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Gene Review

CTSH  -  cathepsin H

Homo sapiens

Synonyms: ACC-4, ACC-5, CPSB, Pro-cathepsin H, minichain
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Disease relevance of CTSH


Psychiatry related information on CTSH


High impact information on CTSH

  • It inhibits two other cysteine proteases, cathepsin H and papain, but to much lesser extent [7].
  • We have determined the subcellular distribution of this enzyme and three additional lysosomal hydrolases (cathepsin H, beta-hexosaminidase, and beta-glucuronidase) in normal murine liver and six metastatic variants of the B16 melanoma [8].
  • Faint staining of cathepsin H was also seen at the sites of rimmed vacuoles [9].
  • Amino acid sequence comparison revealed that oryzains alpha and beta are similar not only to each other (70% similarity) but also to actinidin and papain (about 50%), whereas oryzain gamma was rather similar to aleurain (85%) and cathepsin H (60%) [10].
  • The three oryzains are similar to one another and also to other known cysteine proteinases such as papain and cathepsin H with respect to the sequences around the active site residues and the COOH-terminal Trp-rich region [10].

Biological context of CTSH


Anatomical context of CTSH


Associations of CTSH with chemical compounds

  • Cathepsin H is a lysosomal cysteine protease that may participate in tumor progression [3].
  • Cathepsin L and cathepsin H were assayed in the presence of dithiothreitol and Na2EDTA (2 mM each) with Z-Phe-Arg-NHMec (pH 5.5) and Lys-NNa (pH 6.5) respectively [20].
  • Both proteinases are inhibited by traditional inhibitors of cysteine proteinases and E-64, but leupeptin turned to be more effective inhibitor of cathepsin L (Ki = 2.4 nM) than of cathepsin H (Ki = 9.2 microM), the latter enzyme being sensitive to puromycin and benzethonium chloride as well.(ABSTRACT TRUNCATED AT 250 WORDS)[20]
  • In comparison to normal sera, cathepsin H concentrations were elevated in all asthmatic patients, concentrations of both stefins were decreased in steroid-independent asthmatics, and stefin A concentrations were increased in steroid-dependent asthmatics before therapy [21].
  • The enzyme is stable over the pH range 5-7.5, whereas it becomes inactive on heating to 50 degrees C. Cathepsin H of human placenta, like the enzyme from other sources, hydrolyses protein and naphthylamide substrates, showing within the latter group the strongest preference towards arginine-beta-naphthylamide (pH optimum 6.8) [4].

Physical interactions of CTSH


Regulatory relationships of CTSH


Other interactions of CTSH

  • The approach of stefin A to cathepsin H induces structural changes along the interaction surface of both molecules, whereas no such changes were observed in the stefin B-papain complex [12].
  • The introduction of a charged residue into S2 (variant V10R) created a more specific inhibitor to distinguish cathepsin B from cathepsin H [27].
  • Exclusion of the COL1A2 and CTSH genes was possible in the large family that was analysed separately [11].
  • 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) [28].
  • Such N-terminal truncation of cystatin C caused >300-fold lower inhibition of papain, cathepsin B, L and K, whereas the cathepsin H activity was compromised by a factor of ca. 10. Similarly, truncation of cystatin D caused alleviated inhibition of all endogenous target enzymes investigated [29].

