Chymase

Last updated
chymase 1, mast cell
1KLT.png
Chymase with PMSF bound PDB: 1KLT
Identifiers
SymbolCMA1
NCBI gene 1215
HGNC 2097
OMIM 118938
RefSeq NM_001836
UniProt P23946
Other data
EC number 3.4.21.39
Locus Chr. 14 q11.2
Search for
Structures Swiss-model
Domains InterPro

Chymases (EC 3.4.21.39, mast cell protease 1, skeletal muscle protease, skin chymotryptic proteinase, mast cell serine proteinase, skeletal muscle protease) are a family of serine proteases found primarily in mast cells, though also present in basophil granulocytes (e.g. alpha chymase mcpt8). Recently, Derakhshan et al. reported that a specific mast cell population expressed transcripts for Mcpt8. [1] They show broad peptidolytic activity and are involved in a variety of functions. For example, chymases are released by connective tissue-type mast cells upon challenge with parasites and parasite antigens promoting an inflammatory response, and chymase mcp1 and mcp2 are used for marker for mast cell degranulation in parasite infection such as Nematode, [2] Trichuris muris [3] [4] Chymases are also known to convert angiotensin I to angiotensin II and thus play a role in hypertension and atherosclerosis. [5]

Because of its role in inflammation it has been investigated as a target in the treatment of asthma. [6]

Related Research Articles

<span class="mw-page-title-main">Mast cell</span> Cell found in connective tissue

A mast cell is a resident cell of connective tissue that contains many granules rich in histamine and heparin. Specifically, it is a type of granulocyte derived from the myeloid stem cell that is a part of the immune and neuroimmune systems. Mast cells were discovered by Paul Ehrlich in 1877. Although best known for their role in allergy and anaphylaxis, mast cells play an important protective role as well, being intimately involved in wound healing, angiogenesis, immune tolerance, defense against pathogens, and vascular permeability in brain tumours.

<span class="mw-page-title-main">Immunoglobulin E</span> Immunoglobulin E (IgE) Antibody

Immunoglobulin E (IgE) is a type of antibody that has been found only in mammals. IgE is synthesised by plasma cells. Monomers of IgE consist of two heavy chains and two light chains, with the ε chain containing four Ig-like constant domains (Cε1–Cε4). IgE is thought to be an important part of the immune response against infection by certain parasitic worms, including Schistosoma mansoni, Trichinella spiralis, and Fasciola hepatica. IgE is also utilized during immune defense against certain protozoan parasites such as Plasmodium falciparum. IgE may have evolved as a defense to protect against venoms.

<span class="mw-page-title-main">Granulocyte</span> Category of white blood cells

Granulocytes are cells in the innate immune system characterized by the presence of specific granules in their cytoplasm. Such granules distinguish them from the various agranulocytes. All myeloblastic granulocytes are polymorphonuclear. They have varying shapes (morphology) of the nucleus ; and are referred to as polymorphonuclear leukocytes. In common terms, polymorphonuclear granulocyte refers specifically to "neutrophil granulocytes", the most abundant of the granulocytes; the other types have varying morphology. Granulocytes are produced via granulopoiesis in the bone marrow.

<span class="mw-page-title-main">Serpin</span> Superfamily of proteins with similar structures and diverse functions

Serpins are a superfamily of proteins with similar structures that were first identified for their protease inhibition activity and are found in all kingdoms of life. The acronym serpin was originally coined because the first serpins to be identified act on chymotrypsin-like serine proteases. They are notable for their unusual mechanism of action, in which they irreversibly inhibit their target protease by undergoing a large conformational change to disrupt the target's active site. This contrasts with the more common competitive mechanism for protease inhibitors that bind to and block access to the protease active site.

<span class="mw-page-title-main">Tryptase</span> Class of enzymes

Tryptase is the most abundant secretory granule-derived serine proteinase contained in mast cells and has been used as a marker for mast cell activation. 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.

<span class="mw-page-title-main">Helminthic therapy</span> Deliberate infestation with parasitic worms

Helminthic therapy, an experimental type of immunotherapy, is the treatment of autoimmune diseases and immune disorders by means of deliberate infestation with a helminth or with the eggs of a helminth. Helminths are parasitic worms such as hookworms, whipworms, and threadworms that have evolved to live within a host organism on which they rely for nutrients. These worms are members of two phyla: nematodes, which are primarily used in human helminthic therapy, and flat worms (trematodes).

<span class="mw-page-title-main">Proteinase 3</span> Mammalian protein found in Homo sapiens

Proteinase 3, also known as PRTN3, is an enzyme that in humans is encoded by the PRTN3 gene.

<i>Heligmosomoides polygyrus</i> Species of roundworm

Heligmosomoides polygyrus, previously named Nematospiroides dubius, is a naturally occurring intestinal roundworm of rodents. It belongs to the family Trychostrongylidae, and male and female worms are morphologically distinguishable. The parasite has a direct lifecycle, with its larval form being the infective stage. H. polygyrus has the ability to establish chronic infections in rodents and alter host immune responses. This nematode is widely used as a gastrointestinal parasitic model in immunological, pharmacological, and toxicological studies.

<span class="mw-page-title-main">CCL2</span> Mammalian protein found in Homo sapiens

For the ICAO airport code see Candle Lake Airpark, for the diradical compound see Dichlorocarbene.

<span class="mw-page-title-main">Cysteine protease</span> Class of enzymes

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.

<span class="mw-page-title-main">Granzyme A</span> Class of enzymes

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.

