GUCY2C » Heat-stable enterotoxin receptor (STA receptor)

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Protein also known as: Intestinal guanylate cyclase.

Gene name: GUCY2C

Family name: Adenylyl cyclase class-4/guanylyl cyclase

This protein has been shown to exist at protein level

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GENE REF ISO

Function

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Overview

Receptor for the E.coli heat-stable enterotoxin (E.coli enterotoxin markedly stimulates the accumulation of cGMP in mammalian cells expressing GC-C). Also activated by the endogenous peptide guanylin.

CuratedUniProtKB

GO molecular function

ATP bindingdefinition[GO:0005524] ‹silver

IEAInterPro 2 GO

GTP bindingdefinition[GO:0005525]

IEAUniProtKB KW

Guanylate cyclase activitydefinition[GO:0004383]

IEAEC 2 GO

Protein bindingdefinition[GO:0005515]

Evidence 1: Inferred from Physical Interaction UniProtKB

A novel PDZ protein regulates the activity of guanylyl cyclase C, the heat-stable enterotoxin receptor.

Scott R.O., Thelin W.R., Milgram S.L.

J. Biol. Chem. 277, 22934-22941 (2002) [Full text:10.1074/jbc.M202434200] [PubMed:11950846]

Secretory diarrhea is the leading cause of infectious diarrhea in humans. Secretory diarrhea may be caused by binding of heat-stable enterotoxins to the intestinal receptor guanylyl cyclase C (GCC). Activation of GCC catalyzes the formation of cGMP, initiating a signaling cascade that opens the cystic fibrosis transmembrane conductance regulator chloride channel at the apical cell surface. To identify proteins that regulate the trafficking or function of GCC, we used the unique COOH terminus of GCC as the "bait" to screen a human intestinal yeast two-hybrid library. We identified a novel protein, IKEPP (intestinal and kidney-enriched PDZ protein) that associates with the COOH terminus of GCC in biochemical assays and by co-immunoprecipitation. IKEPP is expressed in the intestinal epithelium, where it is preferentially accumulated at the apical surface. The GCC-IKEPP interaction is not required for the efficient targeting of GCC to the apical cell surface. Rather, the association with IKEPP significantly inhibits heat-stable enterotoxin-mediated activation of GCC. Our findings are the first to identify a regulatory protein that associates with GCC to modulate the catalytic activity of the enzyme and provides new insights in mechanisms that regulate GCC activity in response to bacterial toxin.

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IPIUniProtKB

Protein kinase activitydefinition[GO:0004672] ‹silver

IEAInterPro 2 GO

Toxin bindingdefinition[GO:0015643] ‹silver

IEAOrtholog Compara

GO biological process

Intracellular signal transductiondefinition[GO:0035556] ‹silver

IEAInterPro 2 GO

Receptor guanylyl cyclase signaling pathwaydefinition[GO:0007168]

ref

TASPINC

Regulation of cell proliferationdefinition[GO:0042127] ‹silver

IEAOrtholog Compara

Response to toxindefinition[GO:0009636] ‹silver

IEAOrtholog Compara

Enzymatic activity

This protein acts as an enzyme. It is known to catalyze the following reaction

EC 4.6.1.2: GTP ⇄ 3',5'-cyclic GMP + diphosphate.

CuratedUniProtKB

Pathways

According to KEGG, this protein belongs to the following pathway:

Purine metabolism hsa00230+2984

Keywords

Biological process

cGMP biosynthesis definition [KW-0141]

Molecular function

Lyase definition [KW-0456]

Receptor definition [KW-0675]

Technical term

Reference proteome definition [KW-1185]

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Function

Keywords

neXtProt