PROSITE documentation PDOC00124

{PDOC00124}
{PS00134; TRYPSIN_HIS}
{PS00135; TRYPSIN_SER}
{PS50240; TRYPSIN_DOM}
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* Serine proteases, trypsin family, signatures and profile *
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The catalytic activity  of the  serine proteases from the  trypsin  family  is
provided by a charge relay system involving an aspartic acid residue hydrogen-
bonded  to a histidine,  which  itself  is hydrogen-bonded to  a serine.   The
sequences in the vicinity of the active site serine and histidine residues are
well conserved  in  this family of proteases [1].  A partial list of proteases
known to belong to the trypsin family is shown below.

 - Acrosin.
 - Blood coagulation factors VII, IX, X, XI  and XII,  thrombin,  plasminogen,
   and protein C.
 - Cathepsin G.
 - Chymotrypsins.
 - Complement components C1r, C1s, C2, and complement factors B, D and I.
 - Complement-activating component of RA-reactive factor.
 - Cytotoxic cell proteases (granzymes A to H).
 - Duodenase I.
 - Elastases 1, 2, 3A, 3B (protease E), leukocyte (medullasin).
 - Enterokinase (EC 3.4.21.9) (enteropeptidase).
 - Hepatocyte growth factor activator.
 - Hepsin.
 - Glandular (tissue) kallikreins (including EGF-binding  protein  types A, B,
   and C,  NGF-gamma  chain,  gamma-renin, prostate specific antigen (PSA) and
   tonin).
 - Plasma kallikrein.
 - Mast cell proteases (MCP) 1 (chymase) to 8.
 - Myeloblastin (proteinase 3) (Wegener's autoantigen).
 - Plasminogen activators (urokinase-type, and tissue-type).
 - Trypsins I, II, III, and IV.
 - Tryptases.
 - Snake venom proteases such as ancrod,  batroxobin,  cerastobin, flavoxobin,
   and protein C activator.
 - Collagenase  from  common cattle  grub  and  collagenolytic  protease  from
   Atlantic sand fiddler crab.
 - Apolipoprotein(a).
 - Blood fluke cercarial protease.
 - Drosophila trypsin like proteases: alpha, easter, snake-locus.
 - Drosophila protease stubble (gene sb).
 - Major mite fecal allergen Der p III.

All the above proteins belong to family S1 in the classification of peptidases
[2,E1] and  originate  from  eukaryotic  species.  It  should  be  noted  that
bacterial proteases  that  belong  to  family  S2A  are  similar enough in the
regions of  the  active  site  residues that they can be picked up by the same
patterns. These proteases are listed below.

 - Achromobacter lyticus protease I.
 - Lysobacter alpha-lytic protease.
 - Streptogrisin A and B (Streptomyces proteases A and B).
 - Streptomyces griseus glutamyl endopeptidase II.
 - Streptomyces fradiae proteases 1 and 2.

We also developed a profile specific for the S1 family that spans the complete
domain. In addition to proteases from the S1 family, this profile also detects
proteins that have lost active site residues and which are therefore no longer
catalytically active. Examples of such proteins are haptoglobin and protein Z.

-Consensus pattern: [LIVM]-[ST]-A-[STAG]-H-C
                    [H is the active site residue]
-Sequences known to belong to this class detected by the pattern: ALL,  except
 for complement  components  C1r  and  C1s, pig plasminogen, bovine protein C,
 rodent urokinase, ancrod, gyroxin and two insect trypsins.
-Other sequence(s) detected in Swiss-Prot: 18.

-Consensus pattern: [DNSTAGC]-[GSTAPIMVQH]-x(2)-G-[DE]-S-G-[GS]-[SAPHV]-
                    [LIVMFYWH]-[LIVMFYSTANQH]
                    [S is the active site residue]
-Sequences known to belong to this class detected by the pattern: ALL,  except
 for 18 different proteases which have lost the first conserved glycine.
-Other sequence(s) detected in Swiss-Prot: 8.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.

-Note: If a  protein  includes  both  the serine and the histidine active site
 signatures,  the  probability of it being a trypsin family serine protease is
 100%

-Last update: May 2002 / Text revised.

[ 1] Brenner S.
     "The molecular evolution of genes and proteins: a tale of two
     serines."
     Nature 334:528-530(1988).
     PubMed=3136396; DOI=10.1038/334528a0
[ 2] Rawlings N.D., Barrett A.J.
     "Families of serine peptidases."
     Methods Enzymol. 244:19-61(1994).
     PubMed=7845208
[E1] https://www.uniprot.org/docs/peptidas

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