Affinage

PRTN3

Myeloblastin · UniProt P24158

Round 2 corrected
Length
256 aa
Mass
27.8 kDa
Annotated
2026-04-28
130 papers in source corpus 27 papers cited in narrative 27 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PRTN3 encodes proteinase 3 (PR3/myeloblastin), a neutrophil serine proteinase with elastase-like specificity that functions as a multifaceted effector of innate immunity, inflammation, and myeloid cell fate. Stored in azurophil granules and secretory vesicles, PR3 degrades extracellular matrix proteins (fibronectin, laminin, vitronectin, collagen IV), generates the antimicrobial peptide LL-37 by cleaving hCAP-18, and processes pro-inflammatory cytokines TNF-α, IL-1β, and IL-18 through converting enzyme/caspase-1–independent pathways (PMID:2033050, PMID:11389039, PMID:10339575, PMID:11714826). PR3 also binds IL-32α with nanomolar affinity independently of catalytic activity and proteolytically enhances IL-32 bioactivity (PMID:16488976), and catalyzes histone H3 N-terminal cleavage in monocytes to regulate chromatin accessibility during monocyte-to-macrophage differentiation (PMID:34017121). PR3 is the major target autoantigen of c-ANCA in granulomatosis with polyangiitis (Wegener's granulomatosis), where genetically determined membrane PR3 expression—controlled independently of intracellular content—is a risk factor for disease relapse, and a functional PRTN3 locus variant contributes to disease susceptibility (PMID:2679910, PMID:12506139, PMID:28029757).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1989 High

    Identification of PR3 as a novel neutrophil serine proteinase and the c-ANCA autoantigen in Wegener's granulomatosis established the molecular identity of the protein and its disease relevance simultaneously.

    Evidence Affinity purification from neutrophils, DFP binding, N-terminal sequencing, Western blot with monoclonal antibodies

    PMID:2377228 PMID:2679910

    Open questions at the time
    • Enzymatic specificity and substrate repertoire not yet defined
    • Subcellular localization beyond azurophil granules unknown
    • No structural model available
  2. 1989 High

    Demonstrating that antisense suppression of myeloblastin causes growth arrest and differentiation of myeloid progenitors revealed a non-proteolytic role in maintaining the proliferative state of myeloid cells.

    Evidence Antisense oligodeoxynucleotide knockdown in HL-60 cells with proliferation and differentiation assays

    PMID:2598267

    Open questions at the time
    • Mechanism linking PR3 expression to proliferative maintenance not elucidated
    • Whether catalytic activity is required for this function is unknown
  3. 1991 High

    Biochemical characterization of PR3's substrate specificity (preference for small aliphatic P1 residues) and inhibitor profile (inhibited by α1-antitrypsin and α2-macroglobulin but not SLPI) distinguished it from neutrophil elastase and cathepsin G, defining its unique proteolytic niche.

    Evidence In vitro enzymatic assays with chromogenic substrates, ECM protein degradation, inhibitor profiling

    PMID:2033050

    Open questions at the time
    • In vivo substrates beyond ECM not yet identified
    • Physiological contexts of proteolysis unclear
  4. 1992 High

    Mapping the PRTN3/ELA2/AZU locus on chromosome 19pter and demonstrating coordinate down-regulation during differentiation established the genomic organization and transcriptional co-regulation of neutrophil serine protease genes.

    Evidence Cosmid cloning, FISH, Northern blot during U937 differentiation

    PMID:1518849

    Open questions at the time
    • Specific promoter elements driving PR3 transcription not fully defined
    • Whether coordinate regulation extends to protein-level control unknown
  5. 1996 High

    The 2.2 Å crystal structure revealed the chymotrypsin-fold architecture and the S1 pocket residues (Val190→Ile, Ala213→Asp) that dictate small aliphatic P1 preference, providing the first structural explanation for PR3's distinctive specificity.

    Evidence X-ray crystallography at 2.2 Å resolution with molecular replacement

    PMID:8757293

    Open questions at the time
    • No substrate-bound or inhibitor-bound co-crystal structures
    • Structural basis for membrane association not addressed
  6. 1999 High

    Discovery that PR3 is stored in secretory vesicles (the most mobilizable pool) in addition to azurophil granules, and that membrane PR3 increases sequentially upon stimulation, resolved how PR3 reaches the cell surface and distinguished its trafficking from elastase.

    Evidence Subcellular fractionation, immunoelectron microscopy, FACS after fMLP stimulation

    PMID:10498622

    Open questions at the time
    • Molecular mechanism of membrane anchoring (apparently covalent) not identified
    • Sorting signal directing PR3 to secretory vesicles unknown
  7. 1999 High

    Identification of PR3 as a converting enzyme–independent processor of TNF-α and IL-1β from monocytic cells established an alternative pro-inflammatory cytokine activation pathway distinct from TACE and caspase-1.

