The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

CTSL  -  cathepsin L

Homo sapiens

Synonyms: CATL, CTSL1, Cathepsin L, Cathepsin L1, FLJ31037, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of CTSL1

  • Similarly, simultaneous inhibition of CTSB/CTSL was followed by a significant amelioration of colitis [1].
  • To find out which cell types produce CTSB and CTSL and to evaluate the prognostic impact of these proteases, 70 specimens from curatively resected patients with pancreatic adenocarcinoma were examined by in situ hybridization and immunohisto-chemistry [2].
  • Taken together with previous data that demonstrates that cathepsin L inactivates alpha(1)-antitrypsin, these findings indicate the involvement of cathepsins in the diminution of the lung antiprotease screen possibly leading to lung destruction in emphysema [3].
  • Enzyme-specific activities were increased 15-fold for CB and 9-fold for CL in papillary carcinoma compared with normal adjacent thyroid tissue or normal thyroid from autopsies [4].
  • Cathepsin B and Cathepsin L are cysteine proteases important in the process of invasion and metastasis [5].

Psychiatry related information on CTSL1

  • The mucoid exopolysaccharide (MEP or alginate) of Pseudomonas aeruginosa is thought to be a virulence factor for this organism by virtue of its ability to suppress local host defense mechanisms [6].
  • MEP and t-SEP recordings were abnormal on the left side, while EMG and neuropsychological tests gave normal results, which were unmodified over time [7].
  • MEP abnormalities correlated with the duration of motor symptoms and the severity of choreic motor activity [8].

High impact information on CTSL1


Chemical compound and disease context of CTSL1


Biological context of CTSL1


Anatomical context of CTSL1


Associations of CTSL1 with chemical compounds

  • OBJECTIVES: The cysteine proteases cathepsin B (CTSB) and L (CTSL) have been implicated in tumor spread and metastatic formation [2].
  • Human cathepsin L catalytically inactivated human alpha 1PI by cleavage of the bonds Glu354-Ala355 and Met358-Ser359 (the serine proteinase inhibitory site) [23].
  • The activities of cathepsin B and L towards the substrate were differentiated by use of the diazomethane inhibitor, Z-Phe-Phe-CHN2 (0.01 microM), which selectively inhibits cathepsin L at this concentration [24].
  • A 20-mer peptide, whose sequence encompassed kininogen residues Ile376 to Ile393, released bradykinin (BK; 80%) and Lys-bradykinin (20%) when incubated with cathepsin L. By contrast, cathepsin K did not release any kinin, but a truncated kinin metabolite BK(5-9) [FSPFR(385-389)] [25].
  • The effect of methylprednisolone treatment was demonstrated on decreased cathepsin B and increased cathepsin L concentrations in post-therapy serum samples [26].

Physical interactions of CTSL1

  • Cystatin A bound tightly and rapidly to papain and cathepsin L, with dissociation equilibrium constants of approximately 10(-11)-10(-13) M and association rate constants of 3 x 10(6)-5 x 10(6) M-1.s-1 [27].
  • T-kininogen did not release any immunoreactive kinins when complexed with cathepsin L, as previously observed using tissue kallikreins [28].
  • 2. At neutral pH, testican-1 also stabilizes cathepsin L, slowing pH-induced denaturation and allowing the protease to remain active longer, although the rate of proteolysis is reduced [29].

Enzymatic interactions of CTSL1

  • Cathepsin L hydrolyzed the majority of them with similar or higher catalytic efficiency than cathepsin X, acting as an endopeptidase mimicking a carboxymonopeptidase (pseudo-carboxymonopeptidase) [30].
  • The best substrates for CPB2.8 Delta CTE were also well hydrolysed by cathepsin L, however, the best inhibitors of the parasite enzyme have low affinity to cathepsin L. These promising data provide leads for the design of anti-parasitic drugs directed against the leishmanial enzyme [31].
  • Human cathepsin L and the corresponding mouse enzyme in low-density endosomes were identified in vitro to catalyze this site-specific MUC1 proteolysis [32].
  • Purified cathepsin L also efficiently cleaved HMG-CoA reductase in isolated ER preparations [33].
  • Amino-terminal amino acid sequence of the purified enzyme showed it to be a thiol protease with homology to cathepsin L. It catalyzed the in vitro degradation of extracellular matrix and had a cytopathic effect on mammalian cells [34].

