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Information on EC 3.4.21.76 - Myeloblastin and Organism(s) Homo sapiens and UniProt Accession P24158
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3.4.21.76 MyeloblastinSpecify your search results
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- 3.4.21.76
-
ancas
- myeloperoxidase
- elastase
-
antineutrophil
- autoantibody
-
anca-associated
- cathepsin
-
pr3-anca
- polyangiitis
- autoimmune
- granule
- glomerulonephritis
-
mpo-anca
- vasculitides
-
remission
- autoantigens
- anti-pr3
-
perinuclear
-
polymorphonuclear
- cyclophosphamide
-
azurophilic
- gpa
-
crescent
-
anti-mpo
-
anca-positive
- lactoferrin
-
pauci-immune
-
churg-strauss
-
granulomatous
- elafin
-
vasculitic
-
anti-myeloperoxidase
- rituximab
-
small-vessel
-
antibody-associated
-
azurocidin
-
anti-proteinase
-
neutrophil-derived
- polyarteritis
-
antinuclear
-
mpo-anca-associated
-
ethanol-fixed
-
goodpasture
- drug development
- diagnostics
-
chapel
- medicine
- analysis
- nsp4
-
aspartate-specific
-
necrotising
- nodosa
- anti-gbm
-
anti-glomerular
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
Hydrolysis of proteins, including elastin, by preferential cleavage: -Ala-/- > -Val-/-
Synonyms
proteinase 3, proteinase-3, protease 3, prtn3, myeloblastin, neutrophil serine protease, human pr3, neutrophil proteinase 3, human proteinase 3, proteinase3, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
PR3
-
proteinase 3
-
AGP7
-
-
-
-
C-ANCA antigen
-
-
-
-
Leukocyte proteinase 3
-
-
-
-
Leukocyte proteinase 4
-
-
-
-
P29
-
-
-
-
PMNL proteinase
-
-
-
-
PR3
proteinase 3
-
-
Proteinase PR-3
-
-
-
-
Proteinase-3
Wegener's autoantigen
-
-
-
-
Wegener's granulomatosis autoantigen
-
-
-
-
PR3
-
-
-
-
PR3
-
-
Proteinase-3
-
-
-
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
hydrolysis of peptide bond
-
-
-
-
CAS REGISTRY NUMBER
COMMENTARY
128028-50-2
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
2-aminobenzoyl-Gln-Asp-Met-Ala-Val-Val-Gln-Ser-Val-Pro-Gln-N-(2,4-dinitrophenyl)-ethylenediamine + H2O
?
-
-
-
?
2-aminobenzoyl-Gln-Pro-Met-Ala-Val-Val-Gln-Ser-Val-Pro-Gln-N-(2,4-dinitrophenyl)-ethylenediamine + H2O
?
-
-
-
?
2-aminobenzoyl-Tyr-Tyr-aminobutyl-(5-amino-2-nitrobenzoyl)-Gln-NH2 + H2O
?
-
-
-
?
2-aminobenzoyl-Tyr-Tyr-aminobutyl-(5-amino-2-nitrobenzoyl)-NH2 + H2O
?
-
-
-
?
2-aminobenzoyl-Tyr-Tyr-aminobutyl-Asn-Glu-Pro-Tyr(3-NO2)-NH2 + H2O
?
-
-
-
?
2-aminobenzoyl-Val-Ala-Asp-Cys-Ala-Gln-N-(2,4-dinitrophenyl)-ethylenediamine + H2O
?
-
-
-
?
2-aminobenzoyl-Val-Ala-Asp-Cys-Arg-Asp-Arg-Gln-N-(2,4-dinitrophenyl)-ethylenediamine + H2O
?
-
-
-
?
2-aminobenzoyl-Val-Ala-Asp-Nva-Ala-Asp-Tyr-Gln-N-(2,4-dinitrophenyl)-ethylenediamine + H2O
?
-
-
-
?
5-TAMRA-VADnVADYQ-DAP(CF) + H2O
?
a fluorescence resonance energy transfer, FRET, substrate. The reaction is inhibited by antibody MCPR3-7 binding
-
-
?
5-TAMRA-VADnVRDYQ-diaminopropionyl-fluorescein + H2O
?
fluorogenic substrate
-
-
?
Abz-APEEIMDDQ-ethylene diamine 2,4 dinitrophenyl + H2O
?
37°C, pH 7.4, 150 mM NaCl, kcat/KM = 2.5/mM/s
-
-
?
Abz-APEEIMDQQ-ethylene diamine 2,4 dinitrophenyl + H2O
?
37°C, pH 7.4, 150 mM NaCl, kcat/KM = 2/mM/s
-
-
?
Abz-APEEIMDRQ-ethylene diamine 2,4 dinitrophenyl + H2O
?
37°C, pH 7.4, 150 mM NaCl, kcat/KM = 14.6/mM/s
-
-
?
Abz-APEEIMDRY-ethylene diamine 2,4 dinitrophenyl + H2O
?
37°C, pH 7.4, 150 mM NaCl, kcat/KM = lower than 1/mM/s
-
-
?
Abz-APEEIMDRYQ-ethylene diamine 2,4 dinitrophenyl + H2O
?
37°C, pH 7.4, 150 mM NaCl, kcat/KM = 3.2/mM/s
-
-
?
Abz-APEEIMDYQ-ethylene diamine 2,4 dinitrophenyl + H2O
?
