The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

PRTN3  -  proteinase 3

Homo sapiens

Synonyms: ACPA, AGP7, C-ANCA, C-ANCA antigen, CANCA, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of PRTN3


Psychiatry related information on PRTN3

  • The loss of cortical cholinergic innervation in senile dementia of the Alzheimer's type (SDAT) is associated with cell loss in the nucleus basalis and related cell groups (magnocellular basal nucleus, MBN) [5].
  • Sixty individuals seeking outpatient treatment for marijuana dependence were randomly assigned to 1 of 3 treatments: motivational enhancement (M), M plus behavioral coping skills therapy (MBT), or MBT plus voucher-based incentives (MBTV) [6].

High impact information on PRTN3

  • Associated metabolic events and the loss of endothelial barrier properties suggest that anti-PR3-induced activation of endothelial cells may contribute to the pathogenetic sequelae of autoimmune vasculitis characterizing WG [7].
  • We conclude that anti-PR3 antibodies are potent inductors of the preformed phosphoinositide hydrolysis-related signal tranduction pathway in human endothelial cells [7].
  • Anti-neutrophil cytoplasmic antibodies (ANCAs) targeting proteinase 3 (PR3) have a high specifity for Wegener's granulomatosis (WG), and their role in activating leukocytes is well appreciated [7].
  • Priming of HUVECs with tumor necrosis factor alpha induced endothelial upregulation of PR3 message and surface expression of this antigen, as measured by Cyto-ELISA, with a maximum occurrence after 2 h [7].
  • When TNF-alpha-primed neutrophils were stimulated by anti-PR3 antibodies, superoxide and elastase secretion was provoked in the absence of lipid mediator generation [8].

Chemical compound and disease context of PRTN3


Biological context of PRTN3


Anatomical context of PRTN3


Associations of PRTN3 with chemical compounds

  • The NH2-terminal sequence and the amino-acid composition of NP4 were distinct from those of elastase and cathepsin G [19].
  • NP4 was purified and electrophoresis of the affinity-purified enzyme in sodium dodecyl sulfate polyacrylamide gels resulted in a single Mr = 30,000 polypeptide [19].
  • The expression of PAR-2 on the cell surface was promoted by PR3, and inhibited by cytochalasin B, but not by cycloheximide [20].
  • Treatment of intact azurophil granules with [3H]diisopropyl fluorophosphate resulted in labeling of elastase, cathepsin G, and AGP7, whereas azurocidin was not labeled [21].
  • The analysis of peptides generated by PR-3 digestion of insulin chains and the activity profile against a panel of chromogenic synthetic peptide substrates show that PR-3 prefers small aliphatic amino acids (alanine, serine, and valine) at the P1 site [9].

Physical interactions of PRTN3


Enzymatic interactions of PRTN3

  • During in vitro studies, purified p21 was cleaved by PR3, resulting in a 10-kDa p21 fragment [18].
  • PR3 cleaved the peptide corresponding to the N terminus of PAR-2 with exposure of its tethered ligand [20].
  • In vitro, purified PR3 cleaved procaspase-3 into an active 22-kDa fragment [24].

Regulatory relationships of PRTN3

  • Proper selection of the primary specificity group (R(I)) was found to lead to selective inhibition of HLE over Cat G, however, those compounds that inhibited HLE also inhibited PR 3, albeit less efficiently [25].
  • LPS mediated TNF-alpha production in whole blood was significantly inhibited when preincubated with PR3 [26].
  • The present study was conducted to investigate if proteinase-3 (PR3) is able to influence lipopolysaccharide (LPS) responses of monocytes via degradation of CD14 and if antineutrophil cytoplasmic antibodies (ANCA) may modify this process [26].
  • These findings suggest that neutrophil PR3 activates oral epithelial cells through G protein-coupled PAR-2 and actively participates in the process of inflammation such as periodontitis [20].
  • CONCLUSION: This study showed that anti-PR3 treatment of HUVEC induces sequential expression of IL-1alpha mRNA and TF mRNA, as well as their corresponding proteins [27].

Other interactions of PRTN3

  • This finding suggested that the augmented release was attributable to PR3 but not NE nor Cat G [28].
  • The physiopathological implications of the cleavage of p21 by PR3 have to be determined [18].
  • PR3 and MPO are colocalized in the azurophilic granules of neutrophils and translocated to the cell surface during activation and thus are able to interact with ANCA after neutrophil preactivation [29].
  • By IFA on alcohol-fixed neutrophils, monoclonal and polyclonal anti-BPI antibodies produced a C-ANCA pattern, whereas rabbit anti-azurocidin antibody produced a P-ANCA pattern [30].
  • It is of importance that anti-neutrophil cytoplasmic antibodies (ANCA) in patients with Wegener's granulomatosis (WG) are mainly directed against PR3 only [2].
  • We conclude that PR3 membrane expression on neutrophils is mediated by the NB1 receptor [31].

