Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUSF75G)

DOT Name	Guanylin (GUCA2A)
Synonyms	Guanylate cyclase activator 2A; Guanylate cyclase-activating protein 1; Guanylate cyclase-activating protein I; GCAP-I
Gene Name	GUCA2A
Related Disease	Adenoma ( ) Chronic kidney disease ( ) Chronic renal failure ( ) Colitis ( ) Colon adenocarcinoma ( ) Colon cancer ( ) Colon carcinoma ( ) Colon polyp ( ) Colorectal neoplasm ( ) Cone-rod dystrophy ( ) Cone-rod dystrophy 2 ( ) Congestive heart failure ( ) End-stage renal disease ( ) Inflammatory bowel disease ( ) Inherited retinal dystrophy ( ) Intestinal cancer ( ) Intestinal neoplasm ( ) Kidney failure ( ) Nasal polyp ( ) Neoplasm ( ) Nephropathy ( ) Nephrotic syndrome ( ) Obesity ( ) Ulcerative colitis ( ) Adenocarcinoma ( ) Colorectal carcinoma ( ) Intestinal disorder ( ) Leber congenital amaurosis 1 ( ) Meconium ileus ( ) Secretory diarrhea ( )
UniProt ID	GUC2A_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	1GNA; 1GNB; 1O8R
Pfam ID	PF02058
Sequence	MNAFLLSALCLLGAWAALAGGVTVQDGNFSFSLESVKKLKDLQEPQEPRVGKLRNFAPIP GEPVVPILCSNPNFPEELKPLCKEPNAQEILQRLEEIAEDPGTCEICAYAACTGC
Function	Endogenous activator of intestinal guanylate cyclase. It stimulates this enzyme through the same receptor binding region as the heat-stable enterotoxins.
Tissue Specificity	Highly expressed in ileum and colon. Found in plasma.
Reactome Pathway	Digestion (R-HSA-8935690 )

Molecular Interaction Atlas (MIA) of This DOT

30 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Adenoma	DIS78ZEV	Strong	Altered Expression	[1]
Chronic kidney disease	DISW82R7	Strong	Biomarker	[2]
Chronic renal failure	DISGG7K6	Strong	Biomarker	[2]
Colitis	DISAF7DD	Strong	Biomarker	[3]
Colon adenocarcinoma	DISDRE0J	Strong	Altered Expression	[4]
Colon cancer	DISVC52G	Strong	Biomarker	[5]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[5]
Colon polyp	DIS7V594	Strong	Biomarker	[6]
Colorectal neoplasm	DISR1UCN	Strong	Biomarker	[7]
Cone-rod dystrophy	DISY9RWN	Strong	Genetic Variation	[8]
Cone-rod dystrophy 2	DISX2RWY	Strong	Genetic Variation	[9]
Congestive heart failure	DIS32MEA	Strong	Biomarker	[2]
End-stage renal disease	DISXA7GG	Strong	Biomarker	[2]
Inflammatory bowel disease	DISGN23E	Strong	Altered Expression	[3]
Inherited retinal dystrophy	DISGGL77	Strong	Genetic Variation	[10]
Intestinal cancer	DISYCNF1	Strong	Altered Expression	[1]
Intestinal neoplasm	DISK0GUH	Strong	Genetic Variation	[1]
Kidney failure	DISOVQ9P	Strong	Biomarker	[11]
Nasal polyp	DISLP3XE	Strong	Biomarker	[12]
Neoplasm	DISZKGEW	Strong	Biomarker	[13]
Nephropathy	DISXWP4P	Strong	Biomarker	[14]
Nephrotic syndrome	DISSPSC2	Strong	Biomarker	[2]
Obesity	DIS47Y1K	Strong	Biomarker	[14]
Ulcerative colitis	DIS8K27O	Strong	Altered Expression	[15]
Adenocarcinoma	DIS3IHTY	Limited	Biomarker	[6]
Colorectal carcinoma	DIS5PYL0	Limited	Biomarker	[14]
Intestinal disorder	DISGPMUQ	Limited	Biomarker	[16]
Leber congenital amaurosis 1	DISY2B33	Limited	Genetic Variation	[17]
Meconium ileus	DISOWS20	Limited	Genetic Variation	[4]
Secretory diarrhea	DISBX8WG	Limited	Biomarker	[16]
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⏷ Show the Full List of 30 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