37°C, pH 7.4, 150 mM NaCl, kcat/KM = 2.6/mM/s
-
-
?
Abz-APEEIMPRQ-ethylene diamine 2,4 dinitrophenyl + H2O
?
37°C, pH 7.4, 150 mM NaCl, kcat/KM = lower than 1/mM/s
-
-
?
Abz-APEEIMRRQ-ethylene diamine 2,4 dinitrophenyl + H2O
?
37°C, pH 7.4, 150 mM NaCl, kcat/KM = lower than 1/mM/s
-
-
?
Abz-Tyr-Tyr-Abu-ANB-NH2 + H2O
?
a fluorescence resonance energy transfer, FRET, substrate. The reaction is inhibited by antibody MCPR3-7 binding
-
-
?
Abz-VADCADQ-ethylene diamine 2,4 dinitrophenyl + H2O
?
37°C, pH 7.4, 150 mM NaCl, kcat/KM = 614/mM/s
-
-
?
Abz-VADCADRY(NO2) + H2O
?
37°C, pH 7.4, 150 mM NaCl, kcat/KM = 651/mM/s
-
-
?
Abz-VADCADY(NO2) + H2O
?
37°C, pH 7.4, 150 mM NaCl, kcat/KM = 630/mM/s
-
-
?
Abz-VADCAPY(NO2) + H2O
?
37°C, pH 7.4, 150 mM NaCl, kcat/KM = lower than 1/mM/s
-
-
?
Abz-VADCAQ-ethylene diamine 2,4 dinitrophenyl + H2O
?
37°C, pH 7.4, 150 mM NaCl, kcat/KM = 292/mM/s
-
-
?
Abz-VADCARY(NO2) + H2O
?
37°C, pH 7.4, 150 mM NaCl, kcat/KM = 3.8/mM/s
-
-
?
Abz-VADCAY(NO2) + H2O
?
37°C, pH 7.4, 150 mM NaCl, kcat/KM = 10.9/mM/s
-
-
?
Abz-VADCRDRQ-EDDnp + H2O
Abz-VADCR + DRQ-EDDnp
best synthetic substrate
-
-
?
acetyl-Glu(O-benzyl)-Lys(Ac)-Pro(4-O-benzyl)-Nva-7-amido-4-carbamoylmethylcoumarin + H2O
?
-
-
-
?
Ahx-PYFA-4-nitroanilide + H2O
?
the reaction is inhibited by antibody MCPR3-7 binding
-
-
?
Boc-Ala-ONp + H2O
?
the reaction is not inhibited by antibody MCPR3-7 binding
-
-
?
Boc-Ala-Pro-Nva-thiobenzylester + H2O
?
pH 7.5, serine-protease activity of PR3
-
-
?
Boc-Ala-Pro-nVal-SBzl + H2O
?
the reaction is not inhibited by antibody MCPR3-7 binding
-
-
?
For-Ala-Ala-Pro-Abu-SBzl + H2O
?
the reaction is partly inhibited by antibody MCPR3-7 binding
-
-
?
MeO-Suc-Ala-Ala-Pro-Val-4-nitroanilide + H2O
MeO-Suc-Ala-Ala-Pro-Val + 4-nitroaniline
-
-
-
?
MeOSuc-AAPV-4-nitroanilide + H2O
MeOSuc-AAPV + 4-nitroaniline
52 mM NaCl, 0.5% Triton X-100 (w/v), 10% dimethylformamide (v/v), pH 8.0
-
-
?
MeOSuc-AIPM-4-nitroanilide + H2O
MeOSuc-AIPM + 4-nitroaniline
52 mM NaCl, 0.5% Triton X-100 (w/v), 10% dimethylformamide (v/v), pH 8.0
-
-
?
methoxysuccinyl-lysyl-(2-picolinoyl)-Ala-Pro-Val-p-nitroanilide + H2O
?
pH 7.4, 150 mM NaCl
-
-
?
methoxysuccinyl-lysyl-(2-picolinoyl)-Ala-Pro-Val-thiobenzylester + H2O
?
pH 7.4, 150 mM NaCl, 3 mM 4,4-dithiodipyridine
-
-
?
procaspase-3 + H2O
?
37°C
in vitro, purified PR3 cleaves procaspase-3 into an active 22 kDa fragment
-
?
Suc-AAA-4-nitroanilide + H2O
Suc-AAA + 4-nitroaniline
52 mM NaCl, 0.5% Triton X-100 (w/v), 10% dimethylformamide (v/v), pH 8.0, very low activity
-
-
?
Suc-AAPL-4-nitroanilide + H2O
Suc-AAPL + 4-nitroaniline
52 mM NaCl, 0.5% Triton X-100 (w/v), 10% dimethylformamide (v/v), pH 8.0, very low activity
-
-
?
Suc-AAPV-4-nitroanilide + H2O
Suc-AAPV + 4-nitroaniline
52 mM NaCl, 0.5% Triton X-100 (w/v), 10% dimethylformamide (v/v), pH 8.0
-
-
?
surfactant protein D + H2O
?
37°C, pH 7.4
a fragment of about 35000 Da
-
?
(7-methoxycoumarin-4-yl)acetyl-Ala-Ala-Ala-Ala-Lys-Gly-Asp-Dpa-NH2 + H2O
?
-
-
-
?