Analytical, diagnostic and therapeutic context of PRTN3

  • This review will focus on PR3 and the characteristics of PR3 that might implicate this particular antigen in the pathogenesis of WG and as target for immunotherapy in myeloid leukemias [2].
  • By ELISA, sera from 229 P-ANCA-positive patients, 99 C-ANCA-positive patients and 48 ANCA-negative (by IFA) patients with renal biopsies were tested for reactivity with recombinant human BPI and purified human azurocidin [30].
  • The major subtypes of anti-neutrophil cytoplasmic antibodies (ANCA) detected by indirect immunofluorescence assay (IFA) are P-ANCA and C-ANCA [30].
  • Immunohistochemistry showed that inflamed oral epithelium actually expresses PR3 protein [32].
  • Azurocidin and AGP7 represent significant protein components of the azurophil granule, together comprising approximately 15% of the acid-extractable protein as judged by reverse-phase high performance liquid chromatography analysis [21].


  1. Structure of the azurocidin, proteinase 3, and neutrophil elastase genes. Implications for inflammation and vasculitis. Jenne, D.E. Am. J. Respir. Crit. Care Med. (1994) [Pubmed]
  2. Proteinase 3, Wegener's autoantigen: from gene to antigen. van der Geld, Y.M., Limburg, P.C., Kallenberg, C.G. J. Leukoc. Biol. (2001) [Pubmed]
  3. Release of immunoreactive human neutrophil proteinase 4, normally and in peritonitis. Lundberg, E., Bergenfeldt, M., Ohlsson, K. Scand. J. Clin. Lab. Invest. (1991) [Pubmed]
  4. Proteinase 3. A distinct human polymorphonuclear leukocyte proteinase that produces emphysema in hamsters. Kao, R.C., Wehner, N.G., Skubitz, K.M., Gray, B.H., Hoidal, J.R. J. Clin. Invest. (1988) [Pubmed]
  5. Neuronal pathology in the nucleus basalis and associated cell groups in senile dementia of the Alzheimer's type: possible role in cell loss. Saper, C.B., German, D.C., White, C.L. Neurology (1985) [Pubmed]
  6. Adding voucher-based incentives to coping skills and motivational enhancement improves outcomes during treatment for marijuana dependence. Budney, A.J., Higgins, S.T., Radonovich, K.J., Novy, P.L. Journal of consulting and clinical psychology. (2000) [Pubmed]
  7. Wegener's granulomatosis: anti-proteinase 3 antibodies are potent inductors of human endothelial cell signaling and leakage response. Sibelius, U., Hattar, K., Schenkel, A., Noll, T., Csernok, E., Gross, W.L., Mayet, W.J., Piper, H.M., Seeger, W., Grimminger, F. J. Exp. Med. (1998) [Pubmed]
  8. Neutrophil activation by anti-proteinase 3 antibodies in Wegener's granulomatosis: role of exogenous arachidonic acid and leukotriene B4 generation. Grimminger, F., Hattar, K., Papavassilis, C., Temmesfeld, B., Csernok, E., Gross, W.L., Seeger, W., Sibelius, U. J. Exp. Med. (1996) [Pubmed]
  9. Characterization of proteinase-3 (PR-3), a neutrophil serine proteinase. Structural and functional properties. Rao, N.V., Wehner, N.G., Marshall, B.C., Gray, W.R., Gray, B.H., Hoidal, J.R. J. Biol. Chem. (1991) [Pubmed]
  10. Proteinase-3, a serine protease which mediates doxorubicin-induced apoptosis in the HL-60 leukemia cell line, is downregulated in its doxorubicin-resistant variant. Wu, C.H., Gordon, J., Rastegar, M., Ogretmen, B., Safa, A.R. Oncogene (2002) [Pubmed]
  11. Cytotoxic effects of antibodies to proteinase 3 (C-ANCA) on human endothelial cells. Mayet, W.J., Schwarting, A., Meyer zum Büschenfelde, K.H. Clin. Exp. Immunol. (1994) [Pubmed]
  12. The repressive effect of green tea ingredients on amyloid precursor protein (APP) expression in oral carcinoma cells in vitro and in vivo. Ko, S.Y., Chang, K.W., Lin, S.C., Hsu, H.C., Liu, T.Y. Cancer Lett. (2007) [Pubmed]
  13. Positive classic antineutrophil cytoplasmic antibody (C-ANCA) titer at switch to azathioprine therapy associated with relapse in proteinase 3-related vasculitis. Slot, M.C., Tervaert, J.W., Boomsma, M.M., Stegeman, C.A. Arthritis Rheum. (2004) [Pubmed]
  14. The proteinase 3 (PRTN3) gene is localized on 19p13.3 and is distal to the E2A gene. Le Coniat, M., Berger, R. Ann. Genet. (1995) [Pubmed]
