Enzyme Nomenclature. Recommendations 1992

Continued from EC 3.4.22.50 - EC 3.4.22.71


EC 3.4.23

EC 3.4.23 Aspartic Endopeptidases

Contents

EC 3.4.23.1 pepsin A
EC 3.4.23.2 pepsin B
EC 3.4.23.3 gastricsin
EC 3.4.23.4 chymosin
EC 3.4.23.5 cathepsin D
EC 3.4.23.6 now covered by EC 3.4.23.18 to EC 3.4.23.28, EC 3.4.23.30
EC 3.4.23.7 now EC 3.4.24.20
EC 3.4.23.8 now EC 3.4.24.25
EC 3.4.23.9 now EC 3.4.24.21
EC 3.4.23.10 now EC 3.4.24.22
EC 3.4.23.11 deleted
EC 3.4.23.12 nepenthesin
EC 3.4.23.13 deleted
EC 3.4.23.14 deleted
EC 3.4.23.15 renin
EC 3.4.23.16 HIV-1 retropepsin
EC 3.4.23.17 Pro-opiomelanocortin converting enzyme
EC 3.4.23.18 aspergillopepsin I
EC 3.4.23.19 aspergillopepsin II
EC 3.4.23.20 penicillopepsin
EC 3.4.23.21 rhizopuspepsin
EC 3.4.23.22 endothiapepsin
EC 3.4.23.23 mucorpepsin
EC 3.4.23.24 candidapepsin
EC 3.4.23.25 saccharopepsin
EC 3.4.23.26 rhodotorulapepsin
EC 3.4.23.27 now EC 3.4.21.103
EC 3.4.23.28 acrocylindropepsin
EC 3.4.23.29 polyporopepsin
EC 3.4.23.30 pycnoporopepsin
EC 3.4.23.31 scytalidopepsin A
EC 3.4.23.32 scytalidopepsin B
EC 3.4.23.33 now EC 3.4.21.101
EC 3.4.23.34 cathepsin E
EC 3.4.23.35 barrierpepsin
EC 3.4.23.36 signal peptidase II
EC 3.4.23.37 now EC 3.4.21.100
EC 3.4.23.38 plasmepsin I
EC 3.4.23.39 plasmepsin II
EC 3.4.23.40 phytepsin
EC 3.4.23.41 yapsin 1
EC 3.4.23.42 thermopsin
EC 3.4.23.43 prepilin peptidase
EC 3.4.23.44 nodavirus endopeptidase
EC 3.4.23.45 memapsin 1
EC 3.4.23.46 memapsin 2
EC 3.4.23.47 HIV-2 retropepsin
EC 3.4.23.48 plasminogen activator Pla
EC 3.4.23.49 omptin
EC 3.4.23.50 human endogenous retrovirus K endopeptidase
EC 3.4.23.51 HycI peptidase
EC 3.4.23.52 preflagellin peptidase

Entries

EC 3.4.23.1

Accepted name: pepsin A

Reaction: Preferential cleavage: hydrophobic, preferably aromatic, residues in P1 and P1' positions. Cleaves Phe1Val, Gln4His, Glu13Ala, Ala14Leu, Leu15Tyr, Tyr16Leu, Gly23Phe, Phe24Phe and Phe25Tyr bonds in the B chain of insulin

Other names: pepsin; lactated pepsin; pepsin fortior; fundus-pepsin; elixir lactate of pepsin; P I; lactated pepsin elixir; P II; pepsin R; pepsin D

Comments: The predominant endopeptidase in the gastric juice of vertebrates, formed from pepsinogen A by limited proteolysis. Human pepsin A occurs in five molecular forms. Pig pepsin D [1,2] is unphosphorylated pepsin A. Type example of peptidase family A1. Formerly EC 3.4.4.1

Links to other databases: BRENDA, EXPASY, KEGG, GTD, MEROPS, Metacyc, PDB, CAS registry number: 9001-75-6

References:

1. Lee, D. and Ryle, A.P. Pepsinogen D. A fourth proteolytic zymogen from pig gastric mucosa. Biochem. J. 104 (1967) 735-741. [PMID: 4167464]

2. Lee, D. and Ryle, A.P. Pepsin D. A minor component of commercial pepsin preparations. Biochem. J. 104 (1967) 742-748. [PMID: 4860638]

3. Foltmann, R. Gastric proteinases -structure, function, evolution and mechanism of action. Essays Biochem. 17 (1981) 52-84. [PMID: 6795036]

4. James, M.N.G. and Sielecki, A.R. Molecular structure of an aspartic proteinase zymogen, porcine pepsinogen, at 1.8 Å resolution. Nature 319 (1986) 33-38. [PMID: 3941737]

5. Fruton, J.S. Aspartyl proteinases. In New Comprehensive Biochemistry Vol. 16, Hydrolytic Enzymes (Neuberger, A. and Brocklehurst, K., eds), pp. 1-38 (1987) Elsevier, Amsterdam

6. Tang, J. and Wong, R.N.S. Evolution in the structure and function of aspartic proteases. J. Cell. Biochem. 33 (1987) 53-63. [PMID: 3546346]

7. Pohl, J. and Dunn, B.M. Secondary enzyme-substrate interactions: kinetic evidence for ionic interactions between substrate side chains and the pepsin active site. Biochemistry 27 (1988) 4827-4834. [PMID: 3139029]

[EC 3.4.23.1 created 1961 as EC 3.4.4.1, transferred 1972 to EC 3.4.23.1, modified 1986, modified 1989]

EC 3.4.23.2

Accepted name: pepsin B

Reaction: Degradation of gelatin; little activity on hemoglobin. Specificity on B chain of insulin more restricted than that of pepsin A; does not cleave at Phe1-Val, Gln4-His or Gly23-Phe

Other names: parapepsin I; pig gelatinase

Comments: Formed from pig pepsinogen B. In peptidase family A1 (pepsin A family)

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, CAS registry number: 9025-48-3

References:

1. Ryle, A.P. The porcine pepsins and pepsinogens. Methods Enzymol. 19 (1970) 316-336

[EC 3.4.23.2 created 1961 as EC 3.4.4.2, transferred 1972 to EC 3.4.23.2, modified 1986]

EC 3.4.23.3

Accepted name: gastricsin

Reaction: More restricted specificity than pepsin A, but shows preferential cleavage at Tyr bonds. High activity on hemoglobin

Other names: pepsin C; pig parapepsin II; parapepsin II

Comments: Formed from progastricsin, apparently in the gastric juice of most vertebrates. In addition to the fundus, progastricsin is also secreted in antrum and proximal duodenum. Seminal plasma contains a zymogen that is immunologically identical with progastricsin [6]. In peptidase family A1 (pepsin A family). Formerly EC 3.4.4.22

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 9012-71-9

References:

1. Ryle, A.P. The porcine pepsins and pepsinogens. Methods Enzymol. 19 (1970) 316-336

2. Tang, J. Gastricsin and pepsin. Methods Enzymol. 19 (1970) 406-421

3. Foltmann, B. Gastric proteinases - structure, function, evolution and mechanism of action. Essays Biochem. 17 (1981) 52-84. [PMID: 6795036]

4. Foltmann, B. and Jensen, A.L. Human progastricsin - analysis of intermediates during activation into gastricsin and determination of the amino-acid sequence of the propart. Eur. J. Biochem. 128 (1982) 63-70. [PMID: 6816595]

5. Martin, P., Trieu-Cuot, P., Collin, J.-C. and Ribadeau Dumas, B. Purification and characterization of bovine gastricsin. Eur. J. Biochem. 122 (1982) 31-39. [PMID: 6800788]

6. Reid, W.A., Vongsorasak, L., Svasti, J., Valler, M.J. and Kay J. Identification of the acid proteinase in human seminal fluid as a gastricsin originating in the prostate. Cell Tissue Res. 236 (1984) 597-600. [PMID: 6432332]

7. Hayano, T., Sogawa, K., Ichihara, Y., Fujii-Kuriyama, Y. and Takahasi, K. Primary structure of human pepsinogen C gene. J. Biol. Chem. 263 (1988) 1382-1385. [PMID: 3335549]

[EC 3.4.23.3 created 1965 as EC 3.4.4.22, transferred 1972 to EC 3.4.23.3, modified 1986]

EC 3.4.23.4

Accepted name: chymosin

Reaction: Broad specificity similar to that of pepsin A. Clots milk by cleavage of a single Ser-Phe105Met-Ala bond in κ-chain of casein

Other names: rennin (but this should be avoided since it leads to confusion with renin)

Comments: Neonatal gastric enzyme with high milk clotting and weak general proteolytic activity, formed from prochymosin. Found among mammals with postnatal uptake of immunoglobulins. In peptidase family A1(pepsin A family)

Links to other databases: BRENDA, EXPASY, GTD, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 9001-98-3

References:

1. Foltmann, B. A review of prorennin and rennin. C. R. Trav. Lab. Carlsberg 35 (1966) 143-231. [PMID: 5330666]

2. Harris, T.J.R., Lowe, P.A., Lyons, A., Thomas, P.G., Eaton, M.A.W., Millican, T.A., Patel, T.P., Bose, C.C., Carey, N.H. and Doel, M.T. Molecular cloning and nucleotide sequence of cDNA coding for calf preprochymosin. Nucleic Acids Res. 10 (1982) 2177-2187. [PMID: 6283469]

3. Visser, S., Slangen, C.J. and van Rooijen, P.J. Peptide substrates for chymosin (rennin). Interaction sites in κ-casein-related sequences located outside the (103-108)-hexapeptide region that fits into the enzyme's active-site cleft. Biochem. J. 244 (1987) 553-558. [PMID: 3128264]

[EC 3.4.23.4 created 1961 as EC 3.4.4.3, transferred 1972 to EC 3.4.23.4, modified 1986]

EC 3.4.23.5

Accepted name: cathepsin D

Reaction: Specificity similar to, but narrower than, that of pepsin A. Does not cleave the Gln4-His bond in B chain of insulin

Comments: Occurs intracellularly, in lysosomes. A zymogen form is known [4]. In peptidase family A1 (pepsin A family). Formerly EC 3.4.4.23

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 9025-26-7

References:

1. Barrett, A.J. Cathepsin D and other carboxyl proteinases. In Proteinases in Mammalian Cells and Tissues (Barrett, A.J., ed.) p. 209-248 (1977) North-Holland Publishing Co, Amsterdam.

