Details for: PRTN3

Gene ID: 5657

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: PRTN3

Ensembl ID: ENSG00000196415

Description: proteinase 3

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • promyelocyte CL0000836
    CSI 12.47
    rCSI 17.99%
    PRS 99.79
  • granulocyte monocyte progenitor cell CL0000557
    CSI 10.7
    rCSI 9.27%
    PRS 99.89
  • common myeloid progenitor CL0000049
    CSI 8.63
    rCSI 6.97%
    PRS 99.92
  • progenitor cell CL0011026
    CSI 4.14
    rCSI 8.81%
    PRS 99.62
  • professional antigen presenting cell CL0000145
    CSI 3.84
    rCSI 13.22%
    PRS 97.76
  • promonocyte CL0000559
    CSI 3.7
    rCSI 6.34%
    PRS 99.89
  • neutrophil CL0000775
    CSI 3.45
    rCSI 19.27%
    PRS 98.23
  • myeloid lineage restricted progenitor cell CL0000839
    CSI 1.14
    rCSI 5.86%
    PRS 99.87
  • erythroid progenitor cell CL0000038
    CSI 1.07
    rCSI 6.14%
    PRS 99.87
  • myelocyte CL0002193
    CSI 0.96
    rCSI 6.32%
    PRS 99.54

