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Gene Review

CTSC  -  cathepsin C

Homo sapiens

Synonyms: CPPI, Cathepsin C, Cathepsin J, DPP-I, DPP1, ...
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Disease relevance of CTSC


Psychiatry related information on CTSC

  • OBJECTIVE: To evaluate neurocognitive impairment in patients with persistent arthralgia, fatigue, and subjective memory loss in patients after Lyme disease (post-Lyme syndrome, PLS) [4].
  • Neurobehavioral effects of prenatal alcohol: Part III. PLS analyses of neuropsychologic tests [5].
  • PLS model building: a multivariate approach to personality test data [6].
  • PLS algorithms have employed to model the time-response (formation and destruction of emitter).The influence of the presence of two metals and the non-linearity relationship between response and concentration have been evaluated in the signal [7].
  • An ethologist aboard HMS Beagle: the young Darwin's observations on animal behavior [8].

High impact information on CTSC


Chemical compound and disease context of CTSC

  • The myeloid tumor lines U937, HL60, and THP-1 were found to be uniformly enriched in DPPI and susceptible to Leu-Leu-OMe but not Leu-OMe toxicity [10].
  • These peptides were further fragmented by a variety of cleavage reagents such as cyanogen bromide, chymotrypsin, Staphylococcus aureus protease, subtilisin, and cathepsin C to isolate individual S-[14C]carboxymethylcysteine-containing peptides [11].
  • Previous studies have demonstrated that the selective toxicity of leucyl-leucine methyl ester (Leu-Leu-OMe) for cytotoxic lymphocytes and myeloid cells is dependent on intracellular conversion to membranolytic metabolites by the acyl transferase activity of the granule enzyme dipeptidyl peptidase I (DPPI) that is enriched in these cells [12].
  • We found the dog C2 mastocytoma cell line to be the richest source yet described for DPPI, purifying up to 200 microg of enzyme per g of cells [13].
  • In this study, the pulse-amplitude-modulation (PAM)-fluorometric method was used to evaluate the difference in the sensitivity to mercury (Hg) and metolachlor of six algal species: Ankistrodesmus falcatus, Selenastrum capricornutum, Chlorella vulgaris, Nannoplankton (PLS), Microcystis aeruginosa and Pediastrum biwae [14].

Biological context of CTSC


Anatomical context of CTSC


Associations of CTSC with chemical compounds

  • Sequence analysis of CTSC in the proband revealed a homozygous mutation at codon 196 (587T-->C) within exon 4 that altered the conserved leucine to proline (Leu196Pro), whereas the patient's mother was heterozygous for that mutation [20].
  • Structure of human dipeptidyl peptidase I (cathepsin C): exclusion domain added to an endopeptidase framework creates the machine for activation of granular serine proteases [21].
  • Human cathepsin C thus appears to differ qualitatively from other cysteine proteinases of different origin [22].
  • Sequence analysis of the cathepsin C gene from PPP affected subjects from this Jordanian family indicated that all were homozygous for a missense mutation (1040A-->G) that changes a tyrosine to a cysteine [23].
  • In Group I only heparin was given according to the results of the Hepcon HMS Plus. In Group II aprotinin was added with a bolus of 1 x 10(6) kallikrein inhibiting units (KIU) for the patient immediately before initiation of CPB, 1 x 10(6) KIU in the priming solution of the CPB, and a continuous infusion of 250,000 KIU/h during CPB [24].
  • Using novel reversible peptide nitrile inhibitors of cathepsin C, and cell-based assays with U937 and EcoM-G cells, we determined the effects of pharmacological inhibition of cathepsin C on serine protease activity [25].

Regulatory relationships of CTSC


Other interactions of CTSC

  • The enzymes, except cathepsin C, are endopeptidases (reviewed in Kirschke et al., 1995), although cathepsin B was found also to be a dipeptidyl carboxypeptidase (Aronson and Barrett, 1978) and cathepsin H also an aminopeptidase (Koga et al., 1992) [27].
  • Introduction of the nonphysiological homophenylalanine (Hph) residue at P1 resulted in the best substrate Ala-Hph-AMC for DPPI (k(cat)/K(m)=9,000,000M(-1)s(-1)) [26].
  • In the homozygous state, this mutation was associated with an almost complete loss of activity of CTSC, CTSG, and elastase [18].
  • Independent mutations (c.318-1G-->A and c.817G-->C/p.W272C) were identified in CTSC and TYR, respectively, that were shared by the affected individuals in both families [28].
  • Purified DPPI exhibited both hydrolytic and transpeptidase (polymerase) activity [19].