2. Takahashi, T. and Tang, J. Cathepsin D from porcine and bovine spleen. Methods Enzymol. 80 (1981) 565-581. [PMID: 7341918]

3. Faust, P.L., Kornfeld, S. and Chirgwin, J.M. Cloning and sequence analysis of cDNA for human cathepsin D. Proc. Natl. Acad. Sci. USA 82 (1985) 4910-4914. [PMID: 3927292]

4. Conner, G.E. Isolation of procathepsin D from mature cathepsin D by pepstatin affinity chromatography. Autocatalytic proteolysis of the zymogen form of the enzyme. Biochem. J. 263 (1989) 601-604. [PMID: 2512908]

[EC 3.4.23.5 created 1965 as EC 3.4.4.23, transferred 1972 to EC 3.4.23.5, modified 1986]

[EC 3.4.23.6 Transferred entry: now EC 3.4.23.18 - aspergillopepsin I; EC 3.4.23.19 - aspergillopepsin II; EC 3.4.23.20 - penicillopepsin; EC 3.4.23.21 - rhizopuspepsin; EC 3.4.23.22 - endothiapepsin; EC 3.4.23.23 - mucorpepsin; EC 3.4.23.24 - candidapepsin; EC 3.4.23.25 - saccharopepsin; EC 3.4.23.26 - rhodotorulapepsin; EC 3.4.23.27 - physaropepsin; EC 3.4.23.28 - acrocylindropepsin; EC 3.4.23.30 - pycnoporopepsin (EC 3.4.23.6 created 1961 as EC 3.4.4.17, transferred 1972 to EC 3.4.23.6, modified 1981, deleted 1992 [EC 3.4.23.7, EC 3.4.23.8, EC 3.4.23.9, EC 3.4.23.10, EC 3.4.99.1, EC 3.4.99.15 and EC 3.4.99.25 all created 1972 and incorporated 1978])]

[EC 3.4.23.7 Transferred entry: now EC 3.4.23.20 - penicillopepsin (EC 3.4.23.7 created 1972, modified 1981, deleted 1978 [transferred to EC 3.4.23.6, deleted 1992])]

[EC 3.4.23.8 Transferred entry: now EC 3.4.23.25 - saccharopepsin (EC 3.4.23.8 created 1972, modified 1981, deleted 1978 [transferred to EC 3.4.23.6, deleted 1992])]

[EC 3.4.23.9 Transferred entry: now EC 3.4.23.21 - rhizopuspepsin (EC 3.4.23.9 created 1972, modified 1981, deleted 1978 [transferred to EC 3.4.23.6, deleted 1992])]

[EC 3.4.23.10 Transferred entry: now EC 3.4.23.22 - endothiapepsin (EC 3.4.23.10 created 1972, modified 1981, deleted 1978 [transferred to EC 3.4.23.6, deleted 1992])]

[EC 3.4.23.11 Deleted entry: thyroid aspartic proteinase (EC 3.4.23.11 created 1978, modified 1981, deleted 1992)]

EC 3.4.23.12

Accepted name: nepenthesin

Reaction: Similar to pepsin, but also cleaves on either side of Asp and at LysArg

Other names: Nepenthes aspartic proteinase; Nepenthes acid proteinase; nepenthacin; nepenthasin; aspartyl endopeptidase

Comments: From the insectivorous plants Nepenthes spp. (secretions) and Drosera peltata (ground-up leaves). Formerly EC 3.4.99.4. Aspartic endopeptidases are probably present in many other plants, including Lotus [3] (formerly EC 3.4.23.13) and sorghum [2] (formerly EC 3.4.23.14). In peptidase family A1 (pepsin A family)

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, CAS registry number: 9073-80-7

References:

1. Amagase, S., Nakayama, S. and Tsugita, A. Acid protease in Nepenthes. II. Study on the specificty of nepenthesin. J. Biochem. (Tokyo) 66 (1969) 431-439. [PMID: 5354017]

2. Garg, G.K. and Virupaksha, T.K. Acid protease from germinated sorghum. 2. Substrate specificity with synthetic peptides and ribonuclease A. Eur. J. Biochem. 17 (1970) 4-12. [PMID: 5486576]

3. Shinano, S. and Fukushima, K. Studies on lotus seed protease. Part III. Some physicochemical and enzymic properties. Agric. Biol. Chem. 35 (1971) 1488-1494

4. Amagase, S. Digestive enzymes in insectivorous plants. III. Acid proteases in the genus Nepenthes and Drosera peltata. J. Biochem. (Tokyo) 72 (1972) 73-81. [PMID: 5069751]

5. Takahashi, K., Chang, W-J. and Ko, J-S. Specific inhibition of acid proteases from brain, kidney, skeletal muscle, and insectivorous plants by diazoacetyl-DL-norleucine methyl ester and by pepstatin. J. Biochem. (Tokyo) 76 (1974) 897-899. [PMID: 4436292]

6. Tökés, Z.A., Woon, W.C. and Chambers, S.M. Digestive enzymes secreted by the carnivorous plant Nepenthes macferlani L. Planta 119 (1974) 39-46

[EC 3.4.23.12 created 1972 as EC 3.4.99.4, transferred 1978 to EC 3.4.23.12, modified 1981]

[EC 3.4.23.13 Deleted entry: Lotus aspartic proteinase (EC 3.4.23.13 created 1978, modified 1981, deleted 1992)]

[EC 3.4.23.14 Deleted entry: sorghum aspartic proteinase (EC 3.4.23.14 created 1978, modified 1981, deleted 1992)]

EC 3.4.23.15

Accepted name: renin

Reaction: Cleavage of Leu bond in angiotensinogen to generate angiotensin I

Other names: angiotensin-forming enzyme; angiotensinogenase

Comments: Formed from prorenin in plasma and kidney. In peptidase family A1 (pepsin A family). Formerly EC 3.4.99.19

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 9015-94-5

References:

1. Inagami, T. and Murakami, K. Pure renin. Isolation from hog kidney and characterization. J. Biol. Chem. 252 (1977) 2978-2983. [PMID: 16012]

2. Slater, E.E. Renin. Methods Enzymol. 80 (1981) 427-442. [PMID: 7043197]

3. Inagami, T. Structure and function of renin. J. Hypertension 7 (Suppl. 2) (1989) S3-S8. [PMID: 2785652]

4. Sielecki, A.R., Hayakawa, K., Fujinaga, M., Murphy, M.E.P., Fraser, M., Muir, A.K., Carilli, C.T., Lewicki, J.A., Baxter, J.D. and James, M.N.G. Structure of recombinant human renin, a target for cardiovascular-active drugs, at 2.5 Å resolution. Science 243 (1989) 1346-1351. [PMID: 2493678]

[EC 3.4.23.15 created 1961 as EC 3.4.4.15, transferred 1972 to EC 3.4.99.19, transferred 1981 to EC 3.4.23.15]

EC 3.4.23.16

Accepted name: HIV-1 retropepsin

Reaction: Specific for a P1 residue that is hydrophobic, and P1' variable, but often Pro

Other names: human immunodeficiency virus type 1 protease; gag protease; HIV aspartyl protease; HIV proteinase; retroproteinase; HIV-1 protease; HIV-2 protease

Comments: Present in human immunodeficiency virus type 1. Contributes to the maturation of the viral particle, and is a target of antiviral drugs. Active enzyme is a dimer of identical 11-kDa subunits. Similar enzymes occur in other retroviruses [1]. Type example of peptidase family A2

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 144114-21-6

References:

1. Kuo, L.C. and Shafer, J.A. (eds) Retroviral Proteases. Methods Enzymol. 241 (1994) 1-431

2. Dunn, B.M. Human immunodeficiency virus 1 retropepsin. In: : Handbook of Proteolytic Enzymes (Barrett, A.J., Rawlings, N.D. and Woessner, J.F. eds), pp.919-928 (1998) Academic Press, London

[EC 3.4.23.16 created 1992, modified 2000]

EC 3.4.23.17

Accepted name: pro-opiomelanocortin converting enzyme

Reaction: Cleavage at paired basic residues in certain prohormones, either between them, or on the carboxyl side

Other names: prohormone converting enzyme; pro-opiomelanocortin-converting enzyme; proopiomelanocortin proteinase; PCE

Comments: A 70 kDa membrane-bound enzyme isolated from cattle pituitary secretory vesicle. Formerly EC 3.4.99.38