(7-methoxycoumarin-4-yl)acetyl-Ala-Ala-Pro-Leu-Lys-Gly-Asp-Dpa-NH2 + H2O
?
-
-
-
?
(7-methoxycoumarin-4-yl)acetyl-Ala-Ala-Pro-Val-Lys-Gly-Asp-Dpa-NH2 + H2O
?
-
-
-
?
(7-methoxycoumarin-4-yl)acetyl-Lys(2-picolinoyl)-Tyr-Asp-Ala-Lys-Gly-Asp-Dpa-NH2 + H2O
?
-
-
-
?
(7-methoxycoumarin-4-yl)acetyl-Lys(2-picolinoyl)-Tyr-Asp-Ile-Lys-Gly-Asp-Dpa-NH2 + H2O
?
-
-
-
?
(7-methoxycoumarin-4-yl)acetyl-Lys(2-picolinoyl)-Val-Glu-Ala-Lys-Gly-Asp-Dpa-NH2 + H2O
?
-
-
-
?
2-aminobenzoyl-APEEIM(o)DRQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O
?
-
-
-
?
2-aminobenzoyl-APEEIMDRQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O
?
-
-
-
?
2-aminobenzoyl-APEEIMMDRQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O
?
-
-
-
?
2-aminobenzoyl-EAIPMSIPPEVKFNKQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O
?
-
-
-
?
2-aminobenzoyl-EAIPMSIPQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O
?
-
-
-
?
2-aminobenzoyl-GIATFCM(o)LM(o)PEQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O
?
-
-
-
?
2-aminobenzoyl-GIATFCMLMPEQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O
?
-
-
-
?
2-aminobenzoyl-IVSARMAPEEIIMDRQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O
?
-
-
-
?
2-aminobenzoyl-MMRCAQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O
?
-
-
-
?
2-aminobenzoyl-TFCM(o)LEQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O
?
-
-
-
?
2-aminobenzoyl-TFCMLEQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O
?
-
-
-
?
2-aminobenzoyl-VADCAQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O
?
-
-
-
?
2-aminobenzoyl-VAECCQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O
?
-
-
-
?
2-aminobenzoyl-VSARQ-N-(2,4-dinitrophenyl)ethylenediamine + H2O
?
-
-
-
?
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzamide) + H2O
Abz-Tyr-Tyr-Abu + 5-amino-2-nitrobenzamide
-
-
-
-
?
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Ala-NH2 + H2O
Abz-Tyr-Tyr-Abu + (5-amino-2-nitrobenzoyl)-Ala-NH2
-
-
-
-
?
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Arg-NH2 + H2O
Abz-Tyr-Tyr-Abu + (5-amino-2-nitrobenzoyl)-Arg-NH2
-
-
-
-
?
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Asn-NH2 + H2O
Abz-Tyr-Tyr-Abu + (5-amino-2-nitrobenzoyl)-Asn-NH2
-
-
-
-
?
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Asp-NH2 + H2O
Abz-Tyr-Tyr-Abu + (5-amino-2-nitrobenzoyl)-Asp-NH2
-
-
-
-
?
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Gln-NH2 + H2O
Abz-Tyr-Tyr-Abu + (5-amino-2-nitrobenzoyl)-Gln-NH2
-
is hydrolyzed by PR3 within 20 min, yielding (5-amino-2-nitrobenzoyl)-Gln-NH2 and Abz-Tyr-Tyr-Abu fragments with retention times of 10.4 and 12.3 min, respectively
-
-
?
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Glu-NH2 + H2O
Abz-Tyr-Tyr-Abu + (5-amino-2-nitrobenzoyl)-Glu-NH2
-
-
-
-
?
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Gly-NH2 + H2O
Abz-Tyr-Tyr-Abu + (5-amino-2-nitrobenzoyl)-Gly-NH2
-
-
-
-
?
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-His-NH2 + H2O
Abz-Tyr-Tyr-Abu + (5-amino-2-nitrobenzoyl)-His-NH2
-
-
-
-
?
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Ile-NH2 + H2O
Abz-Tyr-Tyr-Abu + (5-amino-2-nitrobenzoyl)-Ile-NH2
-
-
-
-
?
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Leu-NH2 + H2O
Abz-Tyr-Tyr-Abu + (5-amino-2-nitrobenzoyl)-Leu-NH2
-
-
-
-
?
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Lys-NH2 + H2O
Abz-Tyr-Tyr-Abu + (5-amino-2-nitrobenzoyl)-Lys-NH2
-
-
-
-
?
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Phe-NH2 + H2O
Abz-Tyr-Tyr-Abu + (5-amino-2-nitrobenzoyl)-Phe-NH2
-
-
-
-
?
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Pro-NH2 + H2O
Abz-Tyr-Tyr-Abu + (5-amino-2-nitrobenzoyl)-Pro-NH2
-
-
-
-
?
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Ser-NH2 + H2O
Abz-Tyr-Tyr-Abu + (5-amino-2-nitrobenzoyl)-Ser-NH2
-
-
-
-
?
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Thr-NH2 + H2O
Abz-Tyr-Tyr-Abu + (5-amino-2-nitrobenzoyl)-Thr-NH2
-
-
-
-
?
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Trp-NH2 + H2O
Abz-Tyr-Tyr-Abu + (5-amino-2-nitrobenzoyl)-Trp-NH2
-
-
-
-
?
