Top ▲

Guanylyl cyclase-C

Click here for help

Target not currently curated in GtoImmuPdb

Target id: 1750

Nomenclature: Guanylyl cyclase-C

Abbreviated Name: GC-C

Family: Transmembrane guanylyl cyclases

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 1073 12p12.3 GUCY2C guanylate cyclase 2C
Mouse 1 1072 6 66.67 cM Gucy2c guanylate cyclase 2c
Rat 1 1072 4q43 Gucy2c guanylate cyclase 2C
Previous and Unofficial Names Click here for help
STaR | guanylate cyclase 2C (heat stable enterotoxin receptor) | intestinal guanylate cyclase | STA receptor | heat-stable enterotoxin receptor | guanylate cyclase 2C
Database Links Click here for help
Alphafold P25092 (Hs), Q3UWA6 (Mm), P23897 (Rn)
CATH/Gene3D 3.30.70.1230
ChEMBL Target CHEMBL1795197 (Hs)
DrugBank Target P25092 (Hs)
Ensembl Gene ENSG00000070019 (Hs), ENSMUSG00000042638 (Mm), ENSRNOG00000009031 (Rn)
Entrez Gene 2984 (Hs), 14917 (Mm), 25711 (Rn)
Human Protein Atlas ENSG00000070019 (Hs)
KEGG Gene hsa:2984 (Hs), mmu:14917 (Mm), rno:25711 (Rn)
OMIM 601330 (Hs)
Orphanet ORPHA317726 (Hs)
Pharos P25092 (Hs)
RefSeq Nucleotide NM_004963 (Hs), NM_001127318 (Mm), NM_013170 (Rn)
RefSeq Protein NP_004954 (Hs), NP_659504 (Mm), NP_001120790 (Mm), NP_037302 (Rn)
UniProtKB P25092 (Hs), Q3UWA6 (Mm), P23897 (Rn)
Wikipedia GUCY2C (Hs)
Natural/Endogenous Ligands Click here for help
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 go icon to follow link

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[125I]Sta Peptide Ligand is labelled Ligand is radioactive Hs Agonist 7.8 pKd 2
⤷ pKd 7.8 (Kd 1.5x10-8 M) [2]
linaclotide Peptide Approved drug Primary target of this compound 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) Peptide 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 Peptide Approved drug 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} Peptide Ligand is endogenous in the given species Hs Binding - -
⤷
uroguanylin {Sp: Human} Peptide Click here for species-specific activity table Ligand is endogenous in the given species Hs Binding - -
⤷
plecanatide Peptide Approved drug Hs Agonist - - 6
⤷ [6]
dolcanatide Peptide Hs Agonist - - 7
⤷ [7]
View species-specific agonist tables
Antibodies
Key to terms and symbols Click column headers to sort
Antibody Sp. Action Value Parameter Reference
indusatumab vedotin Peptide Primary target of this compound Hs Binding 9.9 pKd 5
⤷ pKd 9.9 (Kd 1.36x10-10 M) [5]
Description: Binding of the unconjugated parent antibody to human GUCY2C.
PF-07062119 Peptide Click here for species-specific activity table Monkey Binding 8.5 pKd 4
⤷ pKd 8.5 (Kd 3.01x10-9 M) [4]
Description: Binding affinity for cynomolgus GUCY2C determined by SPR BIACore assay.
PF-07062119 Peptide Click here for species-specific activity table Hs Binding 8.1 pKd 4
⤷ pKd 8.1 (Kd 7.47x10-9 M) [4]
Description: Binding affinity determined by SPR BIACore assay.
PF-07062119 Peptide Mm Binding 7.8 pKd 4
⤷ pKd 7.8 (Kd 1.727x10-8 M) [4]
Description: Binding affinity determined by SPR BIACore assay.
Clinically-Relevant Mutations and Pathophysiology Click here for help
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

References

Show »

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 USA, 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. Mathur D, Root AR, Bugaj-Gaweda B, Bisulco S, Tan X, Fang W, Kearney JC, Lucas J, Guffroy M, Golas J et al.. (2020) A Novel GUCY2C-CD3 T-Cell Engaging Bispecific Construct (PF-07062119) for the Treatment of Gastrointestinal Cancers. Clin Cancer Res, 26 (9): 2188-2202. [PMID:31996389]

5. 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.

6. 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]

7. 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]

Contributors

Show »

How to cite this page