Ala-, -Leu15Tyr- and -Phe25Tyr-, and angiotensin I at -Tyr4Ile-. A good synthetic substrate is Lys-Pro-Ile-Glu-PhePhe(NO2)-Arg-Leu.Enzyme Nomenclature
An asterisk before 'EC' indicates that this is an amendment to an existing enzyme rather than a new enzyme entry.
Common name: PepB aminopeptidase
Reaction: Release of an N-terminal amino acid, Xaa, from a peptide or arylamide. Xaa is preferably Glu or Asp but may be other amino acids, including Leu, Met, His, Cys and Gln
Other name(s): Salmonella enterica serovar Typhimurium peptidase B
Comments: A 270-kDa protein composed of six 46.3-kDa subunits. The pH optimum is in the alkaline range and activity is stimulated by KCl. In peptidase family M17.
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, SWISS-PROT, WIT, CAS registry number:
References:
1. Mathew, Z., Knox, T.M. and Miller, C.G. Salmonella enterica serovar Typhimurium peptidase B is a leucyl aminopeptidase with specificity for acidic amino acids. J. Bacteriol. 182 (2000) 3383-3393. [PMID: 10852868]
Common name: tripeptidyl-peptidase I
Reaction: Release of an N-terminal tripeptide from a polypeptide, but also has endopeptidase activity.
Other name(s): tripeptidyl aminopeptidase; tripeptidyl peptidase
Comments: A lysosomal enzyme that is active at acidic pH. Deficient in classical late-infantile neuronal ceroid lipofuscinosis brain tissue. Belongs in peptidase family S53. Formerly included in EC 3.4.14.8.
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, WIT, CAS registry number: 151662-36-1
References:
1. Ezaki, J., Tanida, I., Kanehagi, N. and Kominami, E. A lysosomal proteinase, the late infantile neuronal ceroid lipofuscinosis gene (CLN2) product, is essential for degradation of a hydrophobic protein, the subunit c of ATP synthase. J. Neurochem. 72 (1999) 2573-2582. [PMID: 10349869]
2. Rawlings, N.D. and Barrett, A.J. Tripeptidyl-peptidase I is apparently the CLN2 protein absent in classical late-infantile neuronal ceroid lipofuscinosis. Biochim. Biophys. Acta 1429 (1999) 496-500. [PMID: 9989235]
3. Ezaki, J., Takeda-Ezaki, M., Oda, K. and Kominami, E. Characterization of endopeptidase activity of tripeptidyl peptidase-I/CLN2 protein which is deficient in classical late infantile neuronal ceroid lipofuscinosis. Biochem. Biophys. Res. Commun. 268 (2000) 904-908. [PMID: 10679303]
4. Junaid, M.A., Wu, G.X. and Pullarkat, R.K. Purification and characterization of bovine brain lysosomal pepstatin-insensitive proteinase, the gene product deficient in the human late-infantile neuronal ceroid lipofuscinosis. J. Neurochem. 74 (2000) 287-294. [PMID: 10617131]
5. Lin, L., Sohar, I., Lackland, H. and Lobel, P. The human CLN2 protein/tripeptidyl-peptidase I is a serine protease that autoactivates at acidic pH. J. Biol. Chem. 276 (2001) 2249-2255. [PMID: 11054422]
Common name: pseudomonalisin
Reaction: Hydrolysis of the B chain of insulin at -Glu13Ala-, -Leu15Tyr- and -Phe25Tyr-, and angiotensin I at -Tyr4Ile-. A good synthetic substrate is Lys-Pro-Ile-Glu-PhePhe(NO2)-Arg-Leu.
Other name(s): Pseudomonas sp. pepstatin-insensitive carboxyl proteinase; pseudomonapepsin
Comments: An enzyme secreted by Pseudomonas sp. No. 101. Optimum pH is 4. It is distinguished from xanthomonapepsin by its insensitivity to EPNP and from scytalidopepsin B by this property and by its unrelated amino-acid sequence. Inhibited by tyrostatin, a peptide aldehyde [2]. Type example of peptidase family S53.
