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PROSITE documentation PDOC00125 [for PROSITE entry PS00136]

Serine proteases, subtilase family, active sites


Subtilases [1,2] are an extensive family of serine proteases whose catalytic activity is provided by a charge relay system similar to that of the trypsin family of serine proteases but which evolved by independent convergent evolution. The sequence around the residues involved in the catalytic triad (aspartic acid, serine and histidine) are completely different from that of the analogous residues in the trypsin serine proteases and can be used as signatures specific to that category of proteases.

The subtilase family currently includes the following proteases:

  • Subtilisins (EC, these alkaline proteases from various Bacillus species have been the target of numerous studies in the past thirty years.
  • Alkaline elastase YaB from Bacillus sp. (gene ale).
  • Alkaline serine exoprotease A from Vibrio alginolyticus (gene proA).
  • Aqualysin I from Thermus aquaticus (gene pstI).
  • AspA from Aeromonas salmonicida.
  • Bacillopeptidase F (esterase) from Bacillus subtilis (gene bpf).
  • C5A peptidase from Streptococcus pyogenes (gene scpA).
  • Cell envelope-located proteases PI, PII, and PIII from Lactococcus lactis.
  • Extracellular serine protease from Serratia marcescens.
  • Extracellular protease from Xanthomonas campestris.
  • Intracellular serine protease (ISP) from various Bacillus.
  • Minor extracellular serine protease epr from Bacillus subtilis (gene epr).
  • Minor extracellular serine protease vpr from Bacillus subtilis (gene vpr).
  • Nisin leader peptide processing protease nisP from Lactococcus lactis.
  • Serotype-specific antigene 1 from Pasteurella haemolytica (gene ssa1).
  • Thermitase (EC from Thermoactinomyces vulgaris.
  • Calcium-dependent protease from Anabaena variabilis (gene prcA).
  • Halolysin from halophilic bacteria sp. 172p1 (gene hly).
  • Alkaline extracellular protease (AEP) from Yarrowia lipolytica (gene xpr2).
  • Alkaline proteinase from Cephalosporium acremonium (gene alp).
  • Cerevisin (EC (vacuolar protease B) from yeast (gene PRB1).
  • Cuticle-degrading protease (pr1) from Metarhizium anisopliae.
  • KEX-1 protease from Kluyveromyces lactis.
  • Kexin (EC from yeast (gene KEX-2).
  • Oryzin (EC (alkaline proteinase) from Aspergillus (gene alp).
  • Proteinase K (EC from Tritirachium album (gene proK).
  • Proteinase R from Tritirachium album (gene proR).
  • Proteinase T from Tritirachium album (gene proT).
  • Subtilisin-like protease III from yeast (gene YSP3).
  • Thermomycolin (EC from Malbranchea sulfurea.
  • Furin (EC, neuroendocrine convertases 1 to 3 (NEC-1 to -3) and PACE4 protease from mammals, other vertebrates, and invertebrates. These proteases are involved in the processing of hormone precursors at sites comprised of pairs of basic amino acid residues [3].
  • Tripeptidyl-peptidase II (EC (tripeptidyl aminopeptidase) from Human.
  • Prestalk-specific proteins tagB and tagC from slime mold [4]. Both proteins consist of two domains: a N-terminal subtilase catalytic domain and a C- terminal ABC transporter domain (see <PDOC00185>).

PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html --------------------------------------------------------------------------------.


If a protein includes at least two of the three active site signatures, the probability of it being a serine protease from the subtilase family is 100%


These proteins belong to family S8 in the classification of peptidases [5,E1].

Expert(s) to contact by email:

Brannigan J.
Siezen R.J.

Last update:

April 2006 / Pattern revised.


Technical section

PROSITE methods (with tools and information) covered by this documentation:

SUBTILASE_ASP, PS00136; Serine proteases, subtilase family, aspartic acid active site  (PATTERN)

SUBTILASE_HIS, PS00137; Serine proteases, subtilase family, histidine active site  (PATTERN)

SUBTILASE_SER, PS00138; Serine proteases, subtilase family, serine active site  (PATTERN)


1AuthorsSiezen R.J. de Vos W.M. Leunissen J.A.M. Dijkstra B.W.
TitleHomology modelling and protein engineering strategy of subtilases, the family of subtilisin-like serine proteinases.
SourceProtein Eng. 4:719-737(1991).
PubMed ID1798697

2AuthorsSiezen R.J.
Source(In) Proceeding subtilisin symposium, Hamburg, (1992).

3AuthorsBarr P.J.
SourceCell 66:1-3(1991).

4AuthorsShaulsky G. Kuspa A. Loomis W.F.
TitleA multidrug resistance transporter/serine protease gene is required for prestalk specialization in Dictyostelium.
SourceGenes Dev. 9:1111-1122(1995).
PubMed ID7744252

5AuthorsRawlings N.D. Barrett A.J.
TitleFamilies of serine peptidases.
SourceMethods Enzymol. 244:19-61(1994).
PubMed ID7845208


PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see prosite_license.html.


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