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Tyr-NH2 + H2O
Abz-Tyr-Tyr-Abu + (5-amino-2-nitrobenzoyl)-Tyr-NH2
-
-
-
-
?
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Val-NH2 + H2O
Abz-Tyr-Tyr-Abu + (5-amino-2-nitrobenzoyl)-Val-NH2
-
-
-
-
?
Abz-Val-Ala-Asp-Nvl-Ala-Asp-Arg-Gln-N-(2,4-dinitrophenyl)ethylenediamine + H2O
?
-
-
-
-
?
annexin 1 + H2O
?
-
proteinase 3 is the main enzyme responsible for cleavage in the N terminus region of the protein
-
-
?
Collagen type IV + H2O
Hydrolyzed collagen type IV
-
no or minimal activity against interstitial collagens type I and III
-
-
?
endothelial cell protein C receptor + H2O
?
-
PR3 produces multiple cleavages, with early products including 20 kDa N-terminal and C-terminal (after Lys176) fragments. High affinity interaction between PR3 and the endothelial cell protein C receptor (KD of 18.5102 nanomol)
-
-
?
kininogen + H2O
?
-
PR3 incubated with kininogen, or a synthetic peptide derived from kininogen, induces breakdown and release of a novel tridecapeptide termed PR3-kinin, NH2-MKRPPGFSPFRSS-COOH, consisting of bradykinin with two additional amino acids on each terminus. The reaction is specific. PR3-kinin binds to and activates human kinin B1 receptors, but does not bind to B2 receptors, expressed by transfected HEK293 cells in vitro. PR3-kinin is processed to bradykinin and des-Arg-bradykinin by plasma kallikrein. PR3 proteolyzes kininogen in a dose-dependent and specific manner. PR3 in neutrophil extracts induces kininogen proteolysis and induces release of bradykinin-like peptides from kininogen
-
-
?
N-Boc-3-[2-(2'-imidazolyl)benzoxazol-5-yl]-Ala-Tyr-Tyr-Abu-(5-amino-2-nitrobenzamide) + H2O
?
-
-
-
-
?
N-Boc-3-[2-(2'-methoxy-4'-dimethylaminophenyl)benzoxazol-5-yl]-Ala-Tyr-Tyr-Abu-(5-amino-2-nitrobenzamide) + H2O
?
-
-
-
-
?
N-Boc-3-[2-(2-quinolinyl)benzoxazol-5-yl]-Ala-Tyr-Tyr-Abu-(5-amino-2-nitrobenzamide) + H2O
?
-
-
-
-
?
N-Boc-3-[2-[2-(1'-methyl)pyrrolo]benzoxazol-5-yl]-Ala-Tyr-Tyr-Abu-(5-amino-2-nitrobenzamide) + H2O
?
-
is the most efficient PR3 substrate
-
-
?
Peptidyl thiobenzyl ester + H2O
?
-
the preferred P1 residue is a small hydrophobic amino acid such as aminobutyric acid, norvaline, valine or alanine, in decreasing order of preference
-
-
?
procaspase 3 + H2O
?
-
PR3 can cleave membrane-associated procaspase 3 into a 22 kDa fragment
-
-
?
protease-activated receptor-2
?
-
PR3 may possess the capacity to interact and activate protease-activated receptor-2 expressing antigen-presenting cells and thereby potentially link this proinflammatory activity to the initiation of an adaptive immune response (induction of PR3-specific T cells)
-
-
?
Tert-Butyloxycarbonyl-Ala-Ala-norvaline thiobenzyl ester + H2O
?
-
best substrate
-
-
?
tumour necrosis factor-alpha + H2O
?
-
PR-3-mediated cleavage of tumour necrosis factor-alpha in usual interstitial pneumonia, which may have implications for future therapeutic targeting of tumour necrosis factor-alpha converting enzyme (TACE)
-
-
?
Val-Ala-Asp-Val-Lys-Asp-Arg + H2O
?
-
simulations with a neutral Asp213 bound to the peptide reproduce the expected conformation of the catalytic triad: there are strong hydrogen bonds between histidine 57 and serine 195 and between histidine 57 and the aspartic acid 102. When Asp213 is ionized and in the presence of a peptide bound in the enzyme, its side chain moves away from Gly197 and toward Ser195. The resulting interaction between Asp213 and Ser195 is strong with the formation of a hydrogen bond that persists for over 90% of the simulation time. Interaction competes with the crucial Ser-His hydrogen of the catalytic triad altering the proteolytic function of the enzyme. The pKa for Asp213 is of 8.4 (with a fast empirical method or based on molecular dynamics simulations). In simulations with negatively charged form of Asp213 the interaction between the carbonyl of the P1 residue (oxyanion hole) of the substrate and Ser195 (NH) of PR3 has vanished and the favorable interactions between the enzyme and the substrate are disrupted. A strong hydrogen bond is formed between the imidazole ring of His57 and the P1 and P1' residues of the substrate (NH groups) lasting 83 and 55% of the simulation time, respectively. These hydrogen bonds compete with, or replace, the crucial ones between amino acids of the catalytic triad and in particular the Ser-His interaction
-
-
?
oxidized insulin B chain + H2O
?
52 mM NaCl, 0.5% Triton X-100 (w/v), 10% dimethylformamide (v/v), pH 8.0
-
-
?
additional information
?
-
no reaction with VGVAPGV and VAPGVGVAPGV
-
-
?
additional information
?
