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Gene Review

CTSS  -  cathepsin S

Homo sapiens

Synonyms: Cathepsin S
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Disease relevance of CTSS


High impact information on CTSS


Chemical compound and disease context of CTSS


Biological context of CTSS

  • The frequency of the CTSS -25A allele was 0.457 in Caucasians and 0.431 in Canadian Inuit. Because of the importance of the CTSS gene product in vascular matrix remodeling, this polymorphism may be useful in the study of associations with atherosclerosis and related phenotypes [11].
  • This report documents that cathepsin S in human keratinocytes is selectively upregulated, in parallel to major histocompatibility complex class II molecules, in response to a pro-inflammatory cytokine [12].
  • Cleavage between the Gly and Ser residues of the reactive site loop and detection of a stable SCCA1-cathepsin S complex by sodium dodecyl sulfate-polyacrylamide gel electrophoresis suggested that the serpin interacted with the cysteine proteinase in a manner similar to that observed for typical serpin-serine proteinase interactions [13].
  • Interferon-gamma stimulation of primary keratinocytes and HaCaT cells resulted in a selective upregulation of the cathepsin S activity, the extent of which was very similar [12].
  • Papain, and to a minor extent cathepsin H, hydrolyzed the propeptide of cathepsin S, leading to competition with the hydrolysis of the fluorogenic substrates in the respective assays [14].

Anatomical context of CTSS


Associations of CTSS with chemical compounds

  • In contrast, cathepsin S preferred phenylalanine to valine in S2, but bound less tightly to the V10W cystatin variant [18].
  • The NH2-terminal amino acid sequence of the mature polypeptide was confirmed by sequencing cathepsin S purified from human spleen [15].
  • The replacement of Gly-133 in cathepsin S by an alanine residue that is normally found at this position in both cathepsin B and L results in a pattern of specificity toward hydrophobic residues in P2 that is very similar to that of cathepsin B and L [19].
  • Radiosequencing of A beta secreted by cathepsin S-expressing cells revealed that a previously unreported variant beginning at Met -1 (relative to the most common A beta N-terminus, Asp -1) accounted for most of the increase in A beta secretion [20].
  • Epoxy succinate peptide derivatives, CLIK-066, 088, 112, 121, 148, 181, 185 and 187, are typical specific inhibitors for cathepsin L. Aldehyde derivatives CLIK-060 and CLIK-164 showed specific inhibition against cathepsin S and cathepsin K, respectively [21].

Regulatory relationships of CTSS


Other interactions of CTSS

  • The inhibitory properties displayed by cystatin D suggest that it has a function in saliva as inhibitor of either endogenous or exogenous enzymes with cathepsin S- or H-like properties [25].
  • The latter variant proved to be valuable for discriminating between cathepsin L and cathepsin S (Ki 2.4 and 190 pM respectively) [18].
  • In contrast, for cathepsin S inhibition these interactions are of lesser significance, as reflected by a Ki value of 10(-8) M for the cystatin C variant devoid of Arg-8, Leu-9, Val-10, and Trp-106 side chains [26].
  • As with cathepsin B, the activities of the Phe-205-->Glu single and the Gly-133-->Ala/Phen-205-->Glu double mutants of cathepsin S toward the dibasic substrate is modulated by an additional ionizable group with a pKa of 5.7 [19].
  • Fluorescence titrations showed that high-molecular-weight kininogen binds two molecules of papain, cruzipain and cathepsin S with high affinity [27].

