PRSS2

PRSS2 Full Name

protease, serine, 2 (trypsin 2)

PRSS2 Introduction

The PRSS2 gene (serine protease 2 gene) encodes trypsinogen 2, which is one of the main subtypes of digestive enzymes (inactive enzyme precursors) secreted by pancreatic acinar cells. The enzyme is secreted by the pancreas and is cleaved into its active form in the small intestine. It has activity for peptide linkage involving lysine or arginine carboxyl groups. This gene, along with several other trypsinogen genes, is located at the T cell receptor beta locus on chromosome 7. Its main function is to convert into active trypsin in the duodenum, which initiates the digestion of dietary proteins by cleaving other pancreatic enzymes. Although the PRSS2 gene and its products are crucial for normal digestion, they play a central role in the pathogenesis of pancreatitis when their regulation fails, leading to premature and pathological activation of pancreatic trypsin, triggering autonomous digestion and inflammation.

Figure. Structure and activity of human TMPRSS2 protease implicated in SARS-CoV-2 activation.(Source: Fraser BJ, et al, 2022)

Physiological Functions and Regulation
Synthesis and secretion: PRSS2 is specifically and abundantly expressed in pancreatic acinar cells. Its expression is part of the cell specific exocrine function.
Function in digestion: Trypsinogen 2 is packaged as zymogen granules and secreted into the pancreatic duct, which flows into the duodenum. Here, it is activated as trypsin.
Main activator: Active trypsin is the key to the cascade reaction of digestive proteases. It cleaves and activates all other pancreatic proenzymes (such as chymotrypsin, elastase, carboxypeptidase), amplifying digestive signals.

Diagnostic and Research Tools
Genetic testing: PRSS2 gene sequencing is part of the comprehensive genetic group for patients with recurrent acute or chronic pancreatitis, particularly for identifying protective p.Gly191Arg variants and assessing overall risk.
Biochemical testing: Trypsinogen 2 (as part of total serum trypsinogen) and activated trypsin can be detected in the blood. Elevated serum trypsinogen is a sensitive biomarker of acute pancreatitis. Urinary trypsinogen-2 test strip is used for rapid bedside diagnosis.
Research model: Transgenic mice expressing human PRSS2 variants (including * PRSS1-PRSS2 * hybrid genes simulated after complex gene rearrangement) were used to study the occurrence of pancreatitis. In vitro experiments were conducted to measure the self activation and autolysis rates of mutant trypsinogen protein.

Alternate Names for PRSS2

PRSS2 protease, serine, 2; PRSS2; TRYP; 8 anionic trypsin; pancreatic anionic trypsinogen; NP_777115.1; EC 3.4.21.4; Trypsinogen

• 1. Fraser BJ, Beldar S, Seitova A, Hutchinson A, Mannar D, Li Y, Kwon D, Tan R, Wilson RP, Leopold K, Subramaniam S. Structure and activity of human TMPRSS2 protease implicated in SARS-CoV-2 activation. Nature chemical biology. 2022, 8(9):963-71.