Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB)

Proposed Changes to the Enzyme List

The entries below are additions and amendments to the Enzyme Nomenclature list. They were prepared for the NC-IUBMB by Keith Tipton, SinÚad Boyce, Gerry Moss and Hal Dixon, with occasional help from other Committee members, and were put on the web by Gerry Moss. Comments and suggestions on these entries should be sent to Professor K.F. Tipton and Dr S. Boyce (Department of Biochemistry, Trinity College Dublin, Dublin 2, Ireland). These entries were made public September 2006 and approved October 2006.

An asterisk before 'EC' indicates that this is an amendment to an existing enzyme rather than a new enzyme entry.


EC deleted entry.
EC proline 3-hydroxylase
EC prolyltripeptidyl aminopeptidase
*EC muramoylpentapeptide carboxypeptidase
EC hepsin
EC peptidase Do
EC HtrA2 peptidase
EC matriptase
EC C5a peptidase
EC aqualysin 1
EC site-1 protease
EC pestivirus NS3 polyprotein peptidase
EC equine arterivirus serine peptidase
EC infectious pancreatic necrosis birnavirus Vp4 peptidase
EC SpoIVB peptidase
EC stratum corneum chymotryptic enzyme
EC kallikrein 8
EC kallikrein 13

[EC Deleted entry: 1,2-dihydroxy-3-methyl-1,2-dihydrobenzoate dehydrogenase. No evidence the paper cited that the enzyme exists (EC created 2000, deleted 2006)]


Accepted name: proline 3-hydroxylase

Reaction: L-proline + 2-oxoglutarate + O2 = cis-3-hydroxy-L-proline + succinate + CO2

For diagram click here.

Other name(s): P-3-H

Systematic name: L-proline,2-oxoglutarate:oxygen oxidoreductase (3-hydroxylating)

Comments: Requires iron(II) for activity. Unlike the proline hydroxylases involved in collagen biosynthesis [EC (procollagen-proline dioxygenase) and EC (procollagen-proline 3-dioxygenase)], this enzyme does not require ascorbate for activity although it does increase the activity of the enzyme [2]. The enzyme is specific for L-proliine as D-proline, trans-4-hydroxy-L-proline, cis-4-hydroxy-L-proline and 3,4-dehydro-DL-proline are not substrates [2].


1. Mori, H., Shibasaki, T., Uozaki, Y., Ochiai, K. and Ozaki, A. Detection of novel proline 3-hydroxylase activities in Streptomyces and Bacillus spp. by regio- and stereospecific hydroxylation of L-proline. Appl. Environ. Microbiol. 62 (1996) 1903-1907. [PMID: 16535329]

2. Mori, H., Shibasaki, T., Yano, K. and Ozaki, A. Purification and cloning of a proline 3-hydroxylase, a novel enzyme which hydroxylates free L-proline to cis-3-hydroxy-L-proline. J. Bacteriol. 179 (1997) 5677-5683. [PMID: 9294421]

3. Clifton, I.J., Hsueh, L.C., Baldwin, J.E., Harlos, K. and Schofield, C.J. Structure of proline 3-hydroxylase. Evolution of the family of 2-oxoglutarate dependent oxygenases. Eur. J. Biochem. 268 (2001) 6625-6636. [PMID: 11737217]

[EC created 2006]


Accepted name: Xaa-Xaa-Pro tripeptidyl-peptidase

Reaction: Hydrolysis of Xaa-Xaa-ProYaa- releasing the N-terminal tripeptide of a peptide with Pro as the third residue (position P1) and where Yaa is not proline

Other name(s): prolyltripeptidyl amino peptidase; prolyl tripeptidyl peptidase; prolyltripeptidyl aminopeptidase; PTP-A; TPP

Comments: This cell-surface-associated serine exopeptidase is found in the Gram-negative, anaerobic bacterium Porphyromonas gingivalis, which has been implicated in adult periodontal disease [1]. The enzyme releases tripeptides from the free amino terminus of peptides and small proteins, such as interleukin 6. The enzyme possesses an absolute requirement for a proline residue at the P1 position but is completely inactivated by a proline residue at the P1' position [1]. The size of the peptide does not affect the rate of reaction [1].


