Serine proteases, trypsin family, signatures and profile

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-γ chain, γ-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: α, 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 α-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.