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Gene Review

Prtn3  -  proteinase 3

Mus musculus

Synonyms: Myeloblastin, PR-3, PR3, Proteinase 3, mPR3, ...
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Disease relevance of Prtn3

  • Antineutrophil cytoplasmic autoantibodies (ANCAs) recognizing human proteinase 3 of neutrophil granules are a diagnostic hallmark of Wegener granulomatosis, an autoimmune systemic vasculitis with predilection for the respiratory tract and kidneys [1].
  • Myeloblastin is involved in the control of proliferation in myeloid leukemia cells [2].
  • L-658,758 effectively inhibited elastinolysis by NE, proteinase-3 and the pooled sol but did not inhibit the activity of the metalloelastases, human and mouse macrophage metalloelastase and Pseudomonas elastase [3].
  • This new finding was discovered serendipitously using material from patients with inflammatory vascular disease caused by antineutrophil cytoplasmic autoantibodies (ANCA) with specificity for proteinase-3 (PR-3) [4].
  • Anti-neutrophil cytoplasmic Abs, directed primarily toward myeloperoxidase (MPO) and proteinase 3, are detected in the majority of patients with distinct forms of small vessel vasculitides and pauci-immune necrotizing glomerulonephritis [5].

High impact information on Prtn3


Chemical compound and disease context of Prtn3

  • This link between Myb and myeloblastin suggests a previously nonidentified Myb pathway through which growth arrest is induced by retinoic acid in myeloid leukemia cells [2].
  • The existence of a subset of PMN which spontaneously expresses PR3 and varies among individuals, may be relevant to the pathogenesis of anti-PR3 ANCA autoantibody-related vasculitis [8].

Biological context of Prtn3

  • A comparison between the mouse and human PR-3 cDNA reveals 73% homology, however, this drops to 60% when the amino acid sequences are compared [9].
  • This enhancer is located in the second intron of the proteinase-3 gene and so may regulate more than one gene in the myeloid protease cluster [10].
  • 1. Moreover, a GC-rich region, similar to a cis-element in the proteinase 3 promoter, was identified [11].
  • Comparison of mouse PR3 genomic structure with that of its human counterpart indicates that: 1) the mPR3 gene spans 7 kb organized in 5 exons and 4 introns, 2) the codons of His-Asp-Ser of the catalytic site are conserved and spread out over different exons, similar to the human gene, and 3) the gene product encodes a pre-proform of the protein [12].
  • Interestingly enough, mutation of Y-28 to S (mutation Y28S) in the zinc finger results in RNA packaging at a level similar to that observed upon deletion of three prolines and three arginines in the C-terminal domain of NCp10 (mutant delta PR3) [13].

Anatomical context of Prtn3


Associations of Prtn3 with chemical compounds

  • In contrast, our findings suggest that the three subgroups, including (1) GzmK and the potent apoptosis-inducing GzmA, (2) the neutrophil proteases (proteinase 3, N-elastase and azurocidin), and (3) adipsin, have all evolved as distinct groups before the separation of tetrapods from the ray-finned fish approximately 420 million years ago [18].
  • Three months after a boost injection with the human AECA, mice developed endogenous AECA (AB), but not Abs to proteinase-3, cardiolipin, or DNA [19].
  • Other enzymes represented, but at lower levels, included elastase IV, proteinase 3, complement C2, chymotrypsin B, chymotrypsin-like protein, and Hageman factor [20].
  • Enzymatic activation of PR3 was suggested by affinity to diisopropylfluorophosphate and removal of an amino-terminal propeptide [15].
  • Furthermore, coadministration of exogenous murine PR3 or a synthetic PAR2 agonist (ASKH95) with LPS in the anti-Gr-1-treated mice restored the serum IL-18 levels to those in control mice treated with P. acnes and LPS [21].

