Tryptase | |||||||||
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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 | ||||||||
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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]
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.
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]
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]
Human genes that encode proteins with tryptase activity include:
Human Gene | Enzyme |
---|---|
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 Gene | Enzyme |
---|---|
Tryptase MCP-6 | |
Tryptase MCP-7 |
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.
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 is a tryptase and is one of the five granzymes encoded in the human genome. In humans, GzmA is encoded by the GZMA gene in proximity to the GZMK gene on chromosome 5. This enzyme is present in cytotoxic T lymphocyte (CTL) granules.
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.
Maspin is a protein that in humans is encoded by the SERPINB5 gene. This protein belongs to the serpin superfamily. SERPINB5 was originally reported to function as a tumor suppressor gene in epithelial cells, suppressing the ability of cancer cells to invade and metastasize to other tissues. Furthermore, and consistent with an important biological function, Maspin knockout mice were reported to be non-viable, dying in early embryogenesis. However, a subsequent study using viral transduction as a method of gene transfer was not able to reproduce the original findings and found no role for maspin in tumour biology. Furthermore, the latter study demonstrated that maspin knockout mice are viable and display no obvious phenotype. These data are consistent with the observation that maspin is not expressed in early embryogenesis. The precise molecular function of maspin is thus currently unknown.
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 (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, 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).
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.
Factor interacting with PAPOLA and CPSF1 is a protein that in humans is encoded by the FIP1L1 gene. A medically important aspect of the FIP1L1 gene is its fusion with other genes to form fusion genes which cause clonal hypereosinophilia and leukemic diseases in humans.
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.
Serpin B6 is a protein that in humans is encoded by the SERPINB6 gene.
Kallikrein-related peptidase 7 (KLK7) is a serine protease that in humans is encoded by the KLK7 gene. KLK7 was initially purified from the epidermis and characterised as stratum corneum chymotryptic enzyme (SCCE). It was later identified as the seventh member of the human kallikrein family, which includes fifteen homologous serine proteases located on chromosome 19 (19q13).
Prostasin is a protein that in humans is encoded by the PRSS8 gene.
Transmembrane protease, serine 11D is an enzyme that in humans is encoded by the TMPRSS11D gene.
Tryptase delta is an enzyme that in humans is encoded by the TPSD1 gene.
Tryptase beta-2, also known as tryptase II, is a proteolytic enzyme that in humans is encoded by the TPSB2 gene.
Tryptase gamma, also known as serine protease 31 or transmembrane tryptase, is an enzyme that in humans is encoded by the TPSG1 gene.
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.
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.