Enzyme Nomenclature. Recommendations 1992

Continued from EC 3.4.24.1 to EC 3.4.24.50


EC 3.4.24 (continued)

3.4.24 Metalloendopeptidases (Continued)

Contents

EC 3.4.24.51 ophiolysin
EC 3.4.24.52 trimerelysin I
EC 3.4.24.53 trimerelysin II
EC 3.4.24.54 mucrolysin
EC 3.4.24.55 pitrilysin
EC 3.4.24.56 insulysin
EC 3.4.24.57 O-sialoglycoprotein endopeptidase
EC 3.4.24.58 russellysin
EC 3.4.24.59 mitochondrial intermediate peptidase
EC 3.4.24.60 dactylysin
EC 3.4.24.61 nardilysin
EC 3.4.24.62 magnolysin
EC 3.4.24.63 meprin B
EC 3.4.24.64 mitochondrial processing peptidase
EC 3.4.24.65 macrophage elastase
EC 3.4.24.66 choriolysin L
EC 3.4.24.67 choriolysin H
EC 3.4.24.68 tentoxilysin
EC 3.4.24.69 bontoxilysin
EC 3.4.24.70 oligopeptidase A
EC 3.4.24.71 endothelin-converting enzyme
EC 3.4.24.72 fibrolase
EC 3.4.24.73 jararhagin
EC 3.4.24.74 fragilysin
EC 3.4.24.75 lysostaphin
EC 3.4.24.76 flavastacin
EC 3.4.24.77 snapalysin
EC 3.4.24.78 gpr endopeptidase
EC 3.4.24.79 pappalysin-1
EC 3.4.24.80 membrane-type matrix metalloproteinase-1
EC 3.4.24.81 ADAM10 endopeptidase
EC 3.4.24.82 ADAMTS-4 endopeptidase
EC 3.4.24.83 anthrax lethal factor endopeptidase
EC 3.4.24.84 Ste24 endopeptidase
EC 3.4.24.85 S2P endopeptidase
EC 3.4.24.86 ADAM 17 endopeptidase
EC 3.4.24.87 ADAMTS13 endopeptidase
EC 3.4.24.88 now EC 3.4.19.15
EC 3.4.24.89 Pro-Pro endopeptidase

Entries

EC 3.4.24.51

Accepted name: ophiolysin

Reaction: Cleavage of Asn3Gln, Gln4His, His10Leu, Ala14Leu, and Tyr16Leu in insulin B chain

Other names: Ophiophagus metalloendopeptidase

Comments: A 70 kDa endopeptidase from the venom of the king cobra (Ophiophagus hannah)

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, CAS registry number:

References:

1. Yamakawa, Y. and Omori-Satoh, T. A protease in the venom of king cobra (Ophiophagus hannah): purification, characterization and substrate specificity on oxidized insulin B-chain. Toxicon 26 (1988) 1145-1155. [PMID: 3070833]

[EC 3.4.24.51 created 1992]

EC 3.4.24.52

Accepted name: trimerelysin I

Reaction: Cleavage of only two bonds His10Leu and Ala14Leu in the insulin B chain

Other names: Trimeresurus metalloendopeptidase I; hemorrhagic proteinase HR1A; hemorrhagic metalloproteinase HR1A; metalloproteinase HR1A

Comments: A 60 kDa hemorrhagic endopeptidase of pI 4.4 from the venom of the habu snake (Trimeresurus flavoviridis). In peptidase family M12 (astacin family)

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, CAS registry number: 151125-16-5

References:

1. Omori-Satoh, T. and Sadahiro, S. Resolution of the major hemorrhagic component of Trimeresurus flavoviridis venom into two parts. Biochim. Biophys. Acta 580 (1979) 392-404. [PMID: 518906]

2. Yamakawa, Y. and Omori-Satoh, T. The sites of cleavage in oxidized insulin-B chain by a hemorrhagic protease derived from the venom of the habu (Trimeresurus flavoviridis). Toxicon 26 (1988) 227-231 .. [PMID: 3284004]

3. Takeya, H., Oda, K., Miyata, T., Omori-Satoh, T. and Iwanaga, S. The complete amino acid sequence of the high molecular mass hemorrhagic protein HR1B isolated from the venom of Trimeresurus flavoviridis. J. Biol. Chem. 265 (1990) 16068-16073. [PMID: 2398046]

[EC 3.4.24.52 created 1992]

EC 3.4.24.53

Accepted name: trimerelysin II

Reaction: Cleavage of Asn3Gln, His10Leu and Ala14Leu in the insulin B chain, and the bond Z-Gly-ProLeu-Gly-Pro in a small molecule substrate of microbial collagenase

Other names: Trimeresurus metalloendopeptidase II; proteinase H2; H2-proteinase

Comments: A 24 kDa nonhemorrhagic endopeptidase from the venom of the habu snake (Trimeresurus flavoviridis). In peptidase family M12 (astacin family)

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 151125-15-4

References.

1. Takahashi, T. and Ohsaka, A. Purification and characterization of a proteinase in the venom of Trimeresurus flavoviridis. Complete separation of the enzyme from hemorrhagic activity. Biochim. Biophys. Acta 198 (1970) 293-307. [PMID: 4984550]

2. Takeya, H., Arakawa, M., Miyata, T., Iwanaga, S. and Omori-Satoh, T. Primary structure of H2-proteinase, a non-hemorrhagic metalloproteinase, isolated from the venom of the habu snake, Trimeresurus flavoviridis. J. Biochem. (Tokyo) 106 (1989) 151-157. [PMID: 2777746]

[EC 3.4.24.53 created 1992]

EC 3.4.24.54

Accepted name: mucrolysin

Reaction: Cleavage of Ser9His, His10Leu, Ala14Leu, Leu15Tyr and Tyr16Leu bonds in insulin B chain

Other names: Trimeresurus metalloendopeptidase A; mucrotoxin A

Comments: A 94 kDa hemorrhagic and fibrinogenolytic endopeptidase from the Chinese habu snake (Trimeresurus mucrosquamatus) venom. In peptidase family M12 (astacin family)

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, CAS registry number: 85898-38-0

References:

1. Sugihara, H., Moriura, M. and Nikai, T. Purification and properties of a lethal, hemorrhagic protein, "mucrotoxin A", from the venom of the Chinese habu snake (Trimeresurus mucrosquamatus). Toxicon 21 (1983) 247-255. [PMID: 6857709]

2. Kishida, M., Nikai, T., Mori, N., Kohmura, S. and Sugihara, H. Characterization of mucrotoxin A from the venom of Trimeresurus mucrosquamatus (the Chinese habu snake). Toxicon 23 (1985) 637-645. [PMID: 6857709]

[EC 3.4.24.54 created 1992]

EC 3.4.24.55

Accepted name: pitrilysin

Reaction: Preferential cleavage of -Tyr16 Leu- and -Phe25 Tyr-bonds of oxidized insulin B chain. Also acts on other substrates of less than 7 kDa such as insulin and glucagon

Other name(s): Escherichia coli protease III; protease Pi; proteinase Pi; PTR; Escherichia coli metalloproteinase Pi

Comments: From the periplasmic space of Escherichia coli. Inhibited by EDTA and 1,10-phenanthroline; not thiol-dependent. Formerly EC 3.4.99.44. Type example of peptidase family M16

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 81611-78-1

References:

