Tryptase

Last updated
Tryptase
1lto.jpg
alpha1 Tryptase tetramer, Human
Identifiers
EC no. 3.4.21.59
CAS no. 97501-93-4
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / QuickGO

Tryptase (EC 3.4.21.59, ) is the most abundant secretory granule-derived serine proteinase contained in mast cells and has been used as a marker for mast cell activation. [1] [2] [3] [4] [5] Club cells contain tryptase, which is believed to be responsible for cleaving the hemagglutinin surface protein of influenza A virus, thereby activating it and causing the symptoms of flu. [6]

Contents

Nomenclature

Tryptase is also known by mast cell tryptase, mast cell protease II, skin tryptase, lung tryptase, pituitary tryptase, mast cell neutral proteinase, mast cell serine proteinase II, mast cell proteinase II, mast cell serine proteinase tryptase, rat mast cell protease II, and tryptase M.

Clinical use

Serum levels are normally less than 11.5 ng/mL. [7] Elevated levels of serum tryptase occur in both anaphylactic and anaphylactoid reactions, but a negative test does not exclude anaphylaxis. Tryptase is less likely to be elevated in food allergy reactions as opposed to other causes of anaphylaxis. Serum tryptase levels are also elevated in and used as one indication suggesting the presence of eosinophilic leukemias due to genetic mutations resulting in the formation of FIP1L1-PDGFRA fusion genes or the presence of systemic mastocytosis. [8] [9]

Physiology

Tryptase is involved with allergenic response and is suspected to act as a mitogen for fibroblast lines. Tryptase may use the morpheein model of allosteric regulation. [10] Mast cell tryptase-6 is involved in Trichinella spiralis infection in mice through linking adaptive and innate immunity. [11]

Genes

Human genes that encode proteins with tryptase activity include:

Human GeneEnzyme
TPSAB1 Tryptase alpha-1
TPSAB1 Tryptase beta-1
TPSB2 Tryptase beta-2
TPSD1 Tryptase delta
TPSG1 Tryptase gamma
PRSS22 Tryptase epsilon

Mouse genes that encode proteins with tryptase activity include:

Mouse GeneEnzyme
Tryptase MCP-6
Tryptase MCP-7

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.

Protease Enzyme that cleaves other proteins into smaller peptides

A protease is an enzyme that catalyzes proteolysis, the breakdown of proteins into smaller polypeptides or single amino acids. They do this by cleaving the peptide bonds within proteins by hydrolysis, a reaction where water breaks bonds. Proteases are involved in many biological functions, including digestion of ingested proteins, protein catabolism, and cell signaling.

Alpha-1 antitrypsin Mammalian protein found in Homo sapiens

Alpha-1 antitrypsin or α1-antitrypsin is a protein belonging to the serpin superfamily. It is encoded in humans by the SERPINA1 gene. A protease inhibitor, it is also known as alpha1–proteinase inhibitor (A1PI) or alpha1-antiproteinase (A1AP) because it inhibits various proteases. In older biomedical literature it was sometimes called serum trypsin inhibitor, because its capability as a trypsin inhibitor was a salient feature of its early study. As a type of enzyme inhibitor, it protects tissues from enzymes of inflammatory cells, especially neutrophil elastase, and has a reference range in blood of 0.9–2.3 g/L, but the concentration can rise manyfold upon acute inflammation.

Protease-activated receptors (PAR) are a subfamily of related G protein-coupled receptors that are activated by cleavage of part of their extracellular domain. They are highly expressed in platelets, and also on endothelial cells, myocytes and neurons.

Cysteine protease

Cysteine proteases, also known as thiol proteases, are hydrolase enzymes that degrade proteins. These proteases share a common catalytic mechanism that involves a nucleophilic cysteine thiol in a catalytic triad or dyad.

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.

Cathepsin G

Cathepsin G is a protein that in humans is encoded by the CTSG gene. It is one of the three serine proteases of the chymotrypsin family that are stored in the azurophil granules, and also a member of the peptidase S1 protein family. Cathepsin G plays an important role in eliminating intracellular pathogens and breaking down tissues at inflammatory sites, as well as in anti-inflammatory response.

TPSAB1

Tryptase alpha-1 and tryptase beta-1 are enzymes that in humans are encoded by the same TPSAB1 gene. Beta tryptases appear to be the main isoenzymes expressed in mast cells; whereas in basophils, alpha tryptases predominate.

Protease-activated receptor 2

Protease activated receptor 2 (PAR2) also known as coagulation factor II (thrombin) receptor-like 1 (F2RL1) or G-protein coupled receptor 11 (GPR11) is a protein that in humans is encoded by the F2RL1 gene. PAR2 modulates inflammatory responses, obesity, metabolism, cancers and acts as a sensor for proteolytic enzymes generated during infection. In humans, we can find PAR2 in the stratum granulosum layer of epidermal keratinocytes. Functional PAR2 is also expressed by several immune cells such as eosinophils, neutrophils, monocytes, macrophages, dendritic cells, mast cells and T cells.

Trypsin 1

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, and trypsin-3 (meso-trypsinogen).

SLPI

Antileukoproteinase, also known as secretory leukocyte protease inhibitor (SLPI), is an enzyme that in humans is encoded by the SLPI gene. SLPI is a highly cationic single-chain protein with eight intramolecular disulfide bonds. It is found in large quantities in bronchial, cervical, and nasal mucosa, saliva, and seminal fluids. SLPI inhibits human leukocyte elastase, human cathepsin G, human trypsin, neutrophil elastase, and mast cell chymase. X-ray crystallography has shown that SLPI has two homologous domains of 53 and 54 amino acids, one of which exhibits anti-protease activity. The other domain is not known to have any function.