Other interactions of Prtn3


Analytical, diagnostic and therapeutic context of Prtn3

  • Using a polymerase chain reaction (PCR)-based strategy for the isolation of trypsin-related serine proteases, we were able to isolate cDNAs for two of the major neutrophil and monocyte serine proteases in the mouse, cathepsin G and mouse protease 3 (myeloblastin) [14].
  • Mobility gel shift analysis of DNA-protein complexes using competitor DNAs verified the involvement of both OXBOX- and REBOX-binding factors in PR3 [24].
  • The stable expression of transgenic proteinase 3 was characterized by biosynthetic labeling, followed by immunoprecipitation, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and fluorography [15].
  • Translocation of PR3 to granules was shown by subcellular fractionation and immunocytochemistry [15].
  • The proportion of PR3-positive and -negative PMN, observed by flow cytometry with anti-PR3 mAbs or ANCA autoantibodies, varies among individuals but is extremely stable for each individual over prolonged time periods [8].


  1. Antineutrophil cytoplasmic autoantibodies against the murine homolog of proteinase 3 (Wegener autoantigen) are pathogenic in vivo. Pfister, H., Ollert, M., Fröhlich, L.F., Quintanilla-Martinez, L., Colby, T.V., Specks, U., Jenne, D.E. Blood (2004) [Pubmed]
  2. Myeloblastin is an Myb target gene: mechanisms of regulation in myeloid leukemia cells growth-arrested by retinoic acid. Lutz, P.G., Houzel-Charavel, A., Moog-Lutz, C., Cayre, Y.E. Blood (2001) [Pubmed]
  3. Inhibition of neutrophil elastase in CF sputum by L-658,758. Rees, D.D., Brain, J.D., Wohl, M.E., Humes, J.L., Mumford, R.A. J. Pharmacol. Exp. Ther. (1997) [Pubmed]
  4. Autoimmunity is triggered by cPR-3(105-201), a protein complementary to human autoantigen proteinase-3. Pendergraft, W.F., Preston, G.A., Shah, R.R., Tropsha, A., Carter, C.W., Jennette, J.C., Falk, R.J. Nat. Med. (2004) [Pubmed]
  5. Restriction in V kappa gene use and antigen selection in anti-myeloperoxidase response in mice. Jethwa, H.S., Clarke, S.H., Itoh-Lindstrom, Y., Falk, R.J., Jennette, J.C., Nachman, P.H. J. Immunol. (2000) [Pubmed]
  6. Mice lacking neutrophil elastase reveal impaired host defense against gram negative bacterial sepsis. Belaaouaj, A., McCarthy, R., Baumann, M., Gao, Z., Ley, T.J., Abraham, S.N., Shapiro, S.D. Nat. Med. (1998) [Pubmed]
  7. Myeloblastin is a granulocyte colony-stimulating factor-responsive gene conferring factor-independent growth to hematopoietic cells. Lutz, P.G., Moog-Lutz, C., Coumau-Gatbois, E., Kobari, L., Di Gioia, Y., Cayre, Y.E. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  8. Bimodal distribution of proteinase 3 (PR3) surface expression reflects a constitutive heterogeneity in the polymorphonuclear neutrophil pool. Halbwachs-Mecarelli, L., Bessou, G., Lesavre, P., Lopez, S., Witko-Sarsat, V. FEBS Lett. (1995) [Pubmed]
  9. Characterization and localization of the genes for mouse proteinase-3 (Prtn3) and neutrophil elastase (Ela2). Sturrock, A., Franklin, K.F., Wu, S., Hoidal, J.R. Cytogenet. Cell Genet. (1998) [Pubmed]
  10. An enhancer located between the neutrophil elastase and proteinase 3 promoters is activated by Sp1 and an Ets factor. Nuchprayoon, I., Shang, J., Simkevich, C.P., Luo, M., Rosmarin, A.G., Friedman, A.D. J. Biol. Chem. (1999) [Pubmed]
