Guanylin

{{infobox protein

| Name=guanylate cyclase activator 2A (guanylin)

| caption = Solution structure of human proguanylin.{{PDB|1O8R}}; {{cite journal | vauthors = Lauber T, Neudecker P, Rösch P, Marx UC | title = Solution structure of human proguanylin: the role of a hormone prosequence | journal = The Journal of Biological Chemistry | volume = 278 | issue = 26 | pages = 24118–24 | date = June 2003 | pmid = 12707255 | doi = 10.1074/jbc.M300370200 | doi-access = free }}

| image = 1O8R.pdb.jpg

| width =

| HGNCid = 4682

| Symbol = GUCA2A

| AltSymbols = GUCA2

| EntrezGene = 2980

| OMIM = 139392

| RefSeq = NM_033553

| UniProt = Q02747

| PDB = 1O8R

| ECnumber =

| Chromosome = 1

| Arm = p

| Band = 35

| LocusSupplementaryData = -p34

}}

{{Pfam_box

| Symbol = Guanylin

| Name = Guanylin precursor

| image =

| width =

| caption =

| Pfam= PF02058

| InterPro= IPR000879

| SMART=

| Prosite =

| SCOP = 1uyb

| TCDB =

| OPM family=

| OPM protein=

| PDB=

{{PDB3|1gnb}} :103-115 {{PDB3|1gna}} :103-115 {{PDB3|1o8r}}A:22-115

{{PDB3|1uya}} :97-111 {{PDB3|1uyb}} :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.{{cite journal | vauthors = Sciaky D, Kosiba JL, Cohen MB | title = Genomic sequence of the murine guanylin gene | journal = Genomics | volume = 24 | issue = 3 | pages = 583–7 | date = December 1994 | pmid = 7713512 | doi = 10.1006/geno.1994.1670 }}{{cite journal | vauthors = de Sauvage FJ, Keshav S, Kuang WJ, Gillett N, Henzel W, Goeddel DV | title = Precursor structure, expression, and tissue distribution of human guanylin | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 89 | issue = 19 | pages = 9089–93 | date = October 1992 | pmid = 1409606 | pmc = 50070 | doi = 10.1073/pnas.89.19.9089 | bibcode = 1992PNAS...89.9089D | doi-access = free }} Upon receptor binding, guanylin increases the intracellular concentration of cGMP, induces chloride secretion and decreases intestinal fluid absorption, ultimately causing diarrhoea.{{cite journal | vauthors = Currie MG, Fok KF, Kato J, Moore RJ, Hamra FK, Duffin KL, Smith CE | title = Guanylin: an endogenous activator of intestinal guanylate cyclase | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 89 | issue = 3 | pages = 947–51 | date = February 1992 | pmid = 1346555 | pmc = 48362 | doi = 10.1073/pnas.89.3.947 | bibcode = 1992PNAS...89..947C | doi-access = free }} 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.{{cite journal | vauthors = Tanday S | title = Guanylin hormone loss could trigger colon cancer | journal = The Lancet. Oncology | volume = 15 | issue = 12 | pages = e537 | date = November 2014 | pmid = 25602115 | doi = 10.1016/s1470-2045(14)71032-0 | doi-access = free }} 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.{{cite journal | vauthors = Lin JE, Colon-Gonzalez F, Blomain E, Kim GW, Aing A, Stoecker B, Rock J, Snook AE, Zhan T, Hyslop TM, Tomczak M, Blumberg RS, Waldman SA | display-authors = 6 | title = Obesity-Induced Colorectal Cancer Is Driven by Caloric Silencing of the Guanylin-GUCY2C Paracrine Signaling Axis | journal = Cancer Research | volume = 76 | issue = 2 | pages = 339–46 | date = January 2016 | pmid = 26773096 | pmc = 4717834 | doi = 10.1158/0008-5472.CAN-15-1467-T }} This loss of expression then resulted in guanylyl cyclase C inhibition and the formation of tumors, therefore linking diet-induced obesity with colorectal cancer.