1. Banbula, A., Mak, P., Bugno, M., Silberring, J., Dubin, A., Nelson, D., Travis, J. and Potempa, J. Prolyl tripeptidyl peptidase from Porphyromonas gingivalis. A novel enzyme with possible pathological implications for the development of periodontitis. J Biol Chem 274 (1999) 9246-9252. [PMID: 10092598]

2. Fujimura, S., Ueda, O., Shibata, Y. and Hirai, K. Isolation and properties of a tripeptidyl peptidase from a periodontal pathogen Prevotella nigrescens. FEMS Microbiol. Lett. 219 (2003) 305-309. [PMID: 12620636]

[EC created 2006]


Accepted name: muramoylpentapeptide carboxypeptidase

Reaction: Cleavage of the bond UDP-N-acetylmuramoyl-L-alanyl-D-γ-glutamyl-6-carboxy-L-lysyl-D-alanylD-alanine

Other name(s): D-alanine carboxypeptidase I; DD-carboxypeptidase; D-alanine carboxypeptidase; D-alanyl-D-alanine carboxypeptidase; D-alanine-D-alanine-carboxypeptidase; carboxypeptidase D-alanyl-D-alanine; carboxypeptidase I; UDP-N-acetylmuramoyl-tetrapeptidyl-D-alanine alanine-hydrolase; D-alanyl-D-alanine peptidase; DD-peptidase; penicillin binding protein 5; PBP5; PdcA; VanY; VanX (ambiguous)

Comments: A bacterial enzyme that requires a divalent cation for activity. Does not cleave the C-terminal D-alanine from the product of the above reaction, UDP-N-acetyl-muramoyl-L-alanyl-D-γ-glutamyl-6-carboxy-L-lysyl-D-alanine. Competitively inhibited by penicillins and cephalosporins.

Links to other databases: BRENDA, ERGO, EXPASY, KEGG, PDB, CAS registry number: 9077-67-2


1. Izaki, K. and Strominger, J.L. Biosynthesis of the peptidoglycan of bacterial cell walls. XIV. Purification and properties of two D-alanine carboxypeptidases from Escherichia coli. J. Biol. Chem. 243 (1968) 3193-3201. [PMID: 4871206]

[EC created 1972 as EC, transferred 1978 to EC, modified 2006]


Accepted name: hepsin

Reaction: Cleavage after basic amino-acid residues, with Arg strongly preferred to Lys

Comments: This type-II membrane-associated serine peptidase has been implicated in cell growth and development [1,3]. The enzyme has been shown to activate blood coagulation factor VII by cleavage of the Arg152Ile153 peptide bound in BHK cells, thus indicating a possible role in the initiation of blood coagulation [2]. There is no cleavage after aromatic or aliphatic residues [1]. The occupancy of the S2 site is an absolute requirement for catalysis and a basic residue at that site is preferred to an aliphatic residue. The nature of the residue at S3 also affects hydrolysis, with Gln being much more favourable than Ala [1]. Belongs in peptidase family S1A.


1. Zhukov, A., Hellman, U. and Ingelman-Sundberg, M. Purification and characterization of hepsin from rat liver microsomes. Biochim. Biophys. Acta 1337 (1997) 85-95. [PMID: 9003440]

2. Kazama, Y., Hamamoto, T., Foster, D.C. and Kisiel, W. Hepsin, a putative membrane-associated serine protease, activates human factor VII and initiates a pathway of blood coagulation on the cell surface leading to thrombin formation. J. Biol. Chem. 270 (1995) 66-72. [PMID: 7814421]

3. Torres-Rosado, A., O'Shea, K.S., Tsuji, A., Chou, S.H. and Kurachi, K. Hepsin, a putative cell-surface serine protease, is required for mammalian cell growth. Proc. Natl. Acad. Sci. USA 90 (1993) 7181-7185. [PMID: 8346233]

[EC created 2006]


Accepted name: peptidase Do

Reaction: Acts on substrates that are at least partially unfolded. The cleavage site P1 residue is normally between a pair of hydrophobic residues, such as ValVal

Other name(s): DegP; DegP protease; HtrA; high temperature requirement protease A; HrtA heat shock protein; protease Do; Do protease

Comments: This serine endopeptidase is essential for the clearance of denatured or aggregated proteins from the inner-membrane and periplasmic space in Escherichia coli. Natural substrates of the enzyme include colicin A lysis protein, pilin subunits and MalS from E. coli [3]. The enzyme has weak peptidase activity with casein and other non-native substrates [3]. The peptidase acts as a chaperone at low temperatures but switches to a peptidase (heat shock protein) at higher temperatures [1,6]. Molecular chaperones and peptidases control the folded state of proteins by recognizing hydrophobic stretches of polypeptide that become exposed by misfolding or unfolding. They then bind these hydrophobic substrates to prevent aggregation or assist in protein refolding. If attempts at refolding fail, then irreversibly damaged proteins are degraded by peptidases such as this enzyme [6]. Belongs in peptidase family S1C.


