Carboxypeptidase A3 (mast cell carboxypeptidase A), also known as CPA3, is an enzyme which in humans is encoded by the CPA3gene.[5][6] 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.[7] 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.
CPA3 shares significant homology with the CPA subfamily of metalloprecarboxypeptidases and all the residues essential for the coordination of the Zn2+ active site, substrate peptide anchoring, and CP activity are preserved in the putative CPA3 protein. It resembles pancreatic CPA1 in cleaving C-terminalaromatic and aliphaticamino acid residues.CPA3 contains an N-terminal sequence of 16 amino acids and a pro-peptide between the NH2-terminal signal peptide sequence and COOH-terminal CP moiety.[8][7]
CPA3 has a pH optimum in the neutral to basic range. CPA3 functions together with endopeptidases secreted from mast cells such as chymases and tryptases to degrade proteins and peptides, including the apolipoprotein B component of LDL particles and angiotensin I.[9][10] Upon mast cell activation and degranulation, CPA3, the chymases, and tryptases are released in complexes with heparin proteoglycan. The parasitic nematodeAscaris produces CPA3 inhibitors, which increase its survival during infection. This finding implies that CPA3 might be involved in host defense against certain parasites.[11] CPA3 is also reported to have an important role in the protection towards snake venom toxins and vasoconstricting peptide endothelin 1(ET1).[12][13]
CPA3 provides protection from ET-1-induced damage, suggesting CPA3 could have a role in regulating sepsis. The involvement of CPA3 in autoimmune disease models makes it a potential diagnostic parameter of related diseases.[14] The significantly increased concentration of CPA3 in drug-induced anaphylaxis also implies that CPA3 could serve as a diagnostic parameter and detection of it could improve the forensic identification.[15] A new mast cell subtype reported to appear in mucosa is implicated in allergic inflammation and these mast cells have high levels of CPA3. The highly upregulated transcript of CPA3 is readily detected in luminal brushings and biopsies, making it a useful biomarker of allergic inflammation.[16][17]
^ abHuang H, Reed CP, Zhang JS, Shridhar V, Wang L, Smith DI (June 1999). "Carboxypeptidase A3 (CPA3): a novel gene highly induced by histone deacetylase inhibitors during differentiation of prostate epithelial cancer cells". Cancer Research. 59 (12): 2981–8. PMID10383164.
^Ryan CA (September 1971). "Inhibition of carboxypeptidase A by a naturally occurring polypeptide from potatoes". Biochemical and Biophysical Research Communications. 44 (5): 1265–70. doi:10.1016/s0006-291x(71)80222-x. PMID5160409.
^Miller LA, Cochrane DE, Feldberg RS, Carraway RE (June 1998). "Inhibition of neurotensin-stimulated mast cell secretion and carboxypeptidase A activity by the peptide inhibitor of carboxypeptidase A and neurotensin-receptor antagonist SR 48692". International Archives of Allergy and Immunology. 116 (2): 147–53. doi:10.1159/000023938. PMID9652308. S2CID46753844.
Natsuaki M, Stewart CB, Vanderslice P, Schwartz LB, Natsuaki M, Wintroub BU, Rutter WJ, Goldstein SM (August 1992). "Human skin mast cell carboxypeptidase: functional characterization, cDNA cloning, and genealogy". The Journal of Investigative Dermatology. 99 (2): 138–45. doi:10.1111/1523-1747.ep12616776. PMID1629626.