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, CAS registry number: 80891-34-5

References:

1. Loh, Y.P., Parish, D.C. and Tuteja, R. Purification and characterization of a paired basic residue-specific pro-opiomelanocortin converting enzyme from bovine pituitary intermediate lobe secretory vesicles. J. Biol. Chem. 260 (1985) 7194-7205. [PMID: 2987247]

2. Loh, Y.P. Kinetic studies on the processing of human β-lipotropin by bovine pituitary intermediate lobe pro-opiomelanocortin-converting enzyme. J. Biol. Chem. 261 (1986) 11949-11955. [PMID: 3017955]

3. Estivariz, F.E., Birch, N.P. and Loh, Y.P. Generation of Lys-γ3-melanotropin from pro-opiomelanocortin1-77 by a bovine intermediate lobe secretory vesicle membrane-associated aspartic protease and purified pro-opiomelanocortin converting enzyme. J. Biol. Chem. 264 (1989) 17796-17801. [PMID: 2553692]

[EC 3.4.23.17 created 1989 as EC 3.4.99.38, transferred 1992 to EC 3.4.23.17]

EC 3.4.23.18

Accepted name: aspergillopepsin I

Reaction: Hydrolysis of proteins with broad specificity. Generally favours hydrophobic residues in P1 and P1', but also accepts Lys in P1, which leads to activation of trypsinogen. Does not clot milk

Other names: Aspergillus acid protease; Aspergillus acid proteinase; Aspergillus aspartic proteinase; Aspergillus awamori acid proteinase; Aspergillus carboxyl proteinase; (see also Comments); carboxyl proteinase; Aspergillus kawachii aspartic proteinase; Aspergillus saitoi acid proteinase; pepsin-type aspartic proteinase; Aspergillus niger acid proteinase; sumizyme AP; proctase P; denapsin; denapsin XP 271; proctase

Comments: Found in a variety of Aspergillus species (imperfect fungi): Aspergillus awamori (awamorin, aspergillopepsin A: [8]), A. foetidus (aspergillopepsin F: [6]), A. fumigatus [7], A. kawachii [9], A. niger (proteinase B, proctase B: [2,4]), A. oryzae (trypsinogen kinase: [3,10]), A. saitoi (aspergillopeptidase A: [10]), and A. sojae [5,10]. In peptidase family A1 (pepsin A family). Formerly included in EC 3.4.23.6

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 9025-49-4

References:

1. Kovaleva, G.G., Shimanskaya, M.P. and Stepanov, V.M. The site of diazoacetyl inhibitor attachment to acid proteinase of Aspergillus awamori - an analog of penicillopepsin and pepsin. Biochem. Biophys. Res. Commun. 49 (1972) 1075-1082. [PMID: 4565799]

2. Morihara, K. and Oka, T. Comparative specificity of microbial acid proteinases for synthetic peptides. III. Relationship with their trypsinogen activating ability. Arch. Biochem. Biophys. 157 (1973) 561-572. [PMID: 4593189]

3. Davidson, R., Gertler, A. and Hofmann, T. Aspergillus oryzae acid proteinase. Purification and properties, and formation of π-chymotrypsin. Biochem. J. 147 (1975) 45-53. [PMID: 239702]

4. Chang, W.-J., Horiuchi, S., Takahashi, K., Yamasaki, M. and Yamada, Y. The structure and function of acid proteases. VI. Effects of acid protease-specific inhibitors on the acid proteases from Aspergillus niger var. macrosporus. J. Biochem. (Tokyo) 80 (1976) 975-981. [PMID: 12156]

5. Tanaka, N., Takeuchi, M. and Ichishima, E. Purification of an acid proteinase from Aspergillus saitoi and determination of peptide bond specificity. Biochim. Biophys. Acta 485 (1977) 406-416. [PMID: 21699]

6. Ostoslavskaya, V.I., Kotlova, E.K., Stepanov, V.M., Rudenskaya, G.H., Baratova, L.A. and Belyanova, L.P. Aspergillopepsin F-A carboxylic proteinase from Aspergillus foetidus. Bioorg. Khim. 5 (1976) 595-603

7. Panneerselvam, M. and Dhar, S.C. Studies on the peptide bond specificity and the essential groups of an acid proteinase from Aspergillus fumigatus. Ital. J. Biochem. 30 (1981) 207-216. [PMID: 7024192]

8. Ostoslavskaya, V.I., Revina, L.P., Kotlova, E.K., Surova, I.A., Levin, E.D., Timokhima, E.A. and Stepanov, V.M. The primary structure of aspergillopepsin A, aspartic proteinase from Aspergillus awamori. IV. Amino acid sequence of the enzyme. Bioorg. Khim. 12 (1986) 1030-1047

9. Yagi, F., Fan, J., Tadera, K. and Kobayashi, A. Purification and characterization of carboxyl proteinase from Aspergillus kawachii. Agric. Biol. Chem. 50 (1986) 1029-1033

10. Majima, E., Oda, K., Murao, S. and Ichishima, E. Comparative study on the specificities of several fungal aspartic and acidic proteinases towards the tetradecapeptide of a renin substrate. Agric. Biol. Chem. 52 (1988) 787-793

[EC 3.4.23.18 created 1992 (EC 3.4.23.6 created 1961 as EC 3.4.4.17, transferred 1972 to EC 3.4.23.6, modified 1981 [EC 3.4.23.7, EC 3.4.23.8, EC 3.4.23.9, EC 3.4.23.10, EC 3.4.99.1, EC 3.4.99.15 and EC 3.4.99.25 all created 1972 and incorporated 1978], part incorporated 1992)]

EC 3.4.23.19

Accepted name: aspergillopepsin II

Reaction: Preferential cleavage in B chain of insulin: Asn3Gln, Gly13Ala, Tyr26Thr

Other names: proteinase A; proctase A; Aspergillus niger var. macrosporus aspartic proteinase

Comments: Isolated from Aspergillus niger var. macrosporus, distinct from proteinase B (see aspergillopepsin I) in specificity and insensitivity to pepstatin. In peptidase family A4 (scytalidopepsin B family). Formerly included in EC 3.4.23.6

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 9025-49-4

References:

1. Chang, W.-J., Horiuchi, S., Takahashi, K., Yamasaki, M. and Yamada, Y. The structure and function of acid proteases. VI. Effects of acid protease-specific inhibitors on the acid proteases from Aspergillus niger var. macrosporus. J. Biochem. (Tokyo) 80 (1976) 975-981. [PMID: 12156]

2. Iio, K. and Yamasaki, M. Specificity of acid proteinase A from Aspergillus niger var. macrosporus towards B-chain of performic acid oxidized bovine insulin. Biochim. Biophys. Acta 429 (1976) 912-924. [PMID: 1268233]

[EC 3.4.23.19 created 1992 (EC 3.4.23.6 created 1992 (EC 3.4.23.6 created 1961 as EC 3.4.4.17, transferred 1972 to EC 3.4.23.6, modified 1981 [EC 3.4.23.7, EC 3.4.23.8, EC 3.4.23.9, EC 3.4.23.10, EC 3.4.99.1, EC 3.4.99.15 and EC 3.4.99.25 all created 1972 and incorporated 1978], part incorporated 1992)]

EC 3.4.23.20

Accepted name: penicillopepsin

Reaction: Hydrolysis of proteins with broad specificity similar to that of pepsin A, preferring hydrophobic residues at P1 and P1', but also cleaving Gly20Glu in the B chain of insulin. Clots milk, and activates trypsinogen

Other names: peptidase A; Penicillium janthinellum aspartic proteinase; acid protease A; Penicillium citrinum acid proteinase; Penicillium cyclopium acid proteinase; Penicillium expansum acid proteinase; Penicillium janthinellum acid proteinase; Penicillium expansum aspartic proteinase; Penicillium aspartic proteinase; Penicillium caseicolum aspartic proteinase; Penicillium roqueforti acid proteinase; Penicillium duponti aspartic proteinase; Penicillium citrinum aspartic proteinase

Comments: From the imperfect fungus Penicillium janthinellum. In peptidase family A1 (pepsin A family). Closely related enzymes have been isolated from P. roqueforti [2] and P. duponti [3]. Formerly EC 3.4.23.7, and included in EC 3.4.23.6

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 9074-08-2

References:

1. Mains, G., Takahashi, M., Sodek, J. and Hofmann, T. The specificity of penicillopepsin. Can. J. Biochem. 49 (1971) 1134-1149. [PMID: 4946839]

2. Zevaco, C., Hermier, J. and Gripon, J.-C. Le système protéolytique de Penicillium roqueforti. II - Purification et propriétés de la protéase acide. Biochimie 55 (1973) 1353-1360. [PMID: 4790849]

3. Emi, S., Myers, D.V. and Iacobucci, G.A. Purification and properties of the thermostable acid protease of Penicillium duponti. Biochemistry 15 (1976) 842-848. [PMID: 2287]

4. Hofmann, T. Penicillopepsin. Methods Enzymol. 45 (1976) 434-450. [PMID: 1012008]

5. Hsu, I.-N., Delbaere, L.T.J., James, M.N.G. and Hofmann, T. Penicillopepsin from Penicillium janthinellum crystal structure at 2.8 Å and sequence homology with porcine pepsin. Nature 266 (1977) 140-144. [PMID: 323722]

