Yaa-, in which Xaa is preferably D-Ala, D-Ser or D-Thr. D-Amino acid amides and methyl esters also are hydrolysed, as is glycine amideEnzyme Nomenclature. Recommendations 1992
Prepared on behalf of the advisory panel on peptidase nomenclature by Alan J. Barrett, The Babraham Institute, Cambridge, England.
This supplement is as close as possible to the published version [see Eur. J. Biochem., 1994, 223, 1-5]. If you need to cite this supplement please quote this references as its source.
This document contains additions and amendments to Enzyme Nomenclature (1992), published by Academic Press, Orlando, Florida.
Comments and suggestions on enzyme classification and nomenclature may be sent to Prof. K. F. Tipton, Department of Biochemistry, Trinity College, Dublin, Dublin 2, Ireland.
3.4.11.19 D-Stereospecific aminopeptidase
Reaction: Release of an N-terminal D-amino acid from a peptide, XaaYaa-, in which Xaa is preferably D-Ala, D-Ser or D-Thr. D-Amino acid amides and methyl esters also are hydrolysed, as is glycine amide
Comments: A thiol-dependent peptidase known from the bacterium Ochrobactrum anthropi. A homologue of serine-type D-Ala-D-Ala carboxypeptidase (EC 3.4.16.4). Not metal dependent; probably has serine at the active centre [2].
References:
1. Asano, Y., Nakazawa, A., Kato, Y. & Kondo, K. (1989) J. Biol. Chem. 264, 14233-14239
2. Asano, Y., Kato, Y., Yamada, A. & Kondo, K. (1992) Biochemistry 31, 2316-2328
[3.4.16.1 Transferred entry: now EC 3.4.16.5 - Carboxypeptidase C, and EC 3.4.16.6 - Carboxypeptidase D]
[3.4.16.3 Transferred entry: now included with EC 3.4.16.5 - Carboxypeptidase C]
3.4.16.5 Carboxypeptidase C
Reaction: Release of a C-terminal amino acid with broad specificity
Other Names: Carboxypeptidase Y; Serine carboxypeptidase I; Cathepsin A; Lysosomal protective protein; Deamidase; Lysosomal carboxypeptidase A; Phaseolin
Comments: Carboxypeptidase with optimum pH 4.5-6.0, inhibited by diisopropyl fluorophosphate, and sensitive to thiol-blocking reagents (reviewed in [1]). Widely distributed in eukaryotes. Not a homologue of chymotrypsin or subtilisin. Formerly EC 3.4.12.1 and 3.4.21.13, and included in EC 3.4.16.1. This enzyme is probably also identical to lysosomal tyrosine carboxypeptidase, formerly EC 3.4.16.3
References:
1. Breddam, K. (1986) Carlsberg Res. Commun. 51, 83-128
2. Valls, L.A., Hunter, C.P., Rothman, J.H. & Stevens, T.H. (1987) Cell 48, 887-897
3. Jackman, H.L., Morris, P.W., Deddish, P.A., Skidgel, R.A. & Erdös, E.G. (1992) J. Biol. Chem. 267, 2872-2875
4. Miller, J.J., Changaris, D.G. & Levy, R.S. (1992) J. Chromatogr. 627, 153-162
3.4.16.6 Carboxypeptidase D
Reaction: Preferential release of a C-terminal arginine or lysine residue
Other Names: Cereal serine carboxypeptidase II; Saccharomyces cerevisiae KEX1 gene product
Comments: Carboxypeptidase with optimum pH 4.5-6.0, inhibited by diisopropyl fluorophosphate, and sensitive to thiol-blocking reagents (reviewed in [1]). A homologue of carboxypeptidase C. Formerly EC 3.4.12.1 and 3.4.21.13, and included in EC 3.4.16.1
References:
1. Breddam, K. (1986) Carlsberg Res. Commun. 51, 83-128
2. Breddam, K., Sørensen, S.B. & Svendsen, I. (1987) Carlsberg Res. Commun. 52, 297-311
3. Dmochowska, A., Dignard, D., Henning, D., Thomas, D.Y. & Bussey, H. (1987) Cell 50, 573-584
4. Liao, D.-I., Breddam, K., Sweet, R.M., Bullock, T. & Remington, S.J. (1992) Biochemistry 31, 9796-9812
3.4.17.18 Carboxypeptidase T
Reaction: Releases a C-terminal residue, which may be hydrophobic or positively charged
Comments: A homologue of carboxypeptidase A known from Thermoactinomyces vulgaris.
