PRTN3

Summary

PRTN3 (proteinase 3, HGNC:9495) is a protein-coding gene on chromosome 19p13.3, encoding Myeloblastin (P24158). Serine protease that degrades elastin, fibronectin, laminin, vitronectin, and collagen types I, III, and IV (in vitro).

Enables enzyme binding activity; serine-type endopeptidase activity; and signaling receptor binding activity. Involved in several processes, including mature conventional dendritic cell differentiation; neutrophil extravasation; and positive regulation of GTPase activity. Located in azurophil granule lumen; cytosol; and plasma membrane raft.

Source: NCBI Gene 5657 — RefSeq curated summary.

At a glance

• GWAS associations: 13
• Clinical variants (ClinVar): 50 total — 1 pathogenic
• Phenotypes (HPO): 80
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002777

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9495
Approved symbol	PRTN3
Name	proteinase 3
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	PR-3, ACPA, C-ANCA, AGP7, MBT, P29
Ensembl gene	ENSG00000196415
Ensembl biotype	protein_coding
OMIM	177020
Entrez	5657

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000234347, ENST00000544537

RefSeq mRNA: 1 — MANE Select: NM_002777 NM_002777

CCDS: CCDS32860

Canonical transcript exons

ENST00000234347 — 5 exons

Exon	Start	End
ENSE00001234961	847799	848175
ENSE00001234969	840999	841069
ENSE00001290346	843461	843626
ENSE00003699786	843893	844034
ENSE00003700967	846147	846377

Expression profiles

Bgee: expression breadth ubiquitous, 106 present calls, max score 99.13.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 87.8009 / max 48498.2716, expressed in 128 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
172771	86.1038	88
172775	0.5413	32
172777	0.4603	37
172776	0.2061	23
172774	0.2040	22
172773	0.1157	18
172778	0.1044	20
172772	0.0653	21

Top tissues by expression

126 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
bone marrow	UBERON:0002371	99.13	gold quality
bone marrow cell	CL:0002092	98.68	gold quality
spleen	UBERON:0002106	80.41	gold quality
blood	UBERON:0000178	79.76	gold quality
monocyte	CL:0000576	78.67	gold quality
leukocyte	CL:0000738	75.92	gold quality
granulocyte	CL:0000094	73.66	gold quality
right lung	UBERON:0002167	68.72	gold quality
superior frontal gyrus	UBERON:0002661	68.50	gold quality
right frontal lobe	UBERON:0002810	66.92	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	66.64	gold quality
frontal cortex	UBERON:0001870	64.90	gold quality
Brodmann (1909) area 9	UBERON:0013540	64.43	gold quality
upper lobe of left lung	UBERON:0008952	63.32	gold quality
prefrontal cortex	UBERON:0000451	63.14	gold quality
anterior cingulate cortex	UBERON:0009835	62.98	gold quality
cerebral cortex	UBERON:0000956	61.45	gold quality
putamen	UBERON:0001874	60.68	gold quality
temporal lobe	UBERON:0001871	59.58	gold quality
amygdala	UBERON:0001876	59.41	gold quality
caudate nucleus	UBERON:0001873	59.00	gold quality
placenta	UBERON:0001987	58.49	gold quality
adenohypophysis	UBERON:0002196	57.76	gold quality
right lobe of liver	UBERON:0001114	56.66	gold quality
lung	UBERON:0002048	55.40	gold quality
primary visual cortex	UBERON:0002436	55.33	gold quality
hypothalamus	UBERON:0001898	55.22	gold quality
nucleus accumbens	UBERON:0001882	54.81	gold quality
brain	UBERON:0000955	54.17	gold quality
pituitary gland	UBERON:0000007	53.67	gold quality

Single-cell (SCXA)

Detected in 15 experiment(s), a significant marker in 14.

Experiment	Marker?	Max mean expression
E-GEOD-89232	yes	11698.25
E-CURD-112	yes	8242.62
E-MTAB-9067	yes	5528.89
E-MTAB-7407	yes	4038.51
E-MTAB-10042	yes	3043.49
E-MTAB-8884	yes	2924.05
E-CURD-122	yes	2619.65
E-MTAB-10432	yes	2373.57
E-HCAD-6	yes	1729.85
E-CURD-79	yes	662.09
E-GEOD-100618	yes	476.85
E-HCAD-10	yes	383.15
E-ANND-3	yes	6.31
E-MTAB-9801	yes	5.28
E-CURD-98	no	3011.73

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPG, MYB, MYC, SP1, SPI1

miRNA regulators (miRDB)

5 targeting PRTN3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785

Literature-anchored findings (GeneRIF, showing 40)

