Trypsinogen II, TG2 Protein (Active)

Trypsinogen is the precursor form or zymogen of the pancreatic enzyme trypsin. It functions as storage of an inactive form of trypsin so that it may be kept in pancreas and released in significant amount when required for protein digestion. Rowen et al. (1996) found thatonly 2 of 3 pancreatically expressed trypsinogen cDNAs correspond to trypsinogen genes in the TCRB locus; T4 was denoted trypsinogen 1 and T8 was denoted trypsinogen 2. The third pancreatic cDNA, identified independently as trypsinogen 3 and 4, is distinct from the third apparently functional trypsinogen gene (T6) in the TCRB locus but related to the other pancreatic trypsinogens. Teich et al. (2004) demonstrated that the E79K mutation in PRSS1 activated anionic trypsinogen 2-fold better than wildtype cationic trypsin did, whereas the common pancreatitis-associated mutants R122H and N29I had no such effect. The observations not only suggested a novel mechanism of action for pancreatitis-associated trypsinogen mutations, but also highlighted the importance of interactions between the 2 major trypsinogen isoforms in the development of genetically determined chronic pancreatitis.

1. Rowen, L., Koop, B. F., Hood, L. The complete 685-kilobase DNA sequence of the human beta T cell receptor locus. Science 272: 1755-1762, 1996. 2. Teich, N., Le Marechal, C., Kukor, Z., Caca, K., Witzigmann, H., Chen, J.-M., Toth, M., Mossner, J., Keim, V., Ferec, C., Sahin-Toth, M. Interaction between trypsinogen isoforms in genetically determined pancreatitis: mutation E79K in cationic trypsin (PRSS1) causes increased transactivation of anionic trypsinogen (PRSS2) . Hum. Mutat. 23: 22-31, 2004.