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, WIT, CAS registry number:
References:
1. Oda, K., Sugitani, M., Fukuhara, K. and Murao, S. Purification and properties of a pepstatin-insensitive carboxyl proteinase from a Gram-negative bacterium. Biochim. Biophys. Acta 923 (1987) 463-469. [PMID: 3548827]
2. Oda, K., Nakatani, H. and Dunn, B.M. Substrate specificity and kinetic properties of pepstatin-insensitive carboxyl proteinase from Pseudomonas sp. No. 101. Biochim. Biophys. Acta 1120 (1992) 208-214. [PMID: 1562589]
3. Wlodawer, A., Li, M., Dauter, Z., Gustchina, A., Uchida, K., Oyama, H., Dunn, B.M. and Oda, K. Carboxyl proteinase from Pseudomonas defines a novel family of subtilisin-like enzymes. Nat. Struct. Biol. 8 (2001) 442-446. [PMID: 11323721]
4. Wlodawer, A., Li, M., Gustchina, A., Oyama, H., Dunn, B.M. and Oda, K. Structural and enzymatic properties of the sedolisin family of serine-carboxyl peptidases. Acta Biochim. Pol. 50 (2003) 81-102. [PMID: 12673349]
Common name: xanthomonalisin
Reaction: Cleavage of casein
Other name(s): Xanthomonas aspartic proteinase; xanthomonapepsin
Comments: Secreted by the bacterium Xanthomonas sp. Belongs in peptidase family S53.
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, WIT, CAS registry number: 113356-29-9
References:
1. Oda, K., Nakazima, T., Terashita, T., Suzuki, K. and Murao, S. Purification and properties of an S-PI(pepstatin Ac)-insensitive carboxyl proteinase from a Xanthomonas sp. bacterium. Agric. Biol. Chem. 51 (1987) 3073-3080.
2. Wlodawer, A., Li, M., Gustchina, A., Oyama, H., Dunn, B.M. and Oda, K. Structural and enzymatic properties of the sedolisin family of serine-carboxyl peptidases. Acta Biochim. Pol. 50 (2003) 81-102. [PMID: 12673349]
Common name: physarolisin
Reaction: Milk clotting activity. Preferential cleavage of Gly8Ser in B chain of insulin most rapidly, followed by Leu11Val, Cys(SO3H)19Gly and Phe24Phe. No action on Ac-Phe-Tyr(I)2.
Other name(s): Dictyostelium discoideum aspartic proteinase; Dictyostelium discoideum aspartic proteinase E; Physarum flavicomum aspartic proteinase; Physarum polycephalum acid proteinase; Physarum aspartic proteinase; physaropepsin
Comments: Belongs in peptidase family S53. From the slime mold Physarum polycephalum. Is not inhibited by pepstatin, but is blocked by methyl 2-diazoacetamidohexanoate. Closely similar enzymes are found in Dictyostelium discoideum and P. flavicomum. Formerly included in EC 3.4.23.6.
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, WIT, CAS registry number: 94949-28-7
References:
1. Henney, H.R. and Tavana, G. Purification and some properties of an intracellular acid (carboxyl) proteinase from differentiating haploid cells of Physarum flavicomum. Exp. Mycol. 6 (1982) 161-170.
2. Murakami-Murofushi, K., Hiratsuka, A. and Ohta, J. A novel acid protease from haploid amoebae of Physarum polycephalum, and its changes during mating and subsequent differentiation into diploid plasmodia. Cell Struct. Funct. 9 (1984) 311-315.
3. North, M.J. and Whyte, A. Purification and characterization of two acid proteinases from Dictyostelium discoideum. J. Gen. Microbiol. 130 (1984) 123-134.
4. Wlodawer, A., Li, M., Gustchina, A., Oyama, H., Dunn, B.M. and Oda, K. Structural and enzymatic properties of the sedolisin family of serine-carboxyl peptidases. Acta Biochim. Pol. 50 (2003) 81-102. [PMID: 12673349]
5. Nishii, W., Ueki, T., Miyashita, R., Kojima, M., Kim, Y.T., Sasaki, N., Murakami-Murofushi, K. and Takahashi, K. Structural and enzymatic characterization of physarolisin (formerly physaropepsin) proves that it is a unique serine-carboxyl proteinase. Biochem. Biophys. Res. Commun. 301 (2003) 1023-1029. [PMID: 12589815]
[EC 3.4.22.17 Transferred entry: now EC 3.4.22.52, calpain-1 and EC 3.4.22.53, calpain-2 (EC 3.4.22.17 created 1981 [EC 3.4.24.5 created 1978, part incorporated 1989], deleted 2003)]
Common name: gingipain K
Reaction: Endopeptidase with strict specificity for lysyl bonds
Other name(s): Lys-gingipain; PrtP proteinase
Comments: Activity is stimulated by glycine. Known from the bacterium Porphyromonas gingivalis and contributes to the pathogenicity of the organism. In peptidase family C25.
