{PDOC00124} {PS00134; TRYPSIN_HIS} {PS00135; TRYPSIN_SER} {PS50240; TRYPSIN_DOM} {BEGIN} ************************************************************ * 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-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 -------------------------------------------------------------------------------- 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 -------------------------------------------------------------------------------- {END}