Trypsin 1

Last updated
PRSS1
Protein PRSS1 PDB 1trn.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases PRSS1 , TRP1, TRY1, TRY4, TRYP1, Trypsin 1, protease, serine 1, serine protease 1
External IDs OMIM: 276000 MGI: 3687012 HomoloGene: 134623 GeneCards: PRSS1
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_002769

NM_001038996

RefSeq (protein)

NP_002760

NP_001034085

Location (UCSC) Chr 7: 142.75 – 142.75 Mb Chr 6: 41.35 – 41.36 Mb
PubMed search [3] [4]
Wikidata
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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).

Contents

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]

See also

Related Research Articles

Trypsin

Trypsin is a serine protease from the PA clan superfamily, found in the digestive system of many vertebrates, where it hydrolyzes proteins. Trypsin is formed in the small intestine when its proenzyme form, the trypsinogen produced by the pancreas, is activated. Trypsin cuts peptide chains mainly at the carboxyl side of the amino acids lysine or arginine. It is used for numerous biotechnological processes. The process is commonly referred to as trypsin proteolysis or trypsinization, and proteins that have been digested/treated with trypsin are said to have been trypsinized. Trypsin was discovered in 1876 by Wilhelm Kühne and was named from the Ancient Greek word for rubbing since it was first isolated by rubbing the pancreas with glycerin.

Trypsinogen is the precursor form of trypsin, a digestive enzyme. It is produced by the pancreas and found in pancreatic juice, along with amylase, lipase, and chymotrypsinogen. It is cleaved to its active form, trypsin, by enteropeptidase, which is found in the intestinal mucosa. Once activated, the trypsin can cleave more trypsinogen into trypsin, a process called autoactivation. Trypsin cleaves the peptide bond on the carboxyl side of basic amino acids such as arginine and lysine.

Enteropeptidase

Enteropeptidase is an enzyme produced by cells of the duodenum and is involved in digestion in humans and other animals. Enteropeptidase converts trypsinogen into its active form trypsin, resulting in the subsequent activation of pancreatic digestive enzymes. Absence of enteropeptidase results in intestinal digestion impairment.

Hereditary pancreatitis Medical condition

Hereditary pancreatitis (HP) is an inflammation of the pancreas due to genetic causes. It was first described in 1952 by Comfort and Steinberg but it was not until 1996 that Whitcomb et al isolated the first responsible mutation in the trypsinogen gene (PRSS1) on the long arm of chromosome seven (7q35).

Granzyme A

Granzyme A is an enzyme. that in humans is encoded by the GZMA gene, and is one of the five granzymes encoded in the human genome. This enzyme is present in cytotoxic T lymphocyte granules.

Spectrin, alpha 1

Spectrin alpha chain, erythrocyte is a protein that in humans is encoded by the SPTA1 gene.

SPINK1

Pancreatic secretory trypsin inhibitor (PSTI) also known as serine protease inhibitor Kazal-type 1 (SPINK1) or tumor-associated trypsin inhibitor (TATI) is a protein that in humans is encoded by the SPINK1 gene.

HTRA1

Serine protease HTRA1 is an enzyme that in humans is encoded by the HTRA1 gene. The HTRA1 protein is composed of four distinct protein domains. They are from amino-terminus to carboxyl-terminus an Insulin-like growth factor binding domain, a kazal domain, a trypsin-like peptidase domain and a PDZ domain.

KLK4

Kallikrein-related peptidase 4 is a protein which in humans is encoded by the KLK4 gene.

PHKG1

Phosphorylase b kinase gamma catalytic chain, skeletal muscle isoform is an enzyme that in humans is encoded by the PHKG1 gene.

LEKTI

Lympho-epithelial Kazal-type-related inhibitor (LEKTI) also known as serine protease inhibitor Kazal-type 5 (SPINK5) is a protein that in humans is encoded by the SPINK5 gene.

KLK11

Kallikrein-11 is a protein that in humans is encoded by the KLK11 gene.

SERPINB6

Serpin B6 is a protein that in humans is encoded by the SERPINB6 gene.

CELA3B

Chymotrypsin-like elastase family member 3B also known as elastase-3B, protease E, or fecal elastase is an enzyme that in humans is encoded by the CELA3B gene.

SPINK2

Serine protease inhibitor Kazal-type 2 also known as acrosin-trypsin inhibitor is a protein that in humans is encoded by the SPINK2 gene.

Chymotrypsin-C

Chymotrypsin C, also known as caldecrin or elastase 4, is an enzyme that in humans is encoded by the CTRC gene.

PRSS22

Brain-specific serine protease 4 (BSSP-4), also known as serine protease 22 or tryptase epsilon, is an enzyme that in humans is encoded by the PRSS22 gene.

PRSS56

Putative Serine Protease 56 (PRSS56) is a serine protease that in humans is encoded by the PRSS56 gene. This protein has been implicated in human eye development.

PRSS2

Protease, serine, 2 is a protein that in humans is encoded by the PRSS2 gene.

PRSS3

Protease, serine, 3 is a protein that in humans is encoded by the PRSS3 gene.

References

  1. 1 2 3 ENSG00000204983 GRCh38: Ensembl release 89: ENSG00000274247, ENSG00000204983 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000071521 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. "Entrez Gene: PRSS1 protease, serine, 1 (trypsin 1)".
  6. 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.
  7. 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.
  8. 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.
  9. 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.
  10. 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. PMID   8841182. S2CID   21974705.

Further reading

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