-
substrate specificity for small hydrophobic residues at P1 position (Val, Cys, Ala, Met, Ser and Leu)
-
-
?
additional information
?
-
-
substrate specificity for small hydrophobic residues at P1 position (Val, Cys, Ala, Met, Ser and Leu)
-
-
?
additional information
?
-
PR3 is capable of hydrolyzing several extracellular matrix proteins including collagen, elastin, fibronectin and laminin
-
-
?
additional information
?
-
analysis of S4-S5 specificity of human neutrophil proteinase 3
-
-
?
additional information
?
-
-
analysis of S4-S5 specificity of human neutrophil proteinase 3
-
-
?
additional information
?
-
analysis of substrate and cleavage specificity of hPR-3 using elastase substrates, having Val, Ala, and Ile in the P1 position, determination of the extended cleavage specificity, overview. hPR-3 shows good activity against the Val substrate, lower activity on the Ala substrate, and no activity on the other substrates, including one with an Ile in the P1 position
-
-
?
additional information
?
-
-
analysis of substrate and cleavage specificity of hPR-3 using elastase substrates, having Val, Ala, and Ile in the P1 position, determination of the extended cleavage specificity, overview. hPR-3 shows good activity against the Val substrate, lower activity on the Ala substrate, and no activity on the other substrates, including one with an Ile in the P1 position
-
-
?
additional information
?
-
binding of purified recombinant PR3 to phosphatidylserine externalized on apoptotic rat basophilic leukemia (RBL) cells or murine neutrophils (from 12-week-old male C57Bl6 mice). PR3 is a phosphatidylserine (PS)-binding protein and this interaction is dependent on the hydrophobic patch responsible for membrane anchorage. Molecular simulations suggest that PR3 interacts with phosphatidylserine via a small number of amino acids, which engage in long lasting interactions with the lipid heads, molecular modeling of the PR3-PS interaction, detailed overview
-
-
?
additional information
?
-
-
binding of purified recombinant PR3 to phosphatidylserine externalized on apoptotic rat basophilic leukemia (RBL) cells or murine neutrophils (from 12-week-old male C57Bl6 mice). PR3 is a phosphatidylserine (PS)-binding protein and this interaction is dependent on the hydrophobic patch responsible for membrane anchorage. Molecular simulations suggest that PR3 interacts with phosphatidylserine via a small number of amino acids, which engage in long lasting interactions with the lipid heads, molecular modeling of the PR3-PS interaction, detailed overview
-
-
?
additional information
?
-
design, synthesis, and enzymatic evaluation of novel ZnO quantum dot (QD)-based assay for detection of proteinase 3 (PR3) activity, composition and mechanism of action of QD PR3 sensor, overview. The peptide sequence Tyr-Tyr-Abu-Gln-Asp-Pro is exclusively cleaved by PR3, it is connected to QD via functionalized linker oxyethylene linker
-
-
?
additional information
?
-
proteinase 3 can also act via the non-catalytic mechanism. The structure of substrates most susceptible to PR3-mediated hydrolysis provide guidelines for developing ketomethylene compounds, azapeptides, and peptidyl phophonates
-
-
?
additional information
?
-
-
no significant hydrolysis of 2-aminobenzoyl-EAIPM(o)SIPPEVKFNKQN-(2,4dinitrophenyl)ethylenediamine and 2-aminobenzoyl-EAIPM(o)SIPQN-(2,4dinitrophenyl)ethylenediamine
-
?
additional information
?
-
-
PR3 induced cell proliferation is dependent on its serine proteinase activity
-
?
additional information
?
-
-
Suc-Ala-Ala-Ala-Ala-p-nitroanilide, Suc-Ala-Ala-Pro-Met-p-nitroanilide, Suc-Ala-Ala-Pro-Leu, and Suc-Ala-Ala-Pro-Nle-p-nitroanilide -p-nitroanilide are no substrates
-
?
additional information
?
-
-
involved in control of growth and differentiation of human leukemia cells, potent microbicidal activity, is the target antigen of cytoplasmic-staining antineutrophil cytoplasmic autoantibodies circulating in Wegener's granulomatosis
-
-
?
additional information
?
-
-
potent proinflammatory potential, expressed by phagocytic cells of the immune system
-
?
additional information
?
-
-
potent proinflammatory potential, expressed by phagocytic cells of the immune system
-
?
additional information
?
-
-
Asp-61, Lys-99, and Arg-143 in Pr3 are in the vicinity of the substrate binding site that extends from at least subsites S4 to S3'. Subsites S1' to S3' are all in the vicinity of charged residues. Ionic interactions involving residue P3' and Asp-61 are not essential for substrate binding but elongation of the peptide chain helps to stabilize the substrate, improving catalytic efficiency
-
-
?
additional information
?
-
-
PR3 induces phenotypic and functional maturation of blood monocyte-derived iDCs
-
-
?
additional information
?
-
-
CD11b/CD18 (Mac-1, beta2-integrin) is a binding-partner of membrane-bound PR3. Active PR3, but not proPR3 can bind to the surface of CD177-transfected HEK293 cells, suggesting that N-terminal processing is important for binding of PR3 to CD177. FcgammaRIIIb also colocalizes with PR3 on the neutrophil membrane. PR3-CD177 binding may activate beta2-integrins and promote neutrophil firm adhesion
-
-
?
additional information
?