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.

SERPINB6

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

PRSS8

Prostasin is a protein that in humans is encoded by the PRSS8 gene.

TMPRSS11D

Transmembrane protease, serine 11D is an enzyme that in humans is encoded by the TMPRSS11D gene.

TPSD1

Tryptase delta is an enzyme that in humans is encoded by the TPSD1 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.

TPSB2 Protein-coding gene in the species Homo sapiens

Tryptase beta-2, also known as tryptase II, is an enzyme that in humans is encoded by the TPSB2 gene.

TPSG1

Tryptase gamma, also known as serine protease 31 or transmembrane tryptase, is an enzyme that in humans is encoded by the TPSG1 gene.

Kazal domain

The Kazal domain is an evolutionary conserved protein domain usually indicative of serine protease inhibitors. However, kazal-like domains are also seen in the extracellular part of agrins, which are not known to be protease inhibitors.

References

  1. Tanaka T, McRae BJ, Cho K, Cook R, Fraki JE, Johnson DA, Powers JC (November 1983). "Mammalian tissue trypsin-like enzymes. Comparative reactivities of human skin tryptase, human lung tryptase, and bovine trypsin with peptide 4-nitroanilide and thioester substrates" (PDF). The Journal of Biological Chemistry. 258 (22): 13552–7. doi: 10.1016/S0021-9258(17)43949-4 . PMID   6358206. Open Access logo PLoS transparent.svg
  2. Vanderslice P, Ballinger SM, Tam EK, Goldstein SM, Craik CS, Caughey GH (May 1990). "Human mast cell tryptase: multiple cDNAs and genes reveal a multigene serine protease family". Proceedings of the National Academy of Sciences of the United States of America. 87 (10): 3811–5. doi: 10.1073/pnas.87.10.3811 . PMC   53993 . PMID   2187193. Open Access logo PLoS transparent.svg
  3. Kido H, Fukusen N, Katunuma N (June 1985). "Chymotrypsin- and trypsin-type serine proteases in rat mast cells: properties and functions". Archives of Biochemistry and Biophysics. 239 (2): 436–43. doi:10.1016/0003-9861(85)90709-X. PMID   3890754. Closed Access logo transparent.svg
  4. Cromlish JA, Seidah NG, Marcinkiewicz M, Hamelin J, Johnson DA, Chrétien M (January 1987). "Human pituitary tryptase: molecular forms, NH2-terminal sequence, immunocytochemical localization, and specificity with prohormone and fluorogenic substrates". The Journal of Biological Chemistry. 262 (3): 1363–73. doi: 10.1016/S0021-9258(19)75795-0 . PMID   3543004. Open Access logo PLoS transparent.svg
  5. Harvima IT, Schechter NM, Harvima RJ, Fräki JE (November 1988). "Human skin tryptase: purification, partial characterization and comparison with human lung tryptase". Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology. 957 (1): 71–80. doi:10.1016/0167-4838(88)90158-6. PMID   3140898. Closed Access logo transparent.svg
  6. Taubenberger JK (August 1998). "Influenza virus hemagglutinin cleavage into HA1, HA2: no laughing matter". Proceedings of the National Academy of Sciences of the United States of America. 95 (17): 9713–5. doi: 10.1073/pnas.95.17.9713 . PMC   33880 . PMID   9707539.
  7. Mayo Clinic > Test ID: FFTRS91815, Tryptase. Retrieved October, 2012[ dead link ]
  8. Vega F, Medeiros LJ, Bueso-Ramos CE, Arboleda P, Miranda RN (September 2015). "Hematolymphoid neoplasms associated with rearrangements of PDGFRA, PDGFRB, and FGFR1". American Journal of Clinical Pathology. 144 (3): 377–92. doi: 10.1309/AJCPMORR5Z2IKCEM . PMID   26276769. S2CID   10435391.
  9. Valent P, Akin C, Hartmann K, Nilsson G, Reiter A, Hermine O, Sotlar K, Sperr WR, Escribano L, George TI, Kluin-Nelemans HC, Ustun C, Triggiani M, Brockow K, Gotlib J, Orfao A, Schwartz LB, Broesby-Olsen S, Bindslev-Jensen C, Kovanen PT, Galli SJ, Austen KF, Arber DA, Horny HP, Arock M, Metcalfe DD (March 2017). "Advances in the Classification and Treatment of Mastocytosis: Current Status and Outlook toward the Future". Cancer Research. 77 (6): 1261–1270. doi:10.1158/0008-5472.CAN-16-2234. PMC   5354959 . PMID   28254862.
  10. Selwood T, Jaffe EK (March 2012). "Dynamic dissociating homo-oligomers and the control of protein function". Archives of Biochemistry and Biophysics. 519 (2): 131–43. doi:10.1016/j.abb.2011.11.020. PMC   3298769 . PMID   22182754. Open Access logo PLoS transparent.svg
  11. Shin K, Watts GF, Oettgen HC, Friend DS, Pemberton AD, Gurish MF, Lee DM (April 2008). "Mouse mast cell tryptase mMCP-6 is a critical link between adaptive and innate immunity in the chronic phase of Trichinella spiralis infection". Journal of Immunology. 180 (7): 4885–91. doi:10.4049/jimmunol.180.7.4885. PMC   2969178 . PMID   18354212.