Regulatory relationships of CTSL1


Other interactions of CTSL1

  • Cathepsin B is distinguished from both cathepsin L and S by its ability to efficiently hydrolyze substrates containing a basic P2 residue [40].
  • Active cathepsin L was shown to be present in emphysema epithelial lining fluid and inhibition of this protease prevented the cleavage of recombinant SLPI added to emphysema epithelial lining fluid [3].
  • Cathepsins B, L, H, and S readily cleave BGP at the G7-A8 bond; cathepsin L also cleaves at R43-R44; cathepsin B also cleaves at R44-F45; and cathepsin D cleaves only at A41-Y42 [41].
  • Although both cathepsins processed high-molecular weight kininogen under stoichiometric conditions, only cathepsin L generated significant amounts of immunoreactive kinins [25].
  • The cathepsins D (CTSD), B (CTSB) and L (CTSL) are important for the intracellular degradation of proteins [1].

Analytical, diagnostic and therapeutic context of CTSL1


  1. Cathepsins B, L and D in inflammatory bowel disease macrophages and potential therapeutic effects of cathepsin inhibition in vivo. Menzel, K., Hausmann, M., Obermeier, F., Schreiter, K., Dunger, N., Bataille, F., Falk, W., Scholmerich, J., Herfarth, H., Rogler, G. Clin. Exp. Immunol. (2006) [Pubmed]
  2. Prognostic impact of cysteine proteases cathepsin B and cathepsin L in pancreatic adenocarcinoma. Niedergethmann, M., Wostbrock, B., Sturm, J.W., Willeke, F., Post, S., Hildenbrand, R. Pancreas (2004) [Pubmed]
  3. Cathepsin B, L, and S cleave and inactivate secretory leucoprotease inhibitor. Taggart, C.C., Lowe, G.J., Greene, C.M., Mulgrew, A.T., O'Neill, S.J., Levine, R.L., McElvaney, N.G. J. Biol. Chem. (2001) [Pubmed]
  4. Marked increases in cathepsin B and L activities distinguish papillary carcinoma of the thyroid from normal thyroid or thyroid with non-neoplastic disease. Shuja, S., Murnane, M.J. Int. J. Cancer (1996) [Pubmed]
  5. Expression of Cathepsin B and L antigen and activity is associated with early colorectal cancer progression. Troy, A.M., Sheahan, K., Mulcahy, H.E., Duffy, M.J., Hyland, J.M., O'Donoghue, D.P. Eur. J. Cancer (2004) [Pubmed]
  6. Suppression of lymphocyte and neutrophil functions by Pseudomonas aeruginosa mucoid exopolysaccharide (alginate): reversal by physicochemical, alginase, and specific monoclonal antibody treatments. Mai, G.T., Seow, W.K., Pier, G.B., McCormack, J.G., Thong, Y.H. Infect. Immun. (1993) [Pubmed]
  7. Crural amyotrophy associated with a parietal lesion: a case report. Pozzessere, G., Valle, E., Tomaselli, M., D'Alessio, M., Bianco, F., Pierelli, F., Morocutti, C. Acta neurologica Belgica. (1995) [Pubmed]
  8. Motor responses evoked by magnetic brain stimulation in Huntington's disease. Meyer, B.U., Noth, J., Lange, H.W., Bischoff, C., Machetanz, J., Weindl, A., Röricht, S., Benecke, R., Conrad, B. Electroencephalography and clinical neurophysiology. (1992) [Pubmed]
  9. Major histocompatibility complex class II-associated p41 invariant chain fragment is a strong inhibitor of lysosomal cathepsin L. Bevec, T., Stoka, V., Pungercic, G., Dolenc, I., Turk, V. J. Exp. Med. (1996) [Pubmed]
  10. Uptake of extracellular enzyme by a novel pathway is a major determinant of cathepsin L levels in human macrophages. Reilly, J.J., Chen, P., Sailor, L.Z., Mason, R.W., Chapman, H.A. J. Clin. Invest. (1990) [Pubmed]
  11. Cathepsin B- and L-like activities at local gingival sites of chronic periodontitis patients. Eley, B.M., Cox, S.W. Journal of clinical periodontology. (1991) [Pubmed]