1. Finch, P.W., Wilson, R.E., Brown, K., Hickson, I.D. and Emmerson, P.T. Complete nucleotide sequence of the Escherichia coli ptr gene encoding protease III. Nucleic Acids Res. 14 (1986) 7695-7703. [PMID: 3534791]

2. Affholter, J.A., Fried, V.A. and Roth, R.A. Human insulin-degrading enzyme shares structural and functional homologies with E. coli protease III. Science 242 (1988) 1415-1418. [PMID: 3059494]

3. Becker, A.B. and Roth, R.A. An unusual active site identified in a family of zinc metalloendopeptidases. Proc. Natl. Acad. Sci. USA 89, (1992) 3835-3839. [PMID: 1570301]

4. Ding, L., Becker, A.B., Suzuki, A. and Roth, R.A. Comparison of the enzymatic and biochemical properties of human insulin-degrading enzyme and Escherichia coli protease III. J. Biol. Chem. 267 (1992) 2414-2420. [PMID: 1733942]

5. Anastasi, A., Knight, C.G. and Barrett, A.J. Characterization of the bacterial metalloendopeptidase pitrilysin by use of a continuous fluorescence assay. Biochem. J. 290 (1993) 601-607. [PMID: 7680857]

[EC 3.4.24.55 created 1992 as EC 3.4.99.44, transferred 1993 to EC 3.4.24.55 (EC 3.4.99.45 created 1992, incorporated 1993)]

EC 3.4.24.56

Accepted name: insulysin

Reaction: Degradation of insulin, glucagon and other polypeptides. No action on proteins

Other names: insulinase; insulin-degrading enzyme; insulin protease; insulin proteinase; insulin-degrading neutral proteinase; insulin-specific protease; insulin-glucagon protease; metalloinsulinase; IDE

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. In peptidase family M16 (pitrilysin family). Formerly EC 3.4.22.11, EC 3.4.99.10 and EC 3.4.99.45

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 9013-83-6

References

1. Duckworth, W.C. Insulin degradation: mechanisms, products, and significance. Endocrine Rev. 9 (1988) 319-345. [PMID: 3061785]

2. Affholter, J.A., Hsieh, C.-L., Francke, U. and Roth, R.A. Insulin-degrading enzyme: stable expression of the human complementary DNA, characterization of its protein product, and chromosomal mapping of the human and mouse genes. Mol. Endocrinol. 4 (1990) 1125-1135. [PMID: 2293021]

3. Duckworth, W.C., Hamel, F.G., Bennett, R., Ryan, M.P. and Roth, R.A. Human red blood cell insulin-degrading enzyme and rat skeletal muscle insulin protease share antigenic sites and generate identical products from insulin. J. Biol. Chem. 265 (1990) 2984-2987. [PMID: 1689296]

4. Kuo, W.-L., Gehm, B.D. and Rosner, M.R. Cloning and expression of the cDNA for a Drosophila insulin-degrading enzyme. Mol.Endocrinol. 4 (1990) 1580-1591. [PMID: 2126597]

5. Ding, L., Becker, A.B., Suzuki, A. and Roth, R.A. Comparison of the enzymatic and biochemical properties of human insulin-degrading enzyme and Escherichia coli protease III. J. Biol. Chem. 267 (1992) 2414-2420. [PMID: 1733942]

[EC 3.4.24.56 created 1972 as EC 3.4.99.10, transferred 1976 EC 3.4.22.11, transferred 1978 to EC 3.4.99.45, transferred 1993 to to EC 3.4.24.56 (EC 3.4.99.46 created 1992, incorporated 2000)]

EC 3.4.24.57

Accepted name: 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; glycophorin A proteinase; glycoproteinase; sialoglycoprotease; sialoglycoproteinase

Comments: An enzyme secreted by the bacterium Pasteurella haemolytica. Inhibited by EDTA (100 mM) and 1,10-phenanthroline. Type example of peptidase family M22

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, CAS registry number: 129430-53-1

References

1. Abdullah, K.M., Lo, R.Y.C. and Mellors, A. Cloning, nucleotide sequence, and expression of the Pasteurella haemolytica A1 glycoprotease gene. J. Bacteriol. 173 (1991) 5597-5603. [PMID: 1885539]

2. Abdullah, K.M., Udoh, E.A., Shewen, P.E. and Mellors, A. A neutral glycoprotease of Pasteurella haemolytica A1 specifically cleaves O-sialoglycoproteins. Infect. Immun. 60 (1992) 56-62. [PMID: 1729196]

3. Sutherland, D.R., Abdullah, K.M., Cyopick, P. and Mellors, A. Cleavage of the cell-surface O-sialoglycoproteins CD34, CD43, CD44, and CD45 by a novel glycoprotease from Pasteurella haemolytica. J. Immunol. 148 (1992) 1458-1464. [PMID: 1371528]

[EC 3.4.24.57 created 1993]

EC 3.4.24.58

Accepted name: 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; blood-coagulation factor X activating enzyme; metalloproteinase RVV-x; Vipera russelli proteinase; Russell's viper blood coagulation factor X activator; RVV-V

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. In peptidase family M12 (astacin family)

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 79393-92-3

References

1. Furie, B.C. and Furie, B. Coagulant protein of Russell's viper venom. Methods Enzymol. 45 (1976) 191-205. [PMID: 1011991]

2. Lindquist, P.A., Fujikawa, K. and Davie, E.W. Activation of bovine factor IX (Christmas factor) by factor XIa (activated plasma thromboplastin antecent) and a protease from Russell's viper venom. J. Biol. Chem. 253 (1978) 1902-1909. [PMID: 632245]

3. Takeya, H., Nishida, S., Miyata, T., Kawada, S., Saisaka, Y., Morita, T. and Iwanaga, S. Coagulation factor X activating enzyme from Russell's viper venom (RVV-X). A novel metalloproteinase with disintegrin (platelet aggregation inhibitor)-like and C-type lectin-like domains. J. Biol. Chem. 267 (1992) 14109-14117. [PMID: 1629211]

[EC 3.4.24.58 created 1993]

EC 3.4.24.59

Accepted name: mitochondrial intermediate peptidase

Reaction: Release of an N-terminal octapeptide as second stage of processing of some proteins imported into the mitochondrion

Other name(s): mitochondrial intermediate precursor-processing proteinase; MIP

Comments: A homologue of thimet oligopeptidase. Natural substrates are precursor proteins that have already been processed by mitochondrial processing peptidase. In peptidase family M3 (thimet oligopeptidase family)

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, CAS registry number: 136447-30-8

References

1. Isaya, G., Kalousek, F. and Rosenberg, L.E. Amino-terminal octapeptides function as recognition signals for the mitochondrial intermediate peptidase. J. Biol. Chem. 267 (1992) 7904-7910. [PMID: 1560019]

2. Isaya, G., Kalousek, F. and Rosenberg, L.E. Sequence analysis of rat mitochondrial intermediate peptidase: similarity to zinc metallopeptidases and to a putative yeast homologue. Proc. Natl. Acad. Sci. USA 89 (1992) 8317-8321. [PMID: 1518864]

[EC 3.4.24.59 created 1993]

EC 3.4.24.60

Accepted name: dactylysin

Reaction: Hydrolysis of peptides of at least six residues, with bulky hydrophobic residues in the P1' position. Shows a preference for hydrophobic doublets such as -PhePhe- and -PheLeu- in somatostatin-(1-14)-peptide and dynorphin A-(1-6)-peptide, respectively