-
-
most intense proteolysis of peptides with polar noncharged acid residues: Gln and Asn followed by Ser. Less active are peptides with negatively charged Glu and Asp. The presence of Lys and Arg gives substrates with susceptibility rates one order of magnitude lower
-
-
?
additional information
?
-
-
the peptide sequence VADVKDR is highly specific for PR3
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
additional information
?
-
PR3 is capable of hydrolyzing several extracellular matrix proteins including collagen, elastin, fibronectin and laminin
-
-
?
additional information
?
-
-
involved in control of growth and differentiation of human leukemia cells, potent microbicidal activity, is the target antigen of cytoplasmic-staining antineutrophil cytoplasmic autoantibodies circulating in Wegener's granulomatosis
-
-
?
additional information
?
-
-
potent proinflammatory potential, expressed by phagocytic cells of the immune system
-
?
additional information
?
-
-
potent proinflammatory potential, expressed by phagocytic cells of the immune system
-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1-acetyl-L-prolyl-L-tyrosyl-N-[1-[bis(4-chlorophenoxy)phosphoryl]ethyl]-L-alpha-asparagine
-
1-[11,21-dioxo-25-[(3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl]-4,7,14,17-tetraoxa-10,20-diazapentacosanan-1-oyl]-L-prolyl-L-tyrosyl-N-[1-[bis(4-chlorophenoxy)phosphoryl]ethyl]-L-alpha-asparagine
-
1-[5-[(3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl]pentanoyl]-L-prolyl-L-tyrosyl-N-[1-[bis(4-chlorophenoxy)phosphoryl]butyl]-L-alpha-asparagine
-
1-[5-[(3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl]pentanoyl]-L-prolyl-L-tyrosyl-N-[1-[bis(4-chlorophenoxy)phosphoryl]ethyl]-L-alpha-asparagine
-
4-methyl-N-[5-[(3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl]pentanoyl]-L-norleucyl-L-tyrosyl-N-[1-[bis(4-chlorophenoxy)phosphoryl]ethyl]-L-alpha-asparagine
-
Abz-VADnV[PSI](COCH2)ADYQ-EDDnp
best inhibitor, selective for proteinase 3, displays a competitive and reversible inhibition mechanism
alpha-1-Proteinase inhibitor
inhibits the enzyme, inhibition is implicated by anti-neutrophil cytoplasmic antibodies with proteinase 3 specificity
-
alpha1-antitrypsin
MeOSuc-AAPV-4-nitroanilide as substrate, 1% Triton X-100 (w/v), 20% dimethylformamide (v/v), pH 8.0, IC50 = 0.98 M
-
Alpha1-proteinase inhibitor
the inhibition is highly dependent on the proper conformation of an exposed reactive center loop, which serves as a pseudosubstrate. Inhibitor mutant E342K is less effective due to an altered conformation of the reactive center loop
-
anti-neutrophil cytoplasmic antibodies with proteinase 3 specificity
screening: a great majority of PR3-ANCA has inhibitory capacity towards the enzyme, overview. PR3-ANCA with inhibitory properties bind to the active site surface of proteinase 3. Epitopes of inhibitory PR3-ANCA are not masked by elafin
-
biotin-Val-Tyr-Asp-NvaP(O-C6H4-4-Cl)2
occupancy of the S1 subsite of PR3 by a NVA residue and of the S4-S5 subsites by a biotinylated Val residue enhances the second-order inhibition constant toward PR3 by more than 10 times as compared to the best phosphonate PR3 inhibitor reported. The inhibitor shows no significant inhibitory activity toward human neutrophil elastase and resists proteolytic degradation in sputa from cystic fibrosis patients. It also inhibits macaque PR3 but not the PR3 from rodents
Eglin c
MeOSuc-AAPV-4-nitroanilide as substrate, 1% Triton X-100 (w/v), 20% dimethylformamide (v/v), pH 8.0, IC50 = 117 M
N-[5-[(3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl]pentanoyl]-L-leucyl-L-tyrosyl-N-[1-[bis(4-chlorophenoxy)phosphoryl]ethyl]-L-alpha-asparagine
-
N-[5-[(3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl]pentanoyl]-L-norleucyl-L-tyrosyl-N-[1-[bis(4-chlorophenoxy)phosphoryl]ethyl]-L-alpha-asparagine
-