1 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Guanylin (GUCA2A).	[18]
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1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Guanylin (GUCA2A).	[19]
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References

1	Expression of guanylin is downregulated in mouse and human intestinal adenomas.Biochem Biophys Res Commun. 2000 Jun 24;273(1):225-30. doi: 10.1006/bbrc.2000.2917.
2	Structural impact analysis of missense SNPs present in the uroguanylin gene by long-term molecular dynamics simulations.J Theor Biol. 2016 Dec 7;410:9-17. doi: 10.1016/j.jtbi.2016.09.008. Epub 2016 Sep 9.
3	The guanylate cyclase-C signaling pathway is down-regulated in inflammatory bowel disease.Scand J Gastroenterol. 2015;50(10):1241-52. doi: 10.3109/00365521.2015.1038849. Epub 2015 May 15.
4	Computational analyses and prediction of guanylin deleterious SNPs.Peptides. 2015 Jul;69:92-102. doi: 10.1016/j.peptides.2015.04.013. Epub 2015 Apr 18.
5	Can colorectal cancer be prevented or treated by oral hormone replacement therapy?.Curr Mol Pharmacol. 2009 Nov;2(3):285-92. doi: 10.2174/1874467210902030285.
6	Uroguanylin treatment suppresses polyp formation in the Apc(Min/+) mouse and induces apoptosis in human colon adenocarcinoma cells via cyclic GMP.Cancer Res. 2000 Sep 15;60(18):5151-7.
7	The paracrine hormone for the GUCY2C tumor suppressor, guanylin, is universally lost in colorectal cancer.Cancer Epidemiol Biomarkers Prev. 2014 Nov;23(11):2328-37. doi: 10.1158/1055-9965.EPI-14-0440. Epub 2014 Oct 10.
8	Guanylate cyclase activating proteins, guanylate cyclase and disease.Adv Exp Med Biol. 2002;514:411-38. doi: 10.1007/978-1-4615-0121-3_25.
9	RNAi-mediated gene suppression in a GCAP1(L151F) cone-rod dystrophy mouse model.PLoS One. 2013;8(3):e57676. doi: 10.1371/journal.pone.0057676. Epub 2013 Mar 5.
10	Reanalysis of Association of Pro50Leu Substitution in Guanylate Cyclase Activating Protein-1 With Dominant Retinal Dystrophy.JAMA Ophthalmol. 2020 Feb 1;138(2):200-203. doi: 10.1001/jamaophthalmol.2019.4959.
11	Identification of 10-kDa proguanylin as a major guanylin molecule in human intestine and plasma and its increase in renal insufficiency.Biochem Biophys Res Commun. 1994 Dec 30;205(3):1966-75. doi: 10.1006/bbrc.1994.2901.
12	Expression of guanylin and uroguanylin mRNA in human nasal mucosa and nasal polyps.Acta Otolaryngol. 2004 Mar;124(2):179-85. doi: 10.1080/00016480310016073.
13	Silencing the GUCA2A-GUCY2C tumor suppressor axis in CIN, serrated, and MSI colorectal neoplasia.Hum Pathol. 2019 May;87:103-114. doi: 10.1016/j.humpath.2018.11.032. Epub 2019 Feb 2.
14	Guanylate Cyclase C: A Current Hot Target, from Physiology to Pathology.Curr Med Chem. 2018;25(16):1879-1908. doi: 10.2174/0929867325666171205150310.
15	Expression of guanylate cyclase-C, guanylin, and uroguanylin is downregulated proportionally to the ulcerative colitis disease activity index.Sci Rep. 2016 Apr 29;6:25034. doi: 10.1038/srep25034.
16	Guanylin regulatory peptides: structures, biological activities mediated by cyclic GMP and pathobiology.Regul Pept. 1999 May 31;81(1-3):25-39. doi: 10.1016/s0167-0115(99)00033-6.
17	Impaired association of retinal degeneration-3 with guanylate cyclase-1 and guanylate cyclase-activating protein-1 leads to leber congenital amaurosis-1.J Biol Chem. 2015 Feb 6;290(6):3488-99. doi: 10.1074/jbc.M114.616656. Epub 2014 Dec 4.
18	Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
19	Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.