Enzyme Nomenclature. Recommendations 1992
Prepared on behalf of the advisory panel on peptidase nomenclature by Alan J. Barrett, The Babraham Institute, Cambridge CB2 4AT, England
This document contains further additions and amendments to Enzyme Nomenclature 1992, published by Academic Press, Orlando, Florida. Supplements 1, 2, 3, 4 and 5 were published in Eur. J. Biochem. 223 (1994) 1-5 , Eur. J. Biochem. 232 (1995) 1-6 , Eur. J. Biochem. 237 (1996) 1-5 , Eur. J. Biochem. 250 (1997) 1-6 and Eur. J. Biochem. 264 (1999) 610-650, plus the supplement 6. Families of peptidases are referred to by use of the numbering system of Rawlings & Barrett (Methods Enzymol. 244 (1994) 19-61 and 461-486; Methods Enzymol. 248 (1995) 105-120 and 183-228; MEROPS database at http://www.merops.ac.uk/). The full, amended text of subclass EC 3.4 (peptidases) of Enzyme Nomenclature 1992 may be found on the Internet at http://www.qmul.ac.uk/iubmb/enzyme/EC34/ or http://www.qmul.ac.uk/iubmb/enzyme/EC3/4/.Comments and suggestions on these entries should be sent to Alan J. Barrett (The Babraham Institute, Cambridge CB2 4AT, England). These entries were made public May 2001 and approved August 2001.
An asterisk before 'EC' indicates that this is an amendment to an existing enzyme rather than a new enzyme entry.
Recommended name: dipeptidase E
Reaction: Dipeptidase E catalyses the hydrolysis of dipeptides AspXaa. It does not act on peptides with N-terminal Glu, Asn or Gln, nor does it cleave isoaspartyl peptides
Other names: aspartyl dipeptidase; peptidase E; PepE gene product (Salmonella typhimurium)
Comments: A free carboxy group is not absolutely required in the substrate since Asp-Phe-NH2 and Asp-Phe-OMe are hydrolysed somewhat more slowly than dipeptides with free C-termini. No peptide larger than a C-blocked dipeptide is known to be a substrate. Asp-NH-Np is hydrolysed and is a convenient substrate for routine assay. The enzyme is most active near pH 7.0, and is not inhibited by di-isopropylfluorophosphate or phenylmethanesulfonyl fluoride. Belongs in peptidase family S51.
Links to other databases: MEROPS, PDB [1FYE]
1. Håkansson, K., Wang, A.H.J. and Miller, C.G. The structure of aspartyl dipeptidase reveals a unique fold with a Ser-His-Glu catalytic triad. Proc. Natl. Acad. Sci. USA 97 (2000) 14097-14102. [Medline UI: 20570438]
2. Lassy, R.A.L. and Miller, C.G. Peptidase E, a peptidase specific for N-terminal aspartic dipeptides, is a serine hydrolase. J. Bacteriol. 182 (2000) 2536-2543. [Medline UI: 20225853]
Recommended name: dipeptidyl-peptidase III
Reaction: Release of an N-terminal dipeptide from a peptide comprising four or more residues, with broad specificity. Also acts on dipeptidyl 2-naphthylamides.
Other names: dipeptidyl aminopeptidase III; dipeptidyl arylamidase III; enkephalinase B; red cell angiotensinase
Comments: A cytosolic peptidase that is active at neutral pH. It has broad activity on peptides, although it is highly selective for Arg-Arg-2-naphthylamide, at pH 9.2. Active in the hydrolysis of enkephalins. A metallopeptidase, the type example of peptidase family M49.
Links to other databases: BRENDA, EXPASY, MEROPS, CAS registry number: 77464-87-0
1. McDonald, J.K. Dipeptidyl-peptidase III. In: Barrett, A.J., Rawlings, N.D. and Woessner, J.F. (Eds.), Handbook of Proteolytic Enzymes, Academic Press, London, 1998, pp. 536-538.
2. Fukasawa, K., Fukasawa, K.M., Iwamoto, H., Hirose, J. and Harada, M. The HELLGH motif of rat liver dipeptidyl peptidase III is involved in zinc coordination and the catalytic activity of the enzyme. Biochemistry 38 (1999) 8299-8303. [Medline UI: 99315206]
Recommended name: tripeptidyl-peptidase I
Reaction: Release of an N-terminal tripeptide from a polypeptide, but also endopeptidase activity
Other names: tripeptidyl aminopeptidase; tripeptidyl peptidase
Comments: A lysosomal enzyme that is active at acidic pH. Deficient in classical late-infantile neuronal ceroid lipofuscinosis brain tissue. Belongs in peptidase family S53 (pseudomonapepsin family). Formerly included in EC 184.108.40.206, tripeptidyl peptidase.
