Guanylate cyclase 2C

Guanylate Cyclase 2C

Guanylate cyclase 2C

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Guanylate cyclase 2C, also known as guanylyl cyclase C (GC-C), intestinal guanylate cyclase, guanylate cyclase-C receptor, or the heat-stable enterotoxin receptor (hSTAR) is an enzyme that in humans is encoded by the GUCY2C gene.

Guanylyl cyclase is an enzyme found only in the luminal aspect of intestinal epithelium. The receptor has an extracellular ligand-binding domain, a single transmembrane region, a region with sequence similar to that of protein kinases, and a C-terminal guanylate cyclase domain. Tyrosine kinase activity mediates the GC-C signaling pathway within the cell.


GC-C is a key receptor for heat-stable enterotoxins that are responsible for acute secretory diarrhea. Heat-stable enterotoxins are produced by pathogens such as Escherichia coli. Knockout mice deficient in the GC-C gene do not show secretory diarrhea on infection with E. coli, though they do with cholera toxin. This demonstrates the specificity of the GC-C receptor.

Diagnostic application

Because GC-C is tissue-specific for intestinal epithelium, it can be used for exceedingly precise detection of metastatic disease. The presence of GC-C mRNA can be detected at a rate of a single cancer cell out of 10,000,000 normal cells. This is the most precise staging tool available.

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