1. Lipinska, B., Zylicz, M. and Georgopoulos, C. The HtrA (DegP) protein, essential for Escherichia coli survival at high temperatures, is an endopeptidase. J. Bacteriol. 172 (1990) 1791-1797. [PMID: 2180903]

2. Seol, J.H., Woo, S.K., Jung, E.M., Yoo, S.J., Lee, C.S., Kim, K.J., Tanaka, K., Ichihara, A., Ha, D.B. and Chung, C.H. Protease Do is essential for survival of Escherichia coli at high temperatures: its identity with the htrA gene product. Biochem. Biophys. Res. Commun. 176 (1991) 730-736. [PMID: 2025286]

3. Jones, C.H., Dexter, P., Evans, A.K., Liu, C., Hultgren, S.J. and Hruby, D.E. Escherichia coli DegP protease cleaves between paired hydrophobic residues in a natural substrate: the PapA pilin. J. Bacteriol. 184 (2002) 5762-5771. [PMID: 12270835]

4. Swamy, K.H., Chung, C.H. and Goldberg, A.L. Isolation and characterization of protease Do from Escherichia coli, a large serine protease containing multiple subunits. Arch. Biochem. Biophys. 224 (1983) 543-554. [PMID: 6347072]

5. Pallen, M.J. and Wren, B.W. The HtrA family of serine proteases. Mol. Microbiol. 26 (1997) 209-221. [PMID: 9383148]

6. Krojer, T., Garrido-Franco, M., Huber, R., Ehrmann, M. and Clausen, T. Crystal structure of DegP (HtrA) reveals a new protease-chaperone machine. Nature 416 (2002) 455-459. [PMID: 11919638]

[EC created 2006]


Accepted name: HtrA2 peptidase

Reaction: Cleavage of non-polar aliphatic amino-acids at the P1 position, with a preference for Val, Ile and Met. At the P2 and P3 positions, Arg is selected most strongly with a secondary preference for other hydrophilic residues

Other name(s): high temperature requirement protein A2; HtrA2; Omi stress-regulated endoprotease; serine proteinase OMI; HtrA2 protease; OMI/HtrA2 protease; HtrA2/Omi; Omi/HtrA2

Comments: This enzyme is upregulated in mammalian cells in response to stress induced by both heat shock and tunicamycin treatment [4]. It can induce apoptosis in a caspase-independent manner through its peptidase activity and in a caspase-dependent manner by disrupting the interaction between caspase and the inhibitor of apoptosis (IAP) [3]. Belongs in peptidase family S1C.


1. Srinivasula, S.M., Gupta, S., Datta, P., Zhang, Z., Hegde, R., Cheong, N., Fernandes-Alnemri, T. and Alnemri, E.S. Inhibitor of apoptosis proteins are substrates for the mitochondrial serine protease Omi/HtrA2. J. Biol. Chem. 278 (2003) 31469-31472. [PMID: 12835328]

2. Savopoulos, J.W., Carter, P.S., Turconi, S., Pettman, G.R., Karran, E.H., Gray, C.W., Ward, R.V., Jenkins, O. and Creasy, C.L. Expression, purification, and functional analysis of the human serine protease HtrA2. Protein. Expr. Purif. 19 (2000) 227-234. [PMID: 10873535]

3. Martins, L.M., Turk, B.E., Cowling, V., Borg, A., Jarrell, E.T., Cantley, L.C. and Downward, J. Binding specificity and regulation of the serine protease and PDZ domains of HtrA2/Omi. J. Biol. Chem. 278 (2003) 49417-49427. [PMID: 14512424]

4. Gray, C.W., Ward, R.V., Karran, E., Turconi, S., Rowles, A., Viglienghi, D., Southan, C., Barton, A., Fantom, K.G., West, A., Savopoulos, J., Hassan, N.J., Clinkenbeard, H., Hanning, C., Amegadzie, B., Davis, J.B., Dingwall, C., Livi, G.P. and Creasy, C.L. Characterization of human HtrA2, a novel serine protease involved in the mammalian cellular stress response. Eur. J. Biochem. 267 (2000) 5699-5710. [PMID: 10971580]

5. Li, W., Srinivasula, S.M., Chai, J., Li, P., Wu, J.W., Zhang, Z., Alnemri, E.S. and Shi, Y. Structural insights into the pro-apoptotic function of mitochondrial serine protease HtrA2/Omi. Nat. Struct. Biol. 9 (2002) 436-441. [PMID: 11967569]

[EC created 2006]


Accepted name: matriptase

Reaction: Cleaves various synthetic substrates with Arg or Lys at the P1 position and prefers small side-chain amino acids, such as Ala and Gly, at the P2 position

Other name(s): serine protease 14; membrane-type serine protease 1; MT-SP1; prostamin; serine protease TADG-15; tumor-associated differentially-expressed gene 15 protein; ST14; breast cancer 80 kDa protease; epithin; serine endopeptidase SNC19

Comments: This trypsin-like integral-membrane serine peptidase has been implicated in breast cancer invasion and metastasis [1,2]. The enzyme can activate hepatocyte growth factor/scattering factor (HGF/SF) by cleavage of the two-chain form at an Arg residue to give active α- and β-HGF, but It does not activate plasminogen, which shares high homology with HGF [1]. The enzyme can also activate urokinase plasminogen activator (uPA), which initiates the matrix-degrading peptidase cascade [1,2]. Belongs in peptidase family S1A.


