Skip to main content
Springer Nature - PMC COVID-19 Collection logoLink to Springer Nature - PMC COVID-19 Collection
. 1996;6(1):1–11. doi: 10.1007/BF02174042

Families and clans of cysteine peptidases

Alan J Barrett 1,, Neil D Rawlings 1
PMCID: PMC7104565  PMID: 32288275

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.

Keywords: Polymer, Cysteine, Cysteine Peptidase, Catalytic Site, Chymotrypsin

References

  • 1.Morikawa M., Izawa Y., Rashid N., Hoaki T., Imanaka T. Appl. Environ. Microbiol. 1994;60:4559–4559. doi: 10.1128/aem.60.12.4559-4566.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Fusi P., Villa M., Burlini N., Tortora P., Guerritore A. Experientia. 1991;47:1057–1057. [Google Scholar]
  • 3.Light A., Frater R., Kimmel J.R., Smith E.L. Proc. Natl. Acad. Sci. USA. 1964;52:1276–1276. doi: 10.1073/pnas.52.5.1276. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Barrett A.J. Methods Enzymol. 1994;244:1–1. doi: 10.1016/0076-6879(94)44003-4. [DOI] [PubMed] [Google Scholar]
  • 5.Kamphuis I.G., Kalk K.H., Swarte M.B.A., Drenth J. J. Mol. Biol. 1984;179:233–233. doi: 10.1016/0022-2836(84)90467-4. [DOI] [PubMed] [Google Scholar]
  • 6.Allaire M., Chernaia M.M., Malcolm B.A., James M.N.G. Nature. 1994;369:72–72. doi: 10.1038/369072a0. [DOI] [PubMed] [Google Scholar]
  • 7.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., Möller A. Cell. 1994;78:343–343. doi: 10.1016/0092-8674(94)90303-4. [DOI] [PubMed] [Google Scholar]
  • 8.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., Livingston D.J. Nature. 1994;370:270–270. doi: 10.1038/370270a0. [DOI] [PubMed] [Google Scholar]
  • 9.Ding J.Z., McGrath W.J., Sweet R.M., Mangel W.F. EMBO J. 1996;15:1778–1778. [PMC free article] [PubMed] [Google Scholar]
  • 10.Storer A.C., Ménard R. Methods Enzymol. 1994;244:486–486. doi: 10.1016/0076-6879(94)44035-2. [DOI] [PubMed] [Google Scholar]
  • 11.Halász P., Polgár L. Eur. J. Biochem. 1977;79:491–491. doi: 10.1111/j.1432-1033.1977.tb11832.x. [DOI] [PubMed] [Google Scholar]
  • 12.Kembhavi A.A., Buttle D.J., Rauber P., Barrett A.J. FEBS Lett. 1991;283:277–277. doi: 10.1016/0014-5793(91)80607-5. [DOI] [PubMed] [Google Scholar]
  • 13.Csoma C., Polgár L. Biochem. J. 1984;222:769–769. doi: 10.1042/bj2220769. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Kembhavi A.A., Buttle D.J., Knight C.G., Barrett A.J. Arch. Biochem. Biophys. 1993;303:208–208. doi: 10.1006/abbi.1993.1274. [DOI] [PubMed] [Google Scholar]
  • 15.Joshua-Tor L., Xu H.E., Johnston S.A., Rees D.C. Science. 1995;269:945–945. doi: 10.1126/science.7638617. [DOI] [PubMed] [Google Scholar]
  • 16.Stanley S.L., Jr., Zhang T., Rubin D., Li E. Infect. Immun. 1995;63:1587–1587. doi: 10.1128/iai.63.4.1587-1590.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Rosenthal P.J. Exp. Parasitol. 1995;80:272–272. doi: 10.1006/expr.1995.1033. [DOI] [PubMed] [Google Scholar]
  • 18.Reed S.L., Ember J.A., Herdman D.S., DiScipio R.G., Hugli T.E., Gigli I. J. Immunol. 1995;155:266–266. [PubMed] [Google Scholar]