• PR-3 is responsible for the extracellular generation of antimicrobial peptides in human neutrophils (PMID:11389039)
• Neutrophil proteinase 3 combined with LPS induces bioactive IL-18 secretion by IFN-gamma-primed gingival epithelial cells via a caspase-1-independent pathway. (PMID:11714826)
• Human proteinase 3 can inhibits LPS-mediated TNF-alpha production through CD14 degradation (PMID:12067299)
• Proteinase 3 plays a role in neutrophil response to inflammation (PMID:12114510)
• A comparison of proforms and mature forms of proteinase 3 in regulating granulopoiesis (PMID:12135665)
• Proteinase-3, a serine protease which mediates doxorubicin-induced apoptosis in the HL-60 leukemia cell line, is downregulated in its doxorubicin-resistant variant (PMID:12140766)
• PR3 expression on the membrane of neutrophils plays a role in the pathophysiology of PR3-ANCA associated vasculitis. (PMID:12191967)
• CD8 T-cell responses to Wilms tumor gene product WT1 and proteinase 3 were observed in patients with acute myeloid leukemia, and not in controls. (PMID:12200377)
• Cleavage of p21waf1 by proteinase-3, a myeloid-specific serine protease, potentiates cell proliferation (PMID:12354776)
• Interferon-alpha, but not the ABL-kinase inhibitor imatinib (STI571), induces expression of myeloblastin in chronic myeloid leukemia (PMID:12393722)
• Protease entry results in direct cleavage of p65 NF-kappaB in the N-terminal region by PR3 and in the C-terminal region by human neutrophil elastase (HNE). PR3 and HNE have specific, fundamental roles in endothelial responses during inflammation. (PMID:12444202)
• Wegener granulomatosis patients have a higher percentage of membrane proteinase 3 expressing neutrophils. Expression is influenced by genetic variance. (PMID:12506139)
• comparison of the action of this enzyme and neutrophil elastase on model substrates (PMID:12538645)
• PR-3 is able to degrade matrigel componenets and denatured collagen and to directly activate secreted but not membrane-bound pro-MMP-2 (PMID:12832446)
• Wegener’s disease results from the breakdown of self tolerance to PR3 [review] (PMID:12894870)
• Interaction of proteinase 3 with CD11b/CD18 (beta2 integrin) on the cell membrane of human neutrophils. (PMID:12960243)
• PR3 originates from two distinct pools, the granular pool mobilized following degranulation or a plasma membrane pool mobilized upon apoptosis. (PMID:14525959)
• the granulocyte protease, PR3, is an exogenous caspase-like molecule that can sidestep intracellular caspase functions at sites of inflammation. (PMID:14675038)
• relation between membrane expression of PR3 on nonprimed neutrophils of patients with Wegener granulomatosis and their susceptibility for relapses (PMID:15331626)
• A potential novel role is described for proteinase 3, which can mediate compartmentalized caspase-3 activation in resting neutrophils, in the context of neutrophil survival mechanisms or terminal differentiation. (PMID:15879139)
• The Proteinase 3 (PR3), the target autoantigen of antineutrophil cytoplasmic antibodies in the autoimmune vasculitis, Wegener’s granulomatosis, is a serine proteinase stored in granules of human neutrophils. (PMID:15916759)
• p21 is one specific target of PR3; PR3-mediated p21 cleavage prevents monocytic differentiation (PMID:15975933)
• This review discusses the expression of proteinase 3 (PR3) in non-hemopoietic cells and its critical involvement in the regulation of immune function through direct modulation of cell signaling, the cytokine network and innate immunity. (PMID:16167885)
• CFU-GM S-phase arrest is mediated by the first four N-terminal amino acids of PR3, andthis activity is dependent on the configuration of the proform providing the correct presentation of this N-terminal motif (PMID:16263417)
• Wegener autoantigen interacts with a “gateway” receptor (PAR-2) on iDCs in vitro triggering their maturation and licenses them for a T helper 1 (Th1)-type response potentially favoring granuloma formation in Wegener granulomatosis. (PMID:16478888)
• FcgammaRIIIb acts as a membrane adaptor for PR3 (PMID:16598772)
• analysis of human neutrophil protease 3 and elastase active site charge distribution (PMID:17088257)
• glycosylation occurs at both sites in native neutrophil PR3 and in wild type recombinant PR3 (rPR3) expressed in HMC-1 cells. glycosylation at Asn-147, but not at Asn-102, is critical for thermal stability, and for optimal hydrolytic activity of PR3. (PMID:17158864)
• PR-3 and NB1 coimmunoprecipitated from and colocalized on the neutrophil plasma membrane. (PMID:17244676)
• The primary granule proteins elastase (ELA2) and proteinase 3 (PR3) both contain the nonapeptide PR1, which can induce cytotoxic T lymphocyte responses against chronic myeloid leukemia (PMID:17412886)
• These results suggest that anti-PR3 Abs prime human monocytic cells to produce cytokines upon stimulation with various bacterial components by up-regulating the TLR and NOD signaling pathway. (PMID:17452051)
• Rheumatoid arthritis phenotype can be subclassified according to the presence or absence of ACPAs. (PMID:17534941)
• In plasma, anti-PR3 antibodies poorly recognized suspended neutrophils, whereas they bound to mPR3 on adherent cells (PMID:17634439)
• proteinase 3 has a critical role in annexin 1 cleavage in activated neutrophils (PMID:17681950)
• PR3 externalization depended on PLSCR1 (PMID:17712045)
• there are a number of (auto)molecules that bind to PR3, some of them even competitive and each binding interaction seems to have specific implications (PMID:17785293)
• Murine and human proteinase 3 complexes have different interaction patterns with peptidic substrates. (PMID:18023421)
• Computational prediction is made of the binding site of PRTN3 to the plasma membrane. (PMID:18076025)
• About half of the patients were found to have CD4+TH1 memory cells responsive to the cPR3(138-169)-peptide; while only a third of the patients had HI-PR3 protein responsive T cells (PMID:18596726)
• The NB1-bound PR3 was active and was cleared from the surface by alpha-1-protease inhibitor (PMID:18854317)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Prtn3	ENSMUSG00000057729
rattus_norvegicus	Prtn3	ENSRNOG00000029814

Paralogs (6): CELA1 (ENSG00000139610), CELA2A (ENSG00000142615), CELA3A (ENSG00000142789), ELANE (ENSG00000197561), CELA2B (ENSG00000215704), CELA3B (ENSG00000219073)

Protein

Protein identifiers

Myeloblastin — P24158 (reviewed: P24158)

Alternative names: AGP7, C-ANCA antigen, Leukocyte proteinase 3, Neutrophil proteinase 4, P29, Wegener autoantigen

All UniProt accessions (2): P24158, U3KPS2

UniProt curated annotations — full annotation on UniProt →

Function. Serine protease that degrades elastin, fibronectin, laminin, vitronectin, and collagen types I, III, and IV (in vitro). By cleaving and activating receptor F2RL1/PAR-2, enhances endothelial cell barrier function and thus vascular integrity during neutrophil transendothelial migration. Plays a role in neutrophil transendothelial migration, probably when associated with CD177. Triggers inflammatory processes in neutrophils by interacting with ADGRG3 upstream of F2RL1/PAR2 activation.

Subunit / interactions. May form dimers. Interacts with CD177; the interaction tethers PRTN3 to the cell surface; the interaction is direct. Interacts with SERPINB1. Interacts with ADGRG3.

