Proteinase 3 Explained

Proteinase 3, also known as PRTN3, is an enzyme that in humans is encoded by the PRTN3 gene.^[1]

Function

PRTN3 is a serine protease enzyme expressed mainly in neutrophil granulocytes. Its exact role in the function of the neutrophil is unknown, but, in human neutrophils, proteinase 3 contributes to the proteolytic generation of antimicrobial peptides. It is also the target of anti-neutrophil cytoplasmic antibodies (ANCAs) of the c-ANCA (cytoplasmic subtype) class, a type of antibody frequently found in the disease granulomatosis with polyangiitis.^[2]

Further reading

• Martin KR, Witko-Sarsat V . Proteinase 3: the odd one out that became an autoantigen . Journal of Leukocyte Biology . 102 . 3 . 689–698 . September 2017 . 28546501 . 10.1189/jlb.3MR0217-069R . free .
• van der Helm-van Mil AH, Huizinga TW, de Vries RR, Toes RE . Emerging patterns of risk factor make-up enable subclassification of rheumatoid arthritis . Arthritis and Rheumatism . 56 . 6 . 1728–35 . June 2007 . 17534941 . 10.1002/art.22716 .
• Kettritz R . Neutral serine proteases of neutrophils . Immunological Reviews . 273 . 1 . 232–48 . September 2016 . 27558338 . 10.1111/imr.12441 . 29724551 .
• Zimmer M, Medcalf RL, Fink TM, Mattmann C, Lichter P, Jenne DE . Three human elastase-like genes coordinately expressed in the myelomonocyte lineage are organized as a single genetic locus on 19pter . Proceedings of the National Academy of Sciences of the United States of America . 89 . 17 . 8215–9 . September 1992 . 1518849 . 49888 . 10.1073/pnas.89.17.8215 . 1992PNAS...89.8215Z . free .
• Cornec D, Cornec-Le Gall E, Fervenza FC, Specks U . ANCA-associated vasculitis - clinical utility of using ANCA specificity to classify patients . Nature Reviews. Rheumatology . 12 . 10 . 570–9 . October 2016 . 27464484 . 10.1038/nrrheum.2016.123 . 22205737 .
• Rao NV, Wehner NG, Marshall BC, Gray WR, Gray BH, Hoidal JR . Characterization of proteinase-3 (PR-3), a neutrophil serine proteinase. Structural and functional properties . The Journal of Biological Chemistry . 266 . 15 . 9540–8 . May 1991 . 10.1016/S0021-9258(18)92854-1 . 2033050 . free .
• Ohlsson K, Linder C, Rosengren M . Monoclonal antibodies specific for neutrophil proteinase 4. Production and use for isolation of the enzyme . Biological Chemistry Hoppe-Seyler . 371 . 7 . 549–55 . July 1990 . 2121162 . 10.1515/bchm3.1990.371.2.549 .
• Campanelli D, Melchior M, Fu Y, Nakata M, Shuman H, Nathan C, Gabay JE . Cloning of cDNA for proteinase 3: a serine protease, antibiotic, and autoantigen from human neutrophils . The Journal of Experimental Medicine . 172 . 6 . 1709–15 . December 1990 . 2258701 . 2188764 . 10.1084/jem.172.6.1709 .
• Goldschmeding R, Dolman KM, van den Ende ME, van der Meer-Gerritsen CH, Sonnenberg A, von dem Borne AE . The relation of 29 kD C-ANCA antigen to proteinase 3 . . 98 . S19 . 26–7 . 1991 . 2285532 . 10.1111/j.1600-0463.1990.tb05713.x . 37665338 .
• Wilde CG, Snable JL, Griffith JE, Scott RW . Characterization of two azurphil granule proteases with active-site homology to neutrophil elastase . The Journal of Biological Chemistry . 265 . 4 . 2038–41 . February 1990 . 10.1016/S0021-9258(19)39936-3 . 2404977 . free .
• Gabay JE, Scott RW, Campanelli D, Griffith J, Wilde C, Marra MN, Seeger M, Nathan CF . Antibiotic proteins of human polymorphonuclear leukocytes . Proceedings of the National Academy of Sciences of the United States of America . 86 . 14 . 5610–4 . July 1989 . 2501794 . 297672 . 10.1073/pnas.86.14.5610 . 1989PNAS...86.5610G . free .
• Bories D, Raynal MC, Solomon DH, Darzynkiewicz Z, Cayre YE . Down-regulation of a serine protease, myeloblastin, causes growth arrest and differentiation of promyelocytic leukemia cells . Cell . 59 . 6 . 959–68 . December 1989 . 2598267 . 10.1016/0092-8674(89)90752-6 . free .
• Pontremoli S, Melloni E, Michetti M, Sacco O, Sparatore B, Salamino F, Damiani G, Horecker BL . Cytolytic effects of neutrophils: role for a membrane-bound neutral proteinase . Proceedings of the National Academy of Sciences of the United States of America . 83 . 6 . 1685–9 . March 1986 . 3513185 . 323148 . 10.1073/pnas.83.6.1685 . 1986PNAS...83.1685P . free .
• Sugimori T, Cooley J, Hoidal JR, Remold-O'Donnell E . Inhibitory properties of recombinant human monocyte/neutrophil elastase inhibitor . American Journal of Respiratory Cell and Molecular Biology . 13 . 3 . 314–22 . September 1995 . 7654387 . 10.1165/ajrcmb.13.3.7654387 .
• Brunini F, Page TH, Gallieni M, Pusey CD . The role of monocytes in ANCA-associated vasculitides . Autoimmunity Reviews . 15 . 11 . 1046–1053 . November 2016 . 27491570 . 10.1016/j.autrev.2016.07.031 . 10044/1/39150 . free .

Notes and References

1. Campanelli D, Melchior M, Fu Y, Nakata M, Shuman H, Nathan C, Gabay JE . Cloning of cDNA for proteinase 3: a serine protease, antibiotic, and autoantigen from human neutrophils . The Journal of Experimental Medicine . 172 . 6 . 1709–15 . December 1990 . 2258701 . 2188764 . 10.1084/jem.172.6.1709 .
2. Hilhorst M, van Paassen P, Tervaert JW . Proteinase 3-ANCA Vasculitis versus Myeloperoxidase-ANCA Vasculitis . Journal of the American Society of Nephrology . 26 . 10 . 2314–27 . October 2015 . 25956510 . 4587702 . 10.1681/ASN.2014090903 .