GUCY2C trimer binds sta1

Stable Identifier
R-HSA-8936356
Type
Reaction [binding]
Species
Homo sapiens
Related Species
Escherichia coli
Compartment
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Heat-stable enterotoxin receptor (GUCY2C, STAR) is the receptor for the endogenous peptides guanylin (GUCA2A) and uroguanylin (GUCA2B) and E.coli heat-stable enterotoxin (sta1). GUCY2C is an integral membrane protein composed of an extracellular ligand-binding domain, an intracellular domain and a guanylyl cyclase catalytic domain and functions in trimeric form (Vijayachandra et al. 2000). Once activated by its ligands, GUCY2C mediates fluid-ion homeostasis, intestinal inflammation, and cell proliferation in a cGMP-dependent manner (Arshad et al. 2013). In the intestine, E.coli heat-stable enterotoxin (sta1) binding to GUCY2C causes abnormally high levels of intracellular cGMP to be produced resulting in aberrant fluid-ion efflux, leading to secretory diarrhea, the leading cause of infectious diarrhea in humans (Basu et al. 2010, Kopic & Geibel 2010). GUCY2C requires glycosylation for correct ligand binding and cell-surface localisation. When glycosylation is prevented in systematic mutagenesis studies, both ligand binding and localisation were abolished (Arshad et al. 2013).

Na(+)/H(+) exchange regulatory cofactor NHE-RF4 (PDZD3, aka IKEPP, NHERF4) is a regulatory protein that associates with GUCY2C and negatively modulates its heat-stable enterotoxin-mediated activation. PDZD3 is expressed in the intestinal epithelium, where it preferentially accumulates at the apical surface, and there associates with the COOH terminus of GUCY2C (Scott et al. 2002).

Literature References
Participants
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This event is regulated
Negatively by
Disease
Name Identifier Synonyms
dysentery 12384 Infectious diarrhea
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