1. Gene Aliases

Guanylate Cyclase 2C,STAR,Guanylyl Cyclase C,STA Receptor,GUC2C,GC-C,Heat-Stable Enterotoxin Receptor,Intestinal Guanylate Cyclase,EC 4.6.1.2,HSER,GCC,Guanylate Cyclase 2C (Heat Stable Enterotoxin Receptor),Heat Stable Enterotoxin Receptor,EC 4.6.1,DIAR6,MECIL,MUCIL,HSTAR

[https://www.genecards.org/cgi-bin/carddisp.pl?gene=GUCY2C&keywords=Gucy2c]

2. Association with Toxicity and/or Disease at a Transcriptional Level

3. Summary of Protein Family and Structure

4. Proteins Known to Interact with Gene Product

Interactions with experimental support

Interactions with text mining support

5. Links to Gene Databases

6. GO Terms, MSigDB Signatures, Pathways Containing Gene with Descriptions of Gene Sets

Pathways:

GO terms:

cGMP biosynthetic process [The chemical reactions and pathways resulting in the formation of cyclic GMP, guanosine 3',5'-phosphate. GO:0006182]

intracellular signal transduction [The process in which a signal is passed on to downstream components within the cell, which become activated themselves to further propagate the signal and finally trigger a change in the function or state of the cell. GO:0035556]

receptor guanylyl cyclase signaling pathway [The series of molecular signals initiated by an extracellular ligand binding to a receptor on the surface of the target cell where the receptor possesses guanylyl cyclase activity, and ending with the regulation of a downstream cellular process, e.g. transcription. GO:0007168]

regulation of cell population proliferation [Any process that modulates the frequency, rate or extent of cell proliferation. GO:0042127]

response to toxic substance [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a toxic stimulus. GO:0009636]

MSigDB Signatures:

REACTOME_DIGESTION: Digestion [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_DIGESTION.html]

REACTOME_DIGESTION_AND_ABSORPTION: Digestion and absorption [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_DIGESTION_AND_ABSORPTION.html]

REACTOME_INFECTIOUS_DISEASE: Infectious disease [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_INFECTIOUS_DISEASE.html]

KEGG_PURINE_METABOLISM: Purine metabolism [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/KEGG_PURINE_METABOLISM.html]

REACTOME_BACTERIAL_INFECTION_PATHWAYS: Bacterial Infection Pathways [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_BACTERIAL_INFECTION_PATHWAYS.html]

7. Gene Descriptions

NCBI Gene Summary: This gene encodes a transmembrane protein that functions as a receptor for endogenous peptides guanylin and uroguanylin, and the heat-stable E. coli enterotoxin. The encoded protein activates the cystic fibrosis transmembrane conductance regulator. Mutations in this gene are associated with familial diarrhea (autosomal dominant) and meconium ileus (autosomal recessive). [provided by RefSeq, Nov 2016]

GeneCards Summary: GUCY2C (Guanylate Cyclase 2C) is a Protein Coding gene. Diseases associated with GUCY2C include Meconium Ileus and Diarrhea 6. Among its related pathways are Uptake and actions of bacterial toxins and Digestion and absorption. Gene Ontology (GO) annotations related to this gene include transferase activity, transferring phosphorus-containing groups and protein tyrosine kinase activity. An important paralog of this gene is NPR2.

UniProtKB/Swiss-Prot Summary: Guanylyl cyclase that catalyzes synthesis of cyclic GMP (cGMP) from GTP [PMID: 1718270, PMID: 11950846, PMID: 23269669, PMID: 22521417, PMID: 22436048]. Receptor for the E.coli heat-stable enterotoxin; E.coli enterotoxin markedly stimulates the accumulation of cGMP in mammalian cells expressing GUCY2C [PMID: 1718270, PMID: 1680854]. Also activated by the endogenous peptides guanylin and uroguanylin [PMID: 8381596].

8. Cellular Location of Gene Product

Estimation of protein expression could not be performed. View primary data. Localized to vesicles. Predicted location: Membrane [https://www.proteinatlas.org/ENSG00000070019/subcellular]

9. Mechanistic Information

Summary

The GUCY2C gene, which encodes Guanylyl Cyclase C (GCC), is involved in regulation of electrolyte and water balance in the intestinal tract [CS: 10]. Diseases like liver cirrhosis and hepatic encephalopathy often result in fluid imbalances and altered solute concentrations in the body [CS: 10]. The activation of GCC by endogenous peptides or bacterial toxins leads to increased cyclic GMP (cGMP) production [CS: 10]. This increase in cGMP activates cGMP-dependent protein kinase G-II and the cystic fibrosis transmembrane conductance regulator, promoting water secretion into the intestinal lumen [CS: 9]. This mechanism potentially counteracts the fluid retention and osmotic imbalances caused by liver diseases, thereby contributing to homeostasis [CS: 7].

In terms of toxicity, liver diseases often involve oxidative stress and DNA damage, which can contribute to carcinogenesis [CS: 10]. GUCY2C signaling inhibits cell proliferation by reducing beta-catenin and its transcriptional targets, cyclin D and Myc [CS: 8]. This inhibition is crucial because uncontrolled cell proliferation is a hallmark of cancer development [CS: 10]. Additionally, GUCY2C plays a role in tumor suppression by inactivating AKT signaling in intestinal epithelial cells [CS: 8]. When GUCY2C is dysregulated or silenced, there is an increase in DNA oxidation, double-strand breaks, mutagenesis induced by alkylating agents, and chromosomal instability [CS: 9]. This dysregulation can exacerbate liver toxicity and contribute to the progression of liver diseases, as DNA damage and genomic instability are key factors in the development of liver-related carcinogenesis [CS: 9].

10. Upstream Regulators

11. Tissues/Cell Type Where Genes are Overexpressed

Tissue type enchanced: intestine (tissue enriched) [https://www.proteinatlas.org/ENSG00000070019/tissue]

Cell type enchanced: distal enterocytes, enteroendocrine cells, intestinal goblet cells, paneth cells, proximal enterocytes, undifferentiated cells (group enriched) [https://www.proteinatlas.org/ENSG00000070019/single+cell+type]

12. Role of Gene in Other Tissues

13. Chemicals Known to Elicit Transcriptional Response of Biomarker in Tissue of Interest

Compounds that increase expression of the gene:

Compounds that decrease expression of the gene:

14. DisGeNet Biomarker Associations to Disease in Organ of Interest