Analytical, diagnostic and therapeutic context of CTSS


  1. The clinical significance of cathepsin S expression in human astrocytomas. Flannery, T., Gibson, D., Mirakhur, M., McQuaid, S., Greenan, C., Trimble, A., Walker, B., McCormick, D., Johnston, P.G. Am. J. Pathol. (2003) [Pubmed]
  2. The lysosomal cysteine protease, cathepsin S, is increased in Alzheimer's disease and Down syndrome brain. An immunocytochemical study. Lemere, C.A., Munger, J.S., Shi, G.P., Natkin, L., Haass, C., Chapman, H.A., Selkoe, D.J. Am. J. Pathol. (1995) [Pubmed]
  3. Antigen processing and presentation in human muscle: cathepsin S is critical for MHC class II expression and upregulated in inflammatory myopathies. Wiendl, H., Lautwein, A., Mitsdörffer, M., Krause, S., Erfurth, S., Wienhold, W., Morgalla, M., Weber, E., Overkleeft, H.S., Lochmüller, H., Melms, A., Tolosa, E., Driessen, C. J. Neuroimmunol. (2003) [Pubmed]
  4. Cathepsin S in tumours, regional lymph nodes and sera of patients with lung cancer: relation to prognosis. Kos, J., Sekirnik, A., Kopitar, G., Cimerman, N., Kayser, K., Stremmer, A., Fiehn, W., Werle, B. Br. J. Cancer (2001) [Pubmed]
  5. AIDS-associated vacuolar myelopathy. A morphometric study. Tan, S.V., Guiloff, R.J., Scaravilli, F. Brain (1995) [Pubmed]
  6. Essential role for cathepsin S in MHC class II-associated invariant chain processing and peptide loading. Riese, R.J., Wolf, P.R., Brömme, D., Natkin, L.R., Villadangos, J.A., Ploegh, H.L., Chapman, H.A. Immunity (1996) [Pubmed]
  7. Expression of the elastolytic cathepsins S and K in human atheroma and regulation of their production in smooth muscle cells. Sukhova, G.K., Shi, G.P., Simon, D.I., Chapman, H.A., Libby, P. J. Clin. Invest. (1998) [Pubmed]
  8. Localization of cysteine protease, cathepsin S, to the surface of vascular smooth muscle cells by association with integrin alphanubeta3. Cheng, X.W., Kuzuya, M., Nakamura, K., Di, Q., Liu, Z., Sasaki, T., Kanda, S., Jin, H., Shi, G.P., Murohara, T., Yokota, M., Iguchi, A. Am. J. Pathol. (2006) [Pubmed]
  9. Increased serum cathepsin S in patients with atherosclerosis and diabetes. Liu, J., Ma, L., Yang, J., Ren, A., Sun, Z., Yan, G., Sun, J., Fu, H., Xu, W., Hu, C., Shi, G.P. Atherosclerosis (2006) [Pubmed]
  10. Lipopolysaccharide induces expression of genes encoding pro-inflammatory cytokines and the elastin-degrading enzyme, cathepsin S, in human cervical smooth-muscle cells. Watari, M., Watari, H., Nachamkin, I., Strauss, J.F. J. Soc. Gynecol. Investig. (2000) [Pubmed]
  11. Human cathepsin S gene (CTSS) promoter -25G/A polymorphism. Cao, H., Hegele, R.A. J. Hum. Genet. (2000) [Pubmed]
  12. Cathepsin S activity is detectable in human keratinocytes and is selectively upregulated upon stimulation with interferon-gamma. Schwarz, G., Boehncke, W.H., Braun, M., Schröter, C.J., Burster, T., Flad, T., Dressel, D., Weber, E., Schmid, H., Kalbacher, H. J. Invest. Dermatol. (2002) [Pubmed]
  13. Cross-class inhibition of the cysteine proteinases cathepsins K, L, and S by the serpin squamous cell carcinoma antigen 1: a kinetic analysis. Schick, C., Pemberton, P.A., Shi, G.P., Kamachi, Y., Cataltepe, S., Bartuski, A.J., Gornstein, E.R., Brömme, D., Chapman, H.A., Silverman, G.A. Biochemistry (1998) [Pubmed]
  14. 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]
  15. Phylogenetic conservation of cysteine proteinases. Cloning and expression of a cDNA coding for human cathepsin S. Wiederanders, B., Brömme, D., Kirschke, H., von Figura, K., Schmidt, B., Peters, C. J. Biol. Chem. (1992) [Pubmed]
  16. Molecular cloning and expression of human alveolar macrophage cathepsin S, an elastinolytic cysteine protease. Shi, G.P., Munger, J.S., Meara, J.P., Rich, D.H., Chapman, H.A. J. Biol. Chem. (1992) [Pubmed]
  17. Molecular cloning of human cathepsin O, a novel endoproteinase and homologue of rabbit OC2. Shi, G.P., Chapman, H.A., Bhairi, S.M., DeLeeuw, C., Reddy, V.Y., Weiss, S.J. FEBS Lett. (1995) [Pubmed]
  18. Amino acid substitutions in the N-terminal segment of cystatin C create selective protein inhibitors of lysosomal cysteine proteinases. Mason, R.W., Sol-Church, K., Abrahamson, M. Biochem. J. (1998) [Pubmed]
  19. 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]
  20. Lysosomal processing of amyloid precursor protein to A beta peptides: a distinct role for cathepsin S. Munger, J.S., Haass, C., Lemere, C.A., Shi, G.P., Wong, W.S., Teplow, D.B., Selkoe, D.J., Chapman, H.A. Biochem. J. (1995) [Pubmed]
  21. Study of the functional share of lysosomal cathepsins by the development of specific inhibitors. Katunuma, N., Matsui, A., Kakegawa, T., Murata, E., Asao, T., Ohba, Y. Adv. Enzyme Regul. (1999) [Pubmed]
  22. Expression and upregulation of cathepsin S and other early molecules required for antigen presentation in activated hepatic stellate cells upon IFN-gamma treatment. Maubach, G., Lim, M.C., Kumar, S., Zhuo, L. Biochim. Biophys. Acta (2007) [Pubmed]
  23. Pro-inflammatory cytokines induce expression of matrix-metabolizing enzymes in human cervical smooth muscle cells. Watari, M., Watari, H., DiSanto, M.E., Chacko, S., Shi, G.P., Strauss, J.F. Am. J. Pathol. (1999) [Pubmed]
  24. Comparison of cathepsins K and S expression within the rheumatoid and osteoarthritic synovium. Hou, W.S., Li, W., Keyszer, G., Weber, E., Levy, R., Klein, M.J., Gravallese, E.M., Goldring, S.R., Brömme, D. Arthritis Rheum. (2002) [Pubmed]
  25. Structural and functional characterization of two allelic variants of human cystatin D sharing a characteristic inhibition spectrum against mammalian cysteine proteinases. Balbín, M., Hall, A., Grubb, A., Mason, R.W., López-Otín, C., Abrahamson, M. J. Biol. Chem. (1994) [Pubmed]
  26. Structural basis for the biological specificity of cystatin C. Identification of leucine 9 in the N-terminal binding region as a selectivity-conferring residue in the inhibition of mammalian cysteine peptidases. Hall, A., Håkansson, K., Mason, R.W., Grubb, A., Abrahamson, M. J. Biol. Chem. (1995) [Pubmed]
  27. High-molecular-weight kininogen binds two molecules of cysteine proteinases with different rate constants. Turk, B., Stoka, V., Turk, V., Johansson, G., Cazzulo, J.J., Björk, I. FEBS Lett. (1996) [Pubmed]
  28. Structure and chromosomal assignment of the human cathepsin K gene. Gelb, B.D., Shi, G.P., Heller, M., Weremowicz, S., Morton, C., Desnick, R.J., Chapman, H.A. Genomics (1997) [Pubmed]
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