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, SWISS-PROT, WIT, CAS registry number:
References:
1. Pike, R., McGraw, W., Potempa, J. and Travis, J. Lysine- and arginine-specific proteinases from Porphyromonas gingivalis. Isolation, characterization, and evidence for the existence of complexes with hemagglutinins. J. Biol. Chem. 269 (1994) 406-411. [PMID: 8276827]
2. Curtis, M.A., Aduse, O.J., Rangarajan, M., Gallagher, A., Sterne, J.A., Reid, C.R., Evans, H.E. and Samuelsson, B. Attenuation of the virulence of Porphyromonas gingivalis by using a specific synthetic Kgp protease inhibitor 2. Infect. Immun. 70 (2002) 6968-6975. [PMID: 12438376]
Common name: staphopain
Reaction: Broad endopeptidase action on proteins including elastin, but rather limited hydrolysis of small-molecule substrates. Assays are conveniently made with hemoglobin, casein or Z-Phe-Arg-NHMec as substrate
Other name(s): staphylopain
Comments: Known from species of Staphylococcus. Type example of peptidase family C47.
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, SWISS-PROT, WIT, CAS registry number:
References:
1. Hofmann, B., Hecht, H.J., Kiess, M. and Schomburg, D. Crystal structure of a thiol proteinase from Staphylococcus aureus V8 in the E-64 inhibitor complex. Acta Crystallogr. Sect. A (Suppl.) 49 (1993) 102 only.
2. Potempa, J., Dubin, A. and Travis, J. Staphylopain. In: Barrett, A.J., Rawlings, N.D. and Woessner, J.F. (Eds.), Handbook of Proteolytic Enzymes, Academic Press, London, 1998, pp. 669-671.
3. Dubin, G., Chmiel, D., Mak, P., Rakwalska, M., Rzychon, M. and Dubin, A. Molecular cloning and biochemical characterisation of proteases from Staphylococcus epidermidis. Biol. Chem. 382 (2001) 1575-1582. [PMID: 11767947]
Common name: separase
Reaction: All bonds known to be hydrolysed by this endopeptidase have arginine in P1 and an acidic residue in P4. P6 is often occupied by an acidic residue or by an hydroxy-amino-acid residue, the phosphorylation of which enhances cleavage
Other name(s): separin
Comments: In both budding yeast and human cells, cleavage of the cohesin subunit Scc1 by separase is required for sister chromatid separation in mitosis. Budding yeast separase is also known to cleave the Rec8 subunit of a meiotic cohesin complex and the kinetochore protein Slk19. Type example of peptidase family C50.
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, SWISS-PROT, WIT, CAS registry number:
References:
1. Waizenegger, I., Gimenez-Abian, J., Wernic, D. and Peters, J. Regulation of human separase by securin binding and autocleavage. Curr. Biol. 12 (2002) 1368-1378. [PMID: 12194817]
Common name: V-cath endopeptidase
Reaction: Endopeptidase of broad specificity, hydrolyzing substrates of both cathepsin L and cathepsin B
Other name(s): AcNPV protease; BmNPV protease; NPV protease; baculovirus cathepsin; nucleopolyhedrosis virus protease; viral cathepsin
Comments: In peptidase family C1. Contributes to the liquefaction of the tissues of the insect host in the late stages of infection by the baculovirus.