    Evidence Neutrophil-monocyte co-culture with purified PR3, specific serine protease inhibitors, ELISA

    PMID:10339575

    Open questions at the time
    • Cleavage sites on TNF-α and IL-1β not mapped
    • Relative contribution versus canonical processing in vivo unknown
  8. 2001 High

    PR3 was identified as the sole protease responsible for cleaving hCAP-18 to generate the antimicrobial peptide LL-37 after neutrophil exocytosis, establishing a specific antimicrobial effector function.

    Evidence Immunoelectron microscopy, comparison of purified NE/PR3/cathepsin G, immunoblotting of exocytosed material

    PMID:11389039

    Open questions at the time
    • Whether PR3 processes other antimicrobial precursors unknown
    • In vivo validation in infection models not reported
  9. 2003 High

    Twin studies demonstrating that membrane PR3 expression is genetically determined (r=0.99 in monozygotic twins) and independent of intracellular PR3 content revealed that membrane targeting is under separate genetic control, explaining inter-individual variation in ANCA-vasculitis susceptibility.

    Evidence FACS in 27 monozygotic vs. dizygotic twin pairs, intracellular flow cytometry, Western blot

    PMID:12506139

    Open questions at the time
    • Causal genetic variant(s) controlling membrane targeting not identified at this time
    • Whether membrane PR3 has distinct functional properties versus granule PR3 unknown
  10. 2006 High

    Demonstration that PR3 binds IL-32α with nanomolar affinity independent of catalytic activity, while also proteolytically enhancing IL-32 bioactivity, revealed a dual catalytic/non-catalytic mechanism for amplifying cytokine signaling.

    Evidence Surface plasmon resonance, enzymatic inactivation, IL-32α affinity chromatography, cytokine induction assays

    PMID:16488976

    Open questions at the time
    • Structural basis for non-catalytic IL-32 binding unknown
    • In vivo relevance of PR3–IL-32 axis not established
  11. 2017 Medium

    A GWAS identified a functional PRTN3 locus variant that increases neutrophil PRTN3 expression and contributes to ANCA-associated vasculitis susceptibility, providing the genetic link between expression level and disease risk.

    Evidence GWAS in 1,986 AAV cases and 4,723 controls with eQTL analysis in primary neutrophils

    PMID:28029757

    Open questions at the time
    • Specific causal variant and regulatory mechanism not fully resolved
    • How expression level interacts with membrane targeting genetics is unclear
  12. 2019 High

    Identification of SERPINB1 as a dual checkpoint that limits PR3 activity via its reactive center loop and independently constrains inflammatory caspases via a CARD-binding motif placed PR3 within a broader intracellular protease control network.

    Evidence SERPINB1 knockout mice, domain mutagenesis, siRNA knockdown, protease activity and IL-1β release assays

    PMID:30692621

    Open questions at the time
    • Whether SERPINB1 is the primary intracellular PR3 inhibitor in neutrophils versus monocytes not distinguished
    • Relative contribution of PR3 versus NE/CatG to SERPINB1-regulated phenotypes not fully separated
  13. 2021 High

    Discovery that PR3 (with NE and CatG) catalyzes histone H3 N-terminal cleavage in monocytes, regulating chromatin accessibility and gene expression reprogramming during monocyte-to-macrophage differentiation, revealed an unexpected nuclear/epigenomic function.

    Evidence NSP depletion, ChIP-seq, ATAC-seq, primary monocyte differentiation, systemic JIA patient monocytes

    PMID:34017121

    Open questions at the time
    • Individual contribution of PR3 versus NE and CatG to H3ΔN not fully dissected
    • Mechanism of PR3 nuclear import not established
    • Whether H3ΔN activity extends to other cell lineages unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • The mechanism by which PR3 is targeted to the plasma membrane independently of intracellular content, and the structural determinants of its non-catalytic IL-32 binding, remain unresolved.
  • Membrane anchoring mechanism (GPI-anchor versus transmembrane partner) not definitively identified
  • No co-crystal structure of PR3 with IL-32
  • In vivo contribution of individual PR3 functions (antimicrobial, cytokine processing, chromatin remodeling) to host defense not separately quantified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 8 GO:0016787 hydrolase activity 4 GO:0042393 histone binding 1
Localization
GO:0005886 plasma membrane 3 GO:0005576 extracellular region 2 GO:0005634 nucleus 1 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-168256 Immune System 7 R-HSA-1643685 Disease 3 R-HSA-1474244 Extracellular matrix organization 1 R-HSA-4839726 Chromatin organization 1
Partners
CAMPCTSGELANEIL1BIL32SERPINA1SERPINB1TNF