References:
1. Osterman, A.L., Stepanov, V.M., Rudenskaya, G.N., Khodova, O.M., Tsaplina, I.A., Yakovleva, M.B. & Loginova, L.G. (1984) Biochemistry (USSR) 49, 292-301
2. Smulevitch, S.V., Osterman, A.L., Galperina, O.V., Matz, M.V., Zagnitko, O.P., Kadyrov, R.M., Tsaplina, I.A., Grishin, N.V., Chestukhina, G.G. & Stepanov, V.M. (1991) FEBS Lett. 291, 75-78
3. Teplyakov, A., Polyakov, K., Obmolova, G., Strokopytov, B., Kuranova, I., Osterman, A., Grishin, N., Smulevitch, S., Zagnitko, O., Galperina, O., Matz, M. & Stepanov, V. (1992) Eur. J. Biochem. 208, 281-288
3.4.21.75 Furin
Reaction: Release of mature proteins from their proproteins by cleavage of -Arg-Xaa-Yaa-Arg bonds, where Xaa can by any amino acid and Yaa is Arg or Lys. Releases albumin, complement component C3 and von Willebrand factor from their respective precursors
Other Names: Prohormone convertase; Dibasic processing enzyme
Comments: One of a group of subtilisin homologues structurally and functionally similar to kexin. All are activated by Ca2+, contain Cys near the active site His, and inhibited by p-mercuribenzoate. At least three related enzymes are recognized in mammals: PC2, PC3 and PC4, which have somewhat different specificities
References:
1. Van de Ven, W.J.M., Voorberg, J., Fontijn, R., Pannekoek, H., van den Ouweland, A.M.W., van Duijnhoven, H.L.P., Roebroek, A.J.M. & Siezen, R.J. (1990) Mol. Biol. Rep. 14, 265-275
2. Van de Ven, W.J.M., Creemers, J.W.M. & Roebroek, A.J.M. (1991) Enzyme 45, 257-270
3. Hatsuzawa, K., Murakami, K. & Nakayama, K. (1992) J. Biochem. (Tokyo) 111, 296-301
4. Seidah, N.G. & Chrétien, M. (1992) Trends Endocrinol. Metab. 3, 133-140
5. Steiner, D.F., Smeekens, S.P., Ohagi, S. & Chan, S.J. (1992) J. Biol. Chem. 267, 23435-23438
3.4.21.76 Myeloblastin
Reaction: Hydrolysis of proteins, including elastin, by preferential cleavage: -Ala > -Val
Other Names: Leukocyte proteinase 3; Leukocyte proteinase 4; Wegener's granulomatosis autoantigen
Comments: From polymorphonuclear leukocyte granules. A homologue of chymotrypsin. Not inhibited by secretory leukocyte proteinase inhibitor
References:
1. Labbaye, C., Musette, P. & Cayre, Y.E. (1991) Proc. Natl. Acad. Sci. USA 88, 9253-9256
2. Rao, N.V., Wehner, N.G., Marshall, B.C., Gray, W.R., Gray, B.H. & Hoidal, J.R. (1991) J. Biol. Chem. 266, 9540-9548
3. Brubaker, M.J., Groutas, W.C., Hoidal, J.R. & Rao, N.V. (1992) Biochem. Biophys. Res. Commun. 188, 1318-1324
4. Kam, C.-M., Kerrigan, J.E., Dolman, K.M., Goldschmeding, R., von dem Borne, A.E.G.K. & Powers, J.C. (1992) FEBS Lett. 297, 119-123
3.4.21.77 Semenogelase
Reaction: Preferential cleavage: -Tyr
Other Names: Prostate-specific antigen; γ-Seminoprotein; Seminin; P-30 antigen
Comments: A chymotrypsin homologue from seminal plasma. Slowly inhibited by α1-antichymotrypsin
References:
1. Digby, M., Zhang, X.- Y. & Richards, R.I. (1989) Nucleic Acids Res. 15, 2137 only
2. Christensson, A., Laurell, C.-B. & Lilja, H. (1990) Eur. J. Biochem. 194, 755-763
