Prss1

PRSS1 is the acronym for "protease serine1" an enzyme encoded by the PRSS1 gene of the same name located on chromsome 7q34. Mutations in PRSS1 lead to the clinical picture of autosomal dominant "PRSS1-related hereditary pancreatitis".

Human pancreatic juice contains 3 isoforms of trypsinogen. These are commonly called cationic trypsinogen (PRSS1), anionic trypsinogen (PRSS2) and mesotrypsinogen (PRSS3). Normally, cationic trypsinogen accounts for about 2/3 of the total trypsinogen, while anionic trypsinogen accounts for about 1/3, while mesotrypsinogen accounts for less than 5% of trypsinogens or 0.5% of pancreatic juice proteins (Scheele et al. 1981)

Whitcomb et al. 1996 found out that not a single gene is responsible for encoding PRSS1, but a cluster of 5 trypsinogen genes that show a high degree of DNA sequence homology (more than 91%) ( Rowen et al. 1996). In a family with hereditary pancreatitis, it was shown in several patients that only a single G-to-A transition mutation had occurred in the third exon of the cationic trypsinogen (Whitcomb et al. 1996). The mutations R122H and N29I are by far the most common mutations with 50% of all mutations detected in hereditary pancreatitis. They are associated with an increased autoactivation of human cationic trypsinogen. Additionally, the R122H mutation inhibited the autocatalytic inactivation of trypsin. It is assumed that increased trypsinogen activation in the pancreas is the most common initiation step in certain forms of hereditary pancreatitis (Sahin-Toth et al. 2000)

1. Rowen L et al (1996) The complete 685-kilobase DNA sequence of the human beta T cell receptor locus. Science 272: 1755-1762
2. Sahin-Toth M et al (2000) Gain-of-function mutations associated with hereditary pancreatitis enhance autoactivation of human cationic trypsinogen. Biochem Biophys Res Commun. 278: 286-289
3. Scheele G et al (1981) Characterization of human exocrine pancreatic proteins by two-dimensional isoelectric focusing/sodium dodecyl sulfate gel electrophoresis. Gastroenterology 80: 461-473
4. Whitcomb D C et al (1996) Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene. Nature Genet 14: 141-145