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1989 PRTN3 (proteinase 3/myeloblastin) was identified as a novel neutrophil serine proteinase and the target autoantigen of c-ANCA autoantibodies in Wegener's granulomatosis. The 29-kDa protein was purified from neutrophils, showed a novel N-terminal sequence homologous to serine proteinases, and bound radiolabeled diisopropyl fluorophosphate, confirming serine protease activity. Affinity purification, Western blot, monoclonal antibody generation, N-terminal sequencing, DFP binding assay Blood High 2679910
1989 PRTN3 (myeloblastin) expression is down-regulated during induced differentiation of HL-60 promyelocytic leukemia cells, and antisense oligodeoxynucleotide-mediated inhibition of myeloblastin expression inhibits proliferation and induces differentiation, demonstrating a functional role for PRTN3 in maintaining the proliferative state of myeloid progenitor cells. Antisense oligodeoxynucleotide knockdown, flow cytometry, Northern blot, cell proliferation assays Cell High 2598267
1990 PRTN3 cDNA was cloned from human bone marrow, revealing a primary structure with high homology to elastase, cathepsin G, and other serine proteases. The protein contains the catalytic triad and elastase-like substrate binding pocket, is more abundant in neutrophils than elastase, and has a similar proteolytic profile. It is encoded by a single gene. cDNA cloning, N-terminal sequencing, CNBr fragment sequencing, Southern blot The Journal of experimental medicine High 2258701
1990 The autoantigen of anti-neutrophil cytoplasm antibodies (ANCA) in Wegener's granulomatosis was identified as proteinase 3, an elastinolytic neutral serine proteinase isolated by affinity chromatography from degranulated neutrophils, with 17 NH2-terminal amino acids showing homology to serine proteinases. Affinity chromatography, phorbol ester-induced neutrophil degranulation, N-terminal sequence analysis, elastinolytic activity assay The Journal of experimental medicine High 1688612
1990 The Wegener's granulomatosis autoantigen was decoded as proteinase 3, a member of the serine proteinase family. Biochemical characterization, sequence analysis Nature High 2377228
1991 PRTN3 was biochemically characterized as a serine proteinase with elastase-like specificity (preference for small aliphatic amino acids at P1 site: alanine, serine, valine). It degrades extracellular matrix proteins including fibronectin, laminin, vitronectin, and collagen type IV but not interstitial collagens I and III. It is inhibited by alpha1-proteinase inhibitor and alpha2-macroglobulin but NOT by secretory leukoprotease inhibitor or alpha1-antichymotrypsin, distinguishing it from elastase and cathepsin G. In vitro enzymatic assays with chromogenic substrates and matrix proteins, inhibitor profiling, peptide substrate analysis The Journal of biological chemistry High 2033050
1992 The genes for PRTN3 (PR3), neutrophil elastase (NE), and azurocidin (AZU) are organized as a single genetic locus on chromosome 19pter, with PR3 separated by 8 kb from AZU and 3 kb from NE. All three genes are coordinately down-regulated during terminal differentiation of the premonocytic cell line U937, and share the same five-exon structure typical of granule-associated serine proteases. Cosmid cloning, FISH, physical mapping, exon-intron analysis, Northern blot during differentiation Proceedings of the National Academy of Sciences of the United States of America High 1518849
1993 C-ANCA (anti-PR3 antibodies) interfere with PR3 proteolytic activity and inhibit complexation of PR3 with its major physiologic inhibitor alpha1-antitrypsin (alpha1-AT). The degree of C-ANCA inhibition of PR3-alpha1-AT complexation correlates with disease activity in Wegener's granulomatosis, whereas C-ANCA titer alone does not. Serial serum sample analysis, PR3-alpha1-AT complexation assay, disease activity scoring, correlation analysis Clinical and experimental immunology Medium 8370167
1994 Anti-PR3 antibodies (C-ANCA) recognize PR3 translocated to the membrane of TNF-alpha-treated human endothelial cells and mediate cytotoxicity against those cells in a complement-independent manner requiring co-cultivation with cytokine-primed neutrophils. Cytotoxicity was measured by Cr-release assay and was inhibited by preincubation with purified PR3 antigen. Chromium release cytotoxicity assay, affinity-purified antibodies, TNF-alpha priming of endothelial cells, neutrophil co-culture Clinical and experimental immunology Medium 8082300
1995 PR3 enzymatically cleaves human IgG of all subclasses, including C-ANCA IgG complexed to the enzyme. Cleavage products differ from those generated by neutrophil elastase, demonstrating a distinct proteolytic specificity of PR3 toward immunoglobulins. In vitro proteolysis assay, gel electrophoresis analysis of cleavage products, comparison with human neutrophil elastase Clinical and experimental immunology Medium 7621597