  15. Three human elastase-like genes coordinately expressed in the myelomonocyte lineage are organized as a single genetic locus on 19pter. Zimmer, M., Medcalf, R.L., Fink, T.M., Mattmann, C., Lichter, P., Jenne, D.E. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  16. Structure, chromosomal assignment, and expression of the gene for proteinase-3. The Wegener's granulomatosis autoantigen. Sturrock, A.B., Franklin, K.F., Rao, G., Marshall, B.C., Rebentisch, M.B., Lemons, R.S., Hoidal, J.R. J. Biol. Chem. (1992) [Pubmed]
  17. Neutrophil serine proteinases activate human nonepithelial cells to produce inflammatory cytokines through protease-activated receptor 2. Uehara, A., Muramoto, K., Takada, H., Sugawara, S. J. Immunol. (2003) [Pubmed]
  18. Cleavage of p21waf1 by proteinase-3, a myeloid-specific serine protease, potentiates cell proliferation. Witko-Sarsat, V., Canteloup, S., Durant, S., Desdouets, C., Chabernaud, R., Lemarchand, P., Descamps-Latscha, B. J. Biol. Chem. (2002) [Pubmed]
  19. Monoclonal antibodies specific for neutrophil proteinase 4. Production and use for isolation of the enzyme. Ohlsson, K., Linder, C., Rosengren, M. Biol. Chem. Hoppe-Seyler (1990) [Pubmed]
  20. Activation of human oral epithelial cells by neutrophil proteinase 3 through protease-activated receptor-2. Uehara, A., Sugawara, S., Muramoto, K., Takada, H. J. Immunol. (2002) [Pubmed]
  21. Characterization of two azurphil granule proteases with active-site homology to neutrophil elastase. Wilde, C.G., Snable, J.L., Griffith, J.E., Scott, R.W. J. Biol. Chem. (1990) [Pubmed]
  22. Endothelial cells and renal epithelial cells do not express the Wegener's autoantigen, proteinase 3. King, W.J., Adu, D., Daha, M.R., Brooks, C.J., Radford, D.J., Pall, A.A., Savage, C.O. Clin. Exp. Immunol. (1995) [Pubmed]
  23. A hydrophobic patch on proteinase 3, the target of autoantibodies in Wegener granulomatosis, mediates membrane binding via NB1 receptors. Korkmaz, B., Kuhl, A., Bayat, B., Santoso, S., Jenne, D.E. J. Biol. Chem. (2008) [Pubmed]
  24. Proteinase-3 induces procaspase-3 activation in the absence of apoptosis: potential role of this compartmentalized activation of membrane-associated procaspase-3 in neutrophils. Pederzoli, M., Kantari, C., Gausson, V., Moriceau, S., Witko-Sarsat, V. J. Immunol. (2005) [Pubmed]
  25. Utilization of the 1,2,5-thiadiazolidin-3-one 1,1 dioxide scaffold in the design of potent inhibitors of serine proteases: SAR studies using carboxylates. Kuang, R., Epp, J.B., Ruan, S., Chong, L.S., Venkataraman, R., Tu, J., He, S., Truong, T.M., Groutas, W.C. Bioorg. Med. Chem. (2000) [Pubmed]
  26. Human proteinase 3 can inhibits LPS-mediated TNF-alpha production through CD14 degradation: lack of influence of antineutrophil cytoplasmic antibodies. Yard, B.A., Wille, A.I., Haak, M., van der Woude, F.J. Clin. Exp. Immunol. (2002) [Pubmed]
  27. Induction of interleukin-1 and subsequent tissue factor expression by anti-proteinase 3 antibodies in human umbilical vein endothelial cells. de Bandt, M., Ollivier, V., Meyer, O., Babin-Chevaye, C., Khechaï, F., de Prost, D., Hakim, J., Pasquier, C. Arthritis Rheum. (1997) [Pubmed]
  28. Converting enzyme-independent release of tumor necrosis factor alpha and IL-1beta from a stimulated human monocytic cell line in the presence of activated neutrophils or purified proteinase 3. Coeshott, C., Ohnemus, C., Pilyavskaya, A., Ross, S., Wieczorek, M., Kroona, H., Leimer, A.H., Cheronis, J. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  29. Antineutrophil cytoplasmic autoantibodies antigen specificity. Lesavre, P. Am. J. Kidney Dis. (1991) [Pubmed]
  30. Frequency of anti-bactericidal/permeability-increasing protein (BPI) and anti-azurocidin in patients with renal disease. Yang, J.J., Tuttle, R., Falk, R.J., Jennette, J.C. Clin. Exp. Immunol. (1996) [Pubmed]
  31. NB1 mediates surface expression of the ANCA antigen proteinase 3 on human neutrophils. von Vietinghoff, S., Tunnemann, G., Eulenberg, C., Wellner, M., Cristina Cardoso, M., Luft, F.C., Kettritz, R. Blood (2007) [Pubmed]
  32. Proinflammatory cytokines induce proteinase 3 as membrane-bound and secretory forms in human oral epithelial cells and antibodies to proteinase 3 activate the cells through protease-activated receptor-2. Uehara, A., Sugawara, Y., Sasano, T., Takada, H., Sugawara, S. J. Immunol. (2004) [Pubmed]
WikiGenes - Universities