3.4.21.78 Granzyme A
Reaction: Hydrolysis of proteins, including fibronectin, type IV collagen and nucleolin. Preferential cleavage: -Arg, -Lys >> -Phe in small molecule substrates
Other Names: CTLA3; HuTPS; T-cell associated protease 1
Comments: From cytotoxic T lymphocyte granules. A homologue of chymotrypsin. The human enzyme does not cleave Phe
References:
1. Simon, M.M., Hoschützky, H., Fruth, U., Simon, H.-G. & Kramer, M.D. (1986) EMBO J. 5, 3267-3274
2. Gershenfeld, H.K., Hershberger, R.J., Shows, T.B. & Weissman, I.L. (1988) Proc. Natl. Acad. Sci. USA 85, 1184-1188
3. Odake, S., Kam, C.-M., Narasimhan, L., Poe, M., Blake, J.T., Krahenbuhl, O., Tschopp, J. & Powers, J.C. (1991) Biochemistry 30, 2217-2227
3.4.21.79 Granzyme B
Reaction: Preferential cleavage: -Asp >> -Asn > -Met , -Ser
Other Names: CTLA1; CCPII
Comments: From cytotoxic T lymphocyte granules. A homologue of chymotrypsin
References:
1. Schmid, J. & Weissmann, C. (1987) J. Immunol. 139, 250-256
2. Odake, S., Kam, C.-M., Narasimhan, L., Poe, M., Blake, J.T., Krahenbuhl, O., Tschopp, J. & Powers, J.C. (1991) Biochemistry 30, 2217-2227
3. Poe, M., Blake, J.T., Boulton, D.A., Gammon, M., Sigal, N.H., Wu, J.K. & Zweerink, H.J. (1991) J. Biol. Chem. 266, 98-103
3.4.21.80 Streptogrisin A
Reaction: Hydrolysis of proteins with specificity similar to chymotrypsin
Other Names: Streptomyces griseus protease A
Comments: From Streptomyces griseus. A component of Pronase, and a homologue of α-lytic endopeptidase not inhibited by Tos-Phe-CH2Cl or ovomucoid
References:
1. Johnson, P. & Smillie, L.B. (1971) Can. J. Biochem. 49, 548-562
2. Sielecki, A.R., Hendrickson, W.A., Broughton, C.G., Delbaere, L.T.J., Brayer, G.D. & James, M.N.G. (1979) J. Mol. Biol. 134, 781- 804
3. James, M.N.G., Sielecki, A.R., Brayer, G.D., Delbaere, L.T.J. & Bauer, C.-A. (1980) J. Mol. Biol. 144, 43-88
4. Delbaere, L.T.J. & Brayer, G.D. (1985) J. Mol. Biol. 183, 89-103
5. Henderson, G., Krygsman, P., Liu, C.J., Davey, C.C. & Malek, L.T. (1987) J. Bacteriol. 169, 3778-3784
3.4.21.81 Streptogrisin B
Reaction: Hydrolysis of proteins with trypsin-like specificity
Other Names: Streptomyces griseus protease B
Comments: From Streptomyces griseus. A component of Pronase, and a homologue of α-lytic endopeptidase, distinct from Streptomyces trypsin
References:
1. Jurasek, L., Fackre, D. & Smillie, L.B. (1969) Biochem. Biophys. Res. Commun. 37, 99-105
2. Fujinaga, M., Read, R.J., Sielecki, A., Ardelt, W., Laskowski, M., Jr & James, M.N.G. (1982) Proc. Natl Acad. Sci. USA 79, 4868-4872
3. Read, R.J., Fujinaga, M., Sielecki, A.R. & James, M.N.G. (1983) Biochemistry 22, 4420-4433
4. Henderson, G., Krygsman, P., Liu, C.J., Davey, C.C. & Malek, L.T. (1987) J. Bacteriol. 169, 3778-3784
5. Greenblatt, H.M., Ryan, C.A. & James, M.N.G. (1989) J. Mol. Biol. 205, 201- 228
3.4.21.82 Glutamyl endopeptidase II
Reaction: Preferential cleavage: -Glu >> -Asp. Preference for Pro or Leu at P2 and Phe at P3. Cleavage of -GluAsp- and -GluPro- bonds is slow