Subcellular location. Cytoplasmic granule. Secreted. Cell membrane. Membrane raft.

Tissue specificity. Expressed in polymorphonuclear leukocytes (at protein level). Expressed in neutrophils (at protein level). Expressed in differentiating neutrophils.

Disease relevance. Is the major autoantigen in anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (Wegener’s granulomatosis). This complex, systemic disease is characterized by granulomatous inflammation with necrotizing lesions in the respiratory tract, glomerulonephritis, vasculitis, and anti-neutrophil cytoplasmic autoantibodies detected in patient sera. PRTN3 causes emphysema when administered by tracheal insufflation to hamsters.

Activity regulation. Inhibited by phenylmethanesulfonyl fluoride (PMSF) and diisopropyl fluorophosphate (DFP).

Induction. Induced during CSF3/G-CSF-mediated neutrophil differentiation.

Similarity. Belongs to the peptidase S1 family. Elastase subfamily.

RefSeq proteins (1): NP_002768* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001254	Trypsin_dom	Domain
IPR001314	Peptidase_S1A	Family
IPR009003	Peptidase_S1_PA	Homologous_superfamily
IPR018114	TRYPSIN_HIS	Active_site
IPR033116	TRYPSIN_SER	Active_site
IPR043504
IPR050850	Peptidase_S1_Elastase_sf	Family

Pfam: PF00089

Enzyme classification (BRENDA):

• EC 3.4.21.76 — Myeloblastin (BRENDA: 8 organisms, 261 substrates, 173 inhibitors, 68 Km, 51 kcat entries)

Substrate kinetics (BRENDA)

70 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
MEOSUC-AAPV-4-NITROANILIDE	1.1–1.2	2
MEOSUC-AIPM-4-NITROANILIDE	0.61–1.5	2
SUC-AAPV-4-NITROANILIDE	2.5–3.7	2
2-AMINOBENZOYL-TYR-TYR-AMINOBUTYL-(5-AMINO-2-NIT	0.0174	1
2-AMINOBENZOYL-TYR-TYR-AMINOBUTYL-(5-AMINO-2-NIT	0.0314	1
2-AMINOBENZOYL-TYR-TYR-AMINOBUTYL-ASN-GLU-PRO-TY	0.0032	1
2-AMINOBENZOYL-VADCADQ-EDDNP	6.5	1
2-AMINOBENZOYL-VADCAQ-EDDNP	12.3	1
2-AMINOBENZOYL-VAL-ALA-ASP-CYS-ALA-GLN-N-(2,4-DI	0.0123	1
2-AMINOBENZOYL-VAL-ALA-ASP-CYS-ARG-ASP-ARG-GLN-N	0.0033	1
2-AMINOBENZOYL-VAL-ALA-ASP-NVA-ALA-ASP-TYR-GLN-N	0.0011	1
ABZ-TYR-TYR-ABU-(5-AMINO-2-NITROBENZAMIDE)	0.0314	1
ABZ-TYR-TYR-ABU-(5-AMINO-2-NITROBENZOYL)-ALA-NH2	0.1731	1
ABZ-TYR-TYR-ABU-(5-AMINO-2-NITROBENZOYL)-ARG-NH2	0.0642	1
ABZ-TYR-TYR-ABU-(5-AMINO-2-NITROBENZOYL)-ASN-NH2	0.0251	1

UniProt features (47 total): strand 17, sequence conflict 8, disulfide bond 4, helix 4, sequence variant 3, active site 3, propeptide 2, glycosylation site 2, signal peptide 1, chain 1, turn 1, domain 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
9IGO	X-RAY DIFFRACTION	1.5
1FUJ	X-RAY DIFFRACTION	2.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P24158-F1	90.06	0.78

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (3): 71 (charge relay system); 118 (charge relay system); 203 (charge relay system)

Disulfide bonds (4): 56–72, 152–209, 182–188, 199–224

Glycosylation sites (2): 129, 174

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-449836	Other interleukin signaling
R-HSA-6798695	Neutrophil degranulation
R-HSA-6803157	Antimicrobial peptides
R-HSA-9769739	Regulation of clotting cascade
R-HSA-140875

MSigDB gene sets: 363 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_UP, GOBP_MYELOID_CELL_DIFFERENTIATION, VERHAAK_AML_WITH_NPM1_MUTATED_DN, GOBP_DENDRITIC_CELL_DIFFERENTIATION, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, GOBP_MYELOID_LEUKOCYTE_MIGRATION, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOCC_SECRETORY_GRANULE, MATTIOLI_MGUS_VS_PCL, GOBP_REGULATION_OF_GTPASE_ACTIVITY, GOBP_NEGATIVE_REGULATION_OF_ENDOCYTOSIS, GOBP_CELLULAR_COMPONENT_MAINTENANCE, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_MYELOID_LEUKOCYTE_DIFFERENTIATION

GO Biological Process (10): proteolysis (GO:0006508), membrane protein ectodomain proteolysis (GO:0006509), positive regulation of cell population proliferation (GO:0008284), antimicrobial humoral response (GO:0019730), collagen catabolic process (GO:0030574), positive regulation of GTPase activity (GO:0043547), cell-cell junction maintenance (GO:0045217), negative regulation of phagocytosis (GO:0050765), neutrophil extravasation (GO:0072672), mature conventional dendritic cell differentiation (GO:0097029)

GO Molecular Function (7): serine-type endopeptidase activity (GO:0004252), signaling receptor binding (GO:0005102), serine-type peptidase activity (GO:0008236), enzyme binding (GO:0019899), protein binding (GO:0005515), peptidase activity (GO:0008233), hydrolase activity (GO:0016787)