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

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  • Node Color (Target Cell CSI, relative to current network):
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    • High
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  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary [PRTN3](/details-gene/5657), also known as Proteinase 3 or Myeloblastin, is a serine protease primarily located within the azurophil granules of neutrophils and on the cell surface. It is a key component of the innate immune system, contributing to host defense through proteolysis and antimicrobial activity. Its expression is highly specific to the myeloid lineage, showing the greatest significance in progenitor cells such as the [promyelocyte](/details-cell/CL0000836) and [granulocyte monocyte progenitor cell](/details-cell/CL0000557), as well as in mature [neutrophils](/details-cell/CL0000775). Clinically, [PRTN3](/details-gene/5657) is well-established as the primary autoantigen in granulomatosis with polyangiitis (formerly Wegener's granulomatosis), an autoimmune vasculitis characterized by anti-neutrophil cytoplasmic antibodies (ANCA) that target [PRTN3](/details-gene/5657) ([Link](https://pubmed.ncbi.nlm.nih.gov/2679910/), [OMIM: 177020](https://omim.org/entry/177020)). Research indicates that down-regulation of [PRTN3](/details-gene/5657) can induce differentiation in promyelocytic leukemia cells, suggesting a role in myeloid cell maturation and hematological malignancies ([Link](https://doi.org/10.1016/0092-8674(89)90752-6)). ## Cellular Roles and Expression Landscape The expression profile of [PRTN3](/details-gene/5657) firmly establishes it as a defining marker of the myeloid lineage, particularly during granulopoiesis. **Overall**, the gene exhibits its highest significance in early myeloid progenitors, including [promyelocytes](/details-cell/CL0000836) (CSI: 12.47), [granulocyte monocyte progenitor cells](/details-cell/CL0000557) (CSI: 10.70), and [common myeloid progenitors](/details-cell/CL0000049) (CSI: 8.63). This strong association with precursor cells suggests a fundamental role for [PRTN3](/details-gene/5657) in the differentiation and commitment of cells toward the granulocytic fate. While its significance is highest in progenitors, [PRTN3](/details-gene/5657) maintains a substantial presence in mature [neutrophils](/details-cell/CL0000775) (CSI: 3.45), where its protein product is stored in granules and becomes functionally active. The sustained expression throughout the neutrophil lifecycle, from progenitor to terminally differentiated cell, underscores its continuous importance, first in development and later in effector functions like host defense and inflammation. Its expression in [professional antigen presenting cells](/details-cell/CL0000145) (CSI: 3.84) further highlights its broader role within the innate immune system. ## Pathways and Molecular Function The molecular functions of [PRTN3](/details-gene/5657) are intrinsically linked to its identity as a serine protease active in the immune system. Its annotation with [Serine-type endopeptidase activity (GO:0004252)](https://www.ebi.ac.uk/QuickGO/term/GO:0004252) is consistent with its role in proteolytic cascades. This function is executed primarily from [Azurophil granule lumen (GO:0035578)](https://www.ebi.ac.uk/QuickGO/term/GO:0035578), supporting its high expression in [neutrophils](/details-cell/CL0000775) and its involvement in [Neutrophil degranulation (R-HSA-6798695)](https://reactome.org/content/detail/R-HSA-6798695). At a systemic level, [PRTN3](/details-gene/5657) is a crucial player in the [Innate immune system (R-HSA-168249)](https://reactome.org/content/detail/R-HSA-168249) and contributes to [Antimicrobial peptides (R-HSA-6803157)](https://reactome.org/content/detail/R-HSA-6803157), a function directly tied to its ability to degrade microbial proteins ([Link](https://doi.org/10.1084/jem.172.6.1709)). Furthermore, its participation in pathways such as [Hemostasis (R-HSA-109582)](https://reactome.org/content/detail/R-HSA-109582) and [Cytokine signaling in immune system (R-HSA-1280215)](https://reactome.org/content/detail/R-HSA-1280215) suggests it has a broader regulatory role, capable of influencing coagulation and intercellular communication during an inflammatory response. ## Research Directions Given its established role in both normal myeloid function and autoimmune pathology, future research should focus on the mechanisms that regulate its expression, localization, and enzymatic activity. **Testable Hypotheses:** 1. The level of [PRTN3](/details-gene/5657) expression in myeloid progenitors acts as a critical regulator of granulopoiesis. Aberrantly high expression may accelerate proliferation and block terminal differentiation, contributing to the pathogenesis of acute myeloid leukemia (AML), whereas its controlled down-regulation is necessary for normal maturation. 2. In the context of ANCA-associated vasculitis, specific post-translational modifications (e.g., glycosylation, citrullination) of [PRTN3](/details-gene/5657) are induced by pro-inflammatory signals. These modifications may enhance its translocation to the neutrophil surface and break immune tolerance by creating neoantigens that are preferentially recognized by autoantibodies. **Experimental Approach:** To test the second hypothesis, one could isolate [neutrophils](/details-cell/CL0000775) from healthy donors and patients with active granulomatosis with polyangiitis. Cells would be stimulated in vitro with inflammatory cytokines (e.g., TNF-alpha) or microbial products (e.g., LPS). Surface-expressed [PRTN3](/details-gene/5657) would be isolated via cell-surface biotinylation followed by immunoprecipitation. Advanced mass spectrometry (e.g., LC-MS/MS) could then be used to compare the post-translational modification profiles of surface [PRTN3](/details-gene/5657) between resting and stimulated states, and between healthy and patient cells. This could identify disease-specific modifications that trigger the autoimmune response. **Therapeutic Potential:** As a well-defined autoantigen and a potent protease, [PRTN3](/details-gene/5657) is a compelling therapeutic target. The primary strategy would be **inhibition**. Its high specificity to the myeloid lineage suggests that systemic inhibitors might have a manageable safety profile. Development of highly specific small molecule inhibitors of its serine protease activity could serve as a targeted therapy for ANCA-associated vasculitis, potentially dampening neutrophil-mediated tissue damage without broad immunosuppression. Furthermore, therapeutic antibodies designed to block the binding of autoantibodies to surface-expressed [PRTN3](/details-gene/5657) could prevent neutrophil activation and degranulation, representing another precise intervention strategy.