[EC 3.4.23.20 created 1992 (EC 3.4.23.6 created 1992 (EC 3.4.23.6 created 1961 as EC 3.4.4.17, transferred 1972 to EC 3.4.23.6, modified 1981 [EC 3.4.23.7, EC 3.4.23.8, EC 3.4.23.9, EC 3.4.23.10, EC 3.4.99.1, EC 3.4.99.15 and EC 3.4.99.25 all created 1972 and incorporated 1978], part incorporated 1992)]

EC 3.4.23.21

Accepted name: rhizopuspepsin

Reaction: Hydrolysis of proteins with broad specificity similar to that of pepsin A, preferring hydrophobic residues at P1 and P1'. Clots milk and activates trypsinogen. Does not cleave Gln4-His, but does cleave His10Leu and Val12Glu in B chain of insulin

Other names: Rhizopus aspartic proteinase; neurase; Rhizopus acid protease; Rhizopus acid proteinase

Comments: From the zygomycete fungus Rhizopus chinensis. A similar endopeptidase is found in R. niveus [2]. In peptidase family A1 (pepsin A family). Formerly EC 3.4.23.9, and included in EC 3.4.23.6

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 9074-09-3

References:

1. Tsuru, D., Hattori, A., Tsuji, H., Yamamoto, T. and Fukumoto, J. Studies on mold proteases. Part II. Substrate specificity of acid protease of Rhizopus chinensis. Agric. Biol. Chem. 33 (1969) 1419-1426

2. Kurono, Y., Chidimatsu, M., Horikoshi, K. and Ikeda, Y. Isolation of a protease from a Rhizopus product. Agric. Biol. Chem. 35 (1971) 1668-1675

3. Ohtsuru, M., Tang, J. and Delaney, R. Purification and characterization of rhizopuspesin isozymes from a liquid culture of Rhizopus chinensis. Int. J. Biochem. 14 (1982) 925-932. [PMID: 6751894]

4. Suguna, K., Padlan, E.A., Smith, C.W., Carlson, W.D. and Davies, D.R. Binding of a reduced peptide inhibitor to the aspartic proteinase from Rhizopus chinensis: implications for a mechanism of action. Proc. Natl. Acad. Sci. USA 84 (1987) 7009-7013. [PMID: 3313384]

[EC 3.4.23.21 created 1992 (EC 3.4.23.6 created 1992 (EC 3.4.23.6 created 1961 as EC 3.4.4.17, transferred 1972 to EC 3.4.23.6, modified 1981 [EC 3.4.23.7, EC 3.4.23.8, EC 3.4.23.9, EC 3.4.23.10, EC 3.4.99.1, EC 3.4.99.15 and EC 3.4.99.25 all created 1972 and incorporated 1978], part incorporated 1992)]

EC 3.4.23.22

Accepted name: endothiapepsin

Reaction: Hydrolysis of proteins with specificity similar to that of pepsin A; prefers hydrophobic residues at P1 and P1', but does not cleave Ala14-Leu in the B chain of insulin or Z-Glu-Tyr. Clots milk

Other names: Endothia aspartic proteinase; Endothia acid proteinase; Endothia parasitica acid proteinase; Endothia parasitica aspartic proteinase

Comments: From the ascomycete Endothia parasitica. In peptidase family A1 (pepsin A family). Formerly EC 3.4.23.10, and included in EC 3.4.23.6

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 37205-60-0

References:

1. Whitaker, J.R. Protease of Endothia parasitica. Methods Enzymol. 19 (1970) 436-445

2. Williams, D.C., Whitaker, J.R. and Caldwell, P.V. Hydrolysis of peptide bonds of the oxidized B-chain of insulin by Endothia parasitica protease. Arch. Biochem. Biophys. 149 (1972) 52-61. [PMID: 4552802]

3. Barkholt, V. Amino acid sequence of endothiapepsin. Complete primary structure of the aspartic protease from Endothia parasitica. Eur. J. Biochem. 167 (1987) 327-338. [PMID: 3305016]

4. Cooper, J., Foundling, S., Hemmings, A., Blundell, T., Jones, D.M., Hallett, A. and Szelke, M. The structure of a synthetic pepsin inhibitor complexed with endothiapepsin. Eur. J. Biochem. 169 (1987) 215-221 [PMID: 3119339]

[EC 3.4.23.22 created 1992 (EC 3.4.23.6 created 1992 (EC 3.4.23.6 created 1961 as EC 3.4.4.17, transferred 1972 to EC 3.4.23.6, modified 1981 [EC 3.4.23.7, EC 3.4.23.8, EC 3.4.23.9, EC 3.4.23.10, EC 3.4.99.1, EC 3.4.99.15 and EC 3.4.99.25 all created 1972 and incorporated 1978], part incorporated 1992)]

EC 3.4.23.23

Accepted name: mucorpepsin

Reaction: Hydrolysis of proteins, favouring hydrophobic residues at P1 and P1'. Clots milk. Does not accept Lys at P1, and hence does not activate trypsinogen

Other names: Mucor rennin; Mucor aspartic proteinase; Mucor acid proteinase; Mucor acid protease; Mucor miehei aspartic proteinase; Mucor miehei aspartic protease; Mucor aspartic proteinase; Mucor pusillus emporase; Fromase 100; Mucor pusillus rennin; Fromase 46TL; Mucor miehei rennin

Comments: Isolated from the zygomycete fungi Mucor pusillus and M. miehei. The two species variants show 83% sequence identity and are immunologically crossreactive. In peptidase family A1 (pepsin A family). Formerly included in EC 3.4.23.6

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 148465-73-0

References:

1. Arima, K., Yu, J. and Iwasaki, S. Milk-clotting enzyme from Mucor pusillus var. lindt. Methods Enzymol. 19 (1970) 446-459

2. Ottesen, M. and Rickert, W. The acid protease of Mucor miehei. Methods Enzymol. 19 (1970) 459-460

3. Sternberg, M. Bond specificity, active site and milk cloting mechanism of the Mucor miehei protease. Biochim. Biophys. Acta 285 (1972) 383-392. [PMID: 4573298]

4. Oka, T., Ishino, K., Tsuzuki, H., Morihara, K. and Arima, K. On the specificity of a rennin-like enzyme from Mucor pusillus. Agric. Biol. Chem. 37 (1973) 1177-1184

5. Baudy, M., Foundling, S., Pavlik, M., Blundell, T. and Kostka, V. Protein chemical characterization of Mucor pusillus aspartic proteinase. Amino acid sequence homology with the other aspartic proteinases, disulfide bond arrangement and site of carbohydrate attachment. FEBS Lett. 235 (1988) 271-274. [PMID: 3042459]

[EC 3.4.23.23 created 1992 (EC 3.4.23.6 created 1992 (EC 3.4.23.6 created 1961 as EC 3.4.4.17, transferred 1972 to EC 3.4.23.6, modified 1981 [EC 3.4.23.7, EC 3.4.23.8, EC 3.4.23.9, EC 3.4.23.10, EC 3.4.99.1, EC 3.4.99.15 and EC 3.4.99.25 all created 1972 and incorporated 1978], part incorporated 1992)]

EC 3.4.23.24

Accepted name: candidapepsin

Reaction: Preferential cleavage at the carboxyl of hydrophobic amino acids, but fails to cleave Leu15-Tyr, Tyr16-Leu and Phe24-Phe of insulin B chain. Activates trypsinogen, and degrades keratin

Other names: Candida albicans aspartic proteinase; Candida albicans carboxyl proteinase; Candida albicans secretory acid proteinase; Candida olea acid proteinase; Candida aspartic proteinase; Candida olea aspartic proteinase; Candida albicans aspartic proteinase

Comments: This endopeptidase from the imperfect yeast Candida albicans is inhibited by pepstatin, but not by methyl 2-diazoacetamidohexanoate or 1,2-epoxy-3-(p-nitrophenoxy)propane. In peptidase family A1 (pepsin A family). Formerly included in EC 3.4.23.6

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 69458-91-9

References:

1. Remold, H., Fasold, H. and Staib, F. Purification and characterization of a proteolytic enzyme from Candida albicans. Biochim. Biophys. Acta 167 (1968) 399-406. [PMID: 5729955]

2. Rüchel, R. Properties of a purified proteinase from the yeast Candida albicans. Biochim. Biophys. Acta 659 (1981) 99-113. [PMID: 7018586]

3. Negi, M., Tsuboi, R., Matsui, T. and Ogawa, H. Isolation and characterization of proteinase from Candida albicans: substrate specificity. J. Invest. Dermatol. 83 (1984) 32-36. [PMID: 6203988]

4. Lott, T.J., Page, L.S., Boiron, P., Benson, J. and Reiss, E. Nucleotide sequence of the Candida albicans aspartyl proteinase gene. Nucleic Acids Res. 17 (1989) 1779 only. [PMID: 2646602]

[EC 3.4.23.24 created 1992 (EC 3.4.23.6 created 1992 (EC 3.4.23.6 created 1961 as EC 3.4.4.17, transferred 1972 to EC 3.4.23.6, modified 1981 [EC 3.4.23.7, EC 3.4.23.8, EC 3.4.23.9, EC 3.4.23.10, EC 3.4.99.1, EC 3.4.99.15 and EC 3.4.99.25 all created 1972 and incorporated 1978], part incorporated 1992)]