Other Names: GluSGP
Comments: From Streptomyces griseus. A homologue of α-lytic endopeptidase. Inhibited by [Leu18
Glu]-modified turkey ovomucoid third domain
References:
1. Yoshida, N., Tsuruyama, S., Nagata, K., Hirayama, K., Noda, K. & Makisumi, S. (1988) J. Biochem. (Tokyo) 104, 451-456
2. Komiyama, T., Bigler, T.L., Yoshida, N., Noda, K. & Laskowski, M., Jr (1991) J. Biol. Chem. 266, 10727-10730
3. Nagata, K., Yoshida, N., Ogata, F., Araki, M. & Noda, K. (1991) J. Biochem. (Tokyo) 110, 859-862
4. Svendsen, I., Jensen, M.R. & Breddam, K. (1991) FEBS Lett. 292, 165-167
5. Breddam, K. & Meldal, M. (1992) Eur. J. Biochem. 206, 103-107
3.4.21.83 Oligopeptidase B
Reaction: Hydrolysis of -Arg, -Lys bonds in oligopeptides, even when P1' residue is proline
Other Names: Protease II
Comments: Known from Escherichia coli. Inhibited by Tos-Lys-CH2Cl. A homologue of prolyl oligopeptidase
References:
1. Kanatani, A., Masuda, T., Shimoda, T., Misoka, F., Lin, X.S., Yoshimoto, T. & Tsuru, D. (1991) J. Biochem. (Tokyo) 110, 315-320
3.4.21.84 Limulus clotting factor 
Reaction: Selective cleavage of -Arg103Ser- and -Ile124Ile- bonds in limulus clotting factor B to form factor 
. Cleavage of -Pro-Arg bonds in synthetic substrates
Comments: From the hemocyte granules of the horseshoe crabs Limulus and Tachypleus. Factor C is activated by Gram-negative bacterial lipopolysaccharides and chymotrypsin. Inhibited by antithrombin III. A homologue of chymotrypsin
References:
1. Nakamura, T., Morita, T. & Iwanaga, S. (1986) Eur. J. Biochem. 154, 511-521
2. Muta, T., Miyata, T., Misumi, Y., Tokunaga, F., Nakamura, T., Toh, Y., Ikehara, Y. & Iwanaga, S. (1991) J. Biol. Chem. 266, 6554-6561
3. Tokunaga, F., Nakajima, H. & Iwanaga, S. (1991) J. Biochem. (Tokyo) 109, 150-157
3.4.21.85 Limulus clotting factor
Reaction: Selective cleavage of -Arg98Ile- bond in limulus proclotting enzyme to form active clotting enzyme
Comments: From the hemocyte granules of the horseshoe crabs Limulus and Tachypleus. Factor B is activated by limulus clotting factor . A homologue of chymotrypsin
References:
1. Nakamura, T., Horiuchi, T., Morita, T. & Iwanaga, S. (1986) J. Biochem. (Tokyo) 99, 847-857
3.4.21.86 Limulus clotting enzyme
Reaction: Selective cleavage of -Arg18 and -Arg47 bonds in coagulogen to form coagulin and fragments
Comments: From the hemocyte granules of horseshoe crabs Limulus and Tachypleus. Proclotting enzyme is activated by limulus clotting factor . A homologue of chymotrypsin
References:
1. Muta, T., Hashimoto, R., Miyata, T., Nishimura, H., Toh, Y. & Iwanaga, S. (1990) J. Biol. Chem. 265, 22426-22433
2. Tokunaga, F., Nakajima, H. & Iwanaga, S. (1991) J. Biochem. (Tokyo) 109, 150-157
3.4.21.87 Omptin
Reaction: Preferential cleavage: -XaaYaa- in which both Xaa and Yaa are Lys or Arg
Other Names: Protease VII; Protease A
Comments: A product of the ompT gene of Escherichia coli, and associated with the outer membrane. Not a homologue of chymotrypsin or subtilisin.