1996 The crystal structure of PR3 was solved at 2.2 Å resolution by molecular replacement. The overall fold consists of two beta-barrel domains typical of the chymotrypsin family. The substrate binding site S1 pocket is defined by a Val-to-Ile substitution at position 190 (explaining preference for small aliphatic P1 residues) and Ala-to-Asp substitution at position 213. An N-linked disaccharide is attached to Asn159. Linear antigenic sites reactive with Wegener's granulomatosis autoantibodies map to surface-accessible regions, implicating the pro-form in pathogenesis. X-ray crystallography at 2.2 Å, molecular replacement, structural refinement (R=0.201) Journal of molecular biology High 8757293
1998 The mouse Prtn3 gene was characterized and mapped by FISH to chromosome 10C2, in close proximity to the neutrophil elastase gene (Ela2). The gene consists of five exons and four introns, conserving the typical granule-associated serine protease structure. The proximal promoter contains a TATA box, c-myb, and ets transcriptional sites. Mouse and human PR3 cDNA share 73% homology (60% at amino acid level); the catalytic triad and placement are conserved. FISH analysis, gene structure characterization, promoter analysis, cDNA sequence comparison Cytogenetics and cell genetics Medium 9925946
1999 PR3 is present not only in azurophil granules but also in specific granules and in secretory vesicles (the most readily mobilizable intracellular pool), distinct from elastase and myeloperoxidase which are exclusively in azurophil granules. Upon FMLP stimulation, membrane PR3 expression increases in a sequential manner: secretory vesicles first, followed by specific granules, then azurophil granules. Membrane association of PR3 appears covalent (not ionic). Subcellular fractionation, immunoelectron microscopy, FACS analysis of membrane PR3 after FMLP stimulation, comparison with elastase and myeloperoxidase Blood High 10498622
1999 PR3 induces IL-8 production in TNF-alpha/IL-1beta-activated endothelial cells through activation of NF-kappaB. Anti-PR3 antibodies acting on membrane-expressed PR3 amplify this response. NF-kappaB activation was confirmed by PAGE of nuclear extracts and Western blot for p65. RT-PCR, ELISA, NF-kappaB activation assay, cycloheximide inhibition, monoclonal anti-PR3 antibody (WGM2) European journal of clinical investigation Medium 10583443
1999 Purified PR3 (but not neutrophil elastase or cathepsin G) is responsible for converting enzyme-independent release of bioactive TNF-alpha and IL-1beta from LPS-stimulated monocytic cells (THP-1). This was demonstrated using specific inhibitors and purified enzymes, identifying an alternative cytokine processing pathway in local inflammatory contexts. Neutrophil-monocyte co-culture, specific serine protease inhibitors, purified enzymes (PR3, NE, Cat G), ELISA for TNF-alpha and IL-1beta Proceedings of the National Academy of Sciences of the United States of America High 10339575
2001 Proteinase 3 is solely responsible for cleavage of the human cathelicidin hCAP-18 to generate the active antimicrobial peptide LL-37 after neutrophil exocytosis. Immunoelectron microscopy showed both hCAP-18 and azurophil granule proteins in phagolysosomes. Cleavage of hCAP-18 to LL-37 occurred only in exocytosed material, not after phagocytosis. Immunoelectron microscopy, immunoblotting, comparison of NE/PR3/cathepsin G with purified enzymes, subcellular fractionation Blood High 11389039
2001 Neutrophil proteinase 3 (PR3) induces secretion of bioactive IL-18 (active 18-kDa form) from human oral epithelial cells via a caspase-1-independent pathway, following IFN-gamma priming plus LPS co-stimulation. PR3 was detected only in membrane fractions (not cytoplasm) of treated cells, and induction was blocked by serine proteinase inhibitors but not caspase-1 inhibitors. Cell stimulation assays, Western blot for IL-18 isoforms, caspase-1 inhibitor controls, serine proteinase inhibitors, subcellular fractionation, RT-PCR, IFN-gamma bioassay Journal of immunology High 11714826
2002 Proteinase 3 is strongly expressed in lung parenchymal cells (type I and II pneumocytes) and macrophages in Wegener's granulomatosis tissue, as well as in normal lung tissue (though up-regulated in WG). This non-neutrophil expression pattern suggests these cells may contribute to lung damage via direct interaction with ANCA. Immunohistochemistry of lung biopsies from WG patients and normal tissue Arthritis research Low 12010574
2002 Neutrophil membrane expression of PR3 (mPR3) is related to relapse in PR3-ANCA-associated vasculitis. An elevated percentage and level of mPR3 expression on resting neutrophils of WG patients significantly associated with increased relapse risk and relapse rate, but not with disease extent or particular manifestations. FACS analysis of membrane PR3 in 89 WG patients and 72 healthy controls, clinical follow-up analysis Journal of the American Society of Nephrology Medium 12191967