Other names: peptide hormone inactivating endopeptidase; PHIE

Comments: An endopeptidase of 100 kDa secreted from the skin of the amphibian, Xenopus laevis (Dactylêtre du Cap). Resembles neprilysin in insensitivity to 1 μM captopril, but differs from it in being insensitive to thiorphan (1 μM) and unable to digest [Met5]enkephalin, [Leu5]enkephalin, oxytocin, and substance P-(7-11)-peptide. A similar endopeptidase is found in human neuroblastoma cells [2]

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, CAS registry number: 139466-40-3

References

1. Carvalho, K.M., Joudiou, C., Boussetta, H., Leseney, A.-M. and Cohen, P. A peptide-hormone-inactivating endopeptidase in Xenopus laevis skin secretion. Proc. Natl. Acad. Sci. USA 89 (1992) 84-88. [PMID: 1729723]

2. Delporte, C., Carvalho, K.M., Leseney, A.-M., Winand, J., Christophe, J. and Cohen, P. A new metallo-endopeptidase from human neuroblastoma NB-OK-1 cells which inactivates atrial natriuretic peptide by selective cleavage at the Ser123-Phe124 bond. Biochem. Biophys. Res. Commun. 182 (1992) 158-164. [PMID: 1531011]

3. Joudiou, C., Carvalho, K.M., Camarao, G., Boussetta, H. and Cohen, P. Characterization of the thermolysin-like cleavage of biologically active peptides by Xenopus laevis peptide hormone inactivating enzyme. Biochemistry 32 (1993) 5959-5966. [PMID: 8507636]

[EC 3.4.24.60 created 1995]

EC 3.4.24.61

Accepted name: nardilysin

Reaction: Hydrolysis of polypeptides, preferably at -XaaArg-Lys-, and less commonly at -ArgArg-Xaa-, in which Xaa is not Arg or Lys

Other names: N-arginine dibasic convertase; NRD-convertase

Comments: Enzyme of 133 kDa from rat brain and testis. A homologue of pitrilysin containing the His-Phe-Leu-Glu-His zinc-binding sequence, and a highly acidic stretch of 71 residues. Unusually for a metalloendopeptidase, inhibited by bestatin, amastatin and N-ethylmaleimide. In peptidase family M16 (pitrilysin family)

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, CAS registry number: 292850-69-2

References

1. Gomez, S., Gluschankof, P., Morel, A. and Cohen, P. The somatostatin-28 convertase of rat brain cortex is associated with secretory granule membranes. J. Biol. Chem. 260 (1985) 10541-10545. [PMID: 3897221]

2. Gluschankof, P., Gomez, S., Morel, A. and Cohen, P. Enzymes that process somatostatin precursors. A novel endoprotease that cleaves before the arginine-lysine doublet is involved in somatostatin-28 convertase activity of rat brain cortex. J. Biol. Chem. 262 (1987) 9615-9620. [PMID: 2885328]

3. Chesneau, V., Pierotti, A.R., Barré, N., Créminon, C., Tougard, C. and Cohen, P. Isolation and characterization of a dibasic selective metalloendopeptidase from rat testes that cleaves at the amino terminus of arginine residues. J. Biol. Chem. 269 (1994) 2056-2061. [PMID: 8294457]

4. Pierotti, A.R., Prat, A., Chesneau, V., Gaudoux, F., Leseney, A.-M., Foulon, T. and Cohen, P. N-Arginine dibasic convertase, a metalloendopeptidase as a prototype of a class of processing enzymes. Proc. Natl. Acad. Sci. USA 91 (1994) 6078-6082. [PMID: 8016118]

[EC 3.4.24.61 created 1995]

EC 3.4.24.62

Accepted name: magnolysin

Reaction: Hydrolysis of polypeptides with Arg or Lys in P1 and P2, e.g. to hydrolyse pro-oxytocin at -Lys-ArgAla-Val-. The specificity further depends on the organization of a β-turn-α-helix of nine or more residues containing the paired basic amino acids near the centre [3]

Other names: bovine neurosecretory granule protease cleaving pro-oxytocin/neurophysin; pro-oxytocin/neurophysin convertase; prooxyphysin proteinase; pro-oxytocin convertase

Comments: An endopeptidase of 58 kDa known from bovine pituitary neurosecretory granules and bovine and human corpus luteum [4,5]. Inhibited by EDTA [1]

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, CAS registry number: 162875-09-4

References

1. Clamagirand, C., Creminon, C., Fahy, C., Boussetta, H. and Cohen, P. Partial purification and functional properties of an endoprotease from bovine neurosecretory granules cleaving proocytosin/neurophysin peptides at the basic amino acid doublet. Biochemistry 26 (1987) 6018-6023. [PMID: 2825769]

2. Créminon, C., Rholam, M., Boussetta, H., Marrakchi, N. and Cohen, P. Synthetic peptide substrates as models to study a pro-ocytocin/neurophysin converting enzyme. J. Chromatogt. 440 (1988) 439-448. [PMID: 3042797]

3. Brakch, N., Boussetta, H., Rholam, M. and Cohen, P. Processing endoprotease recognizes a structural feature at the cleavage site of peptide prohormones. The pro-ocytocin/neurophysin model. J. Biol. Chem. 264 (1989) 15912-15916. [PMID: 2674120]

4. Plevrakis, I, Créminon, C., Clamagirand, C., Brakch, N. Rholam, M. and Cohen, P. Proocytocin/neurophysin convertase from bovine neurohypophysis and corpus luteum secretory granules: complete purification, structure-function relationships, and competitive inhibitor. Biochemistry 28 (1989) 2705-2710. [PMID: 2659078]

5. Guillou, M.D., Camier, M. and Clamagirand, C. Evidence for the presence of pro-oxytocin/neurophysin converting enzyme in the human ovary. J. Endocrinol. 142 (1994) 345-352. [PMID: 7931007]

[EC 3.4.24.62 created 1995]

EC 3.4.24.63

Accepted name: meprin B

Reaction: Hydrolysis of proteins, including azocasein, and peptides. Hydrolysis of -His5Leu-, -Leu6Cys-, -Ala14Leu- and -Cys19Gly- bonds in insulin B chain

Other names: meprin-b

Comments: A brush border membrane-bound metalloendopeptidase known from the intestine of all mouse strains that have been tested, and the kidney of certain inbred strains. A tetramer of meprin β subunits (in contrast to meprin A, which contains both α and β subunits). Occurs in the kidney as a proenzyme that can be activated by trypsin. Meprin B is inhibited by both EDTA and 1,10-phenanthroline, but not by phosphoramidon, captopril or thiorphan. In peptidase family M12 (astacin family)

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 150679-52-0

References

1. Kounnas, M.Z., Wolz, R.L., Gorbea, C.M. and Bond, J.S. Meprin-A and -B. Cell surface endopeptidases of the mouse kidney. J. Biol. Chem. 266 (1991) 17350-17357. [PMID: 1894622]

2. Gorbea, C.M., Marchand, P., Jiang, W., Copeland, N.G., Gilbert, D.J., Jenkins, N.A. and Bond, J.S. Cloning, expression, and chromosomal localization of the mouse meprin β subunit. J. Biol. Chem. 268 (1993) 21035-21043. [PMID: 8407940]

