Guanylate cyclase 2C

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Guanylate cyclase 2C (heat stable enterotoxin receptor)
External IDs OMIM601330 MGI106903 HomoloGene3641 ChEMBL: 1795197 GeneCards: GUCY2C Gene
EC number
Species Human Mouse
Entrez 2984 14917
Ensembl ENSG00000070019 ENSMUSG00000042638
UniProt P25092 Q3UWA6
RefSeq (mRNA) NM_004963 NM_001127318
RefSeq (protein) NP_004954 NP_001120790
Location (UCSC) Chr 12:
14.77 – 14.85 Mb
Chr 6:
136.7 – 136.78 Mb
PubMed search [2] [3]

Guanylate cyclase 2C, also known as guanylyl cyclase C (GC-C), intestinal guanylate cyclase, guanylate cyclase-C receptor, or the heat-stable enterotoxin receptor (hSTAR) is an enzyme that in humans is encoded by the GUCY2C gene.[1][2]

Guanylyl cyclase is an enzyme found in the luminal aspect of intestinal epithelium and dopamine neurons in the brain.[3] The receptor has an extracellular ligand-binding domain, a single transmembrane region, a region with sequence similar to that of protein kinases, and a C-terminal guanylate cyclase domain. Tyrosine kinase activity mediates the GC-C signaling pathway within the cell.


GC-C is a key receptor for heat-stable enterotoxins that are responsible for acute secretory diarrhea.[4] Heat-stable enterotoxins are produced by pathogens such as Escherichia coli. Knockout mice deficient in the GC-C gene do not show secretory diarrhea on infection with E. coli, though they do with cholera toxin. This demonstrates the specificity of the GC-C receptor.

Diagnostic application[edit]

Because GC-C is tissue-specific for intestinal epithelium, it can be used for detection of metastatic disease.[citation needed][clarification needed]

See also[edit]


  1. ^ "Entrez Gene: guanylate cyclase 2C (heat stable enterotoxin receptor)". 
  2. ^ Mann EA, Swenson ES, Copeland NG, Gilbert DJ, Jenkins NA, Taguchi T, Testa JR, Giannella RA (June 1996). "Localization of the guanylyl cyclase C gene to mouse chromosome 6 and human chromosome 12p12". Genomics 34 (2): 265–7. doi:10.1006/geno.1996.0284. PMID 8661067. 
  3. ^ Intestinal Protein May Have Role in ADHD, Other Neurological Disorders. ScienceDaily (Aug. 11, 2011) [1]
  4. ^ Weiglmeier PR, Rösch P, Berkner H (August 2010). "Cure and Curse: E. coli Heat-Stable Enterotoxin and Its Receptor Guanylyl Cyclase C". Toxins 2 (9): 2213–2229. doi:10.3390/toxins2092213. 

Further reading[edit]