GO Cellular Component (10): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), cytosol (GO:0005829), plasma membrane (GO:0005886), azurophil granule lumen (GO:0035578), plasma membrane raft (GO:0044853), extracellular exosome (GO:0070062), membrane (GO:0016020), extracellular matrix (GO:0031012), membrane raft (GO:0045121)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Innate Immune System	2
Signaling by Interleukins	1
Coagulation pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
protein binding	2
protein metabolic process	1
membrane protein proteolysis	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
humoral immune response	1
defense response to symbiont	1
catabolic process	1
collagen metabolic process	1
GTPase activity	1
regulation of GTPase activity	1
positive regulation of hydrolase activity	1
cell junction maintenance	1
cell-cell junction organization	1
phagocytosis	1
negative regulation of endocytosis	1
regulation of phagocytosis	1
cellular extravasation	1
neutrophil migration	1
myeloid leukocyte differentiation	1
dendritic cell differentiation	1
endopeptidase activity	1
serine-type peptidase activity	1
peptidase activity	1
serine hydrolase activity	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
cytoplasm	1
membrane	1
cell periphery	1
vacuolar lumen	1
secretory granule lumen	1
azurophil granule	1
plasma membrane	1
membrane raft	1
plasma membrane region	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

36 interactions, top by confidence:

A	B	Type	Score
IL32	PRTN3	psi-mi:“MI:0915”(physical association)	0.610
IL32	PRTN3	psi-mi:“MI:0407”(direct interaction)	0.610
IL32	PRTN3	psi-mi:“MI:0570”(protein cleavage)	0.610
C1orf174	AHCYL1	psi-mi:“MI:0914”(association)	0.530
EGFL8	MPO	psi-mi:“MI:0914”(association)	0.530
PRTN3	FBXO21	psi-mi:“MI:0914”(association)	0.530
PRTN3	CFP	psi-mi:“MI:0407”(direct interaction)	0.440
PRTN3	S	psi-mi:“MI:0570”(protein cleavage)	0.440
SMAD3	PRTN3	psi-mi:“MI:0915”(physical association)	0.400
PRTN3	SMAD3	psi-mi:“MI:0915”(physical association)	0.400
PHF21B	KDM1A	psi-mi:“MI:0914”(association)	0.350
PRTN3	CPD	psi-mi:“MI:0914”(association)	0.350
GNG8	POTEF	psi-mi:“MI:0914”(association)	0.350
STK11	A2ML1	psi-mi:“MI:0914”(association)	0.350
PRTN3	GOLIM4	psi-mi:“MI:0914”(association)	0.350
ELOA2	XRCC2	psi-mi:“MI:0914”(association)	0.350
KLK3	PRTN3	psi-mi:“MI:0914”(association)	0.350
CCR1	UBA6	psi-mi:“MI:0914”(association)	0.350
EGFL8	IGLC7	psi-mi:“MI:0914”(association)	0.350
AGPAT1	A2ML1	psi-mi:“MI:0914”(association)	0.350
RHBDD1	A2ML1	psi-mi:“MI:0914”(association)	0.350
KLK10	IGLL5	psi-mi:“MI:0914”(association)	0.350
PRTN3	MANBA	psi-mi:“MI:0914”(association)	0.350
ISX	GAPDHS	psi-mi:“MI:0914”(association)	0.350
TMEM69	ACOX3	psi-mi:“MI:0914”(association)	0.350
LRRC17	ZZEF1	psi-mi:“MI:0914”(association)	0.350
SMIM8	HP	psi-mi:“MI:0914”(association)	0.350
CYP3A43	HP	psi-mi:“MI:0914”(association)	0.350
DCK	KLK3	psi-mi:“MI:0914”(association)	0.350

BioGRID (86): PRTN3 (Affinity Capture-MS), ITGAM (Affinity Capture-Western), PRTN3 (Affinity Capture-MS), PRTN3 (Affinity Capture-MS), PRTN3 (Affinity Capture-MS), PRTN3 (Affinity Capture-MS), PRTN3 (Affinity Capture-MS), BIRC2 (Affinity Capture-MS), SPCS1 (Affinity Capture-MS), PRTN3 (Affinity Capture-MS), FBXO21 (Affinity Capture-MS), XIAP (Affinity Capture-MS), SPIN4 (Affinity Capture-MS), SERPINB1 (Affinity Capture-MS), GOLIM4 (Affinity Capture-MS)

ESM2 similar proteins: A7WPL7, O43240, O46683, O60259, O88780, P07288, P09582, P09650, P10144, P15944, P19236, P20151, P20718, P21842, P23946, P24158, P33619, P49862, P50341, P50342, P51124, P52195, P56435, P79204, P80219, P83748, Q03238, Q07276, Q14B24, Q28773, Q61096, Q61955, Q6DT45, Q6IE59, Q6UWY2, Q76B45, Q7JIG6, Q92876, Q9BQR3, Q9BZJ3

Diamond homologs: A7WPL7, O35164, O35205, O46683, O60259, O88780, P00746, P00752, P00760, P00761, P00762, P00763, P00764, P00770, P00772, P00773, P04187, P06870, P06871, P07146, P07288, P08311, P08426, P08882, P08883, P08884, P09582, P09650, P10144, P11032, P11033, P11034, P12323, P12544, P12788, P13366, P15119, P16049, P17977, P18291

SIGNOR signaling

16 interactions.

A	Effect	B	Mechanism
PRTN3	“up-regulates activity”	Pr3-ANCA	binding
PRTN3	“up-regulates activity”	AGT	cleavage
PRTN3	“up-regulates activity”	F2R	cleavage
PRTN3	“down-regulates activity”	F2R	cleavage
PRTN3	“down-regulates activity”	F2RL1	cleavage

Disease & clinical

Clinical variants and AI predictions

ClinVar

50 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	38
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
252977	GRCh37/hg19 19p13.3(chr19:260912-1163934)x3	Pathogenic

SpliceAI

815 predictions. Top by Δscore:

