PRSS3 Gene - Serine Protease 3 (Mesotrypsinogen) | NCBI, UniProt, OMIM

PRSS3 (serine protease 3) encodes mesotrypsinogen, a member of the trypsin family of serine proteases. The gene is located on chromosome 9p13.3 and produces multiple isoforms through alternative splicing. Mesotrypsinogen is activated to mesotrypsin, which has unique resistance to endogenous trypsin inhibitors and is involved in protein digestion, extracellular matrix remodeling, and cancer progression. PRSS3 is expressed in the pancreas, brain, and various epithelial tissues, and its dysregulation is linked to pancreatic cancer, Alzheimer disease, and other conditions.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• KEGG: hsa04610 – Complement and coagulation cascades

• KEGG: hsa04974 – Protein digestion and absorption

• Reactome: R-HSA-114608 – Platelet degranulation

• Reactome: R-HSA-1474228 – Degradation of the extracellular matrix

PRSS3 encodes mesotrypsinogen (UniProt P35030), a 247-amino-acid zymogen that is cleaved to active mesotrypsin. Unlike other trypsins, mesotrypsin is resistant to inhibition by serine protease inhibitors (e.g., SPINK1, soybean trypsin inhibitor) due to a unique arginine-to-glycine substitution at position 198. This resistance allows mesotrypsin to degrade extracellular matrix components (collagen, fibronectin) and activate PAR-2, promoting cell proliferation and migration. In the brain, mesotrypsin cleaves APP and tau, implicating it in Alzheimer disease pathology. The protein is expressed as multiple isoforms (a, b, c) with varying signal peptides and activation sites.