Analytical, diagnostic and therapeutic context of CTSC


  1. Identification of a novel cathepsin C mutation (p.W185X) in a Brazilian kindred with Papillon-Lefèvre syndrome. Hart, P.S., Pallos, D., Zhang, Y., Sanchez, J., Kavamura, I., Brunoni, D., Hart, T.C. Mol. Genet. Metab. (2002) [Pubmed]
  2. The role of cathepsin C in Papillon-Lefèvre syndrome, prepubertal periodontitis, and aggressive periodontitis. Hewitt, C., McCormick, D., Linden, G., Turk, D., Stern, I., Wallace, I., Southern, L., Zhang, L., Howard, R., Bullon, P., Wong, M., Widmer, R., Gaffar, K.A., Awawdeh, L., Briggs, J., Yaghmai, R., Jabs, E.W., Hoeger, P., Bleck, O., Rüdiger, S.G., Petersilka, G., Battino, M., Brett, P., Hattab, F., Al-Hamed, M., Sloan, P., Toomes, C., Dixon, M., James, J., Read, A.P., Thakker, N. Hum. Mutat. (2004) [Pubmed]
  3. Loss-of-function mutations in the cathepsin C gene result in periodontal disease and palmoplantar keratosis. Toomes, C., James, J., Wood, A.J., Wu, C.L., McCormick, D., Lench, N., Hewitt, C., Moynihan, L., Roberts, E., Woods, C.G., Markham, A., Wong, M., Widmer, R., Ghaffar, K.A., Pemberton, M., Hussein, I.R., Temtamy, S.A., Davies, R., Read, A.P., Sloan, P., Dixon, M.J., Thakker, N.S. Nat. Genet. (1999) [Pubmed]
  4. Clinical and neurocognitive features of the post Lyme syndrome. Bujak, D.I., Weinstein, A., Dornbush, R.L. J. Rheumatol. (1996) [Pubmed]
  5. Neurobehavioral effects of prenatal alcohol: Part III. PLS analyses of neuropsychologic tests. Streissguth, A.P., Bookstein, F.L., Sampson, P.D., Barr, H.M. Neurotoxicology and teratology. (1989) [Pubmed]
  6. PLS model building: a multivariate approach to personality test data. Henningsson, M., Sundbom, E., Armelius, B.A., Erdberg, P. Scandinavian journal of psychology. (2001) [Pubmed]
  7. Multivariate calibration applied to simultaneous chemiluminescence determination of cobalt and chromium. Campíns-Falcó, P., Tortajada-Genaro, L.A., Meseguer-Lloret, S., Bosch-Reig, F. Analytical and bioanalytical chemistry. (2002) [Pubmed]
  8. An ethologist aboard HMS Beagle: the young Darwin's observations on animal behavior. Armstrong, P. Journal of the history of the behavioral sciences. (1993) [Pubmed]
  9. The action of leucyl-leucine methyl ester on cytotoxic lymphocytes requires uptake by a novel dipeptide-specific facilitated transport system and dipeptidyl peptidase I-mediated conversion to membranolytic products. Thiele, D.L., Lipsky, P.E. J. Exp. Med. (1990) [Pubmed]
  10. Spectrum of toxicities of amino acid methyl esters for myeloid cells is determined by distinct metabolic pathways. Thiele, D.L., Lipsky, P.E. Blood (1992) [Pubmed]
  11. Assignment of disulfide bonds in the alpha subunit of human chorionic gonadotropin. Mise, T., Bahl, O.P. J. Biol. Chem. (1980) [Pubmed]
  12. Apoptosis is induced in cells with cytolytic potential by L-leucyl-L-leucine methyl ester. Thiele, D.L., Lipsky, P.E. J. Immunol. (1992) [Pubmed]
  13. Regulated expression, processing, and secretion of dog mast cell dipeptidyl peptidase I. Wolters, P.J., Raymond, W.W., Blount, J.L., Caughey, G.H. J. Biol. Chem. (1998) [Pubmed]
  14. Evaluation of different algal species sensitivity to mercury and metolachlor by PAM-fluorometry. Juneau, P., Dewez, D., Matsui, S., Kim, S.G., Popovic, R. Chemosphere (2001) [Pubmed]
  15. Mutations of the cathepsin C gene are responsible for Papillon-Lefèvre syndrome. Hart, T.C., Hart, P.S., Bowden, D.W., Michalec, M.D., Callison, S.A., Walker, S.J., Zhang, Y., Firatli, E. J. Med. Genet. (1999) [Pubmed]
  16. Biochemical and mutational analyses of the cathepsin c gene (CTSC) in three North American families with Papillon Lefèvre syndrome. Zhang, Y., Hart, P.S., Moretti, A.J., Bouwsma, O.J., Fisher, E.M., Dudlicek, L., Pettenati, M.J., Hart, T.C. Hum. Mutat. (2002) [Pubmed]