Variant	Effect	Δscore
19:841067:GCG:G	donor_gain	1.0000
19:843458:CAG:C	acceptor_loss	1.0000
19:843459:A:G	acceptor_loss	1.0000
19:843622:GACAT:G	donor_gain	1.0000
19:843627:G:GG	donor_gain	1.0000
19:843891:A:AG	acceptor_gain	1.0000
19:843892:G:GA	acceptor_gain	1.0000
19:844017:G:GT	donor_gain	1.0000
19:844031:CCAG:C	donor_loss	1.0000
19:844032:CAGGT:C	donor_loss	1.0000
19:844033:AGGT:A	donor_loss	1.0000
19:844034:GGT:G	donor_loss	1.0000
19:844035:GTGG:G	donor_loss	1.0000
19:844036:T:A	donor_loss	1.0000
19:846145:A:AG	acceptor_gain	1.0000
19:846146:G:GG	acceptor_gain	1.0000
19:846373:GCTTC:G	donor_gain	1.0000
19:846374:CTTC:C	donor_gain	1.0000
19:846375:TTC:T	donor_gain	1.0000
19:846376:TC:T	donor_gain	1.0000
19:846377:CGTA:C	donor_loss	1.0000
19:846378:G:GA	donor_loss	1.0000
19:846378:G:GG	donor_gain	1.0000
19:841065:GAGCG:G	donor_gain	0.9900
19:841070:G:GA	donor_loss	0.9900
19:841070:G:GG	donor_gain	0.9900
19:841071:T:G	donor_loss	0.9900
19:841074:G:GG	donor_gain	0.9900
19:843459:A:AG	acceptor_gain	0.9900
19:843459:AGGT:A	acceptor_gain	0.9900

AlphaMissense

1653 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:846248:G:C	W157C	0.998
19:846248:G:T	W157C	0.998
19:844018:A:T	D118V	0.993
19:846231:T:A	C152S	0.993
19:846232:G:C	C152S	0.993
19:847924:G:C	W242C	0.993
19:847924:G:T	W242C	0.993
19:847803:A:T	D202V	0.992
19:846233:C:G	C152W	0.991
19:844018:A:C	D118A	0.990
19:847803:A:C	D202A	0.990
19:847809:G:T	G204V	0.990
19:843565:T:A	C56S	0.989
19:843566:G:C	C56S	0.989
19:844018:A:G	D118G	0.989
19:846246:T:A	W157R	0.989
19:846246:T:C	W157R	0.989
19:846249:G:T	G158C	0.989
19:847895:T:C	F233L	0.989
19:847897:C:A	F233L	0.989
19:847897:C:G	F233L	0.989
19:843566:G:A	C56Y	0.988
19:843578:T:C	L60S	0.988
19:844024:T:C	L120P	0.988
19:846231:T:C	C152R	0.988
19:843615:C:G	C72W	0.987
19:844017:G:C	D118H	0.987
19:847808:G:T	G204C	0.987
19:843592:T:C	F65L	0.986
19:843594:C:A	F65L	0.986

dbSNP variants (sampled 300 via entrez): RS1000024445 (19:841279 C>T), RS1001347644 (19:844276 T>C), RS1001619269 (19:839741 G>A), RS1001960501 (19:843436 T>C), RS1002029059 (19:839586 G>A), RS1002386568 (19:848056 G>A,C), RS1002426666 (19:847101 T>C), RS1003458614 (19:845104 C>T), RS1003489905 (19:844687 G>A), RS1003563451 (19:841018 C>T), RS1004064538 (19:845207 C>G), RS1004246633 (19:846434 C>T), RS1004500694 (19:848337 C>G), RS1004554790 (19:848580 G>A,T), RS1004797319 (19:840053 C>G,T)

Disease associations

OMIM: gene MIM:177020 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

80 total (30 of 80 shown, HPO-id order):

HPO	Term
HP:0000024	Prostatitis
HP:0000071	Ureteral stenosis
HP:0000083	Renal insufficiency
HP:0000093	Proteinuria
HP:0000099	Glomerulonephritis
HP:0000126	Hydronephrosis
HP:0000163	Abnormal oral cavity morphology
HP:0000246	Sinusitis
HP:0000366	Abnormality of the nose
HP:0000388	Otitis media
HP:0000389	Chronic otitis media
HP:0000407	Sensorineural hearing impairment
HP:0000421	Epistaxis
HP:0000488	Retinopathy
HP:0000491	Keratitis
HP:0000505	Visual impairment
HP:0000520	Proptosis
HP:0000579	Nasolacrimal duct obstruction
HP:0000763	Sensory neuropathy
HP:0000790	Hematuria
HP:0000822	Hypertension
HP:0000864	Abnormality of the hypothalamus-pituitary axis
HP:0000873	Diabetes insipidus
HP:0000979	Purpura
HP:0000988	Skin rash
HP:0001250	Seizure
HP:0001287	Meningitis
HP:0001369	Arthritis
HP:0001607	Subglottic stenosis
HP:0001681	Angina pectoris

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST003976_1	Antineutrophil cytoplasmic antibody-associated vasculitis	9.000000e-11
GCST004609_90	Monocyte percentage of white cells	6.000000e-09
GCST004618_44	White blood cell count (basophil)	6.000000e-13
GCST004631_8	Basophil percentage of white cells	7.000000e-14
GCST004634_54	Basophil percentage of granulocytes	1.000000e-11
GCST006585_2775	Blood protein levels	5.000000e-08
GCST006585_946	Blood protein levels	3.000000e-26
GCST010396_23	Gut microbiota (bacterial taxa, hurdle binary method)	6.000000e-07
GCST010396_34	Gut microbiota (bacterial taxa, hurdle binary method)	7.000000e-06
GCST90002379_190	Basophil count	2.000000e-32
GCST90002380_7	Basophil percentage of white cells	2.000000e-37
GCST90002393_626	Monocyte count	1.000000e-25
GCST90002394_428	Monocyte percentage of white cells	2.000000e-26

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0007989	monocyte percentage of leukocytes
EFO:0005090	basophil count
EFO:0007992	basophil percentage of leukocytes
EFO:0007995	basophil percentage of granulocytes
EFO:0007874	gut microbiome measurement
EFO:0005091	monocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3900 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,769 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL76688	SIVELESTAT	3	1,769

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — S1: Chymotrypsin

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
compound 11 [PMID: 29442501]	Inhibition	8.27	pKi
compound 4g [PMID: 22595175]	Inhibition	5.85	pIC50
azapro-3	Inhibition	5.82	pKi