N-[5-[(3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl]pentanoyl]-L-valyl-L-tyrosyl-N-[1-[bis(4-chlorophenoxy)phosphoryl]butyl]-L-alpha-asparagine
-
N-[5-[(3aS,4S,6aR)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl]pentanoyl]-L-valyl-L-tyrosyl-N-[1-[bis(4-chlorophenoxy)phosphoryl]ethyl]-L-alpha-asparagine
-
protein 3-specific MCPR3-7 antibody
the monoclonal antibody interfers with the activity of proteinase 3 by an allosteric mechanism. It can change its conformation and impair interactions with alpha1-proteinase inhibitor. The conformation of the S1 pocket of the enzyme is not changed significantly after binding of MCPR3-7, but rather the S1' subsite of the enzyme is changed
-
SLPI
MeOSuc-AAPV-4-nitroanilide as substrate, 1% Triton X-100 (w/v), 20% dimethylformamide (v/v), pH 8.0, limited inhibition, more than 75% of activity remained in the presence of the highest concentration of inhibitor
trappin
80% inhibition, oxidized with N-chlorosuccinimide: 19% inhibition
-
Val15-aprotinin
MeOSuc-AAPV-4-nitroanilide as substrate, 1% Triton X-100 (w/v), 20% dimethylformamide (v/v), pH 8.0, limited inhibition, more than 75% of activity remained in the presence of the highest concentration of inhibitor
-
(S)-4-isobutyl-2-[(p-chlorobenzylthio)methyl]-5-benzyl-1,2,5-thiadiazolidin-3-one 1,1-dioxide
-
-
(S)-4-isobutyl-2-[(phenylthio)methyl]-1,2,5-thiadiazolidin-3-one 1,1-dioxide
-
-
(S)-4-isobutyl-5-benzyl-2-chloromethyl-1,2,5-thiadiazolidin-3-one 1,1-dioxide
-
-
(S)-4-isobutyl-5-benzyl-2-[(phenylthio)methyl]-1,2,5-thiadiazolidin-3-one 1,1-dioxide
-
-
(S)-4-isobutyl-5-[(m-carboxyl)benzyl]-2-[(phenylsulfonyl)methyl]-1,2,5-thiadiazolidin-3-one 1,1-dioxide
-
-
(S)-4-isobutyl-5-[(m-carboxymethyl)benzyl]-2-[(phenylsulfonyl)methyl]-1,2,5-thiadiazolidin-3-one 1,1-dioxide
-
-
(S)-4-isobutyl-5-[(m-carboxymethyl)benzyl]-2-[(phenylthio)methyl]-1,2,5-thiadiazolidin-3-one 1,1-dioxide
-
-
(S)-4-isobutyl-N-[(4-chlorobenzylsulfonyl)methyl]-5-benzyl-1,2,5-thiadiazolidin-3-one 1,1-dioxide
-
-
2,3-diethyl-5-([1-[(phenylsulfanyl)methyl]-1H-1,2,3-triazol-4-yl]methyl)-1,2,3,5-thiatriazolidin-4-one 1,1-dioxide
-
0.00862 mM inhibits by ca. 14%
2,3-diethyl-5-[[1-(2-oxo-2-phenylethyl)-1H-1,2,3-triazol-4-yl]methyl]-1,2,3,5-thiatriazolidin-4-one 1,1-dioxide
-
0.00862 mM inhibits by ca. 10%, fits into the Pr 3 active site well and engages in multiple interactions with the enzyme
2,3-diethyl-5-[[1-(4-methoxybenzyl)-1H-1,2,3-triazol-4-yl]methyl]-1,2,3,5-thiatriazolidin-4-one 1,1-dioxide
-
0.00862 mM inhibits by ca. 8%
2-(2,3-diethyl-1,1-dioxido-4-oxo-1,2,3,5-thiatriazolidin-5-yl)-N-phenylacetamide
-
0.00862 mM inhibits by ca. 13%
2-(2,3-diethyl-1,1-dioxido-4-oxo-1,2,3,5-thiatriazolidin-5-yl)-N-[2-(2-methoxyphenyl)ethyl]-3-phenylpropanamide
-
0.00862 mM inhibits by ca. 11%
2-(2,3-diethyl-1,1-dioxido-4-oxo-1,2,3,5-thiatriazolidin-5-yl)-N-[4-(morpholin-4-yl)phenyl]-3-phenylpropanamide
-
0.00862 mM inhibits by ca. 13%
4,5-bisbenzyl-2-[[(2-benzoxazolyl)thio]methyl]-1,2,5-thiadiazolidin-3-one-1,1-dioxide
-
-
4,5-bisbenzyl-2-[[(5-phenyl-1,3,4-oxadiazol-2-yl)thio]methyl]-1,2,5-thiadiazolidin-3-one-1,1-dioxide
-
-
4,5-bisbenzyl-2-[[(6-amino-2-benzoxazolyl)thio]methyl]-1,2,5-thiadiazolidin-3-one-1,1-dioxide
-
-
4-benzyl-5-methyl-2-[[(2-benzoxazolyl)thio]methyl]-1,2,5-thiadiazolidin-3-one-1,1-dioxide
-
-
4-isobutyl-5-methyl-2-[[(2-benzoxazolyl)thio]methyl]-1,2,5-thiadiazolidin-3-one-1,1-dioxide
-
-
4-isobutyl-5-methyl-2-[[(3-phenyl-1,2,4-oxadiazol-5-yl)thio]methyl]-1,2,5-thiadiazolidin-3-one-1,1-dioxide
-
-
4-isobutyl-5-methyl-2-[[(4,5-diphenyl-2-oxazolyl)thio]methyl]-1,2,5-thiadiazolidin-3-one-1,1-dioxide
-
-
4-isobutyl-5-methyl-2-[[(5-phenyl-1,3,4-oxadiazol-2-yl)thio]methyl]-1,2,5-thiadiazolidin-3-one-1,1-dioxide
-
-
4-isobutyl-5-methyl-2-[[(5-phenyl-2-benzoxazoyl)thio]methyl]-1,2,5-thiadiazolidin-3-one-1,1-dioxide
-
-
4-isobutyl-5-methyl-2-[[2-benzothiazolthio]methyl]-1,2,5-thiadiazolidin-3-one-1,1-dioxide
