of T7-tagged cathepsin F in COS-7 cells revealed a vesicular distribution of the gene product in the juxtanuclear region of the cells [4].
  • CONCLUSIONS: Elevated cathepsin F and the ability of its inhibitor to produce a more normal phenotype in diabetic corneas suggest increased proteolysis in these corneas [7].
  • The enzyme was named cathepsin F, and was partially purified and characterized; it was detected in human articular cartilage [8].
  • Expression of cathepsin F and hepatocyte growth factor (HGF) genes was increased in ex vivo and organ-cultured DR corneas compared with normal corneas [7].
  • The specific temporal pattern of expression of these genes may indicate a potential role of cathepsin L-like and cathepsin F proteases in the YP processing events occurring during fish oocyte maturation and/or early embryogenesis [9].
 

Associations of CTSF with chemical compounds

  • Human cathepsin F is a recently described papain-like cysteine protease of unknown function [6].
  • We have determined the 1.7A structure of the mature domain of human cathepsin F associated with an irreversible vinyl sulfone inhibitor [10].
  • The methods presented in this report are exemplified through profiling two closely related cysteine proteases, cathepsin K and cathepsin F, across a 625-member PNA-encoded tetrapeptide acrylate library [11].
 

Regulatory relationships of CTSF

  • Stefin A inhibited cathepsin F slowly (kass=1.6 x 10(5) M(-1) s(-1)) and with a lower affinity (Ki=25 nM) [2].
 

Other interactions of CTSF

  • Increased transcription of these genes may result in overexpression of proteins, such as CTSF, MMP11 and MMP12 which could contribute to the pathogenesis of CC [12].
  • Protein sequence comparisons revealed 58% homology with cathepsin W; about 42-43% with cathepsins L, K, S, H, and O; and 38% with cathepsin B. Sequence comparisons of the propeptides indicated that cathepsin F and cathepsin W may form a new cathepsin subgroup [4].
  • For two of the genes, one up-regulated (CTSF gene) and one down-regulated (CYR61 gene), alterations in gene activity were confirmed at the protein level by Western blotting experiments [13].
  • Cathepsin F would therefore be the first cysteine protease zymogen containing a cystatin-like domain [14].
 

Analytical, diagnostic and therapeutic context of CTSF

References

  1. Cysteine protease cathepsin F is expressed in human atherosclerotic lesions, is secreted by cultured macrophages, and modifies low density lipoprotein particles in vitro. Oörni, K., Sneck, M., Brömme, D., Pentikäinen, M.O., Lindstedt, K.A., Mäyränpää, M., Aitio, H., Kovanen, P.T. J. Biol. Chem. (2004) [Pubmed]
  2. Human cathepsin F: expression in baculovirus system, characterization and inhibition by protein inhibitors. Fonovic, M., Brömme, D., Turk, V., Turk, B. Biol. Chem. (2004) [Pubmed]
  3. Role for cathepsin F in invariant chain processing and major histocompatibility complex class II peptide loading by macrophages. Shi, G.P., Bryant, R.A., Riese, R., Verhelst, S., Driessen, C., Li, Z., Bromme, D., Ploegh, H.L., Chapman, H.A. J. Exp. Med. (2000) [Pubmed]
  4. Human cathepsin F. Molecular cloning, functional expression, tissue localization, and enzymatic characterization. Wang, B., Shi, G.P., Yao, P.M., Li, Z., Chapman, H.A., Brömme, D. J. Biol. Chem. (1998) [Pubmed]
  5. The human cathepsin F gene--a fusion product between an ancestral cathepsin and cystatin gene. Wex, T., Wex, H., Brömme, D. Biol. Chem. (1999) [Pubmed]
  6. Human cathepsins F and W: A new subgroup of cathepsins. Wex, T., Levy, B., Wex, H., Brömme, D. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  7. Proteinase and growth factor alterations revealed by gene microarray analysis of human diabetic corneas. Saghizadeh, M., Kramerov, A.A., Tajbakhsh, J., Aoki, A.M., Wang, C., Chai, N.N., Ljubimova, J.Y., Sasaki, T., Sosne, G., Carlson, M.R., Nelson, S.F., Ljubimov, A.V. Invest. Ophthalmol. Vis. Sci. (2005) [Pubmed]
  8. Proteoglycan-degrading enzymes. A radiochemical assay method and the detection of a new enzyme cathepsin F. Dingle, J.T., Blow, A.M., Barrett, A.J., Martin, P.E. Biochem. J. (1977) [Pubmed]
  9. Ovarian cysteine proteinases in the teleost Fundulus heteroclitus: molecular cloning and gene expression during vitellogenesis and oocyte maturation. Fabra, M., Cerdà, J. Mol. Reprod. Dev. (2004) [Pubmed]
  10. The crystal structure of human cathepsin F and its implications for the development of novel immunomodulators. Somoza, J.R., Palmer, J.T., Ho, J.D. J. Mol. Biol. (2002) [Pubmed]
  11. Self-assembled small-molecule microarrays for protease screening and profiling. Urbina, H.D., Debaene, F., Jost, B., Bole-Feysot, C., Mason, D.E., Kuzmic, P., Harris, J.L., Winssinger, N. Chembiochem (2006) [Pubmed]
  12. Overexpression of cathepsin F, matrix metalloproteinases 11 and 12 in cervical cancer. Vazquez-Ortiz, G., Pina-Sanchez, P., Vazquez, K., Duenas, A., Taja, L., Mendoza, P., Garcia, J.A., Salcedo, M. BMC Cancer (2005) [Pubmed]
  13. Identification of specific cellular genes up-regulated late in adenovirus type 12 infection. Dorn, A., Zhao, H., Granberg, F., Hösel, M., Webb, D., Svensson, C., Pettersson, U., Doerfler, W. J. Virol. (2005) [Pubmed]
  14. Full-length cDNA of human cathepsin F predicts the presence of a cystatin domain at the N-terminus of the cysteine protease zymogen. Nägler, D.K., Sulea, T., Ménard, R. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  15. Expression, purification, crystallization and preliminary X-ray diffraction studies of human cathepsin F complexed with an irreversible vinyl sulfone inhibitor. Ho, J.D., Meltser, Y., Buggy, J.J., Palmer, J.T., Elrod, K.C., Chan, H., Mortara, K.D., Somoza, J.R. Acta Crystallogr. D Biol. Crystallogr. (2002) [Pubmed]
 
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