2003 Neutrophil membrane PR3 (mPR3) expression is genetically determined. Twin studies demonstrated near-perfect concordance of mPR3 expression in monozygotic twins (r=0.99) versus dizygotic twins (r=0.06). Critically, mPR3 expression is independent of intracellular PR3 content, indicating that membrane targeting rather than total protein level is under genetic control. FACS analysis, monozygotic vs. dizygotic twin study (27 pairs), intracellular flow cytometry, Western blotting, FACSort-separated subpopulation analysis Journal of the American Society of Nephrology High 12506139
2005 Anti-PR3 antibodies (C-ANCA) prime monocytes and neutrophils for enhanced CD14-dependent activation, resulting in markedly augmented IL-8, TNF-alpha, and IL-6 release upon subsequent LPS or LTA (but not TNF-alpha) challenge. Priming was associated with increased CD14 membrane expression and required 2-6 hours of anti-PR3 pre-incubation. In vitro monocyte/neutrophil stimulation, ELISA for cytokines, flow cytometric analysis of CD14 expression, isotype-matched IgG controls, ANCA-IgG from WG serum Journal of leukocyte biology Medium 16006536
2006 Proteinase 3 (PR3) was identified as a specific binding protein for the proinflammatory cytokine IL-32alpha, with dissociation constants of 2.65 nM (urinary PR3) and 1.2 nM (neutrophil-derived PR3) determined by surface plasmon resonance. Irreversible inactivation of PR3 enzymatic activity did not significantly change IL-32 binding, establishing a non-catalytic binding function. However, limited cleavage of IL-32alpha by PR3 enhanced its cytokine activity (MIP-2 and IL-8 induction) more than intact IL-32alpha. IL-32alpha affinity chromatography, mass spectrometry identification, N-terminal microsequencing, surface plasmon resonance, enzymatic inactivation, cytokine induction assays in mouse macrophages and human PBMCs Proceedings of the National Academy of Sciences of the United States of America High 16488976
2008 ANCA patients with PR3-ANCA have CD4+ TH1 memory T cells responsive to the complementary-PR3 (cPR3) protein encoded by the antisense strand of the PR3 gene. Approximately half of PR3-ANCA patients had cPR3(138-169)-peptide-reactive T cells, whereas MPO-ANCA patients did not, indicating specificity. The HLA-DRB1*15 allele was overrepresented and predicted to bind cPR3(138-169) with high affinity. Memory T cell cultivation, proliferation assays, IFN-gamma secretion assays, HLA-DRB1 typing, peptide binding prediction Kidney international Medium 18596726
2017 A genome-wide association study identified a functional variant at the PRTN3 locus in which the top-scoring SNP correlated with increased PRTN3 expression in neutrophils, contributing to susceptibility to ANCA-associated vasculitis (granulomatosis with polyangiitis). The overall population attributable fraction for identified variants including PRTN3, HLA-DPB1, SERPINA1, and PTPN22 was 77%. GWAS in 1,986 AAV cases and 4,723 controls, functional annotation, eQTL analysis of neutrophil gene expression Arthritis & rheumatology Medium 28029757
2019 SERPINB1 limits the activity of neutrophil serine proteases (including PR3) through its reactive center loop and separately constrains inflammatory caspase (caspase-1/-4/-5/-11) activation through a C-terminal CARD-binding motif. Knockdown or deletion of SERPINB1 caused spontaneous caspase-1/-4/-5/-11 activation, IL-1β release, and pyroptosis, establishing SERPINB1 as a checkpoint for both PR3 activity and inflammatory caspase activation through genetically and functionally separable mechanisms. SERPINB1 knockout mice, siRNA knockdown, IL-1β ELISA, pyroptosis assays, domain mutagenesis, in vitro protease activity assays Nature immunology High 30692621
2021 PRTN3 (proteinase 3), along with cathepsin G and neutrophil elastase, catalyzes proteolytic cleavage of the histone H3 amino terminus (H3ΔN) in human peripheral blood monocytes. This histone mark is repressed as monocytes differentiate into macrophages. Simultaneous NSP depletion in monocytic cells causes H3ΔN loss and increased chromatin accessibility, priming chromatin for gene expression reprogramming during monocyte-to-macrophage differentiation. H3ΔN is enriched at permissive chromatin and actively transcribed genes. NSP depletion, integrative epigenomic analysis (ChIP-seq, ATAC-seq), primary monocyte/macrophage differentiation, patient monocytes from systemic JIA, quantitative histone cleavage assays Nature immunology High 34017121
2023 Fusobacterium nucleatum promotes esophageal squamous cell carcinoma proliferation by upregulating expression of IL-32 and PRTN3, subsequently activating the PI3K/AKT signaling pathway. This was demonstrated in vitro and in vivo. In vitro proliferation assays, in vivo tumor models, FISH, RT-PCR, pathway analysis Cancer science Low 36919771