1. Lee, S.L., Dickson, R.B. and Lin, C.Y. Activation of hepatocyte growth factor and urokinase/plasminogen activator by matriptase, an epithelial membrane serine protease. J. Biol. Chem. 275 (2000) 36720-36725. [PMID: 10962009]

2. Lin, C.Y., Anders, J., Johnson, M., Sang, Q.A. and Dickson, R.B. Molecular cloning of cDNA for matriptase, a matrix-degrading serine protease with trypsin-like activity. J. Biol. Chem. 274 (1999) 18231-18236. [PMID: 10373424]

[EC created 2006]


Accepted name: C5a peptidase

Reaction: The primary cleavage site is at His67Lys68 in human C5a with a minor secondary cleavage site at Ala58Ser59

Other name(s): streptococcal C5a peptidase; ScpA; ScpB; SCPA

Comments: This enzyme is a surface-associated subtilisin-like serine peptidase with very specific substrate specificity. Virulent strains of streptococci, including Streptococcus pyogenes, can evade human detection and phagocytosis by destroying the complement chemotaxin C5a. Cleavage of human C5a by this enzyme reduces the ability of C5a to bind receptors on the surface of polymorphonuclear neutrophil leukocytes (PMNLs) and thereby abolishes its chemotactic properties [1,4]. Belongs in peptidase family S8A.


1. Wexler, D.E., Chenoweth, D.E. and Cleary, P.P. Mechanism of action of the group A streptococcal C5a inactivator. Proc. Natl. Acad. Sci. USA 82 (1985) 8144-8148. [PMID: 3906656]

2. Bohnsack, J.F., Mollison, K.W., Buko, A.M., Ashworth, J.C. and Hill, H.R. Group B streptococci inactivate complement component C5a by enzymic cleavage at the C-terminus. Biochem. J. 273 (1991) 635-640. [PMID: 1996961]

3. Cleary, P.P., Prahbu, U., Dale, J.B., Wexler, D.E. and Handley, J. Streptococcal C5a peptidase is a highly specific endopeptidase. Infect. Immun. 60 (1992) 5219-5223. [PMID: 1452354]

4. Anderson, E.T., Wetherell, M.G., Winter, L.A., Olmsted, S.B., Cleary, P.P. and Matsuka, Y.V. Processing, stability, and kinetic parameters of C5a peptidase from Streptococcus pyogenes. Eur. J. Biochem. 269 (2002) 4839-4851. [PMID: 12354115]

5. Stafslien, D.K. and Cleary, P.P. Characterization of the streptococcal C5a peptidase using a C5a-green fluorescent protein fusion protein substrate. J. Bacteriol. 182 (2000) 3254-3258. [PMID: 10809707]

6. Terao, Y., Yamaguchi, M., Hamada, S. and Kawabata, S. Multifunctional glyceraldehyde-3-phosphate dehydrogenase of Streptococcus pyogenes is essential for evasion from neutrophils. J. Biol. Chem. 281 (2006) 14215-14223. [PMID: 16565520]

[EC created 2006]


Accepted name: aqualysin 1

Reaction: Exhibits low specificity towards esters of amino acids with small hydrophobic or aromatic residues at the P1 position

Other name(s): caldolysin

Comments: This enzyme from the extreme thermophile, Thermus aquaticus, is an alkaline serine peptidase. It has three subsites, S1, S2, and S3, in the substrate binding site. The preferred amino acids at the S1 site are Ala and Phe, at the S2 site are Ala and norleucine and at the S3 site are Phe and Ile [3]. These specificities are similar to those of EC (peptidase K) and EC (subtilisin BPN') [3]. The enzyme displays broad specificity for cleavage of insulin B-chain and hydrolyses elastin substrates such as succinyl-(Ala)n-p-nitroanilide (n = 1,2,3) and some peptide esters [1,3]. Belongs in peptidase family S8A.


1. Matsuzawa, H., Tokugawa, K., Hamaoki, M., Mizoguchi, M., Taguchi, H., Terada, I., Kwon, S.T. and Ohta, T. Purification and characterization of aqualysin I (a thermophilic alkaline serine protease) produced by Thermus aquaticus YT-1. Eur. J. Biochem. 171 (1988) 441-447. [PMID: 3162211]

2. Tanaka, T., Matsuzawa, H., Kojima, S., Kumagai, I., Miura, K. and Ohta, T. P1 specificity of aqualysin I (a subtilisin-type serine protease) from Thermus aquaticus YT-1, using P1-substituted derivatives of Streptomyces subtilisin inhibitor. Biosci. Biotechnol. Biochem. 62 (1998) 2035-2038. [PMID: 9882104]

3. Tanaka, T., Matsuzawa, H. and Ohta, T. Substrate specificity of aqualysin I, a bacterial thermophilic alkaline serine protease from Thermus aquaticus YT-1: Comparison with proteinase K, subtilisin BPN' and subtilisin Carlsberg. Biosci. Biotechnol. Biochem. 62 (1998) 2161-2165.

