PROSITE documentation PDOC00125
Serine proteases, subtilase family, active sites signatures and domain profile


Subtilases [1,2,3] are an extensive family of serine proteases which occur in Archaea, Bacteria, fungi, yeasts, and higher eukaryotes. Their 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 catalytic domain forms the peptidase family S8 of clan SB [4,E1].

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 [5].
  • Tripeptidyl-peptidase II (EC (tripeptidyl aminopeptidase) from Human.
  • Prestalk-specific proteins tagB and tagC from slime mold [6]. Both proteins consist of two domains: a N-terminal subtilase catalytic domain and a C- terminal ABC transporter domain (see <PDOC00185>).

The subtilase catalytic domain consists of a highly twisted seven-stranded parallel β-sheet, flanked on both sides by α helices (see <PDB:2PMW>) [7,8].


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%

Expert(s) to contact by email:

Brannigan J.
Siezen R.J.

Last update:

May 2019 / Text revised; profile added.


Technical section

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

SUBTILASE, PS51892; Serine proteases, subtilase domain profile  (MATRIX)

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).

3AuthorsSiezen R.J. Leunissen J.A.M.
TitleSubtilases: the superfamily of subtilisin-like serine proteases.
SourceProtein. Sci. 6:501-523(1997).
PubMed ID9070434

4AuthorsRawlings N.D. Barrett A.J.
TitleFamilies of serine peptidases.
SourceMethods Enzymol. 244:19-61(1994).
PubMed ID7845208

5AuthorsBarr P.J.
SourceCell 66:1-3(1991).

6AuthorsShaulsky 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

7AuthorsPiper D.E. Jackson S. Liu Q. Romanow W.G. Shetterly S. Thibault S.T. Shan B. Walker N.P.C.
TitleThe crystal structure of PCSK9: a regulator of plasma LDL-cholesterol.
SourceStructure 15:545-552(2007).
PubMed ID17502100

8AuthorsMurayama K. Kato-Murayama M. Hosaka T. Sotokawauchi A. Yokoyama S. Arima K. Shirouzu M.
TitleCrystal structure of cucumisin, a subtilisin-like endoprotease from Cucumis melo L.
SourceJ. Mol. Biol. 423:386-396(2012).
PubMed ID22841692


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