<span class="mw-page-title-main">Cathepsin G</span> Protein-coding gene in the species Homo sapiens

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.

<span class="mw-page-title-main">Cathelicidin</span> Group of antimicrobial peptides in vertebrates

Cathelicidin antimicrobial peptide (CAMP) is a polypeptide that is primarily stored in the lysosomes of macrophages and polymorphonuclear leukocytes (PMNs); in humans, the CAMP gene encodes the peptide precursor CAP-18, which is processed by proteinase 3-mediated extracellular cleavage into the active form LL-37. LL-37 is the only peptide in the Cathelicidin family found in the human body.

<span class="mw-page-title-main">Degranulation</span> Process by which cells lose secretory granules

Degranulation is a cellular process that releases antimicrobial cytotoxic or other molecules from secretory vesicles called granules found inside some cells. It is used by several different cells involved in the immune system, including granulocytes and mast cells. It is also used by certain lymphocytes such as natural killer (NK) cells and cytotoxic T cells, whose main purpose is to destroy invading microorganisms.

<span class="mw-page-title-main">CMA1</span> Protein-coding gene in the species Homo sapiens

Chymase is an enzyme that in humans is encoded by the CMA1 gene.

<span class="mw-page-title-main">TPSAB1</span> Protein-coding gene in the species Homo sapiens

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.

<span class="mw-page-title-main">Protease-activated receptor 2</span> Protein-coding gene in the species Homo sapiens

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.

<span class="mw-page-title-main">Coagulation factor II receptor</span> Mammalian protein found in Homo sapiens

Proteinase-activated receptor 1 (PAR1) also known as protease-activated receptor 1 or coagulation factor II (thrombin) receptor is a protein that in humans is encoded by the F2R gene. PAR1 is a G protein-coupled receptor and one of four protease-activated receptors involved in the regulation of thrombotic response. Highly expressed in platelets and endothelial cells, PAR1 plays a key role in mediating the interplay between coagulation and inflammation, which is important in the pathogenesis of inflammatory and fibrotic lung diseases. It is also involved both in disruption and maintenance of endothelial barrier integrity, through interaction with either thrombin or activated protein C, respectively.

<span class="mw-page-title-main">SLPI</span> Protein-coding gene in the species Homo sapiens

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.

<span class="mw-page-title-main">CPA3</span> Protein-coding gene in the species Homo sapiens

Carboxypeptidase A3 (mast cell carboxypeptidase A), also known as CPA3, is an enzyme which in humans is encoded by the CPA3 gene. The "CPA3" gene expression has only been detected in mast cells and mast-cell-like lines, and CPA3 is located in secretory granules. CPA3 is one of 8-9 members of the A/B subfamily that includes the well-studied pancreatic enzymes carboxypeptidase A1 (CPA1), carboxypeptidase A2 (CPA2), and carboxypeptidase B. This subfamily includes 6 carboxypeptidase A-like enzymes, numbered 1-6. The enzyme now called CPA3 was originally named mast cell carboxypeptidase A, and another protein was initially called CPA3. A gene nomenclature committee renamed mast cell carboxypeptidase A as CPA3, and the original CPA3 reported by Huang et al. became CPA4 to reflect the order of their discovery.

References

  1. Derakhshan, Tahereh; Samuchiwal, Sachin K.; Hallen, Nils; Bankova, Lora G.; Boyce, Joshua A.; Barrett, Nora A.; Austen, K. Frank; Dwyer, Daniel F. (2021-01-04). "Lineage-specific regulation of inducible and constitutive mast cells in allergic airway inflammation". Journal of Experimental Medicine. 218 (1): e20200321. doi:10.1084/jem.20200321. ISSN   0022-1007. PMC   7953627 . PMID   32946563.
  2. McDermott JR, Bartram RE, Knight PA, Miller HR, Garrod DR, Grencis RK (June 2003). "Mast cells disrupt epithelial barrier function during enteric nematode infection". Proceedings of the National Academy of Sciences of the United States of America. 100 (13): 7761–6. Bibcode:2003PNAS..100.7761M. doi: 10.1073/pnas.1231488100 . PMC   164661 . PMID   12796512.
  3. Betts CJ, Else KJ (January 1999). "Mast cells, eosinophils and antibody-mediated cellular cytotoxicity are not critical in resistance to Trichuris muris". Parasite Immunology. 21 (1): 45–52. doi:10.1046/j.1365-3024.1999.00200.x. PMID   10081771. S2CID   31343469.
  4. Blackwell NM, Else KJ (June 2001). "B cells and antibodies are required for resistance to the parasitic gastrointestinal nematode Trichuris muris". Infection and Immunity. 69 (6): 3860–8. doi:10.1128/IAI.69.6.3860-3868.2001. PMC   98409 . PMID   11349052.
  5. Caughey GH (June 2007). "Mast cell tryptases and chymases in inflammation and host defense". Immunological Reviews. 217: 141–54. doi:10.1111/j.1600-065X.2007.00509.x. PMC   2275918 . PMID   17498057.
  6. de Garavilla L, Greco MN, Sukumar N, Chen ZW, Pineda AO, Mathews FS, et al. (May 2005). "A novel, potent dual inhibitor of the leukocyte proteases cathepsin G and chymase: molecular mechanisms and anti-inflammatory activity in vivo". The Journal of Biological Chemistry. 280 (18): 18001–7. doi: 10.1074/jbc.M501302200 . PMID   15741158.