Guanylyl cyclase C

Function

Guanylyl cyclase that catalyzes synthesis of cyclic GMP (cGMP) from GTP. Receptor for the E.coli heat-stable enterotoxin; E.coli enterotoxin markedly stimulates the accumulation of cGMP in mammalian cells expressing GUCY2C. Also activated by the endogenous peptides guanylin and uroguanylin.

Classification

Family (Pfam)

PF00211 Guanylate_cyc, PF07714 PK_Tyr_Ser-Thr

InterPro

A/G_cyclase, A/G_cyclase_CS, Cyclic_nucleotide_synthase, GC-C_PK, Kinase-like_dom_sf, Nucleotide_cyclase, Peripla_BP_I, Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom

Functional cluster

Immunoglobulin-Domain Cell Adhesion Proteins

Experimental structures · PDB · 3

• 8FX4 EM 3.90A
• 8GHO X-ray 1.60A
• 8GHP X-ray 3.52A

A predicted model is available from AlphaFold.

Gene Ontology · 11

• GO:0005789 endoplasmic reticulum membrane
• GO:0005886 plasma membrane
• GO:0005524 ATP binding
• GO:0005525 GTP binding
• GO:0004383 guanylate cyclase activity
• GO:0001653 peptide receptor activity
• GO:0004672 protein kinase activity
• GO:0015643 toxic substance binding
• GO:0006182 cGMP biosynthetic process
• GO:0035556 intracellular signal transduction
• GO:0007168 receptor guanylyl cyclase signaling pathway

Disease associations

• congenital diarrhea 6 MONDO:0013825
• intestinal obstruction in the newborn due to guanylate cyclase 2C deficiency MONDO:0013843

Drugs targeting this protein · 3

• PLECANATIDE agonist
• LINACLOTIDE agonist
• DOLCANATIDE agonist

Related proteins · sequence + function similarity

• Guanylyl cyclase C 0.99
• Guanylyl cyclase C 0.98
• Guanylyl cyclase C 0.98
• Guanylyl cyclase C 0.97
• Receptor-type guanylate cyclase Gyc76C 0.88
• Receptor-type guanylate cyclase gcy-4 0.87
• Guanylate cyclase 32E 0.86
• Receptor-type guanylate cyclase gcy-4 0.86
• Receptor-type guanylate cyclase gcy-17 0.85
• Receptor-type guanylate cyclase gcy-5 0.85
• Receptor-type guanylate cyclase gcy-25 0.84
• Receptor-type guanylate cyclase gcy-20 0.84

Co-cited proteins · studied together in the literature

• Sodium-dependent phosphate transport protein 2A 1 shared papers
• Na(+)/H(+) exchange regulatory cofactor NHE-RF4 1 shared papers

Literature · 12 cited papers

• 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. J. Biol. Chem. · 2013
• Meconium ileus caused by mutations in GUCY2C, encoding the CFTR-activating guanylate cyclase 2C. Am. J. Hum. Genet. · 2012
• Familial diarrhea syndrome caused by an activating GUCY2C mutation. N. Engl. J. Med. · 2012
• Patterns of somatic mutation in human cancer genomes. Nature · 2007
• The finished DNA sequence of human chromosome 12. Nature · 2006
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• A novel PDZ protein regulates the activity of guanylyl cyclase C, the heat-stable enterotoxin receptor. J. Biol. Chem. · 2002
• Biochemical characterization of the intracellular domain of the human guanylyl cyclase C receptor provides evidence for a catalytically active homotrimer. Biochemistry · 2000
• Cell line-specific transcriptional activation of the promoter of the human guanylyl cyclase C/heat-stable enterotoxin receptor gene. Biochim. Biophys. Acta · 1996
• Comparison of receptors for Escherichia coli heat-stable enterotoxin: novel receptor present in IEC-6 cells. Am. J. Physiol. · 1993
• Isolation and expression of a guanylate cyclase-coupled heat stable enterotoxin receptor cDNA from a human colonic cell line. Biochem. Biophys. Res. Commun. · 1991
• Primary structure and functional expression of the human receptor for Escherichia coli heat-stable enterotoxin. J. Biol. Chem. · 1991