  • 19.Leao S.D., Lang T., Prina E., Hellio R., Antoine J.C. J. Cell Sci. 1995;108:3219–3219. doi: 10.1242/jcs.108.10.3219. [DOI] [PubMed] [Google Scholar]
  • 20.Lah T.T., Hawley M., Rock K.L., Goldberg A.L. FEBS Lett. 1995;363:85–85. doi: 10.1016/0014-5793(95)00287-j. [DOI] [PubMed] [Google Scholar]
  • 21.Lee E.R., Lamplugh L., Shepard N.L., Mort J.S. J. Histochem. Cytochem. 1995;43:525–525. doi: 10.1177/43.5.7730591. [DOI] [PubMed] [Google Scholar]
  • 22.Saneshige S., Mano H., Tezuka K., Kakudo S., Mori Y., Honda Y., Itabashi A., Yamada T., Miyata K., Hakeda Y., Ishii J., Kumegawa M. Biochem. J. 1995;309:721–721. doi: 10.1042/bj3090721. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Jean D., Bar-Eli M., Huang S.Y., Xie K.P., Rodrigues-Lima F., Hermann J., Frade R. Cancer Res. 1996;56:254–254. [PubMed] [Google Scholar]
  • 24.Marks N., Berg M.J., Sapirstein V.S., Durrie R., Swistok J., Makofske R.C., Danho W. Int. J. Pept. Protein Res. 1995;46:306–306. doi: 10.1111/j.1399-3011.1995.tb00602.x. [DOI] [PubMed] [Google Scholar]
  • 25.Munger J.S., Haass C., Lemere C.A., Shi G.P., Wong W.S.F., Teplow D.B., Selkoe D.J., Chapman H.A. Biochem. J. 1995;311:299–299. doi: 10.1042/bj3110299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Yamada T., Liepnieks J.J., Kluve-Beckerman B., Benson M.D. Scand. J. Immunol. 1995;41:94–94. doi: 10.1111/j.1365-3083.1995.tb03538.x. [DOI] [PubMed] [Google Scholar]
  • 27.Lanier L.M., Slack J.M., Volkman L.E. Virology. 1996;216:380–380. doi: 10.1006/viro.1996.0073. [DOI] [PubMed] [Google Scholar]
  • 28.Vanderklish P., Saido T.C., Gall C., Arai A., Lynch G. Mol. Brain Res. 1995;32:25–25. doi: 10.1016/0169-328x(95)00057-y. [DOI] [PubMed] [Google Scholar]
  • 29.Du X.P., Saido T.C., Tsubuki S., Indig F.E., Williams M.J., Ginsberg M.H. J. Biol. Chem. 1995;270:26146–26146. doi: 10.1074/jbc.270.44.26146. [DOI] [PubMed] [Google Scholar]
  • 30.Bartus R.T., Elliott P.J., Hayward N.J., Dean R.L., Harbeson S., Straub J.A., Li Z., Powers J.C. Neurol. Res. 1995;17:249–249. doi: 10.1080/01616412.1995.11740322. [DOI] [PubMed] [Google Scholar]
  • 31.Balcerzak D., Poussard S., Brustis J.J., Elamrani N., Soriano M., Cottin P., Ducastaing A. J. Cell Sci. 1995;108:2077–2077. doi: 10.1242/jcs.108.5.2077. [DOI] [PubMed] [Google Scholar]
  • 32.Sorimachi H., Kinbara K., Kimura S., Takahashi M., Ishiura S., Sasagawa N., Sorimachi N., Shimada H., Tagawa K., Maruyama K., Suzuki K. J. Biol. Chem. 1995;270:31158–31158. doi: 10.1074/jbc.270.52.31158. [DOI] [PubMed] [Google Scholar]
  • 33.Shanley T.P., Schrier D., Kapur V., Kehoe M., Musser J.M., Ward P.A. Infect. Immun. 1996;64:870–870. doi: 10.1128/iai.64.3.870-877.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34.Bazan J.F., Fletterick R.J. Proc. Natl. Acad. Sci. USA. 1988;85:7872–7872. doi: 10.1073/pnas.85.21.7872. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 35.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., Worland S. Cell. 1994;77:761–761. doi: 10.1016/0092-8674(94)90059-0. [DOI] [PubMed] [Google Scholar]