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2001 Human cathelicidin, hCAP-18, is processed to the antimicrobial peptide LL-37 by extracellular cleavage with proteinase 3. Blood 672 11389039
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2008 Large-scale proteomics and phosphoproteomics of urinary exosomes. Journal of the American Society of Nephrology : JASN 607 19056867
2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome research 438 15489334
1990 Anti-neutrophil cytoplasm antibodies in Wegener's granulomatosis recognize an elastinolytic enzyme. The Journal of experimental medicine 424 1688612
1989 Wegener's granulomatosis autoantigen is a novel neutrophil serine proteinase. Blood 387 2679910
2006 Tudor, MBT and chromo domains gauge the degree of lysine methylation. EMBO reports 385 16415788
1989 Down-regulation of a serine protease, myeloblastin, causes growth arrest and differentiation of promyelocytic leukemia cells. Cell 294 2598267
1999 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. Proceedings of the National Academy of Sciences of the United States of America 278 10339575
2004 The DNA sequence and biology of human chromosome 19. Nature 271 15057824
1989 Antibiotic proteins of human polymorphonuclear leukocytes. Proceedings of the National Academy of Sciences of the United States of America 257 2501794
1991 Characterization of proteinase-3 (PR-3), a neutrophil serine proteinase. Structural and functional properties. The Journal of biological chemistry 255 2033050
1990 Wegener's autoantigen decoded. Nature 242 2377228
2001 Neutrophil proteinase 3-mediated induction of bioactive IL-18 secretion by human oral epithelial cells. Journal of immunology (Baltimore, Md. : 1950) 232 11714826
2010 Proteomics characterization of extracellular space components in the human aorta. Molecular & cellular proteomics : MCP 231 20551380
2002 CD8 T-cell responses to Wilms tumor gene product WT1 and proteinase 3 in patients with acute myeloid leukemia. Blood 219 12200377
2010 A genome-wide association study suggests contrasting associations in ACPA-positive versus ACPA-negative rheumatoid arthritis. Annals of the rheumatic diseases 214 21156761
2012 The influence of ACPA status and characteristics on the course of RA. Nature reviews. Rheumatology 175 22293763
2014 Increased neutrophil elastase and proteinase 3 and augmented NETosis are closely associated with β-cell autoimmunity in patients with type 1 diabetes. Diabetes 167 25092677
2015 Extensive glycosylation of ACPA-IgG variable domains modulates binding to citrullinated antigens in rheumatoid arthritis. Annals of the rheumatic diseases 164 25587188
2009 Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip. American journal of human genetics 164 19913121
1990 Cloning of cDNA for proteinase 3: a serine protease, antibiotic, and autoantigen from human neutrophils. The Journal of experimental medicine 160 2258701
1999 Presence of proteinase 3 in secretory vesicles: evidence of a novel, highly mobilizable intracellular pool distinct from azurophil granules. Blood 145 10498622
2017 Identification of Functional and Expression Polymorphisms Associated With Risk for Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis. Arthritis & rheumatology (Hoboken, N.J.) 138 28029757
2013 In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine. Proteomics 138 23533145
2002 Neutrophil membrane expression of proteinase 3 (PR3) is related to relapse in PR3-ANCA-associated vasculitis. Journal of the American Society of Nephrology : JASN 137 12191967
1992 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 136 1518849
1996 The crystal structure of PR3, a neutrophil serine proteinase antigen of Wegener's granulomatosis antibodies. Journal of molecular biology 133 8757293
2006 Proteinase 3 is an IL-32 binding protein. Proceedings of the National Academy of Sciences of the United States of America 124 16488976
2009 MBT domain proteins in development and disease. Seminars in cell & developmental biology 123 19778625
2003 Membrane expression of proteinase 3 is genetically determined. Journal of the American Society of Nephrology : JASN 122 12506139
2017 The role of anti-citrullinated protein antibodies (ACPA) in the pathogenesis of rheumatoid arthritis. Central-European journal of immunology 120 29472818
2019 SERPINB1-mediated checkpoint of inflammatory caspase activation. Nature immunology 118 30692621
2002 Interferon-alpha, but not the ABL-kinase inhibitor imatinib (STI571), induces expression of myeloblastin and a specific T-cell response in chronic myeloid leukemia. Blood 115 12393722
2014 The lung in ACPA-positive rheumatoid arthritis: an initiating site of injury? Rheumatology (Oxford, England) 85 24831057
1993 Relevance of classic anti-neutrophil cytoplasmic autoantibody (C-ANCA)-mediated inhibition of proteinase 3-alpha 1-antitrypsin complexation to disease activity in Wegener's granulomatosis. Clinical and experimental immunology 84 8370167
2011 Rheumatoid arthritis: Are ACPA-positive and ACPA-negative RA the same disease? Nature reviews. Rheumatology 74 21455249
2005 Anti-citrullinated protein/peptide antibodies (ACPA) in rheumatoid arthritis: specificity and relation with rheumatoid factor. Autoimmunity reviews 66 16137613
2011 An essential role for transcription before the MBT in Xenopus laevis. Developmental biology 65 21741375
2005 Autoantibodies to citrullinated proteins: ACPA. Autoimmunity 63 15804701
1998 Mouse embryos do not wait for the MBT: chromatin and RNA polymerase remodeling in genome activation at the onset of development. Developmental genetics 63 9499578