ChEMBL bioactivities

35 potent at pChembl≥5 of 44 total, top 35 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.27	Ki	5.4	nM	CHEMBL4071346
8.21	Ki	6.1	nM	CHEMBL4560512
8.15	Ki	7	nM	CHEMBL4557877
8.01	Ki	9.8	nM	CHEMBL4528256
7.77	Ki	17	nM	CHEMBL4455694
7.68	Ki	21	nM	CHEMBL4085013
7.64	Ki	23	nM	CHEMBL4589744
7.29	Ki	51	nM	CHEMBL4470455
6.66	IC50	220	nM	CHEMBL3398148
6.61	Ki	245	nM	CHEMBL4469546
6.51	IC50	310	nM	CHEMBL3398164
6.47	IC50	340	nM	SIVELESTAT
6.44	IC50	360	nM	CHEMBL3398145
6.43	IC50	367	nM	CHEMBL4112323
6.33	IC50	470	nM	CHEMBL3398143
6.28	IC50	530	nM	CHEMBL3359765
6.28	IC50	530	nM	CHEMBL3398153
6.21	IC50	610	nM	CHEMBL3398151
6.21	IC50	610	nM	CHEMBL3398165
5.96	IC50	1090	nM	CHEMBL3398144
5.85	IC50	1400	nM	CHEMBL2029556
5.82	Ki	1500	nM	CHEMBL3359765
5.76	IC50	1730	nM	CHEMBL3398150
5.72	IC50	1910	nM	CHEMBL3359765
5.69	IC50	2050	nM	CHEMBL3398154
5.69	IC50	2050	nM	CHEMBL3398147
5.64	IC50	2310	nM	CHEMBL3398146
5.62	IC50	2370	nM	CHEMBL3398152
5.60	IC50	2500	nM	CHEMBL3398149
5.52	IC50	3020	nM	CHEMBL3398155
5.44	Ki	3600	nM	CHEMBL4102959
5.41	IC50	3910	nM	CHEMBL3398156
5.31	IC50	4940	nM	CHEMBL3398160
5.30	IC50	5000	nM	CHEMBL2029559
5.23	IC50	5900	nM	CHEMBL3093815