Links to other databases: BRENDA, EXPASY, MEROPS, CAS registry number: 151662-36-1
1. Ezaki, J., Tanida, I., Kanehagi, N. and Kominami, E. A lysosomal proteinase, the late infantile neuronal ceroid lipofuscinosis gene (CLN2) product, is essential for degradation of a hydrophobic protein, the subunit c of ATP synthase. J. Neurochem. 72 (1999) 2573-2582. [Medline UI: 99277372]
2. Rawlings, N.D. and Barrett, A.J. Tripeptidyl-peptidase I is apparently the CLN2 protein absent in classical late-infantile neuronal ceroid lipofuscinosis. Biochim. Biophys. Acta 1429 (1999) 496-500. [Medline UI: 99143780]
3. Ezaki, J., Takeda-Ezaki, M., Oda, K. and Kominami, E. Characterization of endopeptidase activity of tripeptidyl peptidase-I/CLN2 protein which is deficient in classical late infantile neuronal ceroid lipofuscinosis. Biochem. Biophys. Res. Commun. 268 (2000) 904-908. [Medline UI: 20145532]
4. Junaid, M.A., Wu, G.X. and Pullarkat, R.K. Purification and characterization of bovine brain lysosomal pepstatin-insensitive proteinase, the gene product deficient in the human late-infantile neuronal ceroid lipofuscinosis. J. Neurochem. 74 (2000) 287-294. [Medline UI: 20083421]
5. Lin, L., Sohar, I., Lackland, H. and Lobel, P. The human CLN2 protein/tripeptidyl-peptidase I is a serine protease that autoactivates at acidic pH. J. Biol. Chem. 276 (2001) 2249-2255. [Medline UI: 21125791]
Recommended Name: spermosin
Reaction: Hydrolyses arginyl bonds, preferably with Pro in the P2 position
Comments: The enzyme from the ascidian (Prochordate) Halocynthia roretzi is localised in the sperm head, and released during sperm activation. A proline-rich region is involved in binding to the vitelline coat of the egg. Belongs in peptidase family S1 (trypsin family).
Links to other databases: MEROPS
1. Sawada, H., Yokosawa, H. and Ishii, S. Purification and characterization of two types of trypsin-like enzymes from sperm of the ascidian (Prochordata) Halocynthia roretzi. Evidence for the presence of spermosin, a novel acrosin-like enzyme. J. Biol. Chem. 259 (1984) 2900-2904. [Medline UI: 84135782]
2. Sawada, H., Yokosawa, H., Someno, T., Saino, T. and Ishii, S. Evidence for the participation of two sperm proteases, spermosin and acrosin, in fertilization of the ascidian, Halocynthia roretzi: inhibitory effects of leupeptin analogs on enzyme activities and fertilization. Dev. Biol. 105 (1984) 246-249. [Medline UI: 84286387]
3. Sawada, H., Iwasaki, K., Kihara-Negishi, F., Ariga, H. and Yokosawa, H. Localization, expression, and the role in fertilization of spermosin, an ascidian sperm trypsin-like protease. Biochem. Biophys. Res. Commun. 222 (1996) 499-504. [Medline UI: 96222532]
4. Sawada, H. and Someno, T. Substrate specificity of ascidian sperm trypsin-like proteases, spermosin and acrosin. Mol. Reprod. Dev. 45 (1996) 240-243. [Medline UI: 97071158]
Recommended name: pseudomonapepsin
Reaction: Hydrolysis of the B chain of insulin at -Glu13Ala-, -Leu15Tyr- and -Phe25Tyr-, and angiotensin I at -Tyr4Ile-. A good synthetic substrate is Lys-Pro-Ile-Glu-PhePhe(NO2)-Arg-Leu.
Other names: Pseudomonas sp. pepstatin-insensitive carboxyl proteinase
Comments: An enzyme secreted by Pseudomonas sp. No. 101. Optimum pH is 4. It is distinguished from xanthomonapepsin by its insensitivity to EPNP and from scytalidopepsin B by this property and by its unrelated amino-acid sequence. Inhibited by tyrostatin, a peptide aldehyde . Type example of peptidase family S53.