3. Johnson, G.D. and Hersh, L.B. Expression of meprin subunit precursors. Membrane anchoring through the β subunit and mechanism of zymogen activation. J. Biol. Chem. 269 (1994) 7682-7688. [PMID: 7510289]

4. Wolz, R.L. and Bond, J.S. Meprins A and B. Methods Enzymol. 248 (1995) 325-345. [PMID: 7674930]

[EC 3.4.24.63 created 1995]

EC 3.4.24.64

Accepted name: mitochondrial processing peptidase

Reaction: Release of N-terminal targetting peptides from precursor proteins imported into the mitochondrion, typically with Arg in position P2

Other names: processing enhancing peptidase (for one of two subunits); mitochondrial protein precursor-processing proteinase; matrix peptidase; matrix processing peptidase; matrix processing proteinase; mitochondrial protein precursor-processing proteinase; MPP

Comments: Known from the mitochondrial matrix of fungi and mammals. Formed from two subunits, both homologous with pitrilysin [3], and the products of the MAS1 and MAS2 genes in yeast. In peptidase family M16 (pitrilysin family). Formerly EC 3.4.99.41

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 86280-61-7

References

1. Jensen, R.E. and Yaffe, M.P. Import of proteins into yeast mitochondria: the nuclear MAS2 gene encodes a component of the processing protease that is homologous to the MAS1-encoded subunit. EMBO J. 7 (1988) 3863-3871. [PMID: 3061808]

2. Witte, C., Jensen, R.E., Yaffe, M.P. and Schatz, G. MAS1, a gene essential for yeast mitochondrial assembly, encodes a subunit of the mitochondrial processing protease. EMBO J. 7 (1988) 1439-1447. [PMID: 3044780]

3. Rawlings, N.D. and Barrett, A.J. Homologues of insulinase, a new superfamily of metalloendopeptidases. Biochem. J. 275 (1991) 389-391. [PMID: 2025223]

4. Kalousek, F., Neupert, W., Omura, T., Schatz, G. and Schmitz, U.K. Uniform nomenclature for the mitochondrial peptidases cleaving precursors of mitochondrial proteins. Trends Biochem. Sci. 18 (1993) 249 only. [PMID: 8212133]

5. Brunner, M. and Neupert, W. Purification and characterization of the mitochondrial processing peptidase of Neurospora crassa. Methods Enzymol. 248 (1994) 717-728

[EC 3.4.24.64 created 1989/90 as EC 3.4.99.41, transferred 1995 to EC 3.4.24.64]

EC 3.4.24.65

Accepted name: macrophage elastase

Reaction: Hydrolysis of soluble and insoluble elastin [1]. Specific cleavages are also produced at -Ala14Leu- and -Tyr16Leu- in the B chain of insulin [2]

Other names: metalloelastase; human macrophage metalloelastase (HME)

Comments: This enzyme is synthesized as a proenzyme of 53 kDa that is converted to an active form of 22 kDa. cDNA sequences have been obtained for the mouse [3] and human [4] enzymes. In peptidase family M10 (interstitial collagenase family)

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 9004-06-2

References:

1. Banda, M.J. and Werb, Z. Mouse macrophage elastase. Purification and characterization as a metalloproteinase. Biochem. J. 193 (1981) 589-605. [PMID: 7030312]

2. Kettner, C., Shaw, E., White, R. and Janoff, A. The specificity of macrophage elastase on the insulin B-chain. Biochem. J. 195 (1981) 369-372. [PMID: 7032505]

3. Shapiro, S.D., Griffin, G.L., Gilbert, D.J., Jenkins, N.A., Copeland, N.G., Welgus, H.G., Senior, R.M. and Ley, T.J. Molecular cloning, chromosomal localization, and bacterial expression of a murine macrophage metalloelastase. J. Biol. Chem. 267 (1992) 4664-4671. [PMID: 1537850]

4. Shapiro, S.D., Kobayashi, D.K. and Ley, T.J. Cloning and characterization of a unique elastolytic metalloproteinase produced by human alveolar macrophages. J. Biol. Chem. 268 (1993) 23824-23829. [PMID: 8226919]

[EC 3.4.24.65 created 1995]

EC 3.4.24.66

Accepted name: choriolysin L

Reaction: Hydrolysis of the inner layer of fish egg envelope. Also hydrolysis of casein and small molecule substrates such as succinyl-Leu-Leu-Val-Tyr7-(4-methyl)coumarylamide

Other names: teleost hatching enzyme (component); low choriolytic enzyme (LCE)

Comments: Known from the teleost fish Oryzias latipes (medaka). Efficient dissolution of the egg membrane requires concerted action with choriolysin H. A 24 kDa peptidase family M12 (astacin family)

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, CAS registry number: 177529-15-6

References

1. Yasumasu, S., Iuchi, I. and Yamagami, K. Medaka hatching enzyme consists of two kinds of proteases which act cooperatively. Zool. Sci. 5 (1988) 191-195

2. Yasumasu, S., Iuchi, I. and Yamagami, K. Isolation and some properties of low choriolytic enzyme (LCE), a component of the hatching enzyme of the teleost, Oryzias latipes. J. Biochem. (Tokyo) 105 (1989) 212-218. [PMID: 2656665]

3. Yasumasu, S., Katow, S., Hamazaki, T.S., Iuchi, I. and Yamagami, K. Two constituent proteases of a teleostean hatching enzyme: concurrent syntheses and packaging in the same secretory granules in discrete arrangement. Dev. Biol. 149 (1992) 349-356. [PMID: 1730389]

4. Yasumasu, S., Yamada, K., Akasaka, K., Mitsunaga, K., Iuchi, I., Shimada, H. and Yamagami, K. Isolation of cDNAs for LCE and HCE, two constituent proteases of the hatching enzyme of Oryzias latipes, and concurrent expression of their mRNAs during development. Dev. Biol. 153 (1992) 250-258. [PMID: 1397682]

[EC 3.4.24.66 created 1995]

EC 3.4.24.67

Accepted name: choriolysin H

Reaction: Hydrolysis of the inner layer of fish egg envelope. Also hydrolysis of casein and small molecule substrates such as succinyl-Leu-Leu-Val-Tyr7-(4-methyl)coumarylamide

Other names: teleost hatching enzyme (component); high choriolytic enzyme (HCE)

Comments: Known from the teleost fish Oryzias latipes (medaka). Efficient dissolution of the egg membrane requires concerted action with choriolysin L. A 25.5 kDa peptidase in family M12 (astacin family)

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, CAS registry number: 177529-16-7

References

1. Yamagami, K. Isolation of a choriolytic enzyme (hatching enzyme) of the teleost, Oryzias latipes. Dev. Biol. 29 (1972) 343-348

2. Yasumasu, S., Iuchi, I. and Yamagami, K. Purification and partial characterization of high choriolytic enzyme (HCE), a component of the hatching enzyme of the teleost, Oryzias latipes. J. Biochem. (Tokyo) 105 (1989) 204-211. [PMID: 2656664]

3. Yasumasu, S., Katow, S., Umino, Y., Iuchi, I. and Yamagami, K. A unique proteolytic action of HCE, a constituent protease of a fish hatching enzyme: tight binding to its natural substrate, egg envelope. Biochem. Biophys. Res. Commun. 162 (1989) 58-63. [PMID: 2751672]

4. Yasumasu, S., Yamada, K., Akasaka, K., Mitsunaga, K., Iuchi, I., Shimada, H. and Yamagami, K. Isolation of cDNAs for LCE and HCE, two constituent proteases of the hatching enzyme of Oryzias latipes, and concurrent expression of their mRNAs during development. Dev. Biol. 153 (1992) 250-258. [PMID: 1397682]