Genular Protein ID: 673592150

Symbol: PRTN3_HUMAN

Name: Myeloblastin

UniProtKB Accession Codes:

P24158 P15637 P18078 Q4VB08 Q4VB09 Q6LBM7 Q6LBN2 Q9UD25 Q9UQD8

Database IDs:

ABCD 1 AGR 1 AlphaFoldDB 1 Antibodypedia 1 BRENDA 1 Bgee 1 BindingDB 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CPTAC 1 CTD 1 ChEMBL 1 DIP 1 DMDM 1 DNASU 1 DisGeNET 1 DrugBank 1 DrugCentral 1 EC 1 EMBL 16 Ensembl 2 EvolutionaryTrace 1 ExpressionAtlas 1 GO 22 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyConnect 1 GlyCosmos 1 GlyGen 1 GuidetoPHARMACOLOGY 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 7 KEGG 1 MANE-Select 1 MEROPS 1 MIM 1 MINT 1 MalaCards 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 Orphanet 1 OrthoDB 1 PANTHER 2 PDB 1 PDBsum 1 PIR 1 PRIDE 1 PRINTS 1 PRO 1 PROSITE 3 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 Reactome 4 RefSeq 1 SABIO-RK 1 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 1681549

Title: Wegener autoantigen and myeloblastin are encoded by a single mRNA.

PubMed ID: 1681549

DOI: 10.1073/pnas.88.20.9253

PubMed ID: 15057824

Title: The DNA sequence and biology of human chromosome 19.

PubMed ID: 15057824

DOI: 10.1038/nature02399

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 1518849

Title: Three human elastase-like genes coordinately expressed in the myelomonocyte lineage are organized as a single genetic locus on 19pter.

PubMed ID: 1518849

DOI: 10.1073/pnas.89.17.8215

PubMed ID: 1400430

Title: Structure, chromosomal assignment, and expression of the gene for proteinase-3. The Wegener's granulomatosis autoantigen.

PubMed ID: 1400430

DOI: 10.1016/s0021-9258(19)36816-4

PubMed ID: 9924693

Title: Donor-recipient polymorphism of the proteinase 3 gene: a potential target for T-cell alloresponses to myeloid leukemia.

PubMed ID: 9924693

DOI: 10.1097/00002371-199901000-00001

PubMed ID: 2001463

Title: Wegener's autoantigen and leukemia.

PubMed ID: 2001463

PubMed ID: 2258701

Title: Cloning of cDNA for proteinase 3: a serine protease, antibiotic, and autoantigen from human neutrophils.

PubMed ID: 2258701

DOI: 10.1084/jem.172.6.1709

PubMed ID: 2598267

Title: Down-regulation of a serine protease, myeloblastin, causes growth arrest and differentiation of promyelocytic leukemia cells.

PubMed ID: 2598267

DOI: 10.1016/0092-8674(89)90752-6

PubMed ID: 2377228

Title: Wegener's autoantigen decoded.

PubMed ID: 2377228

DOI: 10.1038/346520a0

PubMed ID: 2033050

Title: Characterization of proteinase-3 (PR-3), a neutrophil serine proteinase. Structural and functional properties.

PubMed ID: 2033050

DOI: 10.1016/s0021-9258(18)92854-1

PubMed ID: 2404977

Title: Characterization of two azurphil granule proteases with active-site homology to neutrophil elastase.

PubMed ID: 2404977

DOI: 10.1016/s0021-9258(19)39936-3

PubMed ID: 2121162

Title: Monoclonal antibodies specific for neutrophil proteinase 4. Production and use for isolation of the enzyme.

PubMed ID: 2121162

DOI: 10.1515/bchm3.1990.371.2.549

PubMed ID: 2285532

Title: The relation of 29 kD C-ANCA antigen to proteinase 3.

PubMed ID: 2285532

DOI: 10.1111/j.1600-0463.1990.tb05713.x

PubMed ID: 2679910

Title: Wegener's granulomatosis autoantigen is a novel neutrophil serine proteinase.

PubMed ID: 2679910

PubMed ID: 2501794

Title: Antibiotic proteins of human polymorphonuclear leukocytes.