1994 Cytotoxic effects of antibodies to proteinase 3 (C-ANCA) on human endothelial cells. Clinical and experimental immunology 63 8082300
2011 The ACPA recognition profile and subgrouping of ACPA-positive RA patients. Annals of the rheumatic diseases 61 21998120
2017 The Infectious Basis of ACPA-Positive Rheumatoid Arthritis. Frontiers in microbiology 58 29033912
2017 Differences in the symptomatic phase preceding ACPA-positive and ACPA-negative RA: a longitudinal study in arthralgia during progression to clinical arthritis. Annals of the rheumatic diseases 57 28606964
2021 Repression of CTSG, ELANE and PRTN3-mediated histone H3 proteolytic cleavage promotes monocyte-to-macrophage differentiation. Nature immunology 56 34017121
2019 Differential ACPA Binding to Nuclear Antigens Reveals a PAD-Independent Pathway and a Distinct Subset of Acetylation Cross-Reactive Autoantibodies in Rheumatoid Arthritis. Frontiers in immunology 56 30662440
2011 The tumour suppressor L(3)mbt inhibits neuroepithelial proliferation and acts on insulator elements. Nature cell biology 54 21857667
2013 HLA-DRB1 genotypes and the risk of developing anti citrullinated protein antibody (ACPA) positive rheumatoid arthritis. PloS one 51 23737967
2003 Mbt, a Drosophila PAK protein, combines with Cdc42 to regulate photoreceptor cell morphogenesis. Development (Cambridge, England) 48 12490550
1993 Cellular immune responses and pathogenesis in c-ANCA positive vasculitides. Journal of autoimmunity 48 8499060
2015 Coordinating Cell Cycle Remodeling with Transcriptional Activation at the Drosophila MBT. Current topics in developmental biology 46 26358872
2021 Novel autoantibodies identified in ACPA-negative rheumatoid arthritis. Annals of the rheumatic diseases 45 33452006
2017 Anticitrullinated protein/peptide antibody multiplexing defines an extended group of ACPA-positive rheumatoid arthritis patients with distinct genetic and environmental determinants. Annals of the rheumatic diseases 45 29070529
2006 Structure of Francisella tularensis AcpA: prototype of a unique superfamily of acid phosphatases and phospholipases C. The Journal of biological chemistry 45 16899453
2001 Identification of the acid phosphatase (acpA) gene homologues in pathogenic and non-pathogenic Burkholderia spp. facilitates TnphoA mutagenesis. Microbiology (Reading, England) 44 11160805
2020 Bacterial citrullinated epitopes generated by Porphyromonas gingivalis infection-a missing link for ACPA production. Annals of the rheumatic diseases 43 32532752
2015 CCR6(+) Th cell populations distinguish ACPA positive from ACPA negative rheumatoid arthritis. Arthritis research & therapy 43 26617177
2008 ANCA patients have T cells responsive to complementary PR-3 antigen. Kidney international 43 18596726
1998 Pre-MBT patterning of early gene regulation in Xenopus: the role of the cortical rotation and mesoderm induction. Mechanisms of development 43 9510021
2019 On the presence of HLA-SE alleles and ACPA-IgG variable domain glycosylation in the phase preceding the development of rheumatoid arthritis. Annals of the rheumatic diseases 42 31471298
2018 Variable domain N-linked glycosylation and negative surface charge are key features of monoclonal ACPA: Implications for B-cell selection. European journal of immunology 42 29512823
2015 In antisynthetase syndrome, ACPA are associated with severe and erosive arthritis: an overlapping rheumatoid arthritis and antisynthetase syndrome. Medicine 42 25997035
2013 Differential role of the basolateral amygdala 5-HT3 and 5-HT4 serotonin receptors upon ACPA-induced anxiolytic-like behaviors and emotional memory deficit in mice. Behavioural brain research 41 24333573
2013 Low-avidity anticitrullinated protein antibodies (ACPA) are associated with a higher rate of joint destruction in rheumatoid arthritis. Annals of the rheumatic diseases 40 23463689
2013 HLA shared epitope and ACPA: just a marker or an active player? Autoimmunity reviews 40 23958703
2011 Mutational and phylogenetic analyses of the mycobacterial mbt gene cluster. Journal of bacteriology 40 21873494
2010 Anticitrullinated protein antibody (ACPA) in rheumatoid arthritis: influence of an interaction between HLA-DRB1 shared epitope and a deletion polymorphism in glutathione S-transferase in a cross-sectional study. Arthritis research & therapy 40 21087494
2022 Randomized phase I trial of antigen-specific tolerizing immunotherapy with peptide/calcitriol liposomes in ACPA+ rheumatoid arthritis. JCI insight 39 36278483
2005 Impaired maturation of myeloid progenitors in mice lacking novel Polycomb group protein MBT-1. The EMBO journal 38 15889154
2013 The malignant brain tumor (MBT) domain protein SFMBT1 is an integral histone reader subunit of the LSD1 demethylase complex for chromatin association and epithelial-to-mesenchymal transition. The Journal of biological chemistry 37 23928305
2008 The Drosophila p21-activated kinase Mbt modulates DE-cadherin-mediated cell adhesion by phosphorylation of Armadillo. The Biochemical journal 34 18636970
2013 Smoking, the HLA-DRB1 shared epitope and ACPA fine-specificity in Koreans with rheumatoid arthritis: evidence for more than one pathogenic pathway linking smoking to disease. Annals of the rheumatic diseases 31 23505239
2011 H3K9me2/3 binding of the MBT domain protein LIN-61 is essential for Caenorhabditis elegans vulva development. PLoS genetics 31 21437264
2015 ACPA-positive primary Sjögren's syndrome: true primary or rheumatoid arthritis-associated Sjögren's syndrome? RMD open 30 26509066
2010 Anxiolytic-like effect induced by the cannabinoid CB1 receptor agonist, arachydonilcyclopropylamide (ACPA), in the rat amygdala is mediated through the D1 and D2 dopaminergic systems. Journal of psychopharmacology (Oxford, England) 30 20685770
