Guanylyl cyclase-C | Natriuretic peptide receptor family | IUPHAR/BPS Guide to PHARMACOLOGY

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Guanylyl cyclase-C

Target not currently curated in GtoImmuPdb

Target id: 1750

Nomenclature: Guanylyl cyclase-C

Abbreviated Name: GC-C

Family: Natriuretic peptide receptor family, Receptor Guanylyl Cyclase (RGC) family

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 1073 12p12 GUCY2C guanylate cyclase 2C
Mouse 1 1072 6 Gucy2c guanylate cyclase 2c
Rat 1 1072 4q43 Gucy2c guanylate cyclase 2C
Previous and Unofficial Names
STaR | guanylate cyclase 2C (heat stable enterotoxin receptor) | intestinal guanylate cyclase | STA receptor | heat-stable enterotoxin receptor | guanylate cyclase 2C
Database Links
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
RefSeq Nucleotide
RefSeq Protein
Natural/Endogenous Ligands
guanylin {Sp: Human}
uroguanylin {Sp: Human}
Potency order (Human)
uroguanylin (GUCA2B, Q16661) > guanylin (GUCA2A, Q02747)

Download all structure-activity data for this target as a CSV file

Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Parameter Reference
[125I]Sta Hs Agonist 7.8 pKd 2
pKd 7.8 (Kd 1.5x10-8 M) [2]
linaclotide Hs Agonist 8.9 pKi 1,3
pKi 8.9 (Ki 1.24x10-9 M) [1,3]
Description: Competitive-inhibition of [125I]-STa binding to T84 colorectal carcinoma cells
E. coli heat-stable enterotoxin (STa) Hs Agonist 8.8 pKi 1
pKi 8.8 (Ki 1.57x10-9 M) [1]
Description: Competitive-inhibition of [125I]-STa binding to T84 colorectal carcinoma cells
linaclotide Rn Agonist 8.4 pKi 1
pKi 8.4 (Ki 4.2x10-9 M) [1]
Description: Competitive-inhibition of [125I]-STa binding to rat intestinal mucosa
guanylin {Sp: Human} Hs Binding - -
uroguanylin {Sp: Human} Hs Binding - -
plecanatide Hs Agonist - - 5
dolcanatide Hs Agonist - - 6
View species-specific agonist tables
Key to terms and symbols Click column headers to sort
Antibody Sp. Action Affinity Parameter Reference
indusatumab vedotin Hs Binding 9.9 pKd 4
pKd 9.9 (Kd 1.36x10-10 M) [4]
Description: Binding of the unconjugated parent antibody to human GUCY2C.
Clinically-Relevant Mutations and Pathophysiology
Disease:  Diarrhea 6; DIAR6
Synonyms: Chronic diarrhea due to guanylate cyclase 2C overactivity [Orphanet: ORPHA314373]
OMIM: 614616
Orphanet: ORPHA314373
Disease:  Meconium ileus
Synonyms: Intestinal obstruction in the newborn due to guanylate cyclase 2C deficiency [Orphanet: ORPHA314376]
OMIM: 614665
Orphanet: ORPHA314376


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1. Busby RW, Bryant AP, Bartolini WP, Cordero EA, Hannig G, Kessler MM, Mahajan-Miklos S, Pierce CM, Solinga RM, Sun LJ et al.. (2010) Linaclotide, through activation of guanylate cyclase C, acts locally in the gastrointestinal tract to elicit enhanced intestinal secretion and transit. Eur. J. Pharmacol., 649 (1-3): 328-35. [PMID:20863829]

2. Hamra FK, Eber SL, Chin DT, Currie MG, Forte LR. (1997) Regulation of intestinal uroguanylin/guanylin receptor-mediated responses by mucosal acidity. Proc. Natl. Acad. Sci. U.S.A., 94 (6): 2705-10. [PMID:9122260]

3. Harris LA, Crowell MD. (2007) Linaclotide, a new direction in the treatment of irritable bowel syndrome and chronic constipation. Curr. Opin. Mol. Ther., 9 (4): 403-10. [PMID:17694454]

4. Nam SS, Greenfield EA, O'Keefe TL, Qin S, Babcock J. (2014) Anti-GCC antibody molecules and related compositions and methods. Patent number: US8785600 B2. Assignee: Millennium Pharmaceuticals, Inc., Amgen British Columbia. Priority date: 23/10/2009. Publication date: 22/07/2014.

5. Shailubhai K, Comiskey S, Foss JA, Feng R, Barrow L, Comer GM, Jacob GS. (2013) Plecanatide, an oral guanylate cyclase C agonist acting locally in the gastrointestinal tract, is safe and well-tolerated in single doses. Dig. Dis. Sci., 58 (9): 2580-6. [PMID:23625291]

6. Shailubhai K, Palejwala V, Arjunan KP, Saykhedkar S, Nefsky B, Foss JA, Comiskey S, Jacob GS, Plevy SE. (2015) Plecanatide and dolcanatide, novel guanylate cyclase-C agonists, ameliorate gastrointestinal inflammation in experimental models of murine colitis. World J Gastrointest Pharmacol Ther, 6 (4): 213-22. [PMID:26558155]


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How to cite this page

John C. Burnett, Jr., John Garthwaite, Adrian J. Hobbs, Doris Koesling, Michaela Kuhn, Lincoln R. Potter, Michael Russwurm, Harald H.H.W. Schmidt, Johannes-Peter Stasch, Scott A. Waldman.
Natriuretic peptide receptor family: Guanylyl cyclase-C. Last modified on 04/02/2019. Accessed on 24/04/2019. IUPHAR/BPS Guide to PHARMACOLOGY,