PubChem BioAssay actives

34 with measured affinity, of 207 total; 32 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid	1479557: Inhibition of human PR3 using ABZ-VADnVADYQ-EDDnp as substrate by FRET assay	ki	0.0054	uM
2-[(1R,4S,7S,13S,19S,22S,28S,31R,34S,40S,43S,49S)-49-(2-amino-2-oxoethyl)-4-[(2S)-butan-2-yl]-22-(hydroxymethyl)-19,28-bis[(4-hydroxyphenyl)methyl]-3,6,12,18,21,24,27,30,33,36,39,42,48,51-tetradecaoxo-34-[(4-phenylphenyl)methyl]-25-propyl-53,54-dithia-2,5,11,17,20,23,26,29,32,35,38,41,47,50-tetradecazapentacyclo[29.20.4.07,11.013,17.043,47]pentapentacontan-40-yl]acetamide	1511311: Inhibition of purified human proteinase 3 using MeOSuc-AAPV-MCA as substrate by fluorescence based assay	ki	0.0061	uM
2-[(1R,4S,7S,13S,19S,22S,28S,31R,34S,40S,43S,49S)-49-(2-amino-2-oxoethyl)-4-[(2S)-butan-2-yl]-25-ethyl-34-[(1R)-1-hydroxyethyl]-22-(hydroxymethyl)-19,28-bis[(4-hydroxyphenyl)methyl]-3,6,12,18,21,24,27,30,33,36,39,42,48,51-tetradecaoxo-53,54-dithia-2,5,11,17,20,23,26,29,32,35,38,41,47,50-tetradecazapentacyclo[29.20.4.07,11.013,17.043,47]pentapentacontan-40-yl]acetamide	1511311: Inhibition of purified human proteinase 3 using MeOSuc-AAPV-MCA as substrate by fluorescence based assay	ki	0.0070	uM
2-[(1R,4S,7S,13S,19S,22S,28S,31R,34S,40S,43S,49S)-49-(2-amino-2-oxoethyl)-4,19-bis[(2S)-butan-2-yl]-28,34-bis[(1R)-1-hydroxyethyl]-22-(hydroxymethyl)-3,6,12,18,21,24,27,30,33,36,39,42,48,51-tetradecaoxo-25-propyl-53,54-dithia-2,5,11,17,20,23,26,29,32,35,38,41,47,50-tetradecazapentacyclo[29.20.4.07,11.013,17.043,47]pentapentacontan-40-yl]acetamide	1511311: Inhibition of purified human proteinase 3 using MeOSuc-AAPV-MCA as substrate by fluorescence based assay	ki	0.0098	uM
2-[(1R,4S,7S,13S,19S,22S,28S,31R,34S,40S,43S,49S)-49-(2-amino-2-oxoethyl)-4-[(2S)-butan-2-yl]-25-ethyl-22-(hydroxymethyl)-19,28-bis[(4-hydroxyphenyl)methyl]-3,6,12,18,21,24,27,30,33,36,39,42,48,51-tetradecaoxo-34-[(4-phenylphenyl)methyl]-53,54-dithia-2,5,11,17,20,23,26,29,32,35,38,41,47,50-tetradecazapentacyclo[29.20.4.07,11.013,17.043,47]pentapentacontan-40-yl]acetamide	1511311: Inhibition of purified human proteinase 3 using MeOSuc-AAPV-MCA as substrate by fluorescence based assay	ki	0.0170	uM
(3S)-3-[[(2S)-2-[[(2S)-1-[5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoyl]pyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylethylamino]-4-oxobutanoic acid	1479557: Inhibition of human PR3 using ABZ-VADnVADYQ-EDDnp as substrate by FRET assay	ki	0.0210	uM
2-[(1R,4S,7S,13S,19S,22S,28S,31R,34S,40S,43S,49S)-49-(2-amino-2-oxoethyl)-4,19-bis[(2S)-butan-2-yl]-25-ethyl-28,34-bis[(1R)-1-hydroxyethyl]-22-(hydroxymethyl)-3,6,12,18,21,24,27,30,33,36,39,42,48,51-tetradecaoxo-53,54-dithia-2,5,11,17,20,23,26,29,32,35,38,41,47,50-tetradecazapentacyclo[29.20.4.07,11.013,17.043,47]pentapentacontan-40-yl]acetamide	1511311: Inhibition of purified human proteinase 3 using MeOSuc-AAPV-MCA as substrate by fluorescence based assay	ki	0.0230	uM
2-[(1R,4S,7S,13S,19S,22S,25S,28S,31R,34S,40S,43S,49S)-49-(2-amino-2-oxoethyl)-4,19-bis[(2S)-butan-2-yl]-28,34-bis[(1R)-1-hydroxyethyl]-22-(hydroxymethyl)-25-methyl-3,6,12,18,21,24,27,30,33,36,39,42,48,51-tetradecaoxo-53,54-dithia-2,5,11,17,20,23,26,29,32,35,38,41,47,50-tetradecazapentacyclo[29.20.4.07,11.013,17.043,47]pentapentacontan-40-yl]acetamide	1511311: Inhibition of purified human proteinase 3 using MeOSuc-AAPV-MCA as substrate by fluorescence based assay	ki	0.0510	uM
[4-[[2-[(Z)-N-hydroxy-C-methylcarbonimidoyl]phenyl]sulfamoyl]phenyl] 2,2-dimethylpropanoate	1191722: Inhibition of Pr3 (unknown origin) using t-butyloxycarbonyl-Ala-Ala-Nva-thiobenzyl ester as substrate measured for 180 mins by spectrophotometry	ic50	0.2200	uM
2-[(1R,4S,7S,13S,19S,22S,25S,28S,31R,34S,40S,43S,49S)-49-(2-amino-2-oxoethyl)-4,19-bis[(2S)-butan-2-yl]-28,34-bis[(1R)-1-hydroxyethyl]-22-(hydroxymethyl)-3,6,12,18,21,24,27,30,33,36,39,42,48,51-tetradecaoxo-25-propan-2-yl-53,54-dithia-2,5,11,17,20,23,26,29,32,35,38,41,47,50-tetradecazapentacyclo[29.20.4.07,11.013,17.043,47]pentapentacontan-40-yl]acetamide	1511311: Inhibition of purified human proteinase 3 using MeOSuc-AAPV-MCA as substrate by fluorescence based assay	ki	0.2450	uM
[4-[[2-(2-hydroxyethylcarbamoyl)phenyl]sulfamoyl]phenyl] 2,2-dimethylpropanoate	1191722: Inhibition of Pr3 (unknown origin) using t-butyloxycarbonyl-Ala-Ala-Nva-thiobenzyl ester as substrate measured for 180 mins by spectrophotometry	ic50	0.3100	uM
2-[[2-[[4-(2,2-dimethylpropanoyloxy)phenyl]sulfonylamino]benzoyl]amino]acetic acid	1191722: Inhibition of Pr3 (unknown origin) using t-butyloxycarbonyl-Ala-Ala-Nva-thiobenzyl ester as substrate measured for 180 mins by spectrophotometry	ic50	0.3400	uM
[4-[(2-butanoylphenyl)sulfamoyl]phenyl] 2,2-dimethylpropanoate	1191722: Inhibition of Pr3 (unknown origin) using t-butyloxycarbonyl-Ala-Ala-Nva-thiobenzyl ester as substrate measured for 180 mins by spectrophotometry	ic50	0.3600	uM
[4-[(2-acetylphenyl)sulfamoyl]phenyl] 2,2-dimethylpropanoate	1191722: Inhibition of Pr3 (unknown origin) using t-butyloxycarbonyl-Ala-Ala-Nva-thiobenzyl ester as substrate measured for 180 mins by spectrophotometry	ic50	0.4700	uM
(3S)-3-[[(2R,5S)-5-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(2-aminobenzoyl)amino]-3-methylbutanoyl]amino]propanoyl]amino]-3-carboxypropanoyl]amino]-2-methyl-4-oxooctanoyl]amino]-4-[[(2S)-1-[[(2S)-5-amino-1-[2-(2,4-dinitroanilino)ethylamino]-1,5-dioxopentan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-4-oxobutanoic acid	1170279: Inhibition of human PR3 using keto-D-DY-FRET as substrate after 30 mins by HPLC analysis	ic50	0.5300	uM
[4-[[2-[(Z)-hydroxyiminomethyl]phenyl]sulfamoyl]phenyl] 2,2-dimethylpropanoate	1191722: Inhibition of Pr3 (unknown origin) using t-butyloxycarbonyl-Ala-Ala-Nva-thiobenzyl ester as substrate measured for 180 mins by spectrophotometry	ic50	0.5300	uM
[4-[[2-[(E)-N-methoxy-C-methylcarbonimidoyl]phenyl]sulfamoyl]phenyl] 2,2-dimethylpropanoate	1191722: Inhibition of Pr3 (unknown origin) using t-butyloxycarbonyl-Ala-Ala-Nva-thiobenzyl ester as substrate measured for 180 mins by spectrophotometry	ic50	0.6100	uM
2-hydroxyethyl 2-[[4-(2,2-dimethylpropanoyloxy)phenyl]sulfonylamino]benzoate	1191722: Inhibition of Pr3 (unknown origin) using t-butyloxycarbonyl-Ala-Ala-Nva-thiobenzyl ester as substrate measured for 180 mins by spectrophotometry	ic50	0.6100	uM
[4-[(2-propanoylphenyl)sulfamoyl]phenyl] 2,2-dimethylpropanoate	1191722: Inhibition of Pr3 (unknown origin) using t-butyloxycarbonyl-Ala-Ala-Nva-thiobenzyl ester as substrate measured for 180 mins by spectrophotometry	ic50	1.0900	uM
3-(4-methoxybenzoyl)-5,5-dimethyl-1,3-oxazolidine-2,4-dione	662773: Inhibition of proteinase 3 using N-MeOSuc-Ala-Ala-Pro-Val-p-nitroanilide as substrate after 60 mins	ic50	1.4000	uM
[4-[[2-[(Z)-N-hydroxy-C-propylcarbonimidoyl]phenyl]sulfamoyl]phenyl] 2,2-dimethylpropanoate	1191722: Inhibition of Pr3 (unknown origin) using t-butyloxycarbonyl-Ala-Ala-Nva-thiobenzyl ester as substrate measured for 180 mins by spectrophotometry	ic50	1.7300	uM
[4-[(2-formylphenyl)sulfamoyl]phenyl] 2,2-dimethylpropanoate	1191722: Inhibition of Pr3 (unknown origin) using t-butyloxycarbonyl-Ala-Ala-Nva-thiobenzyl ester as substrate measured for 180 mins by spectrophotometry	ic50	2.0500	uM
methyl 2-[[4-(2,2-dimethylpropanoyloxy)benzoyl]amino]benzoate	1191722: Inhibition of Pr3 (unknown origin) using t-butyloxycarbonyl-Ala-Ala-Nva-thiobenzyl ester as substrate measured for 180 mins by spectrophotometry	ic50	2.0500	uM
[4-[(2-pentanoylphenyl)sulfamoyl]phenyl] 2,2-dimethylpropanoate	1191722: Inhibition of Pr3 (unknown origin) using t-butyloxycarbonyl-Ala-Ala-Nva-thiobenzyl ester as substrate measured for 180 mins by spectrophotometry	ic50	2.3100	uM
[4-[[2-[(Z)-N-methoxy-C-methylcarbonimidoyl]phenyl]sulfamoyl]phenyl] 2,2-dimethylpropanoate	1191722: Inhibition of Pr3 (unknown origin) using t-butyloxycarbonyl-Ala-Ala-Nva-thiobenzyl ester as substrate measured for 180 mins by spectrophotometry	ic50	2.3700	uM
[4-[[2-[(Z)-C-ethyl-N-hydroxycarbonimidoyl]phenyl]sulfamoyl]phenyl] 2,2-dimethylpropanoate	1191722: Inhibition of Pr3 (unknown origin) using t-butyloxycarbonyl-Ala-Ala-Nva-thiobenzyl ester as substrate measured for 180 mins by spectrophotometry	ic50	2.5000	uM
ethyl 2-[[4-(2,2-dimethylpropanoyloxy)benzoyl]amino]benzoate	1191722: Inhibition of Pr3 (unknown origin) using t-butyloxycarbonyl-Ala-Ala-Nva-thiobenzyl ester as substrate measured for 180 mins by spectrophotometry	ic50	3.0200	uM
(3S)-3-[[(2S)-2-[[(2S)-1-acetylpyrrolidine-2-carbonyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylethylamino]-4-oxobutanoic acid	1479557: Inhibition of human PR3 using ABZ-VADnVADYQ-EDDnp as substrate by FRET assay	ki	3.6000	uM
propyl 2-[[4-(2,2-dimethylpropanoyloxy)benzoyl]amino]benzoate	1191722: Inhibition of Pr3 (unknown origin) using t-butyloxycarbonyl-Ala-Ala-Nva-thiobenzyl ester as substrate measured for 180 mins by spectrophotometry	ic50	3.9100	uM
methyl 2-[[4-(3,3,3-trifluoro-2,2-dimethylpropanoyl)oxyphenyl]sulfonylamino]benzoate	1191722: Inhibition of Pr3 (unknown origin) using t-butyloxycarbonyl-Ala-Ala-Nva-thiobenzyl ester as substrate measured for 180 mins by spectrophotometry	ic50	4.9400	uM
3-(4-methoxybenzoyl)-5-phenyl-1,3-oxazolidine-2,4-dione	662773: Inhibition of proteinase 3 using N-MeOSuc-Ala-Ala-Pro-Val-p-nitroanilide as substrate after 60 mins	ic50	5.0000	uM
[6-(1,3-benzothiazol-2-ylsulfanylmethyl)-4-oxopyran-3-yl] 2,2-dimethylpropanoate	1058711: Inhibition of human proteinase 3 using N-MeOSuc-Ala-Ala-Pro-Val-p-nitroanilide as substrate measured for 30 mins by spectrophotometry	ic50	5.9000	uM

