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Gene Review

PRSS3  -  protease, serine, 3

Homo sapiens

Synonyms: Brain trypsinogen, MTG, Mesotrypsinogen, PRSS4, Serine protease 3, ...
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Disease relevance of PRSS3


Psychiatry related information on PRSS3

  • Clot initiation (R, reaction time), propagation (MTG, maximum thrombus generation), and strength (MG, maximum elastic modulus) were determined [5].

High impact information on PRSS3

  • Its electrophoretic mobility and isoelectric pH lie between those of the cationic and anionic trypsinogen variants, and we propose the name "mesotrypsinogen" for the new enzyme precursor [6].
  • In the right temporal lobe, the activation was located in the MTG/STS (lower bank) [7].
  • Exposure of cell lines expressing PAR(2) and PAR(4) to trypsin IV increased [Ca(2+)](i) and strongly desensitized cells to PAR agonists, whereas there were no responses in cells lacking these receptors [8].
  • In this regard, it is noteworthy that the well known pathological trypsinogen activator cathepsin B exhibited a preference for the activation of mesotrypsinogen of all three human trypsinogen isoforms, suggesting a biochemical mechanism for mesotrypsinogen activation in pancreatic acinar cells [2].
  • Here, we report a variation of the theme of new gene creation by duplication: the PRSS3 gene was formed by segmental duplications originating from chromosomes 7q35 and 11q24 [9].

Chemical compound and disease context of PRSS3


Biological context of PRSS3


Anatomical context of PRSS3

  • Mesotrypsin (trypsin IV), in contrast to cationic and anionic trypsin, cannot activate or disable PARs in human epithelial cells, demonstrating that the receptors are no substrates for this isoenzyme [14].
  • Age-associated minicolumn thinning was found in temporal lobe association cortex (Tpt and MTG) but not primary auditory cortex (HG) [15].
  • Tumor cells injected subcutaneously in the flank using either Matrigel (MTG, an extract of basement membrane proteins) or growth medium (GM) as a vehicle were compared [13].
  • When NR-stained lipid droplets were specifically bleached, a significant increase in the MTG signal in stained mitochondria was observed (FRET efficiency, E=22.2 +/- 3.18%) [16].
  • Immature and in vitro-matured porcine oocytes were stained with Mitotracker Green (MTG; mitochondria) and Nile Red (NR; lipid droplets) [16].

Associations of PRSS3 with chemical compounds

  • Here we report the X-ray structure of human trypsin IV in complex with the inhibitor benzamidine at 1.7 A resolution [17].
  • The (13)C-mixed triacylglcerol (MTG, 1,3-distearyl, 2-[1-(13)C]octanoyl glycerol) breath test is a non-invasive measure of intraluminal fat digestion [18].
  • We measured the minicolumn spacing and organization of cells in Heschl's gyrus (primary auditory cortex, A1), the Planum Temporale (Tpt, BA22), and middle temporal gyrus (MTG, BA21) of 17 normally aged human adults [15].
  • Glucose uptake (M) value negatively correlated with the MTG level (R2 = -.56, P < .0001), which was increased in obese patients (11.6 +/- 2.2 v 6.2 +/- 1.4 micromol/g wet weight muscle tissue, P < .0001) [19].
  • In general, the DTIs tested prolonged R in a concentration-dependent fashion but did not diminish MTG or MG nearly as well as heparin [5].

Other interactions of PRSS3

  • Epigenetic silencing of RASSF1A and PRSS3 and any of the SFRP genes were each significantly associated with advanced tumor stage (P < 0.001, P < 0.04, and P < 0.005, respectively) [12].
  • Trypsin-I, trypsin-IIA and trypsin-III showed preference for Arg over Lys, but responded differently to proteinaceous or synthetic inhibitors [20].

Analytical, diagnostic and therapeutic context of PRSS3

  • Using methylation-specific PCR, we determined the promoter hypermethylation status of PRSS3 in a case series study of primary NSCLC, and found methylation of this gene to be common, occurring in 53% (86 of 166) of tumors examined [1].
  • Specific peptidyl linkers that result in the heterodimerization of functional proteins, which is catalyzed by microbial transglutaminase from Streptomyces mobaraensis (MTG), were generated based on a ribonuclease S-peptide using site-directed mutagenesis [21].
  • With supernatants from high-speed centrifugation of HBT biopsies or the human breast cancer cell line MCF-7, reducing agents increased the apparent E2R binding in the order: DTT greater than G-SH greater than MTG [22].


