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* Serine proteases, subtilase family, active sites *
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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 3.4.21.62), these alkaline proteases  from various Bacillus
   species have been the target of numerous studies in the past thirty years.

 - Alkaline elastase YaB from Bacillus subtilis (gene ale).
 - Alkaline serine exoprotease A from Vibrio alginolyticus (gene proA).
 - Aqualysin I from Thermus aquaticus (gene pstI).
 - 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).
 - Thermitase (EC 3.4.21.66) 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 3.4.21.48) (vacuolar protease B) from yeast (gene PRB1).
 - Cuticle-degrading protease (pr1) from Metarhizium anisopliae.
 - KEX-1 protease from Kluyveromyces lactis.
 - Kexin (EC 3.4.21.61) from yeast (gene KEX-2).
 - Oryzin (EC 3.4.21.63) (alkaline proteinase) from Aspergillus (gene alp).
 - Proteinase K (EC 3.4.21.64) 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 3.4.21.65) from Malbranchea sulfurea.

 - Furin  (EC 3.4.21.85),  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 3.4.14.10)  (tripeptidyl aminopeptidase) from
   Human.

-Consensus pattern: [SAIV]-x-[LIVM](2)-D-[DSTA]-G-[LIVMFC]-x(2,3)-[DNH]
                    [D is the active site residue]
-Sequences known to belong to this class detected by the pattern: the majority
 of subtilases with a few exceptions.
-Other sequence(s) detected in SWISS-PROT: 15.

-Consensus pattern: H-G-T-x-[VC]-[STAG]-[GS]-x-[LIVMA]
                    [H is the active site residue]
-Sequences known to belong to this class detected by the pattern: ALL,  except
 for L. lactis cell envelope-located proteases PI, PII, and PIII.
-Other sequence(s) detected in SWISS-PROT: Drosophila  neurogenic  locus delta
 protein.

-Consensus pattern: G-T-S-x-[SA]-x-P-x(2)-[STAVC]-[AG]
                    [S is the active site residue]
-Sequences known to belong to this class detected by the pattern: ALL.
-Other sequence(s) detected in SWISS-PROT: human fosB and rabbit apomucin.

-Note: 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.
                                jab5@vaxa.york.ac.uk
                                Siezen R.J.
                                nizo@caos.caos.kun.nl

-Last update: June 1994 / Text revised.

[ 1] Siezen R.J., de Vos W.M., Leunissen J.A.M., Dijkstra B.W.
     Protein Eng. 4:719-737(1991).
[ 2] Siezen R.J.
     (In) Proceeding subtilisin symposium, Hamburg, (1992).
[ 3] Barr P.J.
     Cell 66:1-3(1991).