The reference OMIM entry for this protein is 613578

Protease, serine, 3; prss3
Trypsinogen 3; try3
Mesotrypsinogen
T9 trypsin 3, included
Mesotrypsin, included
Trypsinogen 4, included; try4, included
Trypsin 4, included

DESCRIPTION

Serine proteases are endopeptidases that are involved in multiple biologic processes, including proteolytic processing of proteins, digestion, blood coagulation, immune response, and development. Trypsin-like serine proteases (EC 3.4.21.4), such as PRSS3, catalyze the hydrolysis of peptide bonds on the carboxyl side of lysine or arginine residues (summary by Wiegand et al., 1993).

CLONING

Using a porcine trypsinogen cDNA probe to screen a human pancreas cDNA library, Tani et al. (1990) cloned PRSS3, which they called trypsinogen III. The deduced 247-amino acid protein has N-terminal signal and activation processing sites and shares 85.0% and 86.6% identity with trypsinogen I (PRSS1; 276000) and trypsinogen II (PRSS2; 601564), respectively. Using degenerate primers to amplify cDNAs encoding serine proteases from total human brain mRNA, followed by screening genomic DNA for a 5-prime fragment, Wiegand et al. (1993) cloned a PRSS3 splice variant that they called trypsinogen IV. Trypsinogen IV differs from trypsinogen III (Tani et al., 1990) only in the first exon. The deduced 304-amino acid protein has characteristics of a serine protease, including a conserved his-asp-ser catalytic triad and residues involved in substrate recognition. PCR of brain and pancreas revealed tissue-specific expression of the 2 PRSS3 variants. Nyaruhucha et al. (1997) cloned PRSS3, which they called mesotrypsinogen, from a pancreas cDNA library. The deduced protein contains 247 amino acids.

GENE FUNCTION

Using purified human protein expressed in E. coli, Nyaruhucha et al. (1997) showed that mesotrypsinogen cleaved a synthetic trypsin substrate, but only following activation by enterokinase (PRSS7; 606635). Recombinant mesotrypsin showed resistance to proteinaceous inhibitors and sensitivity to small pharmacologic serine protease inhibitors, similar to purified human mesotrypsin. Significantly, mesotrypsin was resistant to inhibition by soybean trypsin inhibitor (SBTI) and the physiologic pancreatic serine protease inhibitor PSTI (SPINK1; 167790). Szmola et al. (2003) found that mesotrypsin did not autoactivate and did not activate other pancreatic zymogens. They noted that mesotrypsin contains arg198 in place of the signature gly198 found in chymotrypsin-like serine proteases. Mutation of arg198 to gly partially restored the ability of mesotrypsin to activate pancreatic zymogens and restored its binding and sensitivity to the protein trypsin inhibitors SBTI and SPINK1. Szmola et al. (2003) noted that in complexes of proteases and canonical protease inhibitors, the reactive-site peptide bond of the inhibitor is slowly cleaved. On the contrary, mesotrypsin rapidly cleaved and deactivated SBTI and SPINK1. Szmola et al. (2003) concluded that mesotrypsin has a role in degrading trypsin inhibitors and suggested that it may function in digestion of foods high in naturally occurring trypsin inhibitors. Two of the 3 isoforms of amyloid precursor protein (APP; 104760) are ubiquitously expressed and contain a 56-residue Kunitz-type serine protease inhibitor domain. Secreted APP containing the Kunitz domain is called protease nexin-2 and potently inhibits serine proteases. Using an affinity-based proteomic screen, Salameh et al. (2010) showed that mesotrypsin bound protease nexin-2. Mesotrypsin efficiently cleaved protease nexin-2 and thereby compromised its ability to inhibit other serine proteases.

GENE STRUCTURE

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Subscribe to this protein entry history

June 30, 2020: Protein entry updated
Automatic update: OMIM entry 613578 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).