Summary
The known cysteine peptidases have been classified into 35 sequence families. We argue that these have arisen from at least five separate evolutionary origins, each of which is represented by a set of one or more modern-day families, termed a clan. Clan CA is the largest, containing the papain family, C1, and others with the Cys/His catalytic dyad. Clan CB (His/Cys dyad) contains enzymes from RNA viruses that are distantly related to chymotrypsin. The peptidases of clan CC are also from RNA viruses, but have papain-like Cys/His catalytic sites. Clans CD and CE contain only one family each, those of interleukin-1β-converting enzyme and adenovirus L3 proteinase, respectively. A few families cannot yet be assigned to clans. In view of the number of separate origins of enzymes of this type, one should be cautious in generalising about the catalytic mechanisms and other properties of cysteine peptidases as a whole. In contrast, it may be safer to generalise for enzymes within a single family or clan.
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Morikawa, M., Izawa, Y., Rashid, N., Hoaki, T. and Imanaka, T., Appl. Environ. Microbiol., 60 (1994) 4559.
Fusi, P., Villa, M., Burlini, N., Tortora, P. and Guerritore, A., Experientia, 47 (1991) 1057.
Light, A., Frater, R., Kimmel, J.R. and Smith, E.L., Proc. Natl. Acad. Sci. USA, 52 (1964) 1276.
Barrett, A.J., Methods Enzymol., 244 (1994) 1.
Kamphuis, I.G., Kalk, K.H., Swarte, M.B.A. and Drenth, J., J. Mol. Biol., 179 (1984) 233.
Allaire, M., Chernaia, M.M., Malcolm, B.A. and James, M.N.G., Nature, 369 (1994) 72.
Walker, N.P.C., Talanian, R.V., Brady, K.D., Dang, L.C., Bump, N.J., Ferenz, C.R., Franklin, S., Ghayur, T., Hackett, M.C., Hammill, L.D., Herzog, L., Hugunin, M., Houy, W., Mankovich, J.A., McGuiness, L., Orlewicz, E., Paskind, M., Pratt, C.A., Reis, P., Summani, A., Terranova, M., Welch, J.P., Xiong, L. and Möller, A., Cell, 78 (1994) 343.
Wilson, K.P., Black, J.F., Thomson, J.A., Kim, E.E., Griffith, J.P., Navia, M.A., Murcko, M.A., Chambers, S.P., Aldape, R.A., Raybuck, S.A. and Livingston, D.J., Nature, 370 (1994) 270.
Ding, J.Z., McGrath, W.J., Sweet, R.M. and Mangel, W.F., EMBO J., 15 (1996) 1778.
Storer, A.C. and Ménard, R., Methods Enzymol., 244 (1994) 486.
Halász, P. and Polgár, L., Eur. J. Biochem., 79 (1977) 491.
Kembhavi, A.A., Buttle, D.J., Rauber, P. and Barrett, A.J., FEBS Lett., 283 (1991) 277.
Csoma, C. and Polgár, L., Biochem. J., 222 (1984) 769.
Kembhavi, A.A., Buttle, D.J., Knight, C.G. and Barrett, A.J., Arch. Biochem. Biophys., 303 (1993) 208.
Joshua-Tor, L., Xu, H.E., Johnston, S.A. and Rees, D.C., Science, 269 (1995) 945.
Stanley Jr., S.L., Zhang, T., Rubin, D. and Li, E., Infect. Immun., 63 (1995) 1587.
Rosenthal, P.J., Exp. Parasitol., 80 (1995) 272.
Reed, S.L., Ember, J.A., Herdman, D.S., DiScipio, R.G., Hugli, T.E. and Gigli, I., J. Immunol., 155 (1995) 266.
Leao, S.D., Lang, T., Prina, E., Hellio, R. and Antoine, J.C., J. Cell Sci., 108 (1995) 3219.
Lah, T.T., Hawley, M., Rock, K.L. and Goldberg, A.L., FEBS Lett., 363 (1995) 85.
Lee, E.R., Lamplugh, L., Shepard, N.L. and Mort, J.S., J. Histochem. Cytochem., 43 (1995) 525.
Saneshige, S., Mano, H., Tezuka, K., Kakudo, S., Mori, Y., Honda, Y., Itabashi, A., Yamada, T., Miyata, K., Hakeda, Y., Ishii, J. and Kumegawa, M., Biochem. J., 309 (1995) 721.
Jean, D., Bar-Eli, M., Huang, S.Y., Xie, K.P., Rodrigues-Lima, F., Hermann, J. and Frade, R., Cancer Res., 56 (1996) 254.
Marks, N., Berg, M.J., Sapirstein, V.S., Durrie, R., Swistok, J., Makofske, R.C. and Danho, W., Int. J. Pept. Protein Res., 46 (1995) 306.