  • 36.Lamphear B.J., Kirchweger R., Skern T., Rhoads R.E. J. Biol. Chem. 1995;270:21975–21975. doi: 10.1074/jbc.270.37.21975. [DOI] [PubMed] [Google Scholar]
  • 37.Joachims M., Harris K.S., Etchison D. Virology. 1995;211:451–451. doi: 10.1006/viro.1995.1427. [DOI] [PubMed] [Google Scholar]
  • 38.Kirchweger R., Ziegler E., Lamphear B.J., Waters D., Liebig H.D., Sommergruber W., Sobrino F., Hohenadl C., Blaas D., Rhoads R.E., Skern T. J. Virol. 1994;68:5677–5677. doi: 10.1128/jvi.68.9.5677-5684.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 39.Thornberry N.A., Molineaux S.M. Protein Sci. 1995;4:3–3. doi: 10.1002/pro.5560040102. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 40.Schlegel J., Peters I., Orrenius S., Miller D.K., Thornberry N.A., Yamin T.T., Nicholson D.W. J. Biol. Chem. 1996;271:1841–1841. doi: 10.1074/jbc.271.4.1841. [DOI] [PubMed] [Google Scholar]
  • 41.Mangel W.F., McGrath W.J., Toledo D.L., Anderson C.W. Nature. 1993;361:274–274. doi: 10.1038/361274a0. [DOI] [PubMed] [Google Scholar]
  • 42.Webster A., Hay R.T., Kemp G. Cell. 1993;72:97–97. doi: 10.1016/0092-8674(93)90053-s. [DOI] [PubMed] [Google Scholar]
  • 43.Greber U.F., Webster P., Weber J., Helenius A. EMBO J. 1996;15:1766–1766. [PMC free article] [PubMed] [Google Scholar]
  • 44.Witte V., Wolf N., Diefenthal T., Reipen G., Dargatz H. J. Gen. Appl. Microbiol. 1994;140:1175–1175. doi: 10.1099/13500872-140-5-1175. [DOI] [PubMed] [Google Scholar]
  • 45.Rawlings N.D., Barrett A.J. Methods Enzymol. 1994;244:461–461. doi: 10.1016/0076-6879(94)44034-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 46.Ciechanover A. Biol. Chem. Hoppe-Seyler. 1994;375:565–565. doi: 10.1515/bchm3.1994.375.9.565. [DOI] [PubMed] [Google Scholar]
  • 47.Papa F.R., Hochstrasser M. Nature. 1993;366:313–313. doi: 10.1038/366313a0. [DOI] [PubMed] [Google Scholar]
  • 48.Hara-Nishimura I., Shimada T., Hiraiwa N., Nishimura M. J. Plant Physiol. 1995;145:632–632. [Google Scholar]
  • 49.Cornel F.A., Plaxton W.C. Physiol. Plant. 1994;91:599–599. [Google Scholar]
  • 50.Dalton J.P., Brindley P.J. Parasitol. Today. 1996;12:125–125. doi: 10.1016/0169-4758(96)80676-4. [DOI] [PubMed] [Google Scholar]
  • 51.Imamura T., Potempa J., Pike R.N., Travis J. Infect. Immun. 1995;63:1999–1999. doi: 10.1128/iai.63.5.1999-2003.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 52.Potempa J., Travis J. Trends Microbiol. 1995;3:430–430. doi: 10.1016/s0966-842x(00)88996-9. [DOI] [PubMed] [Google Scholar]
  • 53.Richardson J.S. Methods Enzymol. 1985;115:359–359. doi: 10.1016/0076-6879(85)15026-3. [DOI] [PubMed] [Google Scholar]
  • 54.Kabsch W., Sander C. Biopolymers. 1983;22:2577–2577. doi: 10.1002/bip.360221211. [DOI] [PubMed] [Google Scholar]

Articles from Perspectives in Drug Discovery and Design are provided here courtesy of Nature Publishing Group

RESOURCES