Alternative titles; symbols
HGNC Approved Gene Symbol: GUCA2A
Cytogenetic location: 1p34.2 Genomic coordinates (GRCh38): 1:42,162,690-42,164,745 (from NCBI)
Currie et al. (1992) described guanylin, a 15-amino acid peptide purified from rat small intestine, as a potential ligand for intestinal guanylate cyclase. This peptide shares sequence similarity with E. coli heat-stable enterotoxin (STa); see also uroguanylin (601271). The molecular cloning of the human and mouse cDNAs encoding guanylin was reported by de Sauvage et al. (1992). The sequences demonstrated that guanylin is present at the C-terminal end of a larger precursor protein. Expression in mammalian cells indicated that the 94-amino acid proguanylin is inactive. The biologically active guanylin can be released by either chemical or enzymatic treatment of proguanylin. By Northern blot analysis and in situ hybridization, de Sauvage et al. (1992) showed that expression of guanylin mRNA is restricted to cells of the intestinal epithelium, specifically the Paneth cells at the base of the small intestinal crypts. These results demonstrate that guanylin is an endogenous activator of the E. coli heat-stable enterotoxin receptor (STaR).
Wiegand et al. (1992) isolated a cDNA encoding an apparent precursor of guanylin from a human intestinal cDNA library. The mRNA was expressed at high levels in human ileum and colon.
Guanylin is thought to modulate intestinal water/electrolyte transport in a paracrine mode. Hill et al. (1995) reported the nucleotide sequence of the gene, the characteristics of its circulating molecular form, and its localization in enterochromaffin cells of the gut. The hormonal form of guanylin is a 94-amino acid peptide with a molecular mass of 10.3 kD. Guanylin is synthesized by gut enterochromaffin cells as a prohormone of 115 amino acids and is processed to the molecular form of 94 amino acids circulating in the blood.
Hill et al. (1995) determined that the GUCA2A gene, approximately 2.6 kb in size, consists of 3 exons interrupted by 2 introns.
By fluorescence in situ hybridization, Sciaky et al. (1995) mapped the GUCA2 gene to human 1p35-p34. In the mouse, Sciaky et al. (1995) used interspecific backcross analysis to map the Guca2 gene to the distal half of mouse chromosome 4 in a region of homology with human chromosome 1p.
Currie, M. G., Fok, K. F., Kato, J., Moore, R. J., Hamra, F. K., Duffin, K. L., Smith, C. E. Guanylin: an endogenous activator of intestinal guanylate cyclase. Proc. Nat. Acad. Sci. 89: 947-951, 1992. [PubMed: 1346555] [Full Text: https://doi.org/10.1073/pnas.89.3.947]
de Sauvage, F. J., Keshav, S., Kuang, W.-J., Gillett, N., Henzel, W., Goeddel, D. V. Precursor structure, expression, and tissue distribution of human guanylin. Proc. Nat. Acad. Sci. 89: 9089-9093, 1992. [PubMed: 1409606] [Full Text: https://doi.org/10.1073/pnas.89.19.9089]
Hill, O., Kuhn, M., Zucht, H.-D., Cetin, Y., Kulaksiz, H., Adermann, K., Klock, G., Rechkemmer, G., Forssmann, W.-G., Magert, H.-J. Analysis of the human guanylin gene and the processing and cellular localization of the peptide. Proc. Nat. Acad. Sci. 92: 2046-2050, 1995. [PubMed: 7892222] [Full Text: https://doi.org/10.1073/pnas.92.6.2046]
Sciaky, D., Jenkins, N. A., Gilbert, D. J., Copeland, N. G., Sonoda, G., Testa, J. R., Cohen, M. B. Mapping of guanylin to murine chromosome 4 and human chromosome 1p34-p35. Genomics 26: 427-429, 1995. [PubMed: 7601480] [Full Text: https://doi.org/10.1016/0888-7543(95)80238-h]
Wiegand, R. C., Kato, J., Huang, M. D., Fok, K. F., Kachur, J. F., Currie, M. G. Human guanylin: cDNA isolation, structure, and activity. FEBS Lett. 311: 150-154, 1992. [PubMed: 1327879] [Full Text: https://doi.org/10.1016/0014-5793(92)81387-2]