-
-
5-benzyl-4-isobutyl-2-[[(2-benzoxazolyl)thio]methyl]-1,2,5-thiadiazolidin-3-one-1,1-dioxide
-
-
5-benzyl-4-isobutyl-2-[[(3-phenyl-1,2,4-oxadiazol-5-yl)thio]methyl]-1,2,5-thiadiazolidin-3-one-1,1-dioxide
-
-
5-benzyl-4-isobutyl-2-[[(4,5-diphenyl-2-oxazolyl)thio]methyl]-1,2,5-thiadiazolidin-3-one-1,1-dioxide
-
-
5-benzyl-4-isobutyl-2-[[(5-phenyl-1,3,4-oxadiazol-2-yl)thio]methyl]-1,2,5-thiadiazolidin-3-one-1,1-dioxide
-
-
5-benzyl-4-isobutyl-2-[[(5-phenyl-2-benzoxazoyl)thio]methyl]-1,2,5-thiadiazolidin-3-one-1,1-dioxide
-
-
5-benzyl-4-isobutyl-2-[[2-benzothiazolthio]methyl]-1,2,5-thiadiazolidin-3-one-1,1-dioxide
-
-
alpha1-proteinase
-
does not inhibit when PR3 is bound to the outer cell surface of neutrophils
-
MeO-Suc-AAPA-chloromethyl ketone
-
irreversible inhibitor, inhibits about 90% of the activity after 2 h. Membrane-bound Pr3 remains bound to the membrane when inhibited by the chloromethyl ketone inhibitor
N-(1,3-benzodioxol-5-yl)-2-(2,3-diethyl-1,1-dioxido-4-oxo-1,2,3,5-thiatriazolidin-5-yl)-3-phenylpropanamide
-
0.00862 mM inhibits by ca. 23%
[4-[(2,3-diethyl-1,1-dioxido-4-oxo-1,2,3,5-thiatriazolidin-5-yl)methyl]-1H-1,2,3-triazol-1-yl]acetic acid
-
0.00862 mM inhibits by ca. 11%
(E)-4-(N-(2-(1-(hydroxyimino)butyl)phenyl)sulfamoyl)phenyl pivalate
-
(E)-4-(N-(2-(1-(hydroxyimino)ethyl)phenyl)sulfamoyl)phenyl pivalate
the compound has several beneficial effects in inflammatory disease and lipopolysacchride-induced edema, overview
(E)-4-(N-(2-(1-(hydroxyimino)ethyl)phenyl)sulfamoyl)phenyl pivalate
shows dual inhibitory effects on neutrophil elastase and proteinase 3. The compound significantly attenuates histological changes in lung tissue from mice with LPS-induced acute lung injury (ALI)
(E)-4-(N-(2-(1-(hydroxyimino)methyl)phenyl)sulfamoyl)phenyl pivalate
-
(E)-4-(N-(2-(1-(hydroxyimino)propyl)phenyl)sulfamoyl)phenyl pivalate
-
(E)-4-(N-(2-(1-(methoxyimino)ethyl)phenyl)sulfamoyl)phenyl pivalate
-
(Z)-4-(N-(2-(1-(methoxyimino)ethyl)phenyl)sulfamoyl)phenyl pivalate
-
4-(N-(2-(2-hydroxyethylcarbamoyl)phenyl)sulfamoyl)phenyl pivalate
-
4-(N-(2-acetylphenyl)sulfamoyl)phenyl 2-methylpropane-2-sulfinate
-
4-(N-(2-formylphenyl)sulfamoyl)phenyl 2-methylpropane-2-sulfinate
-
elafin
55% inhibition, oxidized with N-chlorosuccinimide: 10% inhibition
-
elafin
MeOSuc-AAPV-4-nitroanilide as substrate, 1% Triton X-100 (w/v), 20% dimethylformamide (v/v), pH 8.0, IC50 = 1.9 M
-
ethyl 2-(4-(3,3,3-trifluoro-2,2-dimethylpropanoyloxy)benzamido)benzoate
-
methyl 2-(4-(3,3,3-trifluoro-2,2-dimethylpropanoyloxy)benzamido)benzoate
-
methyl 2-(4-(3,3,3-trifluoro-2,2-dimethylpropanoyloxy)phenylsulfonamide)benzoate
-
methyl 2-(4-(3,3,3-trifluoro-2,2-dimethylpropanoyloxy)phenylsulfonamide)benzoate
-
-
propyl 2-(4-(3,3,3-trifluoro-2,2-dimethylpropanoyloxy)benzamido)benzoate
-
sivelestat
acetylating, nonpeptidic inhibitor, sivelestat, developed for the treatment of acute lung injury (ALI )in Japan
alpha1-antitrypsin
-
inhibition of bilayer-bound PR3 is more important than that observed for the soluble form of the enzyme
-
alpha1-protease inhibitor
-
membrane-bound Pr3 is inhibited almost as rapidly as the soluble Pr3, but inhibition is not complete after 1 h. No interaction between constitutive membrane-bound Pr3 and the inhibitor
-
elafin
-
does not inhibit when PR3 is bound to the outer cell surface of neutrophils
-
elafin
-
membrane-bound Pr3 is inhibited almost as rapidly as the soluble Pr3, but inhibition is not complete after 1 h. No interaction between constitutive membrane-bound Pr3 and the inhibitor
-
additional information
low molecular weight serine protease inhibitors, but only partially by inhibitors of larger molecular weight such as alpha1-protease inhibitor
-
additional information
-
low molecular weight serine protease inhibitors, but only partially by inhibitors of larger molecular weight such as alpha