Intestinal infectious diseases (Homo sapiens)

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3, 61, 2, 4-6cytosolsta1GUCY2C GUCY2C trimer:sta1GUCY2C trimerGUCY2C PDZD3sta1


Description

Gastroenteritis, also known as infectious diarrhea, is an inflammatory disease of the stomach and small intestine caused by infections by viruses, bacteria, parasites and fungi. Signs and symptoms include diarrhea, vomiting, abdominal pain, fever, lack of energy, and dehydration. Gastroenteritis is usually an acute and self-limiting disease that does not require medication but the preferred method of treatment is oral rehydration therapy. Enterotoxigenic Escherichia coli (ETEC) is one of the leading bacterial causes of gastroenteritis worldwide (Kopic & Geibel 2010, Gonzales-Siles & Sjoling 2016). View original pathway at Reactome.

Comments

Reactome-Converter 
Pathway is converted from Reactome ID: 8942233
Reactome-version 
Reactome version: 75
Reactome Author 
Reactome Author: Jassal, Bijay

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Bibliography

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  1. Arshad N, Ballal S, Visweswariah SS.; ''Site-specific N-linked glycosylation of receptor guanylyl cyclase C regulates ligand binding, ligand-mediated activation and interaction with vesicular integral membrane protein 36, VIP36.''; PubMed Europe PMC Scholia
  2. Vijayachandra K, Guruprasad M, Bhandari R, Manjunath UH, Somesh BP, Srinivasan N, Suguna K, Visweswariah SS.; ''Biochemical characterization of the intracellular domain of the human guanylyl cyclase C receptor provides evidence for a catalytically active homotrimer.''; PubMed Europe PMC Scholia
  3. Gonzales-Siles L, Sjöling Å.; ''The different ecological niches of enterotoxigenic Escherichia coli.''; PubMed Europe PMC Scholia
  4. Scott RO, Thelin WR, Milgram SL.; ''A novel PDZ protein regulates the activity of guanylyl cyclase C, the heat-stable enterotoxin receptor.''; PubMed Europe PMC Scholia
  5. Basu N, Arshad N, Visweswariah SS.; ''Receptor guanylyl cyclase C (GC-C): regulation and signal transduction.''; PubMed Europe PMC Scholia
  6. Kopic S, Geibel JP.; ''Toxin mediated diarrhea in the 21 century: the pathophysiology of intestinal ion transport in the course of ETEC, V. cholerae and rotavirus infection.''; PubMed Europe PMC Scholia

History

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CompareRevisionActionTimeUserComment
114965view16:49, 25 January 2021ReactomeTeamReactome version 75
113409view11:48, 2 November 2020ReactomeTeamReactome version 74
112611view15:59, 9 October 2020ReactomeTeamReactome version 73
101527view11:39, 1 November 2018ReactomeTeamreactome version 66
101062view21:21, 31 October 2018ReactomeTeamreactome version 65
100593view19:55, 31 October 2018ReactomeTeamreactome version 64
100142view16:40, 31 October 2018ReactomeTeamreactome version 63
99692view15:09, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99280view12:45, 31 October 2018ReactomeTeamreactome version 62
93546view11:26, 9 August 2017ReactomeTeamNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
GUCY2C ProteinP25092 (Uniprot-TrEMBL)
GUCY2C trimer:sta1ComplexR-HSA-8936363 (Reactome)
GUCY2C trimerComplexR-HSA-8936213 (Reactome)
PDZD3ProteinQ86UT5 (Uniprot-TrEMBL)
sta1 ProteinP01559 (Uniprot-TrEMBL)
sta1ProteinP01559 (Uniprot-TrEMBL)

Annotated Interactions

SourceTargetTypeDatabase referenceComment
GUCY2C trimer:sta1ArrowR-HSA-8936356 (Reactome)
GUCY2C trimerR-HSA-8936356 (Reactome)
PDZD3TBarR-HSA-8936356 (Reactome)
R-HSA-8936356 (Reactome) Heat-stable enterotoxin receptor (GUCY2C, STAR) is the receptor for the endogenous peptides guanylin (GUCA2A) and uroguanylin (GUCA2B) and E.coli heat-stable enterotoxin (sta1). GUCY2C is an integral membrane protein composed of an extracellular ligand-binding domain, an intracellular domain and a guanylyl cyclase catalytic domain and functions in trimeric form (Vijayachandra et al. 2000). Once activated by its ligands, GUCY2C mediates fluid-ion homeostasis, intestinal inflammation, and cell proliferation in a cGMP-dependent manner (Arshad et al. 2013). In the intestine, E.coli heat-stable enterotoxin (sta1) binding to GUCY2C causes abnormally high levels of intracellular cGMP to be produced resulting in aberrant fluid-ion efflux, leading to secretory diarrhea, the leading cause of infectious diarrhea in humans (Basu et al. 2010, Kopic & Geibel 2010). GUCY2C requires glycosylation for correct ligand binding and cell-surface localisation. When glycosylation is prevented in systematic mutagenesis studies, both ligand binding and localisation were abolished (Arshad et al. 2013).

Na(+)/H(+) exchange regulatory cofactor NHE-RF4 (PDZD3, aka IKEPP, NHERF4) is a regulatory protein that associates with GUCY2C and negatively modulates its heat-stable enterotoxin-mediated activation. PDZD3 is expressed in the intestinal epithelium, where it preferentially accumulates at the apical surface, and there associates with the COOH terminus of GUCY2C (Scott et al. 2002).
sta1R-HSA-8936356 (Reactome)
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