Trypsin 1

Protease, serine, 1 (trypsin 1)
PDB rendering based on 1trn.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1FXY​, 1TRN​, 2RA3​
Identifiers
Symbols	PRSS1 ; TRP1; TRY1; TRY4; TRYP1
External IDs	OMIM: 276000 MGI: 3687012 HomoloGene: 134623 ChEMBL: 209 GeneCards: PRSS1 Gene
EC number	3.4.21.4
Gene ontology Molecular function • serine-type endopeptidase activity • metal ion binding Cellular component • extracellular region • extracellular space • extracellular exosome • blood microparticle Biological process • proteolysis • vitamin metabolic process • water-soluble vitamin metabolic process • digestion • cobalamin metabolic process • extracellular matrix disassembly • extracellular matrix organization • small molecule metabolic process Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	5644	436522
Ensembl	ENSG00000204983	ENSMUSG00000071521
UniProt	P07477	P07146
RefSeq (mRNA)	NM_002769	NM_001038996
RefSeq (protein)	NP_002760	NP_001034085
Location (UCSC)	Chr 7: 142.75 – 142.76 Mb	Chr 6: 41.35 – 41.36 Mb
PubMed search

Trypsin-1, also known as cationic trypsinogen, is a protein that in humans is encoded by the PRSS1 gene. 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.^[1]

Clinical significance

Its malfunction acts in an autosomal dominant manner to cause pancreatitis. Many mutations that can lead to pancreatitis have been found.^[2][3][4][5] 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.^[6]

See also

• Trypsin

References

1. "Entrez Gene: PRSS1 protease, serine, 1 (trypsin 1)".
2. Rebours V, Lévy P, Ruszniewski P (2011). "An overview of hereditary pancreatitiss". Digestive and Liver Disease 44 (1): 8–15. doi:10.1016/j.dld.2011.08.003. PMID 21907651.
3. Teich N, Mössner J, Keim V (1998). "Mutations of the cationic trypsinogen in hereditary pancreatitis". Hum. Mutat. 12 (1): 39–43. doi:10.1002/(SICI)1098-1004(1998)12:1<39::AID-HUMU6>3.0.CO;2-P. PMID 9633818.
4. Chen JM, Ferec C (2000). "Molecular basis of hereditary pancreatitis.". Eur. J. Hum. Genet. 8 (7): 473–9. doi:10.1038/sj.ejhg.5200492. PMID 10909845.
5. 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. PMID 9322498.
6. Whitcomb DC, Gorry MC, Preston RA, Furey W, Sossenheimer MJ, Ulrich CD, Martin SP, Gates LK Jr, 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. PMID 8841182.

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. PMID 11073713.
• 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. PMID 11702203.
• Howes N, Greenhalf W, Stocken DD, Neoptolemos JP (2005). "Cationic trypsinogen mutations and pancreatitis.". Clin. Lab. Med. 25 (1): 39–59. doi:10.1016/j.cll.2004.12.004. PMID 15749231.
• Kandula L, Whitcomb DC, Lowe ME (2006). "Genetic issues in pediatric pancreatitis.". Current gastroenterology reports 8 (3): 248–53. doi:10.1007/s11894-006-0083-8. PMID 16764792.
• Yamamoto KK, Pousette A, Chow P, et al. (1992). "Isolation of a cDNA encoding a human serum marker for acute pancreatitis. Identification of pancreas-specific protein as pancreatic procarboxypeptidase B.". J. Biol. Chem. 267 (4): 2575–81. PMID 1370825.
• Pollard SR, Meier W, Chow P, et al. (1992). "CD4-binding regions of human immunodeficiency virus envelope glycoprotein gp120 defined by proteolytic digestion". Proc. Natl. Acad. Sci. U.S.A. 88 (24): 11320–4. doi:10.1073/pnas.88.24.11320. PMC 53126. PMID 1763044.
• Shieh BH, Travis J (1987). "The reactive site of human alpha 2-antiplasmin". J. Biol. Chem. 262 (13): 6055–9. PMID 2437112.
• 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. PMID 2598466.
• 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. PMID 3011602.
• 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. PMID 6589790.
• Merrill GA, Butler M, Horowitz PM (1993). "Limited tryptic digestion near the amino terminus of bovine liver rhodanese produces active electrophoretic variants with altered refolding". J. Biol. Chem. 268 (21): 15611–20. PMID 8340386.
• Rowen L, Koop BF, Hood L (1996). "The complete 685-kilobase DNA sequence of the human beta T cell receptor locus". Science 272 (5269): 1755–62. doi:10.1126/science.272.5269.1755. PMID 8650574.
• 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. PMID 8683601.
• Gu M, Majerus PW (1996). "The properties of the protein tyrosine phosphatase PTPMEG". J. Biol. Chem. 271 (44): 27751–9. doi:10.1074/jbc.271.44.27751. PMID 8910369.
• Christensen S, Valnickova Z, Thogersen IB, et al. (1997). "Assignment of a single disulphide bridge in human alpha2-antiplasmin: implications for the structural and functional properties". Biochem. J. 323 (Pt 3): 847–52. PMC 1218391. PMID 9169621.
• Dahlen JR, Foster DC, Kisiel W (1998). "Expression, purification, and inhibitory properties of human proteinase inhibitor". Biochemistry 36 (48): 14874–82. doi:10.1021/bi970977p. PMID 9402754.

External links

• GeneReviews/NCBI/NIH/UW entry on PRSS1-Related Hereditary Pancreatitis

This article incorporates text from the United States National Library of Medicine, which is in the public domain.