Munger, J.S., Haass, C., Lemere, C.A., Shi, G.P., Wong, W.S.F., Teplow, D.B., Selkoe, D.J. and Chapman, H.A., Biochem. J., 311 (1995) 299.
Yamada, T., Liepnieks, J.J., Kluve-Beckerman, B. and Benson, M.D., Scand. J. Immunol., 41 (1995) 94.
Lanier, L.M., Slack, J.M. and Volkman, L.E., Virology, 216 (1996) 380.
Vanderklish, P., Saido, T.C., Gall, C., Arai, A. and Lynch, G., Mol. Brain Res., 32 (1995) 25.
Du, X.P., Saido, T.C., Tsubuki, S., Indig, F.E., Williams, M.J. and Ginsberg, M.H., J. Biol. Chem., 270 (1995) 26146.
Bartus, R.T., Elliott, P.J., Hayward, N.J., Dean, R.L., Harbeson, S., Straub, J.A., Li, Z. and Powers, J.C., Neurol. Res., 17 (1995) 249.
Balcerzak, D., Poussard, S., Brustis, J.J., Elamrani, N., Soriano, M., Cottin, P. and Ducastaing, A., J. Cell Sci., 108 (1995) 2077.
Sorimachi, H., Kinbara, K., Kimura, S., Takahashi, M., Ishiura, S., Sasagawa, N., Sorimachi, N., Shimada, H., Tagawa, K., Maruyama, K. and Suzuki, K., J. Biol. Chem., 270 (1995) 31158.
Shanley, T.P., Schrier, D., Kapur, V., Kehoe, M., Musser, J.M. and Ward, P.A., Infect. Immun., 64 (1996) 870.
Bazan, J.F. and Fletterick, R.J., Proc. Natl. Acad. Sci. USA, 85 (1988) 7872.
Matthews, D.A., Smith, W.W., Ferre, R.A., Condon, B., Budahazi, G., Sisson, W., Villafranca, J.E., Janson, C.A., McElroy, H.E., Gribskov, C.L. and Worland, S., Cell, 77 (1994) 761.
Lamphear, B.J., Kirchweger, R., Skern, T. and Rhoads, R.E., J. Biol. Chem., 270 (1995) 21975.
Joachims, M., Harris, K.S. and Etchison, D., Virology, 211 (1995) 451.
Kirchweger, R., Ziegler, E., Lamphear, B.J., Waters, D., Liebig, H.D., Sommergruber, W., Sobrino, F., Hohenadl, C., Blaas, D., Rhoads, R.E. and Skern, T., J. Virol., 68 (1994) 5677.
Thornberry, N.A. and Molineaux, S.M., Protein Sci., 4 (1995) 3.
Schlegel, J., Peters, I., Orrenius, S., Miller, D.K., Thornberry, N.A., Yamin, T.T. and Nicholson, D.W., J. Biol. Chem., 271 (1996) 1841.
Mangel, W.F., McGrath, W.J., Toledo, D.L. and Anderson, C.W., Nature, 361 (1993) 274.
Webster, A., Hay, R.T. and Kemp, G., Cell, 72 (1993) 97.
Greber, U.F., Webster, P., Weber, J. and Helenius, A., EMBO J., 15 (1996) 1766.
Witte, V., Wolf, N., Diefenthal, T., Reipen, G. and Dargatz, H., J. Gen. Appl. Microbiol., 140 (1994) 1175.
Rawlings, N.D. and Barrett, A.J., Methods Enzymol., 244 (1994) 461.
Ciechanover, A., Biol. Chem. Hoppe-Seyler, 375 (1994) 565.
Papa, F.R. and Hochstrasser, M., Nature, 366 (1993) 313.
Hara-Nishimura, I., Shimada, T., Hiraiwa, N. and Nishimura, M., J. Plant Physiol., 145 (1995) 632.
Cornel, F.A. and Plaxton, W.C., Physiol. Plant, 91 (1994) 599.
Dalton, J.P. and Brindley, P.J., Parasitol. Today, 12 (1996) 125.
Imamura, T., Potempa, J., Pike, R.N. and Travis, J., Infect. Immun., 63 (1995) 1999.
Potempa, J. and Travis, J., Trends Microbiol., 3 (1995) 430.
Richardson, J.S., Methods Enzymol., 115 (1985) 359.
Kabsch, W. and Sander, C., Biopolymers, 22 (1983) 2577.
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Barrett, A.J., Rawlings, N.D. Families and clans of cysteine peptidases. Perspectives in Drug Discovery and Design 6, 1–11 (1996). https://doi.org/10.1007/BF02174042
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DOI: https://doi.org/10.1007/BF02174042