Guanylate cyclase 2C

Last updated
GUCY2C
Identifiers
Aliases GUCY2C , DIAR6, GUC2C, MECIL, MUCIL, STAR, guanylate cyclase 2C, GC-C
External IDs OMIM: 601330 MGI: 106903 HomoloGene: 3641 GeneCards: GUCY2C
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_004963

NM_001127318
NM_145067

RefSeq (protein)

NP_004954

NP_001120790
NP_659504

Location (UCSC) Chr 12: 14.61 – 14.7 Mb Chr 6: 136.67 – 136.76 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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]

Contents

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.

Functions

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.

In medicine

Guanylate cyclase 2C is the target of linaclotide and plecanatide, oligopeptide agonists used for the treatment of chronic constipation.

Related Research Articles

<span class="mw-page-title-main">Cyclic guanosine monophosphate</span> Chemical compound

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.

<span class="mw-page-title-main">Guanylate cyclase</span> Lyase enzyme that synthesizes cGMP from GTP

Guanylate cyclase is a lyase enzyme that converts guanosine triphosphate (GTP) to cyclic guanosine monophosphate (cGMP) and pyrophosphate:

<span class="mw-page-title-main">Guanylin</span>

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.

<span class="mw-page-title-main">GM1</span> Biochemical compound important in the brain and intestines

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.

<span class="mw-page-title-main">GUCY2D</span> Protein-coding gene in the species Homo sapiens

Retinal guanylyl cyclase 1 also known as guanylate cyclase 2D, retinal is an enzyme that in humans is encoded by the GUCY2D gene.

<span class="mw-page-title-main">DLG3</span> Protein-coding gene in the species Homo sapiens

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.

<span class="mw-page-title-main">NPR1</span>

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.

<span class="mw-page-title-main">NPR2</span> Protein-coding gene in Homo sapiens

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.

<span class="mw-page-title-main">NPR3</span> Protein-coding gene in humans

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.

<span class="mw-page-title-main">GUCA1A</span> Protein-coding gene in the species Homo sapiens

Guanylyl cyclase-activating protein 1 is an enzyme that in humans is encoded by the GUCA1A gene.

<span class="mw-page-title-main">MAGI2</span>

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.

<span class="mw-page-title-main">Heat-stable enterotoxin</span>

Heat-stable enterotoxins (STs) are secretory peptides produced by some bacterial strains, such as enterotoxigenic Escherichia coli which are in general toxic to animals.

<span class="mw-page-title-main">GUCY1B3</span> Protein-coding gene in the species Homo sapiens

Guanylate cyclase soluble subunit beta-1 is an enzyme that in humans is encoded by the GUCY1B3 gene.

<span class="mw-page-title-main">GUCA1B</span>

Guanylyl cyclase-activating protein 2 is an enzyme that in humans is encoded by the GUCA1B gene. Alternative names:

<span class="mw-page-title-main">GUCY1A3</span> Protein-coding gene in the species Homo sapiens

Guanylate cyclase soluble subunit alpha-3 is an enzyme that in humans is encoded by the GUCY1A3 gene.

<span class="mw-page-title-main">STYK1</span>

Tyrosine-protein kinase STYK1 is an enzyme that in humans is encoded by the STYK1 gene.

<span class="mw-page-title-main">GUCY1A2</span>

Guanylate cyclase soluble subunit alpha-2 is an enzyme that in humans is encoded by the GUCY1A2 gene.

<span class="mw-page-title-main">GUCY2F</span> Protein-coding gene in the species Homo sapiens

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.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000070019 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000042638 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. "Entrez Gene: guanylate cyclase 2C (heat stable enterotoxin receptor)".
  6. Mann EA, Swenson ES, Copeland NG, Gilbert DJ, Jenkins NA, Taguchi T, Testa JR, Giannella RA (June 1996). "Localization of the guanylyl cyclase C gene to mouse chromosome 6 and human chromosome 12p12". Genomics. 34 (2): 265–7. doi:10.1006/geno.1996.0284. PMID   8661067.
  7. Intestinal Protein May Have Role in ADHD, Other Neurological Disorders. ScienceDaily (Aug. 11, 2011)
  8. Weiglmeier PR, Rösch P, Berkner H (August 2010). "Cure and Curse: E. coli Heat-Stable Enterotoxin and Its Receptor Guanylyl Cyclase C". Toxins. 2 (9): 2213–2229. doi: 10.3390/toxins2092213 . PMC   3153297 . PMID   22069681.

Further reading