  11. The proximal promoter of the human cathepsin G gene conferring myeloid-specific expression includes C/EBP, c-myb and PU.1 binding sites. Lennartsson, A., Garwicz, D., Lindmark, A., Gullberg, U. Gene (2005) [Pubmed]
  12. Genomic organization and chromosomal localization of mouse proteinase 3 (Myeloblastin). Belaaouaj, A., Moog-Lutz, C., Just, J., Houzel-Charavel, A., Shapiro, S.D., Cayre, Y. Mamm. Genome (1999) [Pubmed]
  13. The zinc finger of nucleocapsid protein of Friend murine leukemia virus is critical for proviral DNA synthesis in vivo. Yu, Q., Darlix, J.L. J. Virol. (1996) [Pubmed]
  14. Characterization of cDNA clones encoding mouse proteinase 3 (myeloblastine) and cathepsin G. Aveskogh, M., Lützelschwab, C., Huang, M.R., Hellman, L. Immunogenetics (1997) [Pubmed]
  15. Characterization of the processing and granular targeting of human proteinase 3 after transfection to the rat RBL or the murine 32D leukemic cell lines. Garwicz, D., Lindmark, A., Hellmark, T., Gladh, M., Jögi, J., Gullberg, U. J. Leukoc. Biol. (1997) [Pubmed]
  16. Cellular mechanisms of proteinase release from inflammatory cells and the degradation of extracellular proteins. Baggiolini, M., Schnyder, J., Bretz, U., Dewald, B., Ruch, W. Ciba Found. Symp. (1979) [Pubmed]
  17. Control of ion transport in mammalian airways by protease activated receptors type 2 (PAR-2). Kunzelmann, K., Sun, J., Markovich, D., König, J., Mürle, B., Mall, M., Schreiber, R. FASEB J. (2005) [Pubmed]
  18. Granzyme-like sequences in bony fish shed light on the emergence of hematopoietic serine proteases during vertebrate evolution. Wernersson, S., Reimer, J.M., Poorafshar, M., Karlson, U., Wermenstam, N., Bengtén, E., Wilson, M., Pilström, L., Hellman, L. Dev. Comp. Immunol. (2006) [Pubmed]
  19. Pathogenic role of anti-endothelial cell antibodies in vasculitis. An idiotypic experimental model. Damianovich, M., Gilburd, B., George, J., Del Papa, N., Afek, A., Goldberg, I., Kopolovic, Y., Roth, D., Barkai, G., Meroni, P.L., Shoenfeld, Y. J. Immunol. (1996) [Pubmed]
  20. Serine proteases in rodent hippocampus. Davies, B.J., Pickard, B.S., Steel, M., Morris, R.G., Lathe, R. J. Biol. Chem. (1998) [Pubmed]
  21. Involvement of neutrophil recruitment and protease-activated receptor 2 activation in the induction of IL-18 in mice. Ikawa, K., Nishioka, T., Yu, Z., Sugawara, Y., Kawagoe, J., Takizawa, T., Primo, V., Nikolic, B., Kuroishi, T., Sasano, T., Shimauchi, H., Takada, H., Endo, Y., Sugawara, S. J. Leukoc. Biol. (2005) [Pubmed]
  22. Stat6-protease but not Stat5-protease is inhibited by an elastase inhibitor ONO-5046. Suzuki, K., Nakajima, H., Ikeda, K., Tamachi, T., Hiwasa, T., Saito, Y., Iwamoto, I. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  23. Gene expression profiling and localization of Hoechst-effluxing CD45- and CD45+ cells in the embryonic mouse lung. Liang, S.X., Summer, R., Sun, X., Fine, A. Physiol. Genomics (2005) [Pubmed]
  24. OXBOX and REBOX, overlapping promoter elements of the mitochondrial F0F1-ATP synthase beta subunit gene. OXBOX/REBOX in the ATPsyn beta promoter. Haraguchi, Y., Chung, A.B., Neill, S., Wallace, D.C. J. Biol. Chem. (1994) [Pubmed]
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