Target intelligence / Profile preview

Progastricsin (activated form: Gastricsin) (PGC)

Target
PGC
Molecular classification
Enzyme (aspartic proteinase), Peptidase family A1, Zymogen (inactive precursor)
01

Overview

Progastricsin (PGC) is a protein-coding gene product that encodes an aspartic proteinase of the peptidase family A1, primarily expressed as an inactive zymogen in the stomach and seminal plasma. Upon activation in acidic environments by self-cleavage, it acts as the digestive enzyme gastricsin, hydrolyzing a variety of proteins as part of gastric acid production. PGC’s structure features a bilobal fold with a central active cleft (Asp32, Asp215), closely related to other pepsinogens and diverged early in evolution from its ancestors. Clinically, PGC gene polymorphisms and altered serum levels are implicated in gastric cancer susceptibility, diagnosis, and monitoring, as well as in Helicobacter pylori gastritis. Specific inhibitors such as pepstatin and a unique Ascaris protein have demonstrated potent binding to its catalytic site. The gene resides on chromosome 6 and transcript diversity is present owing to alternative splicing.

Other names
GastricsinPepsinogen CPepsinogen IIPEPCPGIIPepsin CPepsinogen group IIPreprogastricsin
02

Mechanism of action

Direct inhibition of the aspartic proteinase active site (Asp32 and Asp215) Inhibitors bind to catalytic site, blocking proteolytic activity.

03

Biological functions

Protein hydrolysis (digestive protease in the stomach)Pro-antimicrobial activity in seminal plasmaComponent of gastric mucosa
04

Disease associations

Cancer (especially susceptibility and progression of gastric cancers)Gastritis (including *Helicobacter pylori* associated gastritis)Duodenal ulcer
05

Safety considerations

Therapeutic manipulation is rare; diagnostic measurement poses minimal safety risk.Serum level interpretation must consider disease states and genetic polymorphisms for accurate risk assignment
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Interacting drugs

Pepstatin (a pentapeptide inhibitor)

1 more in the full profile.

07

Biomarkers

Serum progastricsin/pepsinogen II levels are used to diagnose and monitor gastric diseases, including gastritis and as risk/progression biomarker for gastric cancer

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