  1. Epigenetic silencing of the PRSS3 putative tumor suppressor gene in non-small cell lung cancer. Marsit, C.J., Okpukpara, C., Danaee, H., Kelsey, K.T. Mol. Carcinog. (2005) [Pubmed]
  2. Human mesotrypsin is a unique digestive protease specialized for the degradation of trypsin inhibitors. Szmola, R., Kukor, Z., Sahin-Tóth, M. J. Biol. Chem. (2003) [Pubmed]
  3. Genetic and biochemical characterization of the E32del polymorphism in human mesotrypsinogen. Nemoda, Z., Teich, N., Hugenberg, C., Sahin-Tóth, M. Pancreatology (2005) [Pubmed]
  4. Trypsin IV or mesotrypsin and p23 cleave protease-activated receptors 1 and 2 to induce inflammation and hyperalgesia. Knecht, W., Cottrell, G.S., Amadesi, S., Mohlin, J., Skåregärde, A., Gedda, K., Peterson, A., Chapman, K., Hollenberg, M.D., Vergnolle, N., Bunnett, N.W. J. Biol. Chem. (2007) [Pubmed]
  5. Argatroban, bivalirudin, and lepirudin do not decrease clot propagation and strength as effectively as heparin-activated antithrombin in vitro. Nielsen, V.G., Steenwyk, B.L., Gurley, W.Q., Pereira, S.J., Lell, W.A., Kirklin, J.K. J. Heart Lung Transplant. (2006) [Pubmed]
  6. Mesotrypsin: a new inhibitor-resistant protease from a zymogen in human pancreatic tissue and fluid. Rinderknecht, H., Renner, I.G., Abramson, S.B., Carmack, C. Gastroenterology (1984) [Pubmed]
  7. Controlling for individual differences in fMRI brain activation to tones, syllables, and words. Rimol, L.M., Specht, K., Hugdahl, K. Neuroimage (2006) [Pubmed]
  8. Trypsin IV, a novel agonist of protease-activated receptors 2 and 4. Cottrell, G.S., Amadesi, S., Grady, E.F., Bunnett, N.W. J. Biol. Chem. (2004) [Pubmed]
  9. Interchromosomal segmental duplications explain the unusual structure of PRSS3, the gene for an inhibitor-resistant trypsinogen. Rowen, L., Williams, E., Glusman, G., Linardopoulou, E., Friedman, C., Ahearn, M.E., Seto, J., Boysen, C., Qin, S., Wang, K., Kaur, A., Bloom, S., Hood, L., Trask, B.J. Mol. Biol. Evol. (2005) [Pubmed]
  10. Improving the specificity of the [(13)C]mixed triacylglycerol breath test by estimating carbon dioxide production from heart rate. Slater, C., Preston, T., Weaver, L.T. European journal of clinical nutrition. (2006) [Pubmed]
  11. Long-term ethanol consumption alters pancreatic gene expression in rats: a possible connection to pancreatic injury. Kubisch, C.H., Gukovsky, I., Lugea, A., Pandol, S.J., Kuick, R., Misek, D.E., Hanash, S.M., Logsdon, C.D. Pancreas (2006) [Pubmed]
  12. Carcinogen exposure and epigenetic silencing in bladder cancer. Marsit, C.J., Karagas, M.R., Schned, A., Kelsey, K.T. Ann. N. Y. Acad. Sci. (2006) [Pubmed]
  13. Growth and magnetic resonance characteristics of human squamous cell carcinoma xenografts implanted with cells suspended in Matrigel. Czerski, L., Majors, A., Ng, T.C., Vijayakumar, S., Weichselbaum, R. NMR in biomedicine. (1993) [Pubmed]
  14. Activity of recombinant trypsin isoforms on human proteinase-activated receptors (PAR): mesotrypsin cannot activate epithelial PAR-1, -2, but weakly activates brain PAR-1. Grishina, Z., Ostrowska, E., Halangk, W., Sahin-Tóth, M., Reiser, G. Br. J. Pharmacol. (2005) [Pubmed]
  15. Minicolumn thinning in temporal lobe association cortex but not primary auditory cortex in normal human ageing. Chance, S.A., Casanova, M.F., Switala, A.E., Crow, T.J., Esiri, M.M. Acta Neuropathol. (2006) [Pubmed]
  16. Fluorescence resonance energy transfer analysis of mitochondrial:lipid association in the porcine oocyte. Sturmey, R.G., O'toole, P.J., Leese, H.J. Reproduction (2006) [Pubmed]
  17. Crystal structure reveals basis for the inhibitor resistance of human brain trypsin. Katona, G., Berglund, G.I., Hajdu, J., Gráf, L., Szilágyi, L. J. Mol. Biol. (2002) [Pubmed]
  18. Advantages of deuterium-labelled mixed triacylglycerol in studies of intraluminal fat digestion. Slater, C., Preston, T., Weaver, L.T. Rapid Commun. Mass Spectrom. (2006) [Pubmed]
  19. Insulin resistance directly correlates with increased saturated fatty acids in skeletal muscle triglycerides. Manco, M., Mingrone, G., Greco, A.V., Capristo, E., Gniuli, D., De Gaetano, A., Gasbarrini, G. Metab. Clin. Exp. (2000) [Pubmed]
  20. Diversity of trypsins in the Mediterranean corn borer Sesamia nonagrioides (Lepidoptera: Noctuidae), revealed by nucleic acid sequences and enzyme purification. Díaz-Mendoza, M., Ortego, F., García de Lacoba, M., Magaña, C., de la Poza, M., Farinós, G.P., Castañera, P., Hernández-Crespo, P. Insect Biochem. Mol. Biol. (2005) [Pubmed]
  21. Peptidyl linkers for protein heterodimerization catalyzed by microbial transglutaminase. Tanaka, T., Kamiya, N., Nagamune, T. Bioconjug. Chem. (2004) [Pubmed]
  22. Characteristics of the dextran-coated charcoal assay for estradiol receptor in breast cancer preparations. Shafie, S., Brooks, S.C. J. Lab. Clin. Med. (1979) [Pubmed]
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