Links to other databases: BRENDA, EXPASY, MEROPS, CAS registry number:
1. Oda, K., Sugitani, M., Fukuhara, K. and Murao, S. Purification and properties of a pepstatin-insensitive carboxyl proteinase from a Gram-negative bacterium. Biochim. Biophys. Acta 923 (1987) 463-469. [Medline UI: 87157794]
2. Oda, K., Nakatani, H. and Dunn, B.M. Substrate specificity and kinetic properties of pepstatin-insensitive carboxyl proteinase from Pseudomonas sp. No. 101. Biochim. Biophys. Acta 1120 (1992) 208-214. [Medline UI: 92223080]
3. Wlodawer, A., Li, M., Dauter, Z., Gustchina, A., Uchida, K., Oyama, H., Dunn, B.M. & Oda,K. (2001) Carboxyl proteinase from Pseudomonas defines a novel family of subtilisin-like enzymes. Nat. Struct. Biol. 8 (2001) 442-446. [Medline UI: 21223584]
Recommended name: xanthomonapepsin
Reaction: Cleavage of casein
Other names: Xanthomonas aspartic proteinase
Comments: Secreted by the bacterium Xanthomonas sp. Belongs in peptidase family S53 (pseudomonapepsin family).
Links to other databases: BRENDA, EXPASY, MEROPS, CAS registry number: 113356-29-9
1. Oda, K., Nakazima, T., Terashita, T., Suzuki, K. and Murao, S. Purification and properties of an S-PI(pepstatin Ac)-insensitive carboxyl proteinase from a Xanthomonas sp. bacterium. Agric. Biol. Chem. 51 (1987) 3073-3080
Recommended name: C-terminal processing peptidase
Reaction: The enzyme shows specific recognition of a C-terminal tripeptide, Xaa-Yaa-Zaa, in which Xaa is preferably Ala or Leu, Yaa is preferably Ala or Tyr, and Zaa is preferably Ala, but then cleaves at a variable distance from the C-terminus. A typical cleavage is -Ala-AlaArg-Ala-Ala-Lys-Glu-Asn-Tyr-Ala-Leu-Ala-Ala. In the plant chloroplast, the enzyme removes the C-terminal extension of the D1 polypeptide of photosystem II
Other names: CtpA gene product (Synechocystis sp.); photosystem II D1 protein processing peptidase; protease Re; tail-specific protease; Tsp protease
Comments: Proteolytic processing of the D1 protein of photosystem II is necessary to allow the light-driven assembly of the tetranuclear manganese cluster, which is responsible for photosynthetic water oxidation. The recognition of the substrate is mediated by a PDZ domain, a small protein module that promotes protein-protein interactions by binding to internal or C-terminal sequences of their partner proteins. Type example of peptidase family S41.
Links to other databases: MEROPS; PDB [1FC6, 1FC7, 1FC9, 1FCF]
1. Keiler, K.C. and Sauer, R.T. Tsp protease. In: Barrett, A.J., Rawlings, N.D. and Woessner, J.F. (Eds.), Handbook of Proteolytic Enzymes, Academic Press, London, 1998, pp. 460-461.
2. Beebe, K.D., Shin, J.N., Peng, J., Chaudhury, C., Khera, J. and Pei, D.H. Substrate recognition through a PDZ domain in tail-specific protease. Biochemistry 39 (2000) 3149-3155. [Medline UI: 20181689]
3. Liao, D.I., Qian, J., Chisholm, D.A., Jordan, D.B. and Diner, B.A. Crystal structures of the photosystem II D1 C-terminal processing protease. Nat. Struct. Biol. 7 (2000) 749-753. [Medline UI: 20423080]
Recommended name: helper-component proteinase
Reaction: Hydrolyses a GlyGly bond at its own C-terminus, commonly in the sequence -Tyr-Xaa-Val-GlyGly, in the processing of the potyviral polyprotein
Other names: HC-Pro
Comments: Known from many potyviruses. The helper component-proteinase of the tobacco etch virus is a multifunctional protein with several known activities: the N-terminal region is required for aphid transmission and efficient genome amplification, the central region is required for long-distance movement in plants, and the C-terminal domain has cysteine endopeptidase activity. Type example of peptidase family C6.
Links to other databases: MEROPS
1. Kasschau, K.D. and Carrington, J.C. Requirement for HC-Pro processing during genome amplification of tobacco etch potyvirus. Virology 209 (1995) 268-273.
2. Verchot, J. Potyvirus helper component proteinase. In: Barrett, A.J., Rawlings, N.D. and Woessner, J.F. (Eds.), Handbook of Proteolytic Enzymes, Academic Press, London, 1998, pp. 677-679.
Recommended name: L-peptidase
Reaction: Autocatalytically cleaves itself from the polyprotein of the foot-and-mouth disease virus by hydrolysis of a LysGly bond, but then cleaves host cell initiation factor eIF-4G at bonds -GlyArg- and -LysArg-
Comments: Best known from foot-and-mouth disease virus, but occurs in other aphthoviruses and cardioviruses. Destruction of initiation factor eIF-4G has the effect of shutting off host-cell protein synthesis while allowing synthesis of viral proteins to continue. The tertiary structure reveals a distant relationship to papain and, consistent with this, compound E-64 is inhibitory. Type example of peptidase family C28.