[EC created 2006]


Accepted name: site-1 protease

Reaction: Processes precursors containing basic and hydrophobic/aliphatic residues at P4 and P2, respectively, with a relatively relaxed acceptance of amino acids at P1 and P3

Other name(s): mammalian subtilisin/kexin isozyme 1; membrane-bound transcription factor site-1 protease; proprotein convertase SKI-1; proprotein convertase SKI-1/S1PPS1; S1P endopeptidase; S1P protease; site-1 peptidase; site-1 protease; SKI-1; SREBP proteinase; SREBP S1 protease; SREBP-1 proteinase; SREBP-2 proteinase; sterol regulatory element-binding protein proteinase; sterol regulatory element-binding protein site 1 protease; sterol-regulated luminal protease; subtilase SKI-1; subtilase SKI-1/S1P; subtilisin/kexin-isozyme 1

Comments: Cleaves sterol regulatory element-binding proteins (SREBPs) and thereby initiates a process by which the active fragments of the SREBPs translocate to the nucleus and activate genes controlling the synthesis and uptake of cholesterol and unsaturated fatty acids into the bloodstream [1]. The enzyme also processes pro-brain-derived neurotrophic factor and undergoes autocatalytic activation in the endoplasmic reticulum through sequential cleavages [5]. The enzyme can also process the unfolded protein response stress factor ATF6 at an Arg-His-Lys-Lys site [4,8], and the envelope glycoprotein of the highly infectious Lassa virus [5,8] and Crimean Congo haemorrhagic fever virus at Arg-Arg-Lys-Lys [7,8]. Belongs in peptidase family S8A.


1. Espenshade, P.J., Cheng, D., Goldstein, J.L. and Brown, M.S. Autocatalytic processing of site-1 protease removes propeptide and permits cleavage of sterol regulatory element-binding proteins. J. Biol. Chem. 274 (1999) 22795-22804. [PMID: 10428864]

2. Cheng, D., Espenshade, P.J., Slaughter, C.A., Jaen, J.C., Brown, M.S. and Goldstein, J.L. Secreted site-1 protease cleaves peptides corresponding to luminal loop of sterol regulatory element-binding proteins. J. Biol. Chem. 274 (1999) 22805-22812. [PMID: 10428865]

3. Touré, B.B., Munzer, J.S., Basak, A., Benjannet, S., Rochemont, J., Lazure, C., Chrétien, M. and Seidah, N.G. Biosynthesis and enzymatic characterization of human SKI-1/S1P and the processing of its inhibitory prosegment. J. Biol. Chem. 275 (2000) 2349-2358. [PMID: 10644685]

4. Ye, J., Rawson, R.B., Komuro, R., Chen, X., Dave, U.P., Prywes, R., Brown, M.S. and Goldstein, J.L. ER stress induces cleavage of membrane-bound ATF6 by the same proteases that process SREBPs. Mol. Cell 6 (2000) 1355-1364. [PMID: 11163209]

5. Lenz, O., ter Meulen, J., Klenk, H.D., Seidah, N.G. and Garten, W. The Lassa virus glycoprotein precursor GP-C is proteolytically processed by subtilase SKI-1/S1P. Proc. Natl. Acad. Sci. USA 98 (2001) 12701-12705. [PMID: 11606739]

6. Basak, A., Chrétien, M. and Seidah, N.G. A rapid fluorometric assay for the proteolytic activity of SKI-1/S1P based on the surface glycoprotein of the hemorrhagic fever Lassa virus. FEBS Lett. 514 (2002) 333-339. [PMID: 11943176]

7. Vincent, M.J., Sanchez, A.J., Erickson, B.R., Basak, A., Chretien, M., Seidah, N.G. and Nichol, S.T. Crimean-Congo hemorrhagic fever virus glycoprotein proteolytic processing by subtilase SKI-1. J. Virol. 77 (2003) 8640-8649. [PMID: 12885882]

8. Seidah, N.G. and Chrétien, M. Proprotein convertase SKI-1/S1P. In: Barrett, A.J., Rawlings, N.D. and Woessner, J.F. (Eds), Handbook of Proteolytic Enzymes, 2nd edn, vol. 2, Elsevier, London, 2004, pp. 1845-1847.

