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Guanylin


FieldValue
Nameguanylate cyclase activator 2A (guanylin)
captionSolution structure of human proguanylin.
image1O8R.pdb.jpg
HGNCid4682
SymbolGUCA2A
AltSymbolsGUCA2
EntrezGene2980
OMIM139392
RefSeqNM_033553
UniProtQ02747
PDB1O8R
Chromosome1
Armp
Band35
LocusSupplementaryData-p34

:103-115 :103-115 A:22-115 :97-111 :97-111 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.

Researches have found that a loss in guanylin expression can lead to colorectal cancer due to guanylyl cyclase C's function as an intestinal tumor suppressor. When guanylin expression was measured on over 250 colon cancer patients, more than 85% of patients had a loss of guanylin expression in cancerous tissue samples by 100-1000 times when compared to the same patients's nearby healthy colon tissue. Another study done on genetically engineered mice found that mice on a high calorie diet had reduced guanylin expression in the colon. This loss of expression then resulted in guanylyl cyclase C inhibition and the formation of tumors, therefore linking diet-induced obesity with colorectal cancer.

Human proteins containing this domain

GUCA2A; GUCA2B;

Structure

This peptide has two topogies, both isoforms are shown below:

[[File:PDB 1uya EBI.jpgthumbStructure of the A-form of human uroguanylin.]][[File:PDB 1uyb EBI.jpgthumbStructure of the B-form of human uroguanylin.]]

References

References

  1. (June 2003). "Solution structure of human proguanylin: the role of a hormone prosequence". The Journal of Biological Chemistry.
  2. (December 1994). "Genomic sequence of the murine guanylin gene". Genomics.
  3. (October 1992). "Precursor structure, expression, and tissue distribution of human guanylin". Proceedings of the National Academy of Sciences of the United States of America.
  4. (February 1992). "Guanylin: an endogenous activator of intestinal guanylate cyclase". Proceedings of the National Academy of Sciences of the United States of America.
  5. (November 2014). "Guanylin hormone loss could trigger colon cancer". The Lancet. Oncology.
  6. (January 2016). "Obesity-Induced Colorectal Cancer Is Driven by Caloric Silencing of the Guanylin-GUCY2C Paracrine Signaling Axis". Cancer Research.
  7. (September 1998). "One peptide, two topologies: structure and interconversion dynamics of human uroguanylin isomers". The Journal of Peptide Research.
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