Links to other databases: MEROPS; PDB [1QMY]
1 . Piccone, M.E., Zellner, M., Kumosinski, T.F., Mason, P.W. and Grubman, M.J. Identification of the active-site residues of the L proteinase of foot-and-mouth disease virus. J. Virol. 69 (1995) 4950-4956. [Medline UI: 95333275]
2. Guarné, A., Hampoelz, B., Glaser, W., Carpena, X., Torma, J., Fita, I. and Skern, T. Structural and biochemical features distinguish the foot-and-mouth disease virus leader proteinase from other papain-like enzymes. J. Mol. Biol. 302 (2000) 1227-1240. [Medline UI: 20500114]
[EC 220.127.116.11 Transferred entry: now EC 18.104.22.168, xanthomonapepsin (EC 22.214.171.124 created 1992, deleted 2001)]
[EC 126.96.36.199 Transferred entry: now EC 188.8.131.52, pseudomonapepsin (EC 184.108.40.206 created 1995, deleted 2001)]
Recommended name: prepilin peptidase
Reaction: Typically cleaves a -GlyPhe- bond to release an N-terminal, basic peptide of 5-8 residues from type IV prepilin, and then N-methylates the new N-terminal amino group, the methyl donor being S-adenosyl-L-methionine
Comments: Many species of bacteria carry pili on their cell surfaces. These are virulence determinants in pathogenic strains, and are assembled biosynthetically from type IV prepilin subunits. Before assembly, the prepilin molecules require proteolytic processing, which is done by the prepilin peptidase. Prepilin peptidase and its homologues play a central role not only in type IV pilus biogenesis but also in transport of macromolecules across cell membranes. Although both peptide-bond hydrolysis and N-methylation are catalysed by the same molecule, the methylation can be inhibited without affecting peptidase activity, and it is believed that the enzyme has two separate catalytic sites. Type example of peptidase family A24.
Links to other databases: MEROPS
1. Lory, S. and Strom, M.S. Structure-function relationship of type-IV prepilin peptidase of Pseudomonas aeruginosa - A review. Gene 192 (1997) 117-121. [Medline UI: 97368114]
2. LaPointe, C.F. and Taylor, R.K. The type 4 prepilin peptidases comprise a novel family of aspartic acid proteases. J. Biol. Chem. 275 (2000) 1502-1510. [Medline UI: 20092932]
Recommended name: nodavirus endopeptidase
Reaction: Hydrolysis of an asparaginyl bond involved in the maturation of the structural protein of the virus, typically -AsnAla- or -AsnPhe-
Other names: Black Beetle virus endopeptidase; Flock House virus endopeptidase
Comments: A single aspartic residue is critical for activity, and inhibition by EDTA indicates that a metal ion is also important. The enzyme is known from several nodaviruses that are pathogens of insects. Type example of peptidase family A6, and structurally related to the tetravirus endopeptidase in family A21, although in that family, the catalytic residue is thought to be Glu.
Links to other databases: MEROPS; PDB [2BBV]
1. Zlotnick, A., Reddy, V.S., Dasgupta, R., Schneemann, A., Ray,W.J., Jr., Rueckert, R.R. and Johnson, J.E. Capsid assembly in a family of animal viruses primes an autoproteolytic maturation that depends on a single aspartic acid residue. J. Biol. Chem. 269 (1994) 13680-13684. [Medline UI: 94230483]
2. Johnson, J.E. and Schneemann, A. Nodavirus endopeptidase. In: Barrett, A.J., Rawlings, N.D. and Woessner, J.F. (Eds.), Handbook of Proteolytic Enzymes, Academic Press, London, 1998, pp. 964-967.
Recommended name: snapalysin
Reaction: Hydrolyses proteins with a preference for Tyr or Phe in the P1' position. Has no action on amino-acid p-nitroanilides
Other names: small neutral protease; SnpA gene product (Streptomyces lividans)
Comments: Type example of peptidase family M7.
Links to other databases: MEROPS; PDB [1KUH]
1. Kurisu, G., Sugimoto, A., Harada, S., Takagi, M., Imanaka, T. and Kai, Y. Characterization of a small metalloprotease from Streptomyces caespitosus with high specificity to aromatic residues. J. Ferment. Bioeng. 83 (1997) 590-592.
2. Butler, M.J. Snapalysin. In: Barrett, A.J., Rawlings, N.D. and Woessner, J.F. (Eds.), Handbook of Proteolytic Enzymes, Academic Press, London, 1998, pp. 1134-1135.
3. Kurisu, G., Kai, Y. and Harada, S. Structure of the zinc-binding site in the crystal structure of a zinc endoprotease from Streptomyces caespitosus at 1 Å resolution. J. Inorg. Biochem. 82 (2000) 225-228. [Medline UI: 21018692]