  12. Immunohistochemical localization of cathepsin L and cystatin A in normal skin and skin tumors. Palungwachira, P., Kakuta, M., Yamazaki, M., Yaguchi, H., Tsuboi, R., Takamori, K., Ogawa, H. J. Dermatol. (2002) [Pubmed]
  13. Cysteine and metalloproteinase activities in serum of Duchenne muscular dystrophic genotypes. Sohar, I., Laszlo, A., Gaal, K., Mechler, F. Biol. Chem. Hoppe-Seyler (1988) [Pubmed]
  14. Characterization of downstream Ras signals that induce alternative protease-dependent invasive phenotypes. Silberman, S., Janulis, M., Schultz, R.M. J. Biol. Chem. (1997) [Pubmed]
  15. Human cathepsin L rescues the neurodegeneration and lethality in cathepsin B/L double-deficient mice. Sevenich, L., Pennacchio, L.A., Peters, C., Reinheckel, T. Biol. Chem. (2006) [Pubmed]
  16. Hurpin is a selective inhibitor of lysosomal cathepsin L and protects keratinocytes from ultraviolet-induced apoptosis. Welss, T., Sun, J., Irving, J.A., Blum, R., Smith, A.I., Whisstock, J.C., Pike, R.N., von Mikecz, A., Ruzicka, T., Bird, P.I., Abts, H.F. Biochemistry (2003) [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. Amino acid sequences of the human kidney cathepsins H and L. Ritonja, A., Popović, T., Kotnik, M., Machleidt, W., Turk, V. FEBS Lett. (1988) [Pubmed]
  19. Collagenase, cathepsin B and cathepsin L gene expression in the synovial membrane of patients with early inflammatory arthritis. Cunnane, G., FitzGerald, O., Hummel, K.M., Gay, R.E., Gay, S., Bresnihan, B. Rheumatology (Oxford, England) (1999) [Pubmed]
  20. Colocalization of cystatin M/E and cathepsin V in lamellar granules and corneodesmosomes suggests a functional role in epidermal differentiation. Zeeuwen, P.L., Ishida-Yamamoto, A., van Vlijmen-Willems, I.M., Cheng, T., Bergers, M., Iizuka, H., Schalkwijk, J. J. Invest. Dermatol. (2007) [Pubmed]
  21. Comparative responsiveness of HL-60, HL-60R, and HL-60R+ (LRARSN) cells to retinoic acid, calcitriol, 9 cis-retinoic acid, and sodium butyrate. Atkins, K.B., Troen, B.R. Blood (1995) [Pubmed]
  22. Strong immunoreactivity of cathepsin L at the site of rimmed vacuoles in diseased muscles. Jimi, T., Satoh, Y., Takeda, A., Shibuya, S., Wakayama, Y., Sugita, K. Brain (1992) [Pubmed]
  23. Cathepsin L inactivates alpha 1-proteinase inhibitor by cleavage in the reactive site region. Johnson, D.A., Barrett, A.J., Mason, R.W. J. Biol. Chem. (1986) [Pubmed]
  24. Cathepsin L activity in alveolar macrophages of rats: response to cigarette smoke. Lesser, M., Galicki, N., Cardozo, C., Gariola, C.G. Am. J. Respir. Cell Mol. Biol. (1989) [Pubmed]
  25. Kininogen-derived peptides for investigating the putative vasoactive properties of human cathepsins K and L. Desmazes, C., Galineau, L., Gauthier, F., Brömme, D., Lalmanach, G. Eur. J. Biochem. (2003) [Pubmed]
  26. Serum concentration and circadian profiles of cathepsins B, H and L, and their inhibitors, stefins A and B, in asthma. Cimerman, N., Mesko Brguljan, P., Krasovec, M., Suskovic, S., Kos, J. Clin. Chim. Acta (2001) [Pubmed]
  27. Characterization by spectroscopic, kinetic and equilibrium methods of the interaction between recombinant human cystatin A (stefin A) and cysteine proteinases. Pol, E., Olsson, S.L., Estrada, S., Prasthofer, T.W., Björk, I. Biochem. J. (1995) [Pubmed]
  28. Cathepsin L, but not cathepsin B, is a potential kininogenase. Desmazes, C., Gauthier, F., Lalmanach, G. Biol. Chem. (2001) [Pubmed]