  • Schulz S, Hyslop T, Haaf J, et al. (2006). "A validated quantitative assay to detect occult micrometastases by reverse transcriptase-polymerase chain reaction of guanylyl cyclase C in patients with colorectal cancer.". Clin. Cancer Res. 12 (15): 4545–52. doi:10.1158/1078-0432.CCR-06-0865. PMID 16899600. 
  • Park J, Schulz S, Haaf J, et al. (2002). "Ectopic expression of guanylyl cyclase C in adenocarcinomas of the esophagus and stomach.". Cancer Epidemiol. Biomarkers Prev. 11 (8): 739–44. PMID 12163327. 
  • Tien YW, Lee PH, Hu RH, et al. (2003). "The role of gelatinase in hepatic metastasis of colorectal cancer.". Clin. Cancer Res. 9 (13): 4891–6. PMID 14581363. 
  • Basu N, Bhandari R, Natarajan VT, Visweswariah SS (2009). "Cross talk between receptor guanylyl cyclase C and c-src tyrosine kinase regulates colon cancer cell cytostasis.". Mol. Cell. Biol. 29 (19): 5277–89. doi:10.1128/MCB.00001-09. PMID 19620276. 
  • Mann EA, Steinbrecher KA, Stroup C, et al. (2005). "Lack of guanylyl cyclase C, the receptor for Escherichia coli heat-stable enterotoxin, results in reduced polyp formation and increased apoptosis in the multiple intestinal neoplasia (Min) mouse model.". Int. J. Cancer 116 (4): 500–5. doi:10.1002/ijc.21119. PMID 15825168. 
  • Saha S, Biswas KH, Kondapalli C, et al. (2009). "The linker region in receptor guanylyl cyclases is a key regulatory module: mutational analysis of guanylyl cyclase C.". J. Biol. Chem. 284 (40): 27135–45. doi:10.1074/jbc.M109.020032. PMID 19648115. 
  • Bhandari R, Srinivasan N, Mahaboobi M, et al. (2001). "Functional inactivation of the human guanylyl cyclase C receptor: modeling and mutation of the protein kinase-like domain.". Biochemistry 40 (31): 9196–206. doi:10.1021/bi002595g. PMID 11478887. 
  • Sindiće A, BaÅŸoglu C, Cerçi A, et al. (2002). "Guanylin, uroguanylin, and heat-stable euterotoxin activate guanylate cyclase C and/or a pertussis toxin-sensitive G protein in human proximal tubule cells.". J. Biol. Chem. 277 (20): 17758–64. doi:10.1074/jbc.M110627200. PMID 11889121. 
  • Jaleel M, London RM, Eber SL, et al. (2002). "Expression of the receptor guanylyl cyclase C and its ligands in reproductive tissues of the rat: a potential role for a novel signaling pathway in the epididymis.". Biol. Reprod. 67 (6): 1975–80. doi:10.1095/biolreprod.102.006445. PMID 12444076. 
  • Mejia A, Schulz S, Hyslop T, et al. (2009). "GUCY2C reverse transcriptase PCR to stage pN0 colorectal cancer patients.". Expert Rev. Mol. Diagn. 9 (8): 777–85. doi:10.1586/erm.09.67. PMID 19895223. 
  • Scott RO, Thelin WR, Milgram SL (2002). "A novel PDZ protein regulates the activity of guanylyl cyclase C, the heat-stable enterotoxin receptor.". J. Biol. Chem. 277 (25): 22934–41. doi:10.1074/jbc.M202434200. PMID 11950846. 
  • Ghanekar Y, Chandrashaker A, Tatu U, Visweswariah SS (2004). "Glycosylation of the receptor guanylate cyclase C: role in ligand binding and catalytic activity.". Biochem. J. 379 (Pt 3): 653–63. doi:10.1042/BJ20040001. PMID 14748740. 
  • Kulaksiz H, Cetin Y (2001). "Uroguanylin and guanylate cyclase C in the human pancreas: expression and mutuality of ligand/receptor localization as indicators of intercellular paracrine signaling pathways.". J. Endocrinol. 170 (1): 267–75. doi:10.1677/joe.0.1700267. PMID 11431160. 
  • Debruyne PR, Witek M, Gong L, et al. (2006). "Bile acids induce ectopic expression of intestinal guanylyl cyclase C Through nuclear factor-kappaB and Cdx2 in human esophageal cells.". Gastroenterology 130 (4): 1191–206. doi:10.1053/j.gastro.2005.12.032. PMID 16618413. 
  • Singh R (2003). "Interaction of guanylyl cyclase C with SH3 domain of Src tyrosine kinase. Yet another mechanism for desensitization.". J. Biol. Chem. 278 (27): 24342–9. doi:10.1074/jbc.M301153200. PMID 12649275. 
  • Selvaraj NG, Prasad R, Goldstein JL, Rao MC (2000). "Evidence for the presence of cGMP-dependent protein kinase-II in human distal colon and in T84, the colonic cell line.". Biochim. Biophys. Acta 1498 (1): 32–43. doi:10.1016/s0167-4889(00)00075-6. PMID 11042348. 
  • Ciocca V, Bombonati A, Palazzo JP, et al. (2009). "Guanylyl cyclase C is a specific marker for differentiating primary and metastatic ovarian mucinous neoplasms.". Histopathology 55 (2): 182–8. doi:10.1111/j.1365-2559.2009.03358.x. PMID 19694825. 
  • Strausberg RL, Feingold EA, Grouse LH, et al. (2002). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. 
  • Dias Neto E, Correa RG, Verjovski-Almeida S, et al. (2000). "Shotgun sequencing of the human transcriptome with ORF expressed sequence tags.". Proc. Natl. Acad. Sci. U.S.A. 97 (7): 3491–6. doi:10.1073/pnas.97.7.3491. PMC 16267. PMID 10737800. 

External links[edit]