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, SWISS-PROT, WIT, CAS registry number:
References:
1. Slack, J.M., Kuzio, J. and Faulkner, P. Characterization of V-cath, a cathepsin L-like proteinase expressed by the baculovirus Autographa californica multiple nuclear polyhedrosis-virus. J. Gen. Virol. 76 (1995) 1091-1098. [PMID: 7730794]
2. Hawtin, R.E., Zarkowska, T., Arnold, K., Thomas, C.J., Gooday, G.W., King, L.A., Kuzio, J.A. and Possee, R.D. Liquefaction of Autographa californica nucleopolyhedrovirus-infected insects is dependent on the integrity of virus-encoded chitinase and cathepsin genes. Virology 238 (1997) 243-253. [PMID: 9400597]
Common name: cruzipain
Reaction: Broad endopeptidase specificity similar to that of cathepsin L
Other name(s): congopain; cruzain; evansain; trypanopain
Comments: In peptidase family C1. Is located in the digestive vacuoles of the parasitic trypanosome and contributes to the nutrition of the organism by digestion of host proteins.
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, PDB, SWISS-PROT, WIT, CAS registry number:
References:
1. Cazzulo, J.J., Stoka, V. and Turk, V. The major cysteine proteinase of Trypanosoma cruzi: a valid target for chemotherapy of Chagas disease. Curr. Pharm. Des. 7 (2001) 1143-1156. [PMID: 11472258]
Common name: calpain-1
Reaction: Broad endopeptidase specificity
Other name(s): μ-calpain; calcium-activated neutral protease I
Comments: In peptidase family C2. Requires Ca2+ at micromolar concentrations for activity. Cytosolic in animal cells. The active enzyme molecule is a heterodimer in which the large subunit contains the peptidase unit, and the small subunit is also a component of EC 3.4.22.53, calpain-2.
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, SWISS-PROT, SWISS-PROT, WIT, CAS registry number: 78990-62-2
References:
1. Dutt, P., Spriggs, C.N., Davies, P.L., Jia, Z. and Elce, J.S. Origins of the difference in Ca2+ requirement for activation of μ- and m-calpain. Biochem. J. 367 (2002) 263-269. [PMID: 12014988]
Common name: calpain-2
Reaction: Broad endopeptidase specificity
Other name(s): calcium-activated neutral protease II; m-calpain; milli-calpain
Comments: Type example of peptidase family C2. Requires Ca2+ at millimolar concentrations for activity. Cytosolic in animal cells. The active enzyme molecule is a heterodimer in which the large subunit contains the peptidase unit, and the small subunit is also a component of EC 3.4.22.52, calpain-1.
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, PDB, SWISS-PROT, SWISS-PROT, WIT, CAS registry number: 78990-62-2
References:
1. Strobl, S., Fernandez-Catalan, C., Braun, M., Huber, R., Masumoto, H., Nakagawa, K., Irie, A., Sorimachi, H., Bourenkow, G., Bartunik, H., Suzuki, K. and Bode, W. The crystal structure of calcium-free human m-calpain suggests an electrostatic switch mechanism for activation by calcium. Proc. Natl. Acad. Sci. USA 97 (2000) 588-592. [PMID: 10639123]
2. Dutt, P., Spriggs, C.N., Davies, P.L., Jia, Z. and Elce, J.S. Origins of the difference in Ca2+ requirement for activation of μ- and m-calpain. Biochem. J. 367 (2002) 263-269. [PMID: 12014988]
[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)]
Common 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, SWISS-PROT, WIT, CAS registry number:
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]
Common 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, PDB, SWISS-PROT, WIT, CAS registry number:
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]
Common 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, PDB, SWISS-PROT, WIT, CAS registry number:
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]
Common 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, SWISS-PROT, WIT, CAS registry number:
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]
Common 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, PDB, SWISS-PROT, WIT, CAS registry number:
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]
Common 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, SWISS-PROT, WIT, 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]
Common 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, PDB, SWISS-PROT, WIT, CAS registry number:
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]
Common 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, SWISS-PROT, WIT, CAS registry number:
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]
Common 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, SWISS-PROT, WIT, CAS registry number:
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]
Common 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.
Links to other databases: BRENDA, EXPASY, KEGG, MEROPS, PDB, SWISS-PROT, WIT, CAS registry number:
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]
Common 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, SWISS-PROT, WIT, CAS registry number:
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]
Common 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, SWISS-PROT, WIT, CAS registry number:
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]
Common 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 tumor 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
Other name(s): 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, PDB, SWISS-PROT, WIT, CAS registry number:
References:
1. Black, R.A. Tumor necrosis factor-α converting enzyme. Int. J. Biochem. Cell Biol. 34 (2002) 1-5. [PMID: 11733179]