5. Lee, K.S., Yasumasu, S., Nomura, K. and Iuchi, I. HCE, a constituent of the hatching enzymes of Oryzias latipes embryos, releases unique proline-rich polypeptides from its natural substrate, the hardened chorion. FEBS Lett. 339 (1993) 281-284. [PMID: 8112467]

[EC 3.4.24.67 created 1995]

EC 3.4.24.68

Accepted name: tentoxilysin

Reaction: Hydrolysis of -Gln76Phe- bond in synaptobrevin (also known as neuronal vesicle-associated membrane protein, VAMP)

Other names: tetanus neurotoxin

Comments: Zinc enzyme produced by Clostridium tetani. Proenzyme of 150 kDa is processed to disulfide-linked subunits of 100 and 50 kDa, the latter being responsible for the endopeptidase activity. Weakly inhibited by captopril, and phosphoramidon. The clostridial neurotoxins disable the neuroexocytosis apparatus, and have been described as the most toxic substances known. Tentoxilysin acts at the spinal inhibitory interneurons, blocking the release of various neurotransmitters to produce spastic paralysis. Type example of peptidase family M27 (tentoxilysin family)

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 107231-12-9 (not distinguished from EC 3.4.24.69)

References

1. Fujii, N., Kimura, K., Yashiki, T., Tsuzuki, K., Moriishi, K., Yokosawa, N., Syuto, B. and Oguma, K. A zinc-protease specific domain in botulinum and tetanus neurotoxins. Microbiol. Intern. 36 (1992) 213-220

2. Schiavo, G., Benfenati, F., Poulain, B., Rossetto, O., Polverino de Laureto, P., DasGupta, B.R. and Montecucco, C. Tetanus and botulinum-B neurotoxins block neurotransmitter release by proteolytic cleavage of synaptobrevin. Nature 359 (1992) 832-834. [PMID: 1331807]

3. Schiavo, G., Rossetto, O., Santucci, A., DasGupta, B.R. and Montecucco, C. Botulinum neurotoxins are zinc proteins. J. Biol. Chem. 267 (1992) 23479-23483. [PMID: 1429690]

4. Montecucco, C. and Schiavo, G. Mechanism of action of tetanus and botulinum neurotoxins. Mol. Microbiol. 8 (1994) 1-13. [PMID: 7527117]

5. Schiavo, G. and Montecucco, C. Tetanus and botulism neurotoxins. Methods Enzymol. 248 (1995) 643-652. [PMID: 7674951]

[EC 3.4.24.68 created 1995]

EC 3.4.24.69

Accepted name: bontoxilysin

Reaction: Limited hydrolysis of proteins of the neuroexocytosis apparatus, synaptobrevin (also known as neuronal vesicle-associated membrane protein, VAMP), synaptosome-associated protein of 25 kDa (SNAP25) or syntaxin. No detected action on small molecule substrates

Other names: botulinum neurotoxin; BoNT

Comments: This zinc enzyme, produced by Clostridium botulinum, occurs as forms A-G that differ in specificity of action on the proteins of the neuroexocytosis apparatus [1-5]. The 150-kDa proenzymes of bontoxilysin are processed to disulfide-linked subunits of 100 and 50 kDa, the latter being responsible for the endopeptidase activities. Weakly inhibited by captopril, and phosphoramidon. Toxicity is due to action at the neuromuscular junctions that blocks release of acetylcholine, causing flaccid paralysis, in contrast to the spastic paralysis caused by tentoxilysin. In peptidase family M27 (tentoxilysin family)

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 107231-12-9 (not distinguished from EC 3.4.24.68)

References

1. Schiavo, G., Rossetto, O., Catsicas, S., Polverino De Laureto, P., DasGupta, B.R., Benfenati, F. and Montecucco, C. Identification of the nerve-terminal targets of botulinum neurotoxins serotypes A, D and E. J. Biol. Chem. 268 (1993) 23784-23787. [PMID: 8226912]

2. Schiavo, G., Santucci, A., DasGupta, B.R., Mehta, P.P., Jontes, J., Benfenati, F., Wilson, M.C. and Montecucco, C. Botulinum neurotoxins serotypes A and E cleave SNAP-25 at distinct COOH-terminal peptide bonds. FEBS Lett. 335 (1993) 99-103. [PMID: 8243676]

3. Schiavo, G., Shone, C.C., Rossetto, O., Alexander, F.C.G. and Montecucco, C. Botulinum neurotoxin serotype F is a zinc endopeptidase specific for VAMP/synaptobrevin. J. Biol. Chem. 268 (1993) 11516-11519. [PMID: 8505288]

4. Schiavo, G., Malizio, C., Trimble, W.S., Polverino De Laureto, P., Milan, G., Sugiyama, H., Johnson, E.A. and Montecucco, C. Botulinum G neurotoxin cleaves VAMP/synaptobrevin at a single Ala-Ala peptide bond. J. Biol. Chem. 269 (1994) 20213-20216. [PMID: 8051110]

5. Montecucco, C. and Schiavo, G. Mechanism of action of tetanus and botulinum neurotoxins. Mol. Microbiol. 8 (1994) 1-13. [PMID: 7527117]

6. Schiavo, G. and Montecucco, C. Tetanus and botulism neurotoxins. Methods Enzymol. 248 (1995) 643-652. [PMID: 7674951]

[EC 3.4.24.69 created 1995]

EC 3.4.24.70

Accepted name: oligopeptidase A

Reaction: Hydrolysis of oligopeptides, with broad specificity. Gly or Ala commonly occur as P1 or P1' residues, but more distant residues are also important, as is shown by the fact that Z-Gly-Pro-GlyGly-Pro-Ala is cleaved, but not Z-(Gly)5 [4]

Other name(s): 68000-M signalpeptide hydrolase

Comments: Known from Escherichia coli and Salmonella typhimurium. A zinc metallopeptidase, in peptidase family M3 (thimet oligopeptidase family), but differs from thimet oligopeptidase in lack of thiol-activation

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, CAS registry number: 394250-11-4

References

1. Novak, P. and Dev, I.K. Degradation of a signal peptide by protease IV and oligopeptidase A. J. Bacteriol. 170 (1988) 5067-5075. [PMID: 3053642]

2. Conlin, C.A., Vimr, E.R. and Miller, C.G. Oligopeptidase A is required for normal phage P22 development. J. Bacteriol. 174 (1992) 5869-5880. [PMID: 1522065]

3. Conlin, C.A., Trun, N.J., Silhavy, T.J. and Miller, C.G. Escherichia coli prlC encodes an endopeptidase and is homologous to the Salmonella typhimurium opdA gene. J. Bacteriol. 174 (1992) 5881-5887. [PMID: 1325967]

4. Conlin, C.A. and Miller, C.G. Dipeptidyl carboxypeptidase and oligopeptidase A from Escherichia coli and Salmonella typhimurium. Methods Enzymol. 248 (1995) 567-579. [PMID: 7674945]

[EC 3.4.24.70 created 1996]

EC 3.4.24.71

Accepted name: endothelin-converting enzyme 1

Reaction: Hydrolysis of the -Trp21Val- bond in big endothelin to form endothelin 1