EC 3.4.23.25

Accepted name: saccharopepsin

Reaction: Hydrolysis of proteins with broad specificity for peptide bonds. Cleaves -Leu-LeuVal-Tyr bond in a synthetic substrate. Does not act on esters of Tyr or Arg

Other names: yeast endopeptidase A; Saccharomyces aspartic proteinase; aspartic proteinase yscA; proteinase A; proteinase yscA; yeast proteinase A; Saccharomyces cerevisiae aspartic proteinase A; yeast proteinase A; PRA

Comments: Located in the vacuole of the baker's yeast (Saccharomyces cerevisiae) cell. In peptidase family A1 (pepsin A family). Formerly EC 3.4.23.8, and included in EC 3.4.23.6

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 37228-80-1

References:

1. Hata, T., Hayashi, R. and Dot, E. Purification of yeast proteinases. Part III. Isolation and physicochemical properties of yeast proteinase A and C. Agric. Biol. Chem. 31 (1967) 357-367

2. Meussdoerffer, F., Tortora, P. and Holzer, H. Purification and properties of proteinase A from yeast. J. Biol. Chem. 255 (1980) 12087-12093. [PMID: 7002931]

3. Ammerer, G., Hunter, C.P., Rothman, J.H., Saari, G.C., Valls, L.A. and Stevens, T.H. PEP4 gene of Saccharomyces cerevisiae encodes proteinase A, a vacuolar enzyme required for processing of vacuolar precursors. Mol. Cell. Biol. 6 (1987) 2490-2499. [PMID: 3023936]

[EC 3.4.23.25 created 1992 (EC 3.4.23.6 created 1992 (EC 3.4.23.6 created 1961 as EC 3.4.4.17, transferred 1972 to EC 3.4.23.6, modified 1981 [EC 3.4.23.7, EC 3.4.23.8, EC 3.4.23.9, EC 3.4.23.10, EC 3.4.99.1, EC 3.4.99.15 and EC 3.4.99.25 all created 1972 and incorporated 1978], part incorporated 1992)]

EC 3.4.23.26

Accepted name: rhodotorulapepsin

Reaction: Specificity similar to that of pepsin A. Cleaves Z-LysAla-Ala-Ala and activates trypsinogen

Other names: Rhodotorula aspartic proteinase; Cladosporium acid protease; Cladosporium acid proteinase; Paecilomyces proteinase; Cladosporium aspartic proteinase; Paecilomyces proteinase; Rhodotorula glutinis aspartic proteinase; Rhodotorula glutinis acid proteinase; Rhodotorula glutinis aspartic proteinase II; Rhodotorula acid proteinase

Comments: From the imperfect yeast Rhodotorula glutinis. Formerly included in EC 3.4.23.6. Somewhat similar enzymes have been isolated from the imperfect yeast-like organism Cladosporium sp. [4,6] and the imperfect fungus Paecilomyces varioti ([1,2], formerly EC 3.4.99.15)

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, CAS registry number: 37259-59-9

References:

1. Sawada, J. Studies on the acid-protease of Paecilomyces varioti Bainier TPR-220. Part I. Crystallization of the acid-protease of Paecilomyces varioti Bainier TPR-220. Agric. Biol. Chem. 27 (1963) 677-683

2. Sawada, J. The acid-protease of Paecilomyces varioti. III. The specificity of the crystalline acid-protease on synthetic substrates. Agric. Biol. Chem. 28 (1964) 869-875

3. Kamada, M., Oda, K. and Murao, S. The purification of the extracellular acid protease of Rhodotorula glutinis K-24 and its general properties. Agric. Biol. Chem. 36 (1972) 1095-1101

4. Murao, S., Funakoshi, S. and Oda, K. Purification, crystallization and some enzymatic properties of acid protease of Cladosporium sp. No. 45-2. Agric. Biol. Chem. 36 (1972) 1327-1333

5. Oda, K., Kamada, M. and Murao, S. Some physicochemical properties and substrate specificity of acid protease of Rhodotorula glutinis K-24. Agric. Biol. Chem. 36 (1972) 1103-1108

6. Oda, K., Funakoshi, S. and Murao, S. Some physicochemical properties and substrate specificity of acid protease isolated from Cladosporium sp. No. 45-2. Agric. Biol. Chem. 37 (1973) 1723-1729

7. Takahashi, K. and Chang, W.-J. The structure and function of acid proteases. V. Comparative studies on the specific inhibition of acid proteases by diazoacetyl-DL-norleucine methyl ester, 1,2-epoxy-3-(p-nitrophenoxy)propane and pepstatin. J. Biochem. (Tokyo) 80 (1976) 497-506. [PMID: 10290]

8. Majima, E., Oda, K., Murao, S. and Ichishima, E. Comparative study on the specificities of several fungal aspartic and acidic proteinases towards the tetradecapeptide of a renin substrate. Agric. Biol. Chem. 52 (1988) 787-794

[EC 3.4.23.26 created 1992 (EC 3.4.23.6 created 1992 (EC 3.4.23.6 created 1961 as EC 3.4.4.17, transferred 1972 to EC 3.4.23.6, modified 1981 [EC 3.4.23.7, EC 3.4.23.8, EC 3.4.23.9, EC 3.4.23.10, EC 3.4.99.1, EC 3.4.99.15 and EC 3.4.99.25 all created 1972 and incorporated 1978], part incorporated 1992)]

[EC 3.4.23.27 Transferred entry: now EC 3.4.21.103, physarolisin (EC 3.4.23.27 created 1992 (EC 3.4.23.6 created 1992 (EC 3.4.23.6 created 1961 as EC 3.4.4.17, transferred 1972 to EC 3.4.23.6, modified 1981 [EC 3.4.23.7, EC 3.4.23.8, EC 3.4.23.9, EC 3.4.23.10, EC 3.4.99.1, EC 3.4.99.15 and EC 3.4.99.25 all created 1972 and incorporated 1978], part incorporated 1992), deleted 2003)]

EC 3.4.23.28

Accepted name: acrocylindropepsin

Reaction: Preference for hydrophobic residues at P1 and P1'. Action on the B chain of insulin is generally similar to that of pepsin A, but it also cleaves Leu6Cys(SO3H), Glu21Arg and Asn3Gln, although not Gln4-His

Other names: Acrocylindrium proteinase; Acrocylindrium acid proteinase

Comments: From the imperfect fungus Acrocylindrium sp. Has a very low pH optimum on casein of 2.0. In peptidase family A1 (pepsin A family). Formerly EC 3.4.99.1 and included in EC 3.4.23.6

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, CAS registry number: 37288-84-9

References:

1. Uchino, F., Kurono, Y. and Doi, S. Purification and some properties of crystalline acid protease from Acrocylindrium sp. Agric. Biol. Chem. 31 (1967) 428-434

2. Ichihara, S. and Uchino, F. The specificity of acid proteinase from Acrocylindrium. Agric. Biol. Chem. 39 (1975) 423-428

3. Takahashi, K. and Chang, W.-J. The structure and function of acid proteases. V. Comparative studies on the specific inhibition of acid proteases by diazoacetyl-DL-norleucine methyl ester, 1,2-epoxy-3-(p-nitrophenoxy)propane and pepstatin. J. Biochem. (Tokyo) 80 (1976) 497-506. [PMID: 10290]

[EC 3.4.23.28 created 1992 (EC 3.4.23.6 created 1992 (EC 3.4.23.6 created 1961 as EC 3.4.4.17, transferred 1972 to EC 3.4.23.6, modified 1981 [EC 3.4.23.7, EC 3.4.23.8, EC 3.4.23.9, EC 3.4.23.10, EC 3.4.99.1, EC 3.4.99.15 and EC 3.4.99.25 all created 1972 and incorporated 1978], part incorporated 1992)]

EC 3.4.23.29

Accepted name: polyporopepsin

Reaction: Milk clotting activity, broad specificity, but fails to cleave Leu15-Tyr or Tyr16-Leu of insulin B chain

Other names: Polyporus aspartic proteinase; Irpex lacteus aspartic proteinase; Irpex lacteus carboxyl proteinase B

Comments: From the basidiomycete Polyporus tulipiferae (formerly Irpex lacteus). In peptidase family A1 (pepsin A family)

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 61573-73-7

References:

1. Kobayashi, H., Kusakabe, I. and Murakami, K. Substrate specificity of a carboxyl proteinase from Irpex lacteus. Agric. Biol. Chem. 47 (1983) 1921-1923

2. Kobayashi, H., Sekibata, S., Shibuya, H., Yoshida, S., Kusakabe, I. and Murakami, K. Cloning and sequence analysis of cDNA for Irpex lacteus aspartic proteinase. Agric. Biol. Chem. 53 (1989) 1927-1933

[EC 3.4.23.29 created 1992]

EC 3.4.23.30

Accepted name: pycnoporopepsin

Reaction: Similar to pepsin A, but narrower, cleaving only three bonds in the B chain of insulin: Ala14Leu, Tyr16Leu, and Phe24Phe

Other names: proteinase Ia; Pycnoporus coccineus aspartic proteinase; Trametes acid proteinase

Comments: From the basidiomycete Pycnoporus sanguineus, formerly known as P. coccineus and Trametes sanguinea. Formerly included in EC 3.4.23.6

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, CAS registry number: 77967-78-3

References:

1. Tomoda, K. and Shimazono, H. Acid protease produced by Trametes sanguinea a wood-destroying fungus. Part I. Purification and crystallization of the enzyme. Agric. Biol. Chem. 28 (1964) 770-773

