GUCY2C | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Aliases | GUCY2C , DIAR6, GUC2C, MECIL, MUCIL, STAR, guanylate cyclase 2C, GC-C | ||||||||||||||||||||||||||||||||||||||||||||||||||
External IDs | OMIM: 601330 MGI: 106903 HomoloGene: 3641 GeneCards: GUCY2C | ||||||||||||||||||||||||||||||||||||||||||||||||||
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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. [5] [6]
Guanylyl cyclase is an enzyme found in the luminal aspect of intestinal epithelium and dopamine neurons in the brain. [7] 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. [8] 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.
Guanylate cyclase 2C is the target of linaclotide and plecanatide, oligopeptide agonists used for the treatment of chronic constipation.
Cyclic guanosine monophosphate (cGMP) is a cyclic nucleotide derived from guanosine triphosphate (GTP). cGMP acts as a second messenger much like cyclic AMP. Its most likely mechanism of action is activation of intracellular protein kinases in response to the binding of membrane-impermeable peptide hormones to the external cell surface.
Guanylate cyclase is a lyase enzyme that converts guanosine triphosphate (GTP) to cyclic guanosine monophosphate (cGMP) and pyrophosphate:
Guanylin is a 15 amino acid peptide that is secreted by goblet cells in the colon. Guanylin acts as an agonist of the guanylyl cyclase receptor GC-C and regulates electrolyte and water transport in intestinal and renal epithelia. Upon receptor binding, guanylin increases the intracellular concentration of cGMP, induces chloride secretion and decreases intestinal fluid absorption, ultimately causing diarrhoea. The peptide stimulates the enzyme through the same receptor binding region as the heat-stable enterotoxins.
GM1 (monosialotetrahexosylganglioside) the "prototype" ganglioside, is a member of the ganglio series of gangliosides which contain one sialic acid residue. GM1 has important physiological properties and impacts neuronal plasticity and repair mechanisms, and the release of neurotrophins in the brain. Besides its function in the physiology of the brain, GM1 acts as the site of binding for both cholera toxin and E. coli heat-labile enterotoxin.
Retinal guanylyl cyclase 1 also known as guanylate cyclase 2D, retinal is an enzyme that in humans is encoded by the GUCY2D gene.
Disks large homolog 3 (DLG3) also known as neuroendocrine-DLG or synapse-associated protein 102 (SAP-102) is a protein that in humans is encoded by the DLG3 gene. DLG3 is a member of the membrane-associated guanylate kinase (MAGUK) superfamily of proteins.
Natriuretic peptide receptor A/guanylate cyclase A , also known as NPR1, is an atrial natriuretic peptide receptor. In humans it is encoded by the NPR1 gene.
Natriuretic peptide receptor B/guanylate cyclase B , also known as NPR2, is an atrial natriuretic peptide receptor. In humans it is encoded by the NPR2 gene.
Natriuretic peptide receptor C/guanylate cyclase C , also known as NPR3, is an atrial natriuretic peptide receptor. In humans it is encoded by the NPR3 gene.
Guanylyl cyclase-activating protein 1 is an enzyme that in humans is encoded by the GUCA1A gene.
Membrane-associated guanylate kinase, WW and PDZ domain-containing protein 2 also known as membrane-associated guanylate kinase inverted 2 (MAGI-2) and atrophin-1-interacting protein 1 (AIP-1) is an enzyme that in humans is encoded by the MAGI2 gene.
Heat-stable enterotoxins (STs) are secretory peptides produced by some bacterial strains, such as enterotoxigenic Escherichia coli which are in general toxic to animals.
Guanylate cyclase soluble subunit beta-1 is an enzyme that in humans is encoded by the GUCY1B3 gene.
Guanylyl cyclase-activating protein 2 is an enzyme that in humans is encoded by the GUCA1B gene. Alternative names:
Guanylate cyclase soluble subunit alpha-3 is an enzyme that in humans is encoded by the GUCY1A3 gene.
Tyrosine-protein kinase STYK1 is an enzyme that in humans is encoded by the STYK1 gene.
Guanylate cyclase soluble subunit alpha-2 is an enzyme that in humans is encoded by the GUCY1A2 gene.
Retinal guanylyl cyclase 2 also known as guanylate cyclase F (GUCY2F) is a protein that in humans is encoded by the GUCY2F gene.
Plecanatide, sold under the brand name Trulance, is a medication for the treatment of chronic idiopathic constipation (CIC) and irritable bowel syndrome with constipation. Plecanatide is an agonist of guanylate cyclase-C. Plecanatide increases intestinal transit and fluid through a buildup of cGMP.
Scott A. Waldman is an MD and biomedical scientist at Sidney Kimmel Medical College of Thomas Jefferson University, where he is the Samuel M.V. Hamilton Professor of Medicine, and also tenured professor and chair of the Department of Pharmacology & Experimental Therapeutics. He is author of a pharmacology textbook, and former chief editor of Clinical Pharmacology & Therapeutics. He is known for his work in atrial natriuretic factor intracellular signaling through guanylate cyclase (GC), and the relation of Guanylyl cyclase C (GC-C) to the pathogenesis of colorectal cancer. Also for his hypotheses concerning the roles of intestinal paracrine hormones in satiety, obesity and cancer risk. Waldman also holds a concurrent position as adjunct professor at the University of Delaware, School of Health Sciences.