Other name(s): endothelin-converting enzyme; ECE-1

Comments: A phosphoramidon-sensitive metalloendopeptidase in peptidase family M13 (neprilysin family). An integral membrane protein predominantly of endothelial cells, which generates the potent vasoconstrictor endothelin 1 from its inactive precursor

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 138238-81-0

References

1. Takahashi, M., Matsushita, Y., Iijima, Y. and Tanzawa, K. Purification and characterization of endothelin-converting enzyme from rat lung. J. Biol. Chem. 268 (1993) 21394-21398. [PMID: 8407980]

2. Shimada, K., Takahashi, M. and Tanzawa, K. Cloning and functional expression of endothelin-converting enzyme from rat endothelial cells. J. Biol. Chem. 269 (1994) 18275-18278. [PMID: 94308046]

3. Xu, D., Emoto, N., Giaid, A., Slaughter, C., Kaw, S., DeWit, D. and Yanagisawa, M. ECE-1: A membrane-bound metalloprotease that catalyzes the proteolytic activation of big endothelin-1. Cell 78 (1994) 473-485. [PMID: 8062389]

[EC 3.4.24.71 created 1996]

EC 3.4.24.72

Accepted name: fibrolase

Reaction: Hydrolysis of -Ala14Leu- in insulin B chain and -Lys413Leu- in Aα-chain of fibrinogen

Other names: fibrinolytic proteinase; Agkistrodon contortrix contortrix metalloproteinase; Agkistrodon contortrix contortrix venom metalloproteinase

Comments: A 23-kDa, non-hemorrhagic enzyme from the venom of the southern copperhead snake (Agkistrodon contortix contortix). In peptidase family M12 (astacin family)

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, CAS registry number: 116036-70-5

References

1. Retzios, A.D. and Markland, F.S., Jr. A direct-acting fibrinolytic enzyme from the venom of Agkistrodon contortrix contortrix: effects on various components of the human blood coagulation and fibrinolysis systems. Thromb. Res. 52 (1988) 541-552. [PMID: 3232124]

2. Guan, A.L., Retzios, A.D., Henderson, G.N. and Markland, F.S., Jr. Purification and characterization of a fibrinolytic enzyme from venom of southern copperhead snake (Agkistrodon contortrix contortrix). Arch. Biochem. Biophys. 289 (1991) 197-207. [PMID: 1898066]

3. Randolph, A., Chamberlain, S.H., Chu, H.L.C., Retzios, A.D., Markland, F.S. Jr. and Masiarz, F.R. Amino acid sequence of fibrolase, a direct-acting fibrinolytic enzyme from Agkistrodon contortrix venom. Protein Sci. 1 (1992) 590-600. [PMID: 1304358]

4. Loayza, S.L., Trikha, M., Markland, F.S., Riquelme, P. and Kuo, J. Resolution of isoforms of natural and recombinant fibrolase, the fibrinolytic enzyme from Agkistrodon contortrix contortrix snake venom, and comparison of their EDTA sensitivities. J. Chromatogr. B Biomed. Appl. 662 (1994) 227-243. [PMID: 7719479]

5. Retzios, A.D. and Markland, F.S. Fibrinolytic enzymes from the venoms of Agkistrodon contortrix contortrix and Crotalus basilicus basilicus: cleavage site specificity towards the α-chain of fibrin. Thromb. Res. 74 (1994) 355-367. [PMID: 8085237]

[EC 3.4.24.72 created 1996]

EC 3.4.24.73

Accepted name: jararhagin

Reaction: Hydrolysis of -His10Leu-, -Ala14Leu-, -Tyr16Leu-and -Phe24Phe- bonds in insulin B chain

Other names: HF2-proteinase; JF1

Comments: Hemorrhagic endopeptidase from the venom of the jararaca snake (Bothrops jararaca). The 52-kDa enzyme contains a disintegrin domain [3]. In peptidase family M12 (astacin family)

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 160477-79-2

References

1. Mandelbaum, F.R., Reichl, A.P. and Assakura, M.T. Some physical and biochemical characteristics of HF2, one of the hemorrhagic factors in the venom of Bothrops jararaca. In Animal, Plant and Microbial Toxins (Ohsaka, A., Hayashi, K. and Sawai, Y. eds), pp. 111-121 (1976) Plenum Press, New York

2. Assakura, M.T., Reichl, A.P. and Mandelbaum, F.R. Comparison of immunological, biochemical and biophysical properties of three hemorrhagic factors isolated from the venom of Bothrops jararaca (jararaca). Toxicon 24 (1986) 943-946. [PMID: 3810664]

3. Paine, M.J.I., Desmond, H.P., Theakston, R.D.G. and Crampton, J.M. Purification, cloning, and molecular characterization of a high molecular weight hemorrhagic metalloprotease, jararhagin, from Bothrops jararaca venom. Insights into the disintegrin gene family. J. Biol. Chem. 267 (1992) 22869-22876. [PMID: 1385408]

[EC 3.4.24.73 created 1996]

EC 3.4.24.74

Accepted name: fragilysin

Reaction: Broad proteolytic specificity, bonds hydrolysed including -GlyLeu-, -MetLeu-, -PheLeu-, -CysLeu-, LeuGly

Other names: Bacteroides fragilis (entero)toxin

Comments: Thought to be a cause of diarrhoea in animals and humans. Hydrolyses extracellular matrix proteins, and disrupts tight junctions of intestinal epithelial cells. Also degrades intracellular, cytoskeletal proteins actin, myosin and others. In peptidase family M10 (interstitial collagenase family)

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, CAS registry number: 188596-63-6

References

1. Moncrief, J.S., Obiso, R., Jr., Barroso, L.A., Kling, J.J., Wright, R.L., Van Tassell, R.L., Lyerly, D.M. and Wilkins, T.D. The enterotoxin of Bacteroides fragilis is a metalloprotease. Infect. Immun. 63 (1995) 175-181. [PMID: 7806355]

2. Obiso, R.J., Jr., Lyerly, D.M., Van Tassell, R.L. and Wilkins, T.D. Proteolytic activity of the Bacteroides fragilis enterotoxin causes fluid secretion and intestinal damage in vivo. Infect. Immun. 63 (1995) 3820-3826. [PMID: 7558286]

3. Donelli, G., Fabbri, A. and Fiorentini, C. Bacteroides fragilis enterotoxin induces cytoskeletal changes and surface blebbing in HT-29 cells. Infect. Immun. 64 (1996) 113-119. [PMID: 8557328]

4. Koshy, S.S., Montrose, M.H. and Sears, C.L. Human intestinal epithelial cells swell and demonstrate actin rearrangement in response to the metalloprotease toxin of Bacteroides fragilis. Infect. Immun. 64 (1996) 5022-5028. [PMID: 8945541]

5. Kling, J.J., Wright, R.L., Moncrief, J.S. and Wilkins, T.D. Cloning and characterization of the gene for the metalloprotease enterotoxin of Bacteroides fragilis. FEMS Microbiol. Lett. 146 (1997) 279-284. [PMID: 9011050]

[EC 3.4.24.74 created 1997]

EC 3.4.24.75

Accepted name: lysostaphin

Reaction: Hydrolysis of the -GlyGly- bond in the pentaglycine inter-peptide link joining staphylococcal cell wall peptidoglycans

Other names: glycyl-glycine endopeptidase

Comments: A zinc-dependent, 25-kDa endopeptidase from Staphylococcus simulans. Lyses cells of S. aureus, in particular, by its action on the cross-bridges of the cell wall. Type example of peptidase family M23

