Trypsin-1, also known as cationic trypsinogen, is a protein that in humans is encoded by the PRSS1gene. Trypsin-1 is the main isoform of trypsinogen secreted by pancreas, the others are trypsin-2 (anionic trypsinogen), and trypsin-3 (meso-trypsinogen).
Function
This gene encodes a trypsinogen, which is a member of the trypsin family of serine proteases. This enzyme is secreted by the pancreas and cleaved to its active form in the small intestine. It is active on peptide linkages involving the carboxyl group of lysine or arginine. Mutations in this gene are associated with hereditary pancreatitis. This gene and several other trypsinogen genes are localized to the T cell receptor beta locus on chromosome 7.[5]
Clinical significance
Its malfunction acts in an autosomal dominant manner to cause pancreatitis. Many mutations that can lead to pancreatitis have been found.[6][7][8][9] An example is a mutation at Arg 117. Arg 117 is a trypsin-sensitive site which can be cleaved by another trypsin and becomes inactivated. This site may be a fail-safe mechanism by which trypsin, when activated within the pancreas, may become inactivated. Mutation at this cleavage site would result in a loss of control and permit autodigestion, causing pancreatitis.[10]
^Gorry MC, Gabbaizedeh D, Furey W, et al. (1997). "Mutations in the cationic trypsinogen gene are associated with recurrent acute and chronic pancreatitis". Gastroenterology. 113 (4): 1063–8. doi:10.1053/gast.1997.v113.pm9322498. PMID9322498.
^Whitcomb DC, Gorry MC, Preston RA, Furey W, Sossenheimer MJ, Ulrich CD, Martin SP, Gates LK, Amann ST, Toskes PP, Liddle R, McGrath K, Uomo G, Post JC, Ehrlich GD (1996). "Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene". Nature Genetics. 14 (2): 141–5. doi:10.1038/ng1096-141. PMID8841182. S2CID21974705.
Further reading
Chen JM, Ferec C (2000). "Gene conversion-like missense mutations in the human cationic trypsinogen gene and insights into the molecular evolution of the human trypsinogen family". Mol. Genet. Metab. 71 (3): 463–9. doi:10.1006/mgme.2000.3086. PMID11073713.
Chen JM, Montier T, Férec C (2001). "Molecular pathology and evolutionary and physiological implications of pancreatitis-associated cationic trypsinogen mutations". Hum. Genet. 109 (3): 245–52. doi:10.1007/s004390100580. PMID11702203. S2CID24099557.
Kimland M, Russick C, Marks WH, Borgström A (1990). "Immunoreactive anionic and cationic trypsin in human serum". Clin. Chim. Acta. 184 (1): 31–46. doi:10.1016/0009-8981(89)90254-4. PMID2598466.
Emi M, Nakamura Y, Ogawa M, et al. (1986). "Cloning, characterization and nucleotide sequences of two cDNAs encoding human pancreatic trypsinogens". Gene. 41 (2–3): 305–10. doi:10.1016/0378-1119(86)90111-3. PMID3011602.
Honey NK, Sakaguchi AY, Quinto C, et al. (1984). "Chromosomal assignments of human genes for serine proteases trypsin, chymotrypsin B, and elastase". Somat. Cell Mol. Genet. 10 (4): 369–76. doi:10.1007/BF01535632. PMID6589790. S2CID40599814.
Gaboriaud C, Serre L, Guy-Crotte O, et al. (1996). "Crystal structure of human trypsin 1: unexpected phosphorylation of Tyr151". J. Mol. Biol. 259 (5): 995–1010. doi:10.1006/jmbi.1996.0376. PMID8683601.