2. Tsuru, D., Hattori, A., Tsuji, H., Yamamoto, T. and Fukumoto, J. Studies on mold proteases. Part II. Substrate specificity of acid protease of Rhizopus chinensis. Agric. Biol. Chem. 33 (1969) 1419-1426

3. Ichishima, E., Kumagai, H. and Tomoda, K. Substrate specificity of carboxyl proteinase from Pycnoporus coccineus, a wood-deteriorating fungus. Curr. Microbiol. 3 (1980) 333-337

[EC 3.4.23.30 created 1992 (EC 3.4.23.6 created 1992 (EC 3.4.23.6 created 1961 as EC 3.4.4.17, transferred 1972 to EC 3.4.23.6, modified 1981 [EC 3.4.23.7, EC 3.4.23.8, EC 3.4.23.9, EC 3.4.23.10, EC 3.4.99.1, EC 3.4.99.15 and EC 3.4.99.25 all created 1972 and incorporated 1978], part incorporated 1992)]

EC 3.4.23.31

Accepted name: scytalidopepsin A

Reaction: Hydrolysis of proteins with specificity similar to that of pepsin A, but also cleaves Cys(SO3H)7Gly and Leu17Val in the B chain of insulin

Other names: Scytalidium aspartic proteinase A; Scytalidium lignicolum aspartic proteinase; Scytalidium lignicolum aspartic proteinase A-2; Scytalidium lignicolum aspartic proteinase A-I; Scytalidium lignicolum aspartic proteinase C; Scytalidium lignicolum carboxyl proteinase; Scytalidium lignicolum acid proteinase

Comments: Isolated from the imperfect fungus Scytalidium lignicolum. Not inhibited by pepstatin-Ac, methyl 2-diazoacetamidohexanoate or 1,2-epoxy-3-(p-nitrophenyl)propane. A related enzyme from the same organism, proteinase C, is also insensitive to these inhibitors and has Mr = 406,000 [3]

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, CAS registry number: 42613-34-3

References:

1. Oda, K. and Murao, S. Purification and some enzymatic properties of acid protease A and B of Scytalidium lignicolum ATCC 24568. Agric. Biol. Chem. 38 (1974) 2435-2444

2. Oda, K. and Murao, S. Action of Scytalidium lignicolum acid proteases on insulin B-chain. Agric. Biol. Chem. 40 (1976) 1221-1225

3. Oda, K., Torishima, H. and Murao, S. Purification and characterization of acid proteinase C of Scytalidium lignicolum ATCC 24568. Agric. Biol. Chem. 50 (1986) 651-658

[EC 3.4.23.31 created 1992]

EC 3.4.23.32

Accepted name: scytalidopepsin B

Reaction: Hydrolysis of proteins with broad specificity, cleaving Phe24Phe, but not Leu15-Tyr and Phe25-Tyr in the B chain of insulin

Other names: Scytalidium aspartic proteinase B; Ganoderma lucidum carboxyl proteinase; Ganoderma lucidum aspartic proteinase; Scytalidium lignicolum aspartic proteinase B; SLB

Comments: A second endopeptidase from Scytalidium lignicolum (see scytalidopepsin A) that is insensitive to pepstatin and methyl 2-diazoacetamidohexanoate. 1,2-Epoxy-3-(p-nitrophenoxy)propane reacts with Glu53, which replaces one of the aspartic residues at the active centre. One of the smallest aspartic endopeptidases active as the monomer, with Mr 22,000. Similarly inhibitor-resistant endopeptidases are found in the basidiomycetes Lentinus edodes [1] and Ganoderma lucidum [3], and in Polyporus tulipiferae [4], a second endopeptidase distinct from polyporopepsin, but these are of typical aspartic endopeptidase size, Mr about 36,000. Type example of peptidase family G1

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 104781-89-7

References:

1. Terashita, T., Oda, K., Kono, M. and Murao, S. Streptomyces pepsin inhibitor-insensitive carboxyl proteinase from Lentinus edodes. Agric. Biol. Chem. 45 (1981) 1937-1943

2. Maita, T., Nagata, S., Matsuda, G., Maruta, S., Oda, K., Murao, S. and Tsuru, D. Complete amino acid sequence of Scytalidium lignicolum acid protease B. J. Biochem. (Tokyo) 95 (1984) 465-473

3. Terashita, T., Oda, K., Kono, M. and Murao, S. Streptomyces pepsin inhibitor-insensitive carboxyl proteinase from Ganoderma lucidum. Agric. Biol. Chem. 48 (1984) 1029-1035. [PMID: 6370989]

4. Kobayashi, H., Kusakabe, I. and Murakami, K. Purification and characterization of a pepstatin-insensitive carboxyl proteinase from Polyporus tulipiferae (Irpex lacteus). Agric. Biol. Chem. 49 (1985) 2393-2397

5. Tsuru, D., Shimada, S., Maruta, S., Yoshimoto, T., Oda, K., Murao, S., Miyata, T. and Iwanaga, S. Isolation and amino acid sequence of a peptide containing an epoxide-reactive residue from the thermolysin-digest of Scytalidium lignicolum acid protease B. J. Biochem. (Tokyo) 99 (1986) 1537-1539. [PMID: 3519605]

[EC 3.4.23.32 created 1992]

[EC 3.4.23.33 Transferred entry: now EC 3.4.21.101, xanthomonapepsin (EC 3.4.23.33 created 1992, deleted 2001)]

EC 3.4.23.34

Accepted name: cathepsin E

Reaction: Similar to cathepsin D, but slightly broader specificity

Other names: slow-moving proteinase; erythrocyte membrane aspartic proteinase; SMP; erythrocyte membrane aspartic proteinase; EMAP; non-pepsin proteinase; cathepsin D-like acid proteinase; cathepsin E-like acid proteinase; cathepsin D-type proteinase

Comments: Found in stomach, spleen, erythrocyte membrane; not lysosomal. Pro-cathepsin E is an 86 kDa disulfide-linked dimer; activation or reduction produces monomer. In peptidase family A1 (pepsin A family)

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 110910-42-4

References:

1. Lapresle, C., Puizdar, V., Porchon-Bertolotto, C., Joukoff, E. and Turk, V. Structural differences between rabbit cathepsin E and cathepsin D. Biol. Chem. Hoppe-Seyler 367 (1986) 523-526. [PMID: 3741628]

2. Yonezawa, S., Fujii, K., Maejima, Y., Tamoto, K., Mori, Y. and Muto, N. Further studies on rat cathepsin E: subcellular localization and existence of the active subunit form. Arch. Biochem. Biophys. 267 (1988) 176-183. [PMID: 3058036]

3. Jupp, R.A., Richards, A.D., Kay, J., Dunn, B.M., Wyckoff, J.B., Samloff, I.M. and Yamamoto, K. Identification of the aspartic proteinases from human erythrocyte membranes and gastric mucosa (slow-moving proteinase) as catalytically equivalent to cathepsin E. Biochem. J. 254 (1988) 895-898. [PMID: 3058118]

4. Azuma, T., Pals, G., Mohandas, T.K., Couvreur, J.M. and Taggart, R.T. Human gastric cathepsin E. Predicted sequence, localization to chromosome 1, and sequence homology with other aspartic proteinases. J. Biol. Chem. 264 (1989) 16748-16753. [PMID: 2674141]

[EC 3.4.23.34 created 1992]

EC 3.4.23.35

Accepted name: 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). In peptidase family A1 (pepsin A family)

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, CAS registry number: 152060-38-3

References:

1. Mackay, V.L., Welch, S.K., Insley, M.Y., Manney, T.R., Holly, J., Saari, G.C. and Parker, M.L. The Saccharomyces cerevisiae BAR1 gene encodes an exported protein with homology to pepsin. Proc. Natl. Acad. Sci. USA 85 (1988) 55-59. [PMID: 3124102]

2. Mackay, V.L., Armstrong, J., Yip, C., Welch, S., Walker, K., Osborn, S., Sheppard, P. and Forstrom, J. Characterization of the bar proteinase, an extracellular enzyme from the yeast Saccharomyces cerevisiae. Adv. Exp. Med. Biol. 306 (1991) 161-172. [PMID: 1812704]

[EC 3.4.23.35 created 1993]

EC 3.4.23.36

Accepted name: signal peptidase II

Reaction: Release of signal peptides from bacterial membrane prolipoproteins including murein prolipoprotein. Hydrolyses -Xaa-Yaa-Zaa(S,diacylglyceryl)Cys-, in which Xaa is hydrophobic (preferably Leu), and Yaa (Ala or Ser) and Zaa (Gly or Ala) have small, neutral sidechains

Other names: premurein-leader peptidase; prolipoprotein signal peptidase; leader peptidase II; premurein leader proteinase; leader peptidase II

Comments: An 18-kDa enzyme present in bacterial inner membranes. Inhibited by pepstatin and the antibiotic globomycin. Type example of peptidase family A8. Formerly EC 3.4.99.35

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, CAS registry number: 171715-14-3

References

1. Dev, I.K. and Ray, P.H. Signal peptidases and signal peptide hydrolases. J. Bioenerg. Biomembr. 22 (1990) 271-290

2. Zhao, X.-J. and Wu, H.C. Nucleotide sequence of the Staphylococcus aureus signal peptidase II (lsp) gene. FEBS Lett. 299 (1992) 80-84. [PMID: 1544479]