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 9011-93-2

References

1. Recsei, P.A., Gruss, A.D. and Novick, R.P. Cloning, sequence, and expression of the lysostaphin gene from Staphylococcus simulans. Proc. Natl. Acad. Sci. U.S.A. 84 (1987) 1127-1131

2. Baba, T. and Schneewind, O. Target cell specificity of a bacteriocin molecule: A C-terminal signal directs lysostaphin to the cell wall of Staphylococcus aureus. EMBO J. 15 (1996) 4789-4797

3. Thumm, G. and Götz, F. Studies on prolysostaphin processing and characterization of the lysostaphin immunity factor (Lif) of Staphylococcus simulans biovar staphylolyticus. Mol. Microbiol. 23 (1997) 1251-1265. [PMID: 9106216]

[EC 3.4.24.75 created 1997]

EC 3.4.24.76

Accepted name: flavastacin

Reaction: Hydrolyses polypeptides on the amino-side of Asp in -XaaAsp-. Acts very slowly on -XaaGlu

Comments: A zinc metalloendopeptidase in peptidase family M12 (astacin family), secreted by the bacterium Flavobacterium meningosepticum . The specificity is similar to that of EC 3.4.24.33, peptidyl-Asp metalloendopeptidase from Pseudomonas fragi but the two are reported to be structurally dissimilar

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, CAS registry number: 167973-66-2

References

1. Tarentino, A.L., Quinones, G., Grimwood, B.G., Hauer, C.R. and Plummer, T.H., Jr. Molecular cloning and sequence analysis of flavastacin: an O-glycosylated prokaryotic zinc metalloendopeptidase.Arch. Biochem. Biophys. 319 (1995) 281-285. [PMID: 7771796]

[EC 3.4.24.76 created 2000]

EC 3.4.24.77

Accepted 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: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 945859-47-2

References

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. [PMID: 11132632]

[EC 3.4.24.77 created 2001]

EC 3.4.24.78

Accepted name: gpr endopeptidase

Reaction: Endopeptidase action with P4 Glu or Asp, P1 preferably Glu > Asp, P1' hydrophobic and P2' Ala

Other name(s): germination proteinase

Comments: Initiates the degradation of small, acid-soluble proteins during spore germination in Bacillus megaterium. Type example of peptidase family M63.

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 75718-32-0

References:

1. Ponnuraj, K., Rowland, S., Nessi, C., Setlow, P. and Jedrzejas, M.J. Crystal structure of a novel germination protease from spores of Bacillus megaterium: Structural arrangement and zymogen activation. J. Mol. Biol. 300 (2000) 1-10. [PMID: 10864493]

[EC 3.4.24.78 created 2003]

EC 3.4.24.79

Accepted name: pappalysin-1

Reaction: Cleavage of the Met135Lys bond in insulin-like growth factor binding protein (IGFBP)-4, and the Ser143Lys bond in IGFBP-5

Other name(s): insulin-like growth factor binding protein-4 protease; pregnancy-associated plasma protein-A

Comments: A 400-kDa disulfide-linked dimer. Circulates in human pregnancy mainly as a complex with the proform of eosinophil major basic protein, which acts as an inhibitor of the peptidase. The rate of hydrolysis of IGFBP-4 is increased about 20-fold by the presence of insulin-like growth factor (IGF), whereas that of IGFBP-5 is decreased about two-fold. In peptidase family M43.

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, CAS registry number:

References:

1. Lawrence, J.B., Oxvig, C., Overgaard, M.T., Sottrup-Jensen, L., Gleich, G.J., Hays L.G., Yates, J.R. 3rd, and Conover, C.A. The insulin-like growth factor (IGF)-dependent IGF binding protein-4 protease secreted by human fibroblasts is pregnancy-associated plasma protein-A. Proc. Natl. Acad. Sci. USA 96 (1999) 3149-3153. [PMID: 10077652]

2. Chen, B.K., Overgaard, M.T., Bale, L.K., Resch, Z.T., Christiansen, M., Oxvig, C. and Conover, C.A. Molecular regulation of the IGF-binding protein-4 protease system in human fibroblasts: identification of a novel inducible inhibitor. Endocrinology 143 (2002) 1199-1205. [PMID: 11897673]

[EC 3.4.24.79 created 2003]

EC 3.4.24.80

Accepted name: membrane-type matrix metalloproteinase-1

Reaction: Endopeptidase activity. Activates progelatinase A by cleavage of the propeptide at Asn37Leu. Other bonds hydrolysed include Gly35Ile in the propeptide of collagenase 3, and Asn341Phe, Asp441Leu and Gln354Thr in the aggrecan interglobular domain

Other name(s): matrix metalloproteinase 14

Comments: In peptidase family M10, but, unlike most members of the family, is membrane-anchored. Believed to play an important role in the activation of progelatinase A at cell surfaces.

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 161384-17-4

References:

1. Itoh, Y., Takamura, A., Ito, N., Maru, Y., Sato, H., Suenaga, N., Aoki, T. and Seiki, M. Homophilic complex formation of MT1-MMP facilitates proMMP-2 activation on the cell surface and promotes tumor cell invasion. EMBO J. 20 (2001) 4782-4793. [PMID: 11532942]

[EC 3.4.24.80 created 2003]

EC 3.4.24.81

Accepted name: ADAM10 endopeptidase

Reaction: Endopeptidase of broad specificity

Other name(s): Kuzbanian protein; myelin-associated disintegrin metalloproteinase

Comments: In peptidase family M12. Partially responsible for the "α-secretase" activity in brain that degrades the potentially harmful β-amyloid peptide. Work with ADAM10-deficient mice supports a role in Notch signalling.

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 193099-09-1

References:

1. Gutwein, P., Mechtersheimer, S., Riedle, S., Stoeck, A., Gast, D., Joumaa, S., Zentgraf, H., Fogel, M. and Altevogt, D.P. ADAM10-mediated cleavage of L1 adhesion molecule at the cell surface and in released membrane vesicles. FASEB J. 17 (2003) 292-294. [PMID: 12475894]

[EC 3.4.24.81 created 2003]

EC 3.4.24.82

Accepted name: ADAMTS-4 endopeptidase

Reaction: Glutamyl endopeptidase; bonds cleaved include -Thr-Glu-Gly-Glu373Ala-Arg-Gly-Ser- in the interglobular domain of mammalian aggrecan

Other name(s): aggrecanase-1

Comments: In peptidase family M12. Thought to be biologically significant for the degradation of the aggrecan component of cartilage matrix.

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 147172-61-0

References:

1. Westling, J., Fosang, A.J., Last, K., Thompson, V.P., Tomkinson, K.N., Hebert, T., McDonagh, T., Collins-Racie, L.A., LaVallie, E.R., Morris, E.A. and Sandy, J.D. ADAMTS4 cleaves at the aggrecanase site (Glu373-Ala374) and secondarily at the matrix metalloproteinase site (Asn341-Phe342) in the aggrecan interglobular domain. J. Biol. Chem. 277 (2002) 16059-16066. [PMID: 11854269]

[EC 3.4.24.82 created 2003]

EC 3.4.24.83

Accepted name: anthrax lethal factor endopeptidase

Reaction: Preferred amino acids around the cleavage site can be denoted BBBBxHxH, in which B denotes Arg or Lys, H denotes a hydrophobic amino acid, and x is any amino acid. The only known protein substrates are mitogen-activated protein (MAP) kinase kinases

Other name(s): lethal toxin

Comments: From the bacterium Bacilus anthracis that causes anthrax. One of three proteins that are collectively termed anthrax toxin. Cleaves several MAP kinase kinases near their N-termini, preventing them from phosphorylating the downstream mitogen-activated protein kinases. In peptidase family M34.