  17. Human recombinant pro-dipeptidyl peptidase I (cathepsin C) can be activated by cathepsins L and S but not by autocatalytic processing. Dahl, S.W., Halkier, T., Lauritzen, C., Dolenc, I., Pedersen, J., Turk, V., Turk, B. Biochemistry (2001) [Pubmed]
  18. Clinical, genetic, and biochemical findings in two siblings with Papillon-Lefèvre Syndrome. Cagli, N.A., Hakki, S.S., Dursun, R., Toy, H., Gokalp, A., Ryu, O.H., Hart, P.S., Hart, T.C. J. Periodontol. (2005) [Pubmed]
  19. Purification and characterization of dipeptidyl peptidase I from human spleen. McGuire, M.J., Lipsky, P.E., Thiele, D.L. Arch. Biochem. Biophys. (1992) [Pubmed]
  20. A homozygous cathepsin C mutation associated with Haim-Munk syndrome. Cury, V.F., Gomez, R.S., Costa, J.E., Friedman, E., Boson, W., De Marco, L. Br. J. Dermatol. (2005) [Pubmed]
  21. Structure of human dipeptidyl peptidase I (cathepsin C): exclusion domain added to an endopeptidase framework creates the machine for activation of granular serine proteases. Turk, D., Janjić, V., Stern, I., Podobnik, M., Lamba, D., Dahl, S.W., Lauritzen, C., Pedersen, J., Turk, V., Turk, B. EMBO J. (2001) [Pubmed]
  22. Oligomeric structure and substrate induced inhibition of human cathepsin C. Dolenc, I., Turk, B., Pungercic, G., Ritonja, A., Turk, V. J. Biol. Chem. (1995) [Pubmed]
  23. Localisation of a gene for prepubertal periodontitis to chromosome 11q14 and identification of a cathepsin C gene mutation. Hart, T.C., Hart, P.S., Michalec, M.D., Zhang, Y., Marazita, M.L., Cooper, M., Yassin, O.M., Nusier, M., Walker, S. J. Med. Genet. (2000) [Pubmed]
  24. Heparin-level-based anticoagulation management during cardiopulmonary bypass: a pilot investigation on the effects of a half-dose aprotinin protocol on postoperative blood loss and hemostatic activation and inflammatory response. Koster, A., Huebler, S., Merkle, F., Hentschel, T., Gründel, M., Krabatsch, T., Tambeur, L., Praus, M., Habazettl, H., Kuebler, W.M., Kuppe, H. Anesth. Analg. (2004) [Pubmed]
  25. Inhibition of the activation of multiple serine proteases with a cathepsin C inhibitor requires sustained exposure to prevent pro-enzyme processing. Méthot, N., Rubin, J., Guay, D., Beaulieu, C., Ethier, D., Reddy, T.J., Riendeau, D., Percival, M.D. J. Biol. Chem. (2007) [Pubmed]
  26. Dipeptidyl peptidase I: importance of progranzyme activation sequences, other dipeptide sequences, and the N-terminal amino group of synthetic substrates for enzyme activity. Tran, T.V., Ellis, K.A., Kam, C.M., Hudig, D., Powers, J.C. Arch. Biochem. Biophys. (2002) [Pubmed]
  27. Structural and functional aspects of papain-like cysteine proteinases and their protein inhibitors. Turk, B., Turk, V., Turk, D. Biol. Chem. (1997) [Pubmed]
  28. Coinheritance of two rare genodermatoses (Papillon-Lefèvre syndrome and oculocutaneous albinism type 1) in two families: a genetic study. Hewitt, C., Wu, C.L., Hattab, F.N., Amin, W., Ghaffar, K.A., Toomes, C., Sloan, P., Read, A.P., James, J.A., Thakker, N.S. Br. J. Dermatol. (2004) [Pubmed]
  29. A novel mutation of the cathepsin C gene in a thai family with Papillon-Lefevre syndrome. Nitta, H., Wara-Aswapati, N., Lertsirivorakul, J., Nakamura, T., Yamamoto, M., Izumi, Y., Nakamura, T., Ishikawa, I. J. Periodontol. (2005) [Pubmed]
  30. Multivariate analysis of neuronal interactions in the generalized partial least squares framework: simulations and empirical studies. Lin, F.H., McIntosh, A.R., Agnew, J.A., Eden, G.F., Zeffiro, T.A., Belliveau, J.W. Neuroimage (2003) [Pubmed]
  31. Natural vs synthetic surfactants in neonatal respiratory distress syndrome. Halliday, H.L. Drugs (1996) [Pubmed]
  32. Sleep and apnea in the elderly: reliability and validity of 24-hour recordings in the home. Acebo, C., Watson, R.K., Bakos, L., Thoman, E.B. Sleep. (1991) [Pubmed]
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