GUCY2C

This gene encodes a transmembrane protein that functions as a receptor for endogenous peptides guanylin and uroguanylin, and the heat-stable E. coli enterotoxin. The encoded protein activates the cystic fibrosis transmembrane conductance regulator. Mutations in this gene are associated with familial diarrhea (autosomal dominant) and meconium ileus (autosomal recessive).

Full Name

guanylate cyclase 2C (heat stable enterotoxin receptor)

Function

Guanylyl cyclase that catalyzes synthesis of cyclic GMP (cGMP) from GTP (PubMed:1718270, PubMed:11950846, PubMed:23269669, PubMed:22521417, PubMed:22436048).

Receptor for the E.coli heat-stable enterotoxin; E.coli enterotoxin markedly stimulates the accumulation of cGMP in mammalian cells expressing GUCY2C (PubMed:1718270, PubMed:1680854).

Also activated by the endogenous peptides guanylin and uroguanylin (PubMed:8381596).

Biological Process

cGMP biosynthetic process Source: GO_Central
Intracellular signal transduction Source: InterPro
Receptor guanylyl cyclase signaling pathway Source: GO_Central
Regulation of cell population proliferation Source: Ensembl
Response to toxic substance Source: Ensembl
Signal transduction Source: GO_Central

Cellular Location

Cell membrane; Endoplasmic reticulum membrane. The 145 kDa plasma membrane form of GUCY2C contains sialic acid and galactose residues, while a differencially glycosylated 130 Kda form is a high mannose form that is resident in the endoplasmic reticulum and may serve as the precursor for the cell surface form.

Involvement in disease

Diarrhea 6 (DIAR6):
A relatively mild, early-onset chronic diarrhea that may be associated with increased susceptibility to inflammatory bowel disease, small bowel obstruction, and esophagitis.
Meconium ileus (MECIL):
A condition characterized by intestinal obstruction due to inspissated meconium in the distal ileum and cecum, which develops in utero and presents shortly after birth as a failure to pass meconium. Meconium ileus is a known clinical manifestation of cystic fibrosis.

Topology

Extracellular: 24-430
Helical: 431-454
Cytoplasmic: 455-1073

PTM

Glycosylation at Asn-75 and/or Asn-79 is required for interaction with VIP36 while glycosylation at Asn-345 and Asn-402 modulates ligand-mediated GUCY2C activation.