Analytical, diagnostic and therapeutic context of CTSH


  1. Analysis of a truncated form of cathepsin H in human prostate tumor cells. Waghray, A., Keppler, D., Sloane, B.F., Schuger, L., Chen, Y.Q. J. Biol. Chem. (2002) [Pubmed]
  2. Cysteine proteinase cathepsin H in tumours and sera of lung cancer patients: relation to prognosis and cigarette smoking. Schweiger, A., Staib, A., Werle, B., Krasovec, M., Lah, T.T., Ebert, W., Turk, V., Kos, J. Br. J. Cancer (2000) [Pubmed]
  3. Serum cathepsin H as a potential prognostic marker in patients with colorectal cancer. Schweiger, A., Christensen, I.J., Nielsen, H.J., Sørensen, S., Brünner, N., Kos, J. Int. J. Biol. Markers (2004) [Pubmed]
  4. Cathepsin H from human placenta. Sawicki, G., Warwas, M. Acta Biochim. Pol. (1989) [Pubmed]
  5. Immunocytochemical localization of cathepsins B and H in human pancreatic endocrine cells and insulinoma cells. Im, B., Kominami, E., Grube, D., Uchiyama, Y. Histochemistry (1989) [Pubmed]
  6. Comparison of cathepsin protease activities in brain tissue from normal cases and cases with Alzheimer's disease, Lewy body dementia, Parkinson's disease and Huntington's disease. Mantle, D., Falkous, G., Ishiura, S., Perry, R.H., Perry, E.K. J. Neurol. Sci. (1995) [Pubmed]
  7. 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]
  8. Properties of a plasma membrane-associated cathepsin B-like cysteine proteinase in metastatic B16 melanoma variants. Rozhin, J., Robinson, D., Stevens, M.A., Lah, T.T., Honn, K.V., Ryan, R.E., Sloane, B.F. Cancer Res. (1987) [Pubmed]
  9. 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]
  10. Molecular cloning and gibberellin-induced expression of multiple cysteine proteinases of rice seeds (oryzains). Watanabe, H., Abe, K., Emori, Y., Hosoyama, H., Arai, S. J. Biol. Chem. (1991) [Pubmed]
  11. Genetic linkage of candidate genes in families with abdominal aortic aneurysms? van Vlijmen-van Keulen, C.J., Vahl, A.C., Hennekam, R.C., Rauwerda, J.A., Pals, G. European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery. (2003) [Pubmed]
  12. Crystal structure of Stefin A in complex with cathepsin H: N-terminal residues of inhibitors can adapt to the active sites of endo- and exopeptidases. Jenko, S., Dolenc, I., Guncar, G., Dobersek, A., Podobnik, M., Turk, D. J. Mol. Biol. (2003) [Pubmed]
  13. 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]
  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. Human cathepsin H: deletion of the mini-chain switches substrate specificity from aminopeptidase to endopeptidase. Dodt, J., Reichwein, J. Biol. Chem. (2003) [Pubmed]
  16. Identification of candidate predictive markers of anticancer drug sensitivity using a panel of human cancer cell lines. Dan, S., Shirakawa, M., Mukai, Y., Yoshida, Y., Yamazaki, K., Kawaguchi, T., Matsuura, M., Nakamura, Y., Yamori, T. Cancer Sci. (2003) [Pubmed]
  17. Prognostic value of cathepsins B, H, L, D and their endogenous inhibitors stefins A and B in head and neck carcinoma. Budihna, M., Strojan, P., Smid, L., Skrk, J., Vrhovec, I., Zupevc, A., Rudolf, Z., Zargi, M., Krasovec, M., Svetic, B., Kopitar-Jerala, N., Kos, J. Biol. Chem. Hoppe-Seyler (1996) [Pubmed]
  18. Imbalance between cysteine proteases and inhibitors in a baboon model of bronchopulmonary dysplasia. Altiok, O., Yasumatsu, R., Bingol-Karakoc, G., Riese, R.J., Stahlman, M.T., Dwyer, W., Pierce, R.A., Bromme, D., Weber, E., Cataltepe, S. Am. J. Respir. Crit. Care Med. (2006) [Pubmed]
  19. Involvement of cathepsin B in the motor neuron degeneration of amyotrophic lateral sclerosis. Kikuchi, H., Yamada, T., Furuya, H., Doh-ura, K., Ohyagi, Y., Iwaki, T., Kira, J. Acta Neuropathol. (2003) [Pubmed]
  20. Human and bovine brain cathepsin L and cathepsin H: purification, physico-chemical properties, and specificity. Azaryan, A., Galoyan, A. Neurochem. Res. (1987) [Pubmed]
  21. 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]
  22. Elongation on the amino-terminal part of stefin B decreases inhibition of cathepsin H. Jerala, R., Kroon-Zitko, L., Popovic, T., Turk, V. Eur. J. Biochem. (1994) [Pubmed]
  23. Abnormal cathepsin B activity in Batten disease. Dawson, G., Glaser, P.T. American journal of medical genetics. Supplement. (1988) [Pubmed]
  24. Alterations in cathepsin H activity and protein patterns in human colorectal carcinomas. del Re, E.C., Shuja, S., Cai, J., Murnane, M.J. Br. J. Cancer (2000) [Pubmed]
  25. Cathepsins in basal cell carcinomas: activity, immunoreactivity and mRNA staining of cathepsins B, D, H and L. Fröhlich, E., Möhrle, M., Klessen, C. Arch. Dermatol. Res. (2004) [Pubmed]
  26. Human kidney cathepsins B and H activate and lower the molecular weight of human inactive renin. Luetscher, J.A., Bialek, J.W., Grislis, G. Clinical and experimental hypertension. Part A, Theory and practice. (1982) [Pubmed]
  27. 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]
  28. Structural and functional aspects of papain-like cysteine proteinases and their protein inhibitors. Turk, B., Turk, V., Turk, D. Biol. Chem. (1997) [Pubmed]
  29. Down-regulation of human extracellular cysteine protease inhibitors by the secreted staphylococcal cysteine proteases, staphopain A and B. Vincents, B., Onnerfjord, P., Gruca, M., Potempa, J., Abrahamson, M. Biol. Chem. (2007) [Pubmed]
  30. Demonstration of cathepsins B, H and L in xenografts of normal and Duchenne-muscular-dystrophy muscles transplanted into nude mice. Takeda, A., Jimi, T., Wakayama, Y., Misugi, N., Miyake, S., Kumagai, T. Biochem. J. (1992) [Pubmed]
  31. Molecular cloning and sequencing of a cDNA coding for mature human kidney cathepsin H. Fuchs, R., Machleidt, W., Gassen, H.G. Biol. Chem. Hoppe-Seyler (1988) [Pubmed]
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