  29. Human proteoglycan testican-1 inhibits the lysosomal cysteine protease cathepsin L. Bocock, J.P., Edgell, C.J., Marr, H.S., Erickson, A.H. Eur. J. Biochem. (2003) [Pubmed]
  30. Recombinant human cathepsin X is a carboxymonopeptidase only: a comparison with cathepsins B and L. Puzer, L., Cotrin, S.S., Cezari, M.H., Hirata, I.Y., Juliano, M.A., Stefe, I., Turk, D., Turk, B., Juliano, L., Carmona, A.K. Biol. Chem. (2005) [Pubmed]
  31. Substrate specificity of recombinant cysteine proteinase, CPB, of Leishmania mexicana. Alves, L.C., Judice, W.A., St Hilaire, P.M., Meldal, M., Sanderson, S.J., Mottram, J.C., Coombs, G.H., Juliano, L., Juliano, M.A. Mol. Biochem. Parasitol. (2001) [Pubmed]
  32. O-Linked glycans control glycoprotein processing by antigen-presenting cells: a biochemical approach to the molecular aspects of MUC1 processing by dendritic cells. Hanisch, F.G., Schwientek, T., Von Bergwelt-Baildon, M.S., Schultze, J.L., Finn, O. Eur. J. Immunol. (2003) [Pubmed]
  33. 3-hydroxy-3-methylglutaryl coenzyme A reductase is sterol-dependently cleaved by cathepsin L-type cysteine protease in the isolated endoplasmic reticulum. Moriyama, T., Wada, M., Urade, R., Kito, M., Katunuma, N., Ogawa, T., Simoni, R.D. Arch. Biochem. Biophys. (2001) [Pubmed]
  34. Naegleria fowleri: characterization of a secreted histolytic cysteine protease. Aldape, K., Huizinga, H., Bouvier, J., McKerrow, J. Exp. Parasitol. (1994) [Pubmed]
  35. Effective activation of the proenzyme form of the urokinase-type plasminogen activator (pro-uPA) by the cysteine protease cathepsin L. Goretzki, L., Schmitt, M., Mann, K., Calvete, J., Chucholowski, N., Kramer, M., Günzler, W.A., Jänicke, F., Graeff, H. FEBS Lett. (1992) [Pubmed]
  36. The inhibition of cathepsin S by its propeptide--specificity and mechanism of action. Maubach, G., Schilling, K., Rommerskirch, W., Wenz, I., Schultz, J.E., Weber, E., Wiederanders, B. Eur. J. Biochem. (1997) [Pubmed]
  37. Squamous cell carcinoma antigen is a potent inhibitor of cysteine proteinase cathepsin L. Takeda, A., Yamamoto, T., Nakamura, Y., Takahashi, T., Hibino, T. FEBS Lett. (1995) [Pubmed]
  38. The role of the kininogens as cysteine proteinase inhibitors in local and systemic inflammation. Assfalg-Machleidt, I., Billing, A., Fröhlich, D., Nast-Kolb, D., Joka, T., Jochum, M., Machleidt, W. Agents Actions Suppl. (1992) [Pubmed]
  39. Cystatin M/E is a high affinity inhibitor of cathepsin V and cathepsin L by a reactive site that is distinct from the legumain-binding site. A novel clue for the role of cystatin M/E in epidermal cornification. Cheng, T., Hitomi, K., van Vlijmen-Willems, I.M., de Jongh, G.J., Yamamoto, K., Nishi, K., Watts, C., Reinheckel, T., Schalkwijk, J., Zeeuwen, P.L. J. Biol. Chem. (2006) [Pubmed]
  40. Engineering the S2 subsite specificity of human cathepsin S to a cathepsin L- and cathepsin B-like specificity. Brömme, D., Bonneau, P.R., Lachance, P., Storer, A.C. J. Biol. Chem. (1994) [Pubmed]
  41. Identification of peptide fragments generated by digestion of bovine and human osteocalcin with the lysosomal proteinases cathepsin B, D, L, H, and S. Baumgrass, R., Williamson, M.K., Price, P.A. J. Bone Miner. Res. (1997) [Pubmed]
  42. Cathepsin L is capable of truncating cystatin C of 11 N-terminal amino acids. Popovic, T., Cimerman, N., Dolenc, I., Ritonja, A., Brzin, J. FEBS Lett. (1999) [Pubmed]
WikiGenes - Universities