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tretinoin	decreases expression, increases reaction, increases expression	3
Benzo(a)pyrene	affects methylation, increases expression	2
sotorasib	affects cotreatment, decreases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
hydroxyhydroquinone	decreases expression, decreases reaction	1
sulforaphane	decreases expression	1
aflatoxin B2	increases methylation	1
4-aminobenzhydrazide	decreases expression, decreases reaction	1
tamibarotene	increases expression	1
pazopanib	increases expression	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
Arsenic Trioxide	decreases expression, increases reaction	1
Acetaminophen	decreases expression	1
Atrazine	increases expression	1
Cisplatin	decreases expression	1
Cocaine	affects reaction, affects binding	1
Cyclophosphamide	decreases expression	1
Iron	decreases expression	1
Methotrexate	decreases expression	1
Minocycline	increases expression	1
Selenium	increases expression	1
Silicon Dioxide	decreases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	decreases expression, increases expression	1
Antibodies, Antineutrophil Cytoplasmic	affects binding, affects reaction	1

ChEMBL screening assays

63 unique, capped per target: 62 binding, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1004879	Binding	Inhibition of proteinase-3 in human U937 cells	Inhibition of the activation of multiple serine proteases with a cathepsin C inhibitor requires sustained exposure to prevent pro-enzyme processing. — J Biol Chem
CHEMBL4365230	ADMET	Stability of the compound in cystic fibrosis patient lung sputum assessed as proteinase 3-mediated compound hydrolysis at 40 uM incubated for 24 mins under dark by SDS-PAGE analysis	Positive Charge Patterning and Hydrophobicity of Membrane-Active Antimicrobial Peptides as Determinants of Activity, Toxicity, and Pharmacokinetic Stability. — J Med Chem

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.