[EC created 2006]


Accepted name: pestivirus NS3 polyprotein peptidase

Reaction: Leu is conserved at position P1 for all four cleavage sites. Alanine is found at position P1' of the NS4A-NS4B cleavage site, whereas serine is found at position P1' of the NS3-NS4A, NS4B-NS5A and NS5A-NS5B cleavage sites

Other name(s): border disease virus NS3 endopeptidase; BDV NS3 endopeptidase; bovine viral diarrhea virus NS3 endopeptidase; BVDV NS3 endopeptidase; classical swine fever virus NS3 endopeptidase; CSFV NS3 endopeptidase; p80

Comments: The polyprotein of noncytopathogenic pestiviruses is cleaved co- and post-translationally into at least 11 proteins (Npro, C, Erns, E1, E2, p7, NS2-3, NS4A, NS4B, NS5A, and NS5B) [2]. The genomes of cytopathogenic pestivirus strains express at least one additional protein, called NS3 (p80) [2]. This enzyme, which resides in the N-terminal region of NS3 (nonstructural protein 3), is essential for generation of its own C-terminus and for processing of the downstream cleavage sites, leading to the release of the pestivirus nonstructural proteins NS4A, NS4B, NS5A and NS5B [1,2]. Belongs in peptidase family S31.


1. Wiskerchen, M. and Collett, M.S. Pestivirus gene expression: protein p80 of bovine viral diarrhea virus is a proteinase involved in polyprotein processing. Virology 184 (1991) 341-350. [PMID: 1651596]

2. Tautz, N., Elbers, K., Stoll, D., Meyers, G. and Thiel, H.J. Serine protease of pestiviruses: determination of cleavage sites. J. Virol. 71 (1997) 5415-5422. [PMID: 9188613]

3. Xu, J., Mendez, E., Caron, P.R., Lin, C., Murcko, M.A., Collett, M.S. and Rice, C.M. Bovine viral diarrhea virus NS3 serine proteinase: polyprotein cleavage sites, cofactor requirements, and molecular model of an enzyme essential for pestivirus replication. J. Virol. 71 (1997) 5312-5322. [PMID: 9188600]

4. Tautz, N., Kaiser, A. and Thiel, H.J. NS3 serine protease of bovine viral diarrhea virus: characterization of active site residues, NS4A cofactor domain, and protease-cofactor interactions. Virology 273 (2000) 351-363. [PMID: 10915606]

[EC created 2006]


Accepted name: equine arterivirus serine peptidase

Reaction: Cleavage of (Glu/Gln)(Gly/Ser/Ala) in arterivirus replicase translation products ORF1a and ORF1ab

Glossary: arterivirus nsp4; equine arteritis virus serine peptidase; 3C-like serine protease; 3C-like Ser protease; 3CLSP; nonstructural protein 4 serine protease, Nsp4 serine protease; nsp4 serine protease; Nsp4 SP; chymotrypsin-like serine proteinase nsp4

Comments: In the equine arterivirus (EAV), the replicase gene is translated into open reading frame 1a (ORF1a) and ORF1ab polyproteins. This enzyme is the main viral proteinase and processes five cleavage sites in the ORF1a protein and three in the ORF1b-encoded part of the ORF1ab protein to yield nonstructural proteins (nsp5-nsp12) [3]. It combines the catalytic system of a chymotrypsin-like serine peptidase (His-Asp-Ser catalytic triad) with the substrate specificity of a 3C-like serine peptidase (Glu or Gln) at the P1 position and a small amino-acid residue (Gly, Ser or Ala) at the P1' position [1]. Cleavage of ORF1ab by this enzyme is essential for viral replication [2]. Belongs in peptidase family S32.


1. Snijder, E.J., Wassenaar, A.L., van Dinten, L.C., Spaan, W.J. and Gorbalenya, A.E. The arterivirus nsp4 protease is the prototype of a novel group of chymotrypsin-like enzymes, the 3C-like serine proteases. J. Biol. Chem. 271 (1996) 4864-4871. [PMID: 8617757]

2. van Dinten, L.C., Rensen, S., Gorbalenya, A.E. and Snijder, E.J. Proteolytic processing of the open reading frame 1b-encoded part of arterivirus replicase is mediated by nsp4 serine protease and is essential for virus replication. J. Virol. 73 (1999) 2027-2037. [PMID: 9971783]

3. Barrette-Ng, I.H., Ng, K.K., Mark, B.L., Van Aken, D., Cherney, M.M., Garen, C., Kolodenko, Y., Gorbalenya, A.E., Snijder, E.J. and James, M.N. Structure of arterivirus nsp4. The smallest chymotrypsin-like proteinase with an α/β C-terminal extension and alternate conformations of the oxyanion hole. J. Biol. Chem. 277 (2002) 39960-39966. [PMID: 12163505]

[EC created 2006]


Accepted name: infectious pancreatic necrosis birnavirus Vp4 peptidase

Reaction: Cleaves the (Ser/Thr)-Xaa-Ala(Ser/Ala)-Gly motif in the polyprotein NH2-pVP2-VP4-VP3-COOH of infectious pancreatic necrosis virus at the pVP2-VP4 and VP4-VP3 junctions

Other name(s): infectious pancreatic necrosis virus protease; IPNV Vp4 protease; IPNV Vp4 peptidase; NS protease; NS-associated protease; Vp4 protease

Comments: Infectious pancreatic necrosis virus (IPNV) is a birnavirus that causes an acute, contagious disease in young salmonid fish [2]. As with most viruses that infect eukaryotic cells, the proteolytic processing of viral precursor proteins is a crucial step in the life cycle of this virus [2]. pVP2 is converted into VP2 by cleavage near the carboxy end of pVP2. This cleavage is most likely due to host-cell proteases rather than VP4 [2,3]. Differs from most serine peptidases in not having the catalytic triad Ser-His-Asp [2]. Belongs in peptidase family S50.