2016 Loss of l(3)mbt leads to acquisition of the ping-pong cycle in Drosophila ovarian somatic cells. Genes & development 29 27474440
2021 ACPA decreases non-small cell lung cancer line growth through Akt/PI3K and JNK pathways in vitro. Cell death & disease 28 33431819
2020 Association between number and type of different ACPA fine specificities with lung abnormalities in early, untreated rheumatoid arthritis. RMD open 28 32917833
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2002 Determination of the sensitising activity of the rubber contact sensitisers TMTD, ZDMC, MBT and DEA in a modified local lymph node assay and the effect of sodium dodecyl sulfate pretreatment on local lymph node responses. Toxicology 28 12062936
2023 Fusobacterium nucleatum promotes the early occurrence of esophageal cancer through upregulation of IL-32/PRTN3 expression. Cancer science 27 36919771
2022 ACPA-negative rheumatoid arthritis: From immune mechanisms to clinical translation. EBioMedicine 27 36027873
2020 The P. gingivalis Autocitrullinome Is Not a Target for ACPA in Early Rheumatoid Arthritis. Journal of dental research 27 31905316
2020 Highly Sensitive Dual-Mode Optical Thermometry in Double-Perovskite Oxides via Pr3+/Dy3+ Energy Transfer. Inorganic chemistry 27 32940038
2020 Increased expression of CXCL2 in ACPA-positive rheumatoid arthritis and its role in osteoclastogenesis. Clinical and experimental immunology 27 33010041
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2019 Outcome of patients with early arthritis without rheumatoid factor and ACPA and predictors of rheumatoid arthritis in the ESPOIR cohort. Arthritis research & therapy 26 31171038
2012 LINT, a novel dL(3)mbt-containing complex, represses malignant brain tumour signature genes. PLoS genetics 26 22570633
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2000 Cloning of a novel murine gene Sfmbt, Scm-related gene containing four mbt domains, structurally belonging to the Polycomb group of genes. Gene 26 10806358
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2013 Meta-analysis of expression of l(3)mbt tumor-associated germline genes supports the model that a soma-to-germline transition is a hallmark of human cancers. International journal of cancer 25 24243547
2005 Anti-proteinase 3 antibodies (c-ANCA) prime CD14-dependent leukocyte activation. Journal of leukocyte biology 25 16006536
2020 Inflammatory Proteins HMGA2 and PRTN3 as Drivers of Vulvar Squamous Cell Carcinoma Progression. Cancers 24 33374674
2019 LTF, PRTN3, and MNDA in Synovial Fluid as Promising Biomarkers for Periprosthetic Joint Infection: Identification by Quadrupole Orbital-Trap Mass Spectrometry. The Journal of bone and joint surgery. American volume 24 31644522
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2005 Midblastula transition (MBT) of the cell cycles in the yolk and pigment granule-free translucent blastomeres obtained from centrifuged Xenopus embryos. Development, growth & differentiation 24 16026537
2020 Differential regulation and correlation between galectin-9 and anti-CCP antibody (ACPA) in rheumatoid arthritis patients. Arthritis research & therapy 23 32293530
2017 The prevalence of ACPA is lower in rheumatoid arthritis patients with an older age of onset but the composition of the ACPA response appears identical. Arthritis research & therapy 22 28569212
2015 Anti-citrullinated peptide/protein antibody (ACPA)-negative RA shares a large proportion of susceptibility loci with ACPA-positive RA: a meta-analysis of genome-wide association study in a Japanese population. Arthritis research & therapy 22 25927497
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1995 Proteolysis of classic anti-neutrophil cytoplasmic autoantibodies (C-ANCA) by neutrophil proteinase 3. Clinical and experimental immunology 20 7621597
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2011 The fine specificity of IgM anti-citrullinated protein antibodies (ACPA) is different from that of IgG ACPA. Arthritis research & therapy 19 22129077
2020 Circulating IFN-γ producing CD4+ T cells and IL-17A producing CD4+ T cells, HLA-shared epitope and ACPA may characterize the clinical response to therapy in rheumatoid arthritis patients. Human immunology 18 32107036
2020 Distinctive Clinical Characteristics and Outcome of ILD-Onset Rheumatoid Arthritis and ACPA-Positive ILD: a Longitudinal Cohort of 282 Cases. Clinical reviews in allergy & immunology 18 33170478
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2018 Rap1, Canoe and Mbt cooperate with Bazooka to promote zonula adherens assembly in the fly photoreceptor. Journal of cell science 18 29507112
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1999 Anti-PR-3 antibodies induce endothelial IL-8 release. European journal of clinical investigation 17 10583443
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2019 Synergistic but not additive effect between ACPA and lithium in the dorsal hippocampal region on spatial learning and memory in rats: Isobolographic analyses. Chemico-biological interactions 16 31715133
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2018 L(3)mbt and the LINT complex safeguard cellular identity in the Drosophila ovary. Development (Cambridge, England) 15 29511022
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2014 Chromatin reader L(3)mbt requires the Myb-MuvB/DREAM transcriptional regulatory complex for chromosomal recruitment. Proceedings of the National Academy of Sciences of the United States of America 15 25249635
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