3. Sankaran, K. and Wu, H.C. Bacterial prolipoprotein signal peptidase. Methods Enzymol. 248 (1995) 169-180. [PMID: 7674920]

[EC 3.4.23.36 created 1984 as EC 3.4.99.35, transferred 1995 to EC 3.4.23.36]

[EC 3.4.23.37 Transferred entry: now EC 3.4.21.100, pseudomonapepsin (EC 3.4.23.37 created 1995)]

EC 3.4.23.38

Accepted name: plasmepsin I

Reaction: Hydrolysis of the -Phe33Leu- bond in the α-chain of hemoglobin, leading to denaturation of the molecule

Other names: aspartic hemoglobinase I; PFAPG; malaria aspartic hemoglobinase

Comments: Known from the malaria organism, Plasmodium. About 37 kDa. In peptidase family A1 (pepsin A family), closest to cathepsin D and renin in structure. Inhibited by pepstatin. Formerly included in EC 3.4.23.6

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 180189-87-1

References

1. Goldberg, D.E., Slater, A.F.G., Beavis, R., Chait, B., Cerami, A. and Henderson, G.B. Hemoglobin degradation in the human malaria pathogen Plasmodium falciparum: a catabolic pathway initiated by a specific aspartic protease. J. Exp. Med. 173 (1991) 961-969. [PMID: 2007860]

2. Francis, S.E., Gluzman, I.Y., Oksman, A., Knickerbocker, A., Mueller, R., Bryant, M.L., Sherman, D.R., Russell, D.G. and Goldberg, D.E. Molecular characterization and inhibition of a Plasmodium falciparum aspartic hemoglobinase. EMBO J. 13 (1994) 306-317. [PMID: 8313875]

3. Gluzman, I.Y., Francis, S.E., Oksman, A., Smith, C.E., Duffin, K.L. and Goldberg, D.E. Order and specificity of the Plasmodium falciparum hemoglobin degradation pathway. J. Clin. Invest. 93 (1994) 1602-1608. [PMID: 8163662]

[EC 3.4.23.38 created 1995]

EC 3.4.23.39

Accepted name: plasmepsin II

Reaction: Hydrolysis of the bonds linking certain hydrophobic residues in hemoglobin or globin. Also cleaves the small molecule substrates such as Ala-Leu-Glu-Arg-Thr-PhePhe(NO2)-Ser-Phe-Pro-Thr [3]

Other names: aspartic hemoglobinase II; PFAPD

Comments: Known from the malaria organism, Plasmodium. About 37 kDa. In peptidase family A1 (pepsin A family), and is 73% identical in sequence to plasmepsin I. Inhibited by pepstatin. Formerly included in EC 3.4.23.6

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 159447-18-4

References

1. Dame, J.B., Reddy, G.R., Yowell, C.A., Dunn, B.M., Kay, J. and Berry, C. Sequence, expression and modelled structure of an aspartic proteinase from the human malaria parasite Plasmodium falciparum. Mol. Biochem. Parasitol. 64 (1994) 177-190. [PMID: 7935597]

2. Gluzman, I.Y., Francis, S.E., Oksman, A., Smith, C.E., Duffin, K.L. and Goldberg, D.E. Order and specificity of the Plasmodium falciparum hemoglobin degradation pathway. J. Clin. Invest. 93 (1994) 1602-1608. [PMID: 8163662]

3. Hill, J., Tyas, L., Phylip, L.H., Kay, J., Dunn, B.M. and Berry, C. High level expression and characterisation of plasmepsin II, an aspartic proteinase from Plasmodium falciparum. FEBS Lett. 352 (1994) 155-158. [PMID: 7925966]

[EC 3.4.23.39 created 1995]

EC 3.4.23.40

Accepted name: phytepsin

Reaction: Prefers hydrophobic residues Phe, Val, Ile, Leu, and Ala at P1 and P1', but also cleaves -PheAsp- and -AspAsp- bonds in 2S albumin from plant seeds

Comments: Known particularly from barley grain, but present in other plants also. In peptidase family A1 (pepsin A family), but structurally distinct in containing an internal region of about 100 amino acids not generally present in the family

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 219715-98-7

References

1. Runeberg-Roos, P., Törmäkangas, K. and Östman, A. Primary structure of a barley-grain aspartic proteinase. A plant aspartic proteinase resembling mammalian cathepsin D. Eur. J. Biochem. 202 (1991) 1021-1027. [PMID: 1722454]

2. Kervinen, J., Sarkkinen, P., Kalkkinen, N., Mikola, L. and Saarma, M. Hydrolytic specificity of the barley grain aspartic proteinase. Phytochemistry 32 (1993) 799-803. [PMID: 7763475]

3. Asakura, T., Watanabe, H., Abe, K. and Arai, S. Rice aspartic proteinase, oryzasin, expressed during seed ripening and germination, has a gene organization distinct from those of animal and microbial aspartic proteinases. Eur. J. Biochem. 232 (1995) 77-83. [PMID: 7556174]

4. Kervinen, J., Törmäkangas, K., Runeberg-Roos, P., Guruprasad, K., Blundell, T. and Teeri, T.H. Structure and possible function of aspartic proteinases in barley and other plants. Adv. Exp. Med. Biol. 362 (1995) 241-254. [PMID: 8540324]

[EC 3.4.23.40 created 1997]

EC 3.4.23.41

Accepted name: yapsin 1

Reaction: Hydrolyses various precursor proteins with Arg or Lys in P1, and commonly Arg or Lys also in P2. The P3 amino acid is usually non-polar, but otherwise additional basic amino acids are favourable in both non-prime and prime positions

Other names: yeast aspartic protease 3; Yap3 gene product (Saccharomyces cerevisiae)

Comments: In peptidase family A1 of pepsin, and weakly inhibited by pepstatin. Can partially substitute for kexin in a deficient strain of yeast. The homologous product of the Mkc7 gene (Saccharomyces cerevisiae) has similar catalytic activity and has been termed yapsin 2 [2]

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 205132-58-7

References

1. Cawley, N.X., Chen, H.C., Beinfeld, M.C. and Loh, Y.P. Specificity and kinetic studies on the cleavage of various prohormone mono- and paired-basic residue sites by yeast aspartic protease 3. J. Biol. Chem. 271 (1996) 4168-4176. [PMID: 8626758]

2. Fuller, R.S. Yapsin 2. In: Handbook of Proteolytic Enzymes, (Barrett, A.J., Rawlings, N.D. and Woessner, J.F. eds), pp. 908-909 (1998) Academic Press, London

3. Olsen, V., Guruprasad, K., Cawley, N.X., Chen, H.C., Blundell, T.L. and Loh, Y.P. Cleavage efficiency of the novel aspartic protease yapsin 1 (Yap3p) enhanced for substrates with arginine residues flanking the P1 site: correlation with electronegative active-site pockets predicted by molecular modeling. Biochemistry 37 (1998) 2768-2777. [PMID: 9485427]

[EC 3.4.23.41 created 2000]

EC 3.4.23.42

Accepted name: thermopsin

Reaction: Similar in specificity to pepsin A preferring bulky hydrophobic amino acids in P1 and P1'

Comments: From the thermophilic archaeaon Sulfolobus acidocaldarius. Maximally active at pH 2 and 90 °C. Weakly inhibited by pepstatin but shows no sequence similarity to pepsin. Type example of peptidase family A5. Formerly EC 3.4.99.44

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, CAS registry number: 126125-05-1

References

1. Lin, X. and Tang, J. Thermopsin. Methods Enzymol. 248 (1995) 156-168. [PMID: 7674919]

[EC 3.4.23.42 created 1992 as EC 3.4.99.43, transferred 2000 to EC 3.4.23.42]

EC 3.4.23.43

Accepted 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: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, CAS registry number: 202833-59-8

References

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. [PMID: 9224881]

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. [PMID: 10625704]

[EC 3.4.23.43 created 2001]

EC 3.4.23.44

Accepted 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: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 852954-38-2

References

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. [PMID: 8175803]

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.

[EC 3.4.23.44 created 2001]

EC 3.4.23.45

Accepted name: memapsin 1

Reaction: Broad endopeptidase specificity. Cleaves Glu-Val-Asn-LeuAsp-Ala-Glu-Phe in the Swedish variant of Alzheimer's amyloid precursor protein

Other name(s): β-secretase; β-site Alzheimer's amyloid precursor protein cleaving enzyme 2 (BACE2); ASP1; Down region aspartic protease

Comments: Can cleave β-amyloid precursor protein to form the amyloidogenic β-peptide that is implicated in the pathology of Alzheimer's disease, but is not significantly expressed in human brain. In peptidase family A1, but is atypical in containing a C-terminal membrane-spanning domain.

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 447457-31-0

References:

1. Turner, R.T., Loy, J.A., Nguyen, C., Devasamudram, T., Ghosh, A.K., Koelsch, G. and Tang, J. Specificity of memapsin 1 and its implications on the design of memapsin 2 (β-secretase) inhibitor selectivity. Biochemistry 41 (2002) 8742-8746. [PMID: 12093293]

[EC 3.4.23.45 created 2003]

EC 3.4.23.46

Accepted name: memapsin 2

Reaction: Broad endopeptidase specificity. Cleaves Glu-Val-Asn-LeuAsp-Ala-Glu-Phe in the Swedish variant of Alzheimer's amyloid precursor protein

Other name(s): β-secretase; β-site Alzheimer's amyloid precursor protein cleaving enzyme 1 (BACE1)

Comments: Suggested to be the major "β-secretase" responsible for the cleavage of the β-amyloid precursor protein to form the amyloidogenic β-peptide that is implicated in the pathology of Alzheimer's disease. In peptidase family A1 but is atypical in containing a C-terminal membrane-spanning domain.