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 477950-41-7

References:

1. Pannifer, A.D., Wong, T.Y., Schwarzenbacher, R., Renatus, M., Petosa, C., Bienkowska, J., Lacy, D.B., Collier, R.J., Park, S., Leppla, S.H., Hanna, P. and Liddington, R.C. Crystal structure of the anthrax lethal factor. Nature 414 (2001) 229-233. [PMID: 11700563]

[EC 3.4.24.83 created 2003]

EC 3.4.24.84

Accepted name: Ste24 endopeptidase

Reaction: The peptide bond hydrolysed can be designated -CaaX in which C is an S-isoprenylated cysteine residue, a is usually aliphatic and X is the C-terminal residue of the substrate protein, and may be any of several amino acids

Comments: Type example of peptidase family M48. One of two enzymes that can catalyse this processing step for mating a-factor in yeast. Subsequently, the S-isoprenylated cysteine residue that forms the new C-terminus is methyl-esterified and forms a hydrophobic membrane-anchor.

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 148463-92-7

References:

1. Tam, A., Schmidt, W.K. and Michaelis, S. The multispanning membrane protein Ste24p catalyzes CAAX proteolysis and NH2-terminal processing of the yeast a-factor precursor. J. Biol. Chem. 276 (2001) 46798-46806. [PMID: 11581258]

[EC 3.4.24.84 created 2003]

EC 3.4.24.85

Accepted name: S2P endopeptidase

Reaction: Cleaves several transcription factors that are type-2 transmembrane proteins within membrane-spanning domains. Known substrates include sterol regulatory element-binding protein (SREBP) -1, SREBP-2 and forms of the transcriptional activator ATF6. SREBP-2 is cleaved at the site DRSRILL483CVLTFLCLSFNPLTSLLQWGGA, in which the membrane-spanning segment is underlined. The residues NP (bold), 11 residues distal to the site of cleavage in the membrane-spanning domain, are important for cleavage by S2P endopeptidase. Replacement of either of these residues does not prevent cleavage, but there is no cleavage if both of these residues are replaced.

Comments: Type example of peptidase family M50. The transcription factors SREBP-1 and -2 are synthesized as precursor proteins that are attached to the membranes of the endoplasmic reticulum and two cleavages are needed to release the active factor so that it can move to the nucleus. This enzyme cleaves the second of these, and is thus the "site 2 protease", S2P.

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, CAS registry number: 752251-31-3

References:

1. Brown, M.S., Ye, J., Rawson, R.B. and Goldstein, J.L. Regulated intramembrane proteolysis: a control mechanism conserved from bacteria to humans. Cell 100 (2000) 391-398. [PMID: 10693756]

[EC 3.4.24.85 created 2003]

EC 3.4.24.86

Accepted name: ADAM 17 endopeptidase

Reaction: Narrow endopeptidase specificity. Cleaves Pro-Leu-Ala-Gln-AlaVal-Arg-Ser-Ser-Ser in the membrane-bound, 26-kDa form of tumour necrosis factor α (TNFα). Similarly cleaves other membrane-anchored, cell-surface proteins to "shed" the extracellular domains

Other names: tumor necrosis factor α-converting enzyme; TACE

Comments: In peptidase family M12. In vivo, the cleavage of tumor necrosis factor α precursor releases the soluble, 17-kDa TNFα, which induces inflammation.

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 151769-16-3

References:

1. Black, R.A. Tumor necrosis factor-α converting enzyme. Int. J. Biochem. Cell Biol. 34 (2002) 1-5. [PMID: 11733179]

[EC 3.4.24.86 created 2003]

EC 3.4.24.87

Accepted name: ADAMTS13 endopeptidase

Reaction: The enzyme cleaves the von Willebrand factor at bond Tyr842Met843 within the A2 domain, i.e. Tyr1605Met1606 in von Willebrand factor.

Other name(s): ADAMTS VWF cleaving metalloprotease; ADAMTS-13; ADAMTS13; vWF-cleaving protease; VWF-CP; vWF-degrading protease; Upshaw factor; von Willebrand factor cleaving protease; ADAMTS13 peptidase

Comments: In peptidase family M12.

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number:

References:

1. Fujikawa, K., Suzuki, H., McMullen, B. and Chung, D. Purification of human von Willebrand factor-cleaving protease and its identification as a new member of the metalloproteinase family. Blood 98 (2001) 1662-1666. [PMID: 11535495]

2. Dong, J.F., Moake, J.L., Nolasco, L., Bernardo, A., Arceneaux, W., Shrimpton, C.N., Schade, A.J., McIntire, L.V., Fujikawa, K. and Lopez, J.A. ADAMTS-13 rapidly cleaves newly secreted ultralarge von Willebrand factor multimers on the endothelial surface under flowing conditions. Blood 100 (2002) 4033-4039. [PMID: 12393397]

[EC 3.4.24.87 created 2009]

[EC 3.4.24.88 Transferred entry: desampylase. Transferred to EC 3.4.19.15 desampylase (EC 3.4.24.88 created 2015, deleted 2016)]

EC 3.4.24.89

Accepted name: Pro-Pro endopeptidase

Reaction: The enzyme catalyses the hydrolytic cleavage of peptide bonds between two proline residues

Other name(s): metalloprotease CD2830

Comments: This metalloprotease, which is secreted by the bacterium Peptoclostridium difficile, contains zinc.

Links to other databases: BRENDA, EXPASY, KEGG, MetaCyc, CAS registry number:

References:

1. Cafardi, V., Biagini, M., Martinelli, M., Leuzzi, R., Rubino, J.T., Cantini, F., Norais, N., Scarselli, M., Serruto, D. and Unnikrishnan, M. Identification of a novel zinc metalloprotease through a global analysis of Clostridium difficile extracellular proteins. PLoS One 8 (2013) e81306. [PMID: 24303041]

2. Hensbergen, P.J., Klychnikov, O.I., Bakker, D., van Winden, V.J., Ras, N., Kemp, A.C., Cordfunke, R.A., Dragan, I., Deelder, A.M., Kuijper, E.J., Corver, J., Drijfhout, J.W. and van Leeuwen, H.C. A novel secreted metalloprotease (CD2830) from Clostridium difficile cleaves specific proline sequences in LPXTG cell surface proteins. Mol. Cell. Proteomics 13 (2014) 1231-1244. [PMID: 24623589]

3. Hensbergen, P.J., Klychnikov, O.I., Bakker, D., Dragan, I., Kelly, M.L., Minton, N.P., Corver, J., Kuijper, E.J., Drijfhout, J.W. and van Leeuwen, H.C. Clostridium difficile secreted Pro-Pro endopeptidase PPEP-1 (ZMP1/CD2830) modulates adhesion through cleavage of the collagen binding protein CD2831. FEBS Lett. 589 (2015) 3952-3958. [PMID: 26522134]

[EC 3.4.24.89 created 2015]


Continued with EC 3.4.25
Return to Peptidases Home Page.
Return to Enzymes Home Page.