References:
1. Grodberg, J., Lundrigan, M.D., Toledo, D.L., Mangel, W.F. & Dunn, J.J. (1988) Nucleic Acids Res. 16, 1209 only
2. Sugimura, K. & Nishihara, T. (1988) J. Bacteriol. 170, 5625-5632
3. Hanke, C., Hess, J., Schumacher, G. & Goebel, W. (1992) Mol. Gen. Genet. 233, 42-48
3.4.22.36 Interleukin 1β-converting enzyme
Reaction: Release of interleukin 1β by specific cleavage at -Asp116Ala- and -Asp27Gly- bonds in precursor
Comments: From mammalian monocytes. Inhibited by Ac-Tyr-Val-Ala-Asp-CHN2. Not a homologue of papain
References:
1. Howard, A., Kostura, M.J., Thornberry, M., Ding, G.J.F., Limjuco, G., Weidner, J., Salley, J.P., Hogquist, K.A., Chaplin, D.D., Mumford, R.A., Schmidt, J.A. & Tocci, M.J. (1991) J. Immunol. 147, 2964-2969
2. Thornberry, N.A., Bull, H.G., Calaycay, J.R., Chapman, K.T., Howard, A.D., Kostura, M.J., Miller, D.K., Molineaux, S.M., Weidner, J.R., Aunins, J., Elliston, K.O., Ayala, J.M., Casano, F J., Chin, J., Ding, G.J.-F., Egger, L.A., Gaffney, E.P., Limjuco, G., Palyha, O.C., Raju, S.M., Rolando, A.M., Salley, J.P., Yamin, T.-T. & Tocci, M.J. (1992) Nature 356, 768-774
3.4.23.35 Barrierpepsin
Reaction: Selective cleavage of -Leu6Lys- bond in the pheromone α-mating factor
Other Names: Barrier proteinase; Bar proteinase
Comments: A secreted endopeptidase known from baker's yeast (Saccharomyces cerevisiae). A homologue of pepsin
References:
1. Mackay, V.L., Welch, S.K., Insley, M.Y., Manney, T.R., Holly, J., Saari, G.C. & Parker, M.L. (1988) Proc. Natl. Acad. Sci. USA 85, 55-59
2. Mackay, V.L., Armstrong, J., Yip, C., Welch, S., Walker, K., Osborn, S., Sheppard, P. & Forstrom, J. (1991) Adv. Exp. Med. Biol. 306, 161-172
3.4.24.55 Pitrilysin
Reaction: Preferential cleavage of -Tyr16Leu- and -Phe25Tyr- bonds of oxidized insulin B chain. Also acts on other substrates of less than 7 kDa such as insulin and glucagon
Other Names: Escherichia coli protease III; Protease Pi
Comments: From the periplasmic space of E. coli. Inhibited by EDTA and 1,10-phenanthroline; not thiol-dependent. Formerly EC 3.4.99.44
References:
1. Finch, P.W., Wilson, R.E., Brown, K., Hickson, I.D. & Emmerson, P.T. (1986) Nucleic Acids Res. 14, 7695-7703
2. Affholter, J.A., Fried, V.A. & Roth, R.A. (1988) Science 242, 1415-1418
3. Becker, A.B. & Roth, R.A. (1992) Proc. Natl. Acad. Sci. USA 89, 3835-3839
4. Ding, L., Becker, A.B., Suzuki, A. & Roth, R.A. (1992) J. Biol. Chem. 267, 2414-2420
5. Anastasi, A., Knight, C.G. & Barrett, A.J. (1993) Biochem. J. 290, 601-607
3.4.24.56 Insulysin
Reaction: Degradation of insulin, glucagon and other polypeptides. No action on proteins
Other Names: Insulinase; Insulin-degrading enzyme; Insulin protease