1. Manning, D.S. and Leong, J.C. Expression in Escherichia coli of the large genomic segment of infectious pancreatic necrosis virus. Virology 179 (1990) 16-25. [PMID: 2219718]

2. Petit, S., Lejal, N., Huet, J.C. and Delmas, B. Active residues and viral substrate cleavage sites of the protease of the birnavirus infectious pancreatic necrosis virus. J. Virol. 74 (2000) 2057-2066. [PMID: 10666235]

3. Dobos, P. The molecular biology of infectious pancreatic necrosis virus (IPNV). Annu. Rev. Fish Dis. 5 (1995) 25-54.

[EC created 2006]


Accepted name: SpoIVB peptidase

Reaction: Self-cleaves Val52Asn53, Ala62Phe63 and Val74Thr75 at the N-terminus of SpoIVB

Other name(s): sporulation factor IV B protease

Comments: This enzyme plays a central role in a regulatory checkpoint (the σK checkpoint), which coordinates gene expression during the later stages of spore formation in Bacillus subtilis [1,3]. The enzyme activates proteolytic processing of a sporulation-specific sigma factor, pro-σK, to its mature and active form, σK, by self-cleavage [1,3]. The enzyme is also subject to secondary proteolysis, which presumably inactivates SpoIVB [3]. The enzyme is also essential for the formation of heat-resistant spores. Belongs in peptidase family S55.


1. Wakeley, P.R., Dorazi, R., Hoa, N.T., Bowyer, J.R. and Cutting, S.M. Proteolysis of SpolVB is a critical determinant in signalling of pro-σK processing in Bacillus subtilis. Mol. Microbiol. 36 (2000) 1336-1348. [PMID: 10931284]

2. Hoa, N.T., Brannigan, J.A. and Cutting, S.M. The PDZ domain of the SpoIVB serine peptidase facilitates multiple functions. J. Bacteriol. 183 (2001) 4364-4373. [PMID: 11418578]

3. Hoa, N.T., Brannigan, J.A. and Cutting, S.M. The Bacillus subtilis signaling protein SpoIVB defines a new family of serine peptidases. J. Bacteriol. 184 (2002) 191-199. [PMID: 11741860]

4. Dong, T.C. and Cutting, S.M. SpoIVB-mediated cleavage of SpoIVFA could provide the intercellular signal to activate processing of pro-σK in Bacillus subtilis. Mol. Microbiol. 49 (2003) 1425-1434. [PMID: 12940997]

[EC created 2006]


Accepted name: stratum corneum chymotryptic enzyme

Reaction: Cleavage of proteins with aromatic side chains in the P1 position

Other name(s): kallikrein 7; SCCE; KLK7; PRSS6; hK7

Comments: This enzyme has wide substrate specificity, being able to degrade heat-denatured bovine casein and the α-chain of native human fibrinogen. It cleaves the B chain of bovine insulin at Leu6Cya7, Tyr16Leu17, Phe25Tyr26 and Tyr2Thr27 [1]. It is thought to play a role in the desquamation (skin-shedding) of the outer layer of skin, the stratum corneum, by degrading intercellular cohesive structures [1,2]. Belongs in peptidase family S1A.


1. Skytt, A., Strömqvist, M. and Egelrud, T. Primary substrate specificity of recombinant human stratum corneum chymotryptic enzyme. Biochem. Biophys. Res. Commun. 211 (1995) 586-589. [PMID: 7794273]

2. Egelrud, T. Purification and preliminary characterization of stratum corneum chymotryptic enzyme: a proteinase that may be involved in desquamation. J. Invest. Dermatol. 101 (1993) 200-204. [PMID: 8393902]

3. Hansson, L., Strömqvist, M., Bäckman, A., Wallbrandt, P., Carlstein, A. and Egelrud, T. Cloning, expression, and characterization of stratum corneum chymotryptic enzyme. A skin-specific human serine proteinase. J. Biol. Chem. 269 (1994) 19420-19426. [PMID: 8034709]

4. Yousef, G.M., Scorilas, A., Magklara, A., Soosaipillai, A. and Diamandis, E.P. The KLK7 (PRSS6) gene, encoding for the stratum corneum chymotryptic enzyme is a new member of the human kallikrein gene family - genomic characterization, mapping, tissue expression and hormonal regulation. Gene 254 (2000) 119-128. [PMID: 10974542]