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 158736-49-3

References:

1. Turner, R.T., III, Koelsch, G., Hong, L., Castenheira, P., Ghosh, A. and Tang, J. Subsite specificity of memapsin 2 (β-secretase): implications for inhibitor design. Biochemistry 40 (2001) 10001-10006. [PMID: 11513577]

2. Hong, L., Turner, R.T., Koelsch, G., Shin, D., Ghosh, A.K. and Tang, J. Crystal structure of memapsin 2 (β-secretase) in complex with an inhibitor OM00-3. Biochemistry 41 (2002) 10963-10967. [PMID: 12206667]

[EC 3.4.23.46 created 2003]

EC 3.4.23.47

Accepted name: HIV-2 retropepsin

Reaction: Endopeptidase for which the P1 residue is preferably hydrophobic

Comments: In peptidase family A2. Responsible for the post-translational processing of the human immunodeficiency virus polyprotein.

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 144114-21-6

References:

1. Tözsér, J., Bláha, I., Copeland, T.D., Wondrak, E.M. and Oroszlan, S. Comparison of the HIV-1 and HIV-2 proteinases using oligopeptide substrates representing cleavage sites in Gag and Gag-Pol polyproteins. FEBS Lett. 281 (1991) 77-80. [PMID: 2015912]

2. Chen, Z., Li, Y., Chen, E., Hall, D., Darke, P., Culberson, C., Shafer, J.A. and Kuo, L.A. Crystal structure at 1.9-Å resolution of human immunodeficiency virus (HIV) II protease complexed with L-735,524, an orally bioavailable inhibitor of the HIV proteases. J. Biol. Chem. 269 (1994) 26344-26348. [PMID: 7929352]

[EC 3.4.23.47 created 2003]

EC 3.4.23.48

Accepted name: plasminogen activator Pla

Reaction: Converts human Glu-plasminogen to plasmin by cleaving the Arg560Val peptide bond that is also hydrolysed by the mammalian u-plasminogen activator and t-plasminogen activator. Also cleaves arginyl bonds in other proteins

Comments: In peptidase family A26. From the bacterium Yersinia pestis that causes plague.

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, PDB, CAS registry number: 101028-08-4

References:

1. Kukkonen, M., Lähteenmäki, K., Suomalainen, M., Kalkkinen, N., Emödy, L., Lång, H. and Korhonen, T.K. Protein regions important for plasminogen activation and inactivation of α2-antiplasmin in the surface protease Pla of Yersinia pestis. Mol. Microbiol. 40 (2001) 1097-1111. [PMID: 11401715]

[EC 3.4.23.48 created 2003]

EC 3.4.23.49

Accepted name: omptin

Reaction: Has a virtual requirement for Arg in the P1 position and a slightly less stringent preference for this residue in the P1' position, which can also contain Lys, Gly or Val.

Other name(s): protease VII; protease A; gene ompT proteins; ompT protease; protein a; Pla; protease A; OmpT

Comments: A product of the ompT gene of Escherichia coli, and associated with the outer membrane. Omptin shows a preference for cleavage between consecutive basic amino acids, but is capable of cleavage when P1' is a non-basic residue [5,7]. Belongs in peptidase family A26.

Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, Metacyc, PDB, CAS registry number: 150770-86-8

References:

1. Grodberg, J., Lundrigan, M.D., Toledo, D.L., Mangel, W.F. and Dunn, J.J. Complete nucleotide sequence and deduced amino acid sequence of the ompT gene of Escherichia coli K-12. Nucleic Acids Res. 16 (1988) 1209 only. [PMID: 3278297]

2. Sugimura, K. and Nishihara, T. Purification, characterization, and primary structure of Escherichia coli protease VII with specificity for paired basic residues: identity of protease VII and ompT. J. Bacteriol. 170 (1988) 5625-5632. [PMID: 3056908]

3. Hanke, C., Hess, J., Schumacher, G. and Goebel, W. Processing by OmpT of fusion proteins carrying the HlyA transport signal during secretion by the Escherichia coli hemolysin transport system. Mol. Gen. Genet. 233 (1992) 42-48. [PMID: 1603076]

4. Dekker, N. Omptin. In: Barrett, A.J., Rawlings, N.D. and Woessner, J.F. (Eds), Handbook of Proteolytic Enzymes, 2nd edn, vol. , Elsevier, London, 2004, pp. 212-216.

5. Vandeputte-Rutten, L., Kramer, R.A., Kroon, J., Dekker, N., Egmond, M.R. and Gros, P. Crystal structure of the outer membrane protease OmpT from Escherichia coli suggests a novel catalytic site. EMBO J. 20 (2001) 5033-5039. [PMID: 11566868]

6. Kramer, R.A., Vandeputte-Rutten, L., de Roon, G.J., Gros, P., Dekker, N. and Egmond, M.R. Identification of essential acidic residues of outer membrane protease OmpT supports a novel active site. FEBS Lett. 505 (2001) 426-430. [PMID: 11576541]

7. McCarter, J.D., Stephens, D., Shoemaker, K., Rosenberg, S., Kirsch, J.F. and Georgiou, G. Substrate specificity of the Escherichia coli outer membrane protease OmpT. J. Bacteriol. 186 (2004) 5919-5925. [PMID: 15317797]

[EC 3.4.23.49 created 1993 as EC 3.4.21.87, transferred 2006 to EC 3.4.23.49]

EC 3.4.23.50

Accepted name: human endogenous retrovirus K endopeptidase

Reaction: Processing at the authentic HIV-1 PR recognition site and release of the mature p17 matrix and the p24 capsid protein, as a result of the cleavage of the -SQNYPIVQ- cleavage site.

Other name(s): human endogenous retrovirus K10 endopeptidase; endogenous retrovirus HERV-K10 putative protease; human endogenous retrovirus K retropepsin; HERV K10 endopeptidase; HERV K10 retropepsin; HERV-K PR; HERV-K protease; HERV-K113 protease; human endogenous retrovirus K113 protease; human retrovirus K10 retropepsin

Comments: In peptidase family A2.

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

References:

1. Towler, E.M., Gulnik, S.V., Bhat, T.N., Xie, D., Gustschina, E., Sumpter, T.R., Robertson, N., Jones, C., Sauter, M., Mueller-Lantzsch, N., Debouck, C. and Erickson, J.W. Functional characterization of the protease of human endogenous retrovirus, K10: can it complement HIV-1 protease. Biochemistry 37 (1998) 17137-17144. [PMID: 9860826]

[EC 3.4.23.50 created 2009]

EC 3.4.23.51

Accepted name: HycI peptidase

Reaction: This enzyme specifically removes a 32-amino acid peptide from the C-terminus of the precursor of the large subunit of hydrogenase 3 in Escherichia coli by cleavage at the C-terminal side of Arg537.

Other name(s): HycI; HycE processing protein

Comments: The reaction requires nickel to be bound to the precursor of the large subunit of hydrogenase 3. The endopeptidase uses the metal in the large subunit of [NiFe]-hydrogenases as a recognition motif [1]. In peptidase family A31.

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

References:

1. Theodoratou, E., Paschos, A., Magalon, A., Fritsche, E., Huber, R. and Bock, A. Nickel serves as a substrate recognition motif for the endopeptidase involved in hydrogenase maturation. Eur. J. Biochem. 267 (2000) 1995-1999. [PMID: 10727938]

2. Yang, F., Hu, W., Xu, H., Li, C., Xia, B. and Jin, C. Solution structure and backbone dynamics of an endopeptidase HycI from Escherichia coli: implications for mechanism of the [NiFe] hydrogenase maturation. J. Biol. Chem. 282 (2007) 3856-3863. [PMID: 17150961]

[EC 3.4.23.51 created 2009]

EC 3.4.23.52

Accepted name: preflagellin peptidase

Reaction: Cleaves the signal peptide of 3 to 12 amino acids from the N-terminal of preflagellin, usually at Arg-Gly or Lys-Gly, to release flagellin.

Other name(s): FlaK

Comments: An aspartic peptidase from Archaea but not bacteria. In peptidase family A24 (type IV prepilin peptidase family).

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

References:

1. Bardy, S.L. and Jarrell, K.F. FlaK of the archaeon Methanococcus maripaludis possesses preflagellin peptidase activity. FEMS Microbiol. Lett. 208 (2002) 53-59. [PMID: 11934494]

2. Ng, S.Y., VanDyke, D.J., Chaban, B., Wu, J., Nosaka, Y., Aizawa, S. and Jarrell, K.F. Different minimal signal peptide lengths recognized by the archaeal prepilin-like peptidases FlaK and PibD. J. Bacteriol. 191 (2009) 6732-6740. [PMID: 19717585]

3. Hu, J., Xue, Y., Lee, S. and Ha, Y. The crystal structure of GXGD membrane protease FlaK. Nature 475 (2011) 528-531. [PMID: 21765428]

[EC 3.4.23.52 created 2011]


Continued with EC 3.4.24.
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