Comments: A 110 kDa cytosolic enzyme, known from mammals and the fruit fly, Drosophila melanogaster. Inhibited by bacitracin, chelating agents EDTA and 1,10-phenanthroline, and by thiol-blocking reagents such as N-ethylmaleimide, but not by phosphoramidon. Homologue of pitrilysin. Formerly EC 3.4.22.11, 3.4.99.10 and 3.4.99.45
References:
1. Duckworth, W.C. (1988) Endocrine Rev. 9, 319-345
2. Affholter, J.A., Hsieh, C.-L., Francke, U. & Roth, R.A. (1990) Mol. Endocrinol. 4, 1125-1135
3. Duckworth, W.C., Hamel, F.G., Bennett, R., Ryan, M.P. & Roth, R.A. (1990) J. Biol. Chem. 265, 2984-2987
4. Kuo, W.-L., Gehm, B.D. & Rosner, M.R. (1990) Mol.Endocrinol. 4, 1580-1591
5. Ding, L., Becker, A.B., Suzuki, A. & Roth, R.A. (1992) J. Biol. Chem. 267, 2414-2420
3.4.24.57 O-Sialoglycoprotein endopeptidase
Reaction: Hydrolysis of O-sialoglycoproteins; cleaves -Arg31Asp- bond in glycophorin A. Does not cleave unglycosylated proteins, desialylated glycoproteins or glycoproteins that are only N-glycosylated
Other Names: Glycoprotease
Comments: An enzyme secreted by the bacterium Pasteurella haemolytica. Inhibited by EDTA (100 mM) and 1,10-phenanthroline
References:
1. Abdullah, K.M., Lo, R.Y.C. & Mellors, A. (1991) J. Bacteriol. 173, 5597-5603
2. Abdullah, K.M., Udoh, E.A., Shewen, P.E. & Mellors, A. (1992) Infect. Immun. 60, 56-62
3. Sutherland, D.R., Abdullah, K.M., Cyopick, P. & Mellors, A. (1992) J. Immunol. 148, 1458-1464
3.4.24.58 Russellysin
Reaction: Specifically activates several components of the blood clotting system, including coagulation factor X, coagulation factor IX and protein C by cleavage of -Arg bonds. Has no action on insulin B chain
Other Names: Russell's viper venom factor X activator, RVV-X
Comments: This enzyme from the venom of Russell's viper (Vipera russelli) of 79 kDa comprises a heavy (59 kDa) and a heterogeneous light (18-21 kDa) chain. Contains Ca2+ and Zn2+. The heavy chain contains the zinc-binding endopeptidase domain and a disintegrin. A homologue of adamalysin
References:
1. Furie, B.C. & Furie,B. (1976) Methods Enzymol. 45, 191-205
2. Lindquist, P.A., Fujikawa, K. & Davie, E.W. (1978) J. Biol. Chem. 253, 1902-1909
3. Takeya, H., Nishida, S., Miyata, T., Kawada, S., Saisaka, Y., Morita, T. & Iwanaga, S. (1992) J. Biol. Chem. 267, 14109-14117
3.4.24.59 Mitochondrial intermediate peptidase
Reaction: Release of an N-terminal octapeptide as second stage of processing of some proteins imported into the mitochondrion
Comments: A homologue of thimet oligopeptidase. Natural substrates are precursor proteins that have already been processed by mitochondrial processing peptidase
References:
1. Isaya, G., Kalousek, F. & Rosenberg, L.E. (1992) J. Biol. Chem. 267, 7904-7910
2. Isaya, G., Kalousek, F. & Rosenberg, L.E. (1992) Proc. Natl. Acad. Sci. USA 89, 8317-8321
[3.4.99.44 Transferred entry: now EC 3.4.24.55 - Pitrilysin]
[3.4.99.45 Transferred entry: now EC 3.4.24.56 - Insulysin]
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