PubMed ID: 2501794

DOI: 10.1073/pnas.86.14.5610

PubMed ID: 7897245

Title: Use of proteinase 3 purified by reverse phase HPLC to detect autoantibodies in systemic vasculitis.

PubMed ID: 7897245

DOI: 10.1016/0022-1759(94)00295-8

PubMed ID: 1688612

Title: Anti-neutrophil cytoplasm antibodies in Wegener's granulomatosis recognize an elastinolytic enzyme.

PubMed ID: 1688612

DOI: 10.1084/jem.171.1.357

PubMed ID: 7539799

Title: A novel form of dipeptidylpeptidase IV found in human serum. Isolation, characterization, and comparison with T lymphocyte membrane dipeptidylpeptidase IV (CD26).

PubMed ID: 7539799

DOI: 10.1074/jbc.270.23.14107

PubMed ID: 3198760

Title: Proteinase 3. A distinct human polymorphonuclear leukocyte proteinase that produces emphysema in hamsters.

PubMed ID: 3198760

DOI: 10.1172/jci113816

PubMed ID: 2242436

Title: Identity of Wegener's autoantigen (p29) with proteinase 3 and myeloblastin.

PubMed ID: 2242436

PubMed ID: 17244676

Title: NB1 mediates surface expression of the ANCA antigen proteinase 3 on human neutrophils.

PubMed ID: 17244676

DOI: 10.1182/blood-2006-10-055327

PubMed ID: 18462208

Title: Neutrophil surface presentation of the anti-neutrophil cytoplasmic antibody-antigen proteinase 3 depends on N-terminal processing.

PubMed ID: 18462208

DOI: 10.1111/j.1365-2249.2008.03663.x

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 21193407

Title: Complement receptor Mac-1 is an adaptor for NB1 (CD177)-mediated PR3-ANCA neutrophil activation.

PubMed ID: 21193407

DOI: 10.1074/jbc.m110.171256

PubMed ID: 22266279

Title: Proteinase 3 contributes to transendothelial migration of NB1-positive neutrophils.

PubMed ID: 22266279

DOI: 10.4049/jimmunol.1102540

PubMed ID: 23202369

Title: Neutrophil proteinase 3 acts on protease-activated receptor-2 to enhance vascular endothelial cell barrier function.

PubMed ID: 23202369

DOI: 10.1161/atvbaha.112.300474

PubMed ID: 25944712

Title: N-terminome analysis of the human mitochondrial proteome.

PubMed ID: 25944712

DOI: 10.1002/pmic.201400617

PubMed ID: 28240246

Title: Characterization of the CD177 interaction with the ANCA antigen proteinase 3.

PubMed ID: 28240246

DOI: 10.1038/srep43328

PubMed ID: 30692621

Title: SERPINB1-mediated checkpoint of inflammatory caspase activation.

PubMed ID: 30692621

DOI: 10.1038/s41590-018-0303-z

PubMed ID: 8757293

Title: The crystal structure of PR3, a neutrophil serine proteinase antigen of Wegener's granulomatosis antibodies.

PubMed ID: 8757293

DOI: 10.1006/jmbi.1996.0458

Sequence Information:

  • Length: 256
  • Mass: 27807
  • Checksum: CBECA36D8C4B2A40
  • Sequence:
    • MAHRPPSPAL ASVLLALLLS GAARAAEIVG GHEAQPHSRP YMASLQMRGN PGSHFCGGTL 
IHPSFVLTAA HCLRDIPQRL VNVVLGAHNV RTQEPTQQHF SVAQVFLNNY DAENKLNDVL 
LIQLSSPANL SASVATVQLP QQDQPVPHGT QCLAMGWGRV GAHDPPAQVL QELNVTVVTF 
FCRPHNICTF VPRRKAGICF GDSGGPLICD GIIQGIDSFV IWGCATRLFP DFFTRVALYV 
DWIRSTLRRV EAKGRP