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proteinase 3

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Immunopharmacology Ligand  Target has curated data in GtoImmuPdb

Target id: 2401

Nomenclature: proteinase 3

Family: S1: Chymotrypsin

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 256 19p13.3 PRTN3 proteinase 3
Mouse - 254 10 39.72 cM Prtn3 proteinase 3
Rat - 254 7q11 Prtn3 proteinase 3
Previous and Unofficial Names Click here for help
ACPA | AGP7 | Wegener granulomatosis autoantigen | C-ANCA | MBT | myeloblastin | PR3
Database Links Click here for help
Specialist databases
MEROPS S01.134 (Hs)
Other databases
BRENDA
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Orphanet
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  X-ray crystal structure of human proteinase 3 (PR3).
PDB Id:  1FUJ
Resolution:  2.2Å
Species:  Human
References:  2
Enzyme Reaction Click here for help
EC Number: 3.4.21.76

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
compound 11 [PMID: 29442501] Small molecule or natural product Primary target of this compound Immunopharmacology Ligand Hs Inhibition 8.3 pKi 3
pKi 8.3 (Ki 5.4x10-9 M) [3]
Description: Inhibition of human PR3 in vitro.
azapro-3 Peptide Immunopharmacology Ligand Hs Inhibition 5.8 pKi 1
pKi 5.8 (Ki 1.5x10-6 M) [1]
compound 4g [PMID: 22595175] Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 5.8 pIC50 5
pIC50 5.8 (IC50 1.4x10-6 M) [5]
Immunopharmacology Comments
Proteinase 3 (PR3), called myeloblastin when it was first identified, is an abundant serine protease found principally in neutrophil granules (but is also found on the surface of quiescent human neutrophils from peripheral blood). It is stored in the primary granules of circulating neutrophils alongside other cathepsin C-activated neutrophil serine proteases (NSPs), such as human neutrophil elastase (HNE), CatG, and NSP4. In pathological conditions it is thought that PR3 behaves to accelerate inflammation, by enhancing cytokine bioactivity, inactivating anti-inflammatory mediators and by promoting tissue injury (potentially by degrading extra-cellular matrix components like elastin, collagen, fibronectin, and laminins). In addition, imbalances between NSPs and their endogenous inhibitors can contribute towards pathological tissue damage, such as the damage associated with inflammatory lung diseases like chronic obstructive pulmonary disease (COPD), emphysema, and cystic fibrosis. PR3 inhibitors are considered to be useful clinical candidates for anti-inflammatory drug development [4].
Cell Type Associations
Immuno Cell Type:  Granulocytes
Cell Ontology Term:   neutrophil (CL:0000775)
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 4 GO processes
GO:0006909 phagocytosis IBA
GO:0043312 neutrophil degranulation TAS
GO:0050765 negative regulation of phagocytosis IDA
GO:0072672 neutrophil extravasation IMP
Immuno Process:  Chemotaxis & migration
GO Annotations:  Associated to 1 GO processes
GO:0072672 neutrophil extravasation IMP
Immuno Process:  Immune system development
GO Annotations:  Associated to 1 GO processes
GO:0097029 mature conventional dendritic cell differentiation IDA
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 1 GO processes
GO:0019221 cytokine-mediated signaling pathway TAS
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 1 GO processes
GO:0043312 neutrophil degranulation TAS
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Wegener granulomatosis
Synonyms: Wegener's granulomatosis [Disease Ontology: DOID:12132]
Disease Ontology: DOID:12132
OMIM: 608710
Orphanet: ORPHA900

References

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1. Epinette C, Croix C, Jaquillard L, Marchand-Adam S, Kellenberger C, Lalmanach G, Cadene M, Viaud-Massuard MC, Gauthier F, Korkmaz B. (2012) A selective reversible azapeptide inhibitor of human neutrophil proteinase 3 derived from a high affinity FRET substrate. Biochem Pharmacol, 83 (6): 788-96. [PMID:22209715]

2. Fujinaga M, Chernaia MM, Halenbeck R, Koths K, James MN. (1996) The crystal structure of PR3, a neutrophil serine proteinase antigen of Wegener's granulomatosis antibodies. J Mol Biol, 261 (2): 267-78. [PMID:8757293]

3. Guarino C, Gruba N, Grzywa R, Dyguda-Kazimierowicz E, Hamon Y, Łȩgowska M, Skoreński M, Dallet-Choisy S, Marchand-Adam S, Kellenberger C et al.. (2018) Exploiting the S4-S5 Specificity of Human Neutrophil Proteinase 3 to Improve the Potency of Peptidyl Di(chlorophenyl)-phosphonate Ester Inhibitors: A Kinetic and Molecular Modeling Analysis. J Med Chem, 61 (5): 1858-1870. [PMID:29442501]

4. Korkmaz B, Lesner A, Guarino C, Wysocka M, Kellenberger C, Watier H, Specks U, Gauthier F, Jenne DE. (2016) Inhibitors and Antibody Fragments as Potential Anti-Inflammatory Therapeutics Targeting Neutrophil Proteinase 3 in Human Disease. Pharmacol Rev, 68 (3): 603-30. [PMID:27329045]

5. Santana AB, Lucas SD, Gonçalves LM, Correia HF, Cardote TA, Guedes RC, Iley J, Moreira R. (2012) N-Acyl and N-sulfonyloxazolidine-2,4-diones are pseudo-irreversible inhibitors of serine proteases. Bioorg Med Chem Lett, 22 (12): 3993-7. [PMID:22595175]

How to cite this page

S1: Chymotrypsin: proteinase 3. Last modified on 27/02/2018. Accessed on 20/04/2021. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=2401.