5. Vasilopoulos, Y., Cork, M.J., Murphy, R., Williams, H.C., Robinson, D.A., Duff, G.W., Ward, S.J. and Tazi-Ahnini, R. Genetic association between an AACC insertion in the 3'UTR of the stratum corneum chymotryptic enzyme gene and atopic dermatitis. J. Invest. Dermatol. 123 (2004) 62-66. [PMID: 15191543]

[EC created 2006]


Accepted name: kallikrein 8

Reaction: Cleavage of amide substrates following the basic amino acids Arg or Lys at the P1 position, with a preference for Arg over Lys

Other name(s): KLK8; PRSS19; human kallikrein 8; hK8; mK8; ovasin; tumor-associated differentially expressed gene 14; TADG-14; NP; neuropsin

Comments: The enzyme is activated by removal of an N-terminal prepropeptide [2,4]. The highest amidolytic activity is observed using Boc-Val-Pro-Arg7-amido-4-methylcoumarin, which is a substrate of α-thrombin [2,4]. Substrates lacking basic amino acids in the P1 position are not cleaved [4]. The enzyme degrades casein, fibronectin, gelatin, collagen type IV, fibrinogen, and high-molecular-mass kininogen [3] and is associated with diseases such as ovarian cancer and Alzheimer's disease [4]. Belongs in peptidase family S1A.


1. Chen, Z.L., Yoshida, S., Kato, K., Momota, Y., Suzuki, J., Tanaka, T., Ito, J., Nishino, H., Aimoto, S., Kiyama, H. and Shiosaka, S. Expression and activity-dependent changes of a novel limbic-serine protease gene in the hippocampus. J. Neurosci. 15 (1995) 5088-5097. [PMID: 7623137]

2. Shimizu, C., Yoshida, S., Shibata, M., Kato, K., Momota, Y., Matsumoto, K., Shiosaka, T., Midorikawa, R., Kamachi, T., Kawabe, A. and Shiosaka, S. Characterization of recombinant and brain neuropsin, a plasticity-related serine protease. J. Biol. Chem. 273 (1998) 11189-11196. [PMID: 9556608]

3. Rajapakse, S., Ogiwara, K., Takano, N., Moriyama, A. and Takahashi, T. Biochemical characterization of human kallikrein 8 and its possible involvement in the degradation of extracellular matrix proteins. FEBS Lett. 579 (2005) 6879-6884. [PMID: 16337200]

4. Kishi, T., Cloutier, S.M., Kündig, C., Deperthes, D. and Diamandis, E.P. Activation and enzymatic characterization of recombinant human kallikrein 8. Biol. Chem. 387 (2006) 723-731. [PMID: 16800733]

[EC created 2006]


Accepted name: kallikrein 13

Reaction: Hydrolyses mouse Ren2 protein (a species of prorenin present in the submandibular gland) on the carboxy side of the arginine residue at the Lys-Arg pair in the N-terminus, to yield mature renin

Other name(s): KLK13; kallikrein mK13; mGK-13; mK13; mKLK13; prorenin converting enzyme 1; PRECE-1; prorenin-converting enzyme; PRECE; proteinase P

Comments: The enzyme is specific for prorenin from the mouse submandibular gland, as prorenin from the mouse kidney (Ren1) and human prorenin are not substrates [1]. Site-directed mutagenesis studies have shown that the enzyme will also cleave prorenin when Lys-Arg is replaced by Arg-Arg or Gln-Arg but the rate of reaction is much slower when Lys-Lys is used. This enzyme is also able to process pro-interleukin-1β (pro-IL-1β) in mouse submandibular gland to form IL-1β [4]. Belongs in peptidase family S1A.


1. Nakayama, K., Kim, W.S., Nakagawa, T., Nagahama, M. and Murakami, K. Substrate specificity of prorenin converting enzyme of mouse submandibular gland. Analysis using site-directed mutagenesis. J. Biol. Chem. 265 (1990) 21027-21031. [PMID: 2250008]

2. Kim, W.S., Hatsuzawa, K., Ishizuka, Y., Hashiba, K., Murakami, K. and Nakayama, K. A processing enzyme for prorenin in mouse submandibular gland. Purification and characterization. J. Biol. Chem. 265 (1990) 5930-5933. [PMID: 2180937]

3. Kikkawa, Y., Yamanaka, N., Tada, J., Kanamori, N., Tsumura, K. and Hosoi, K. Prorenin processing and restricted endoproteolysis by mouse tissue kallikrein family enzymes (mK1, mK9, mK13, and mK22). Biochim. Biophys. Acta 1382 (1998) 55-64. [PMID: 9507064]

4. Yao, C., Karabasil, M.R., Purwanti, N., Li, X., Akamatsu, T., Kanamori, N. and Hosoi, K. Tissue kallikrein mK13 is a candidate processing enzyme for the precursor of interleukin-1β in the submandibular gland of mice. J. Biol. Chem. 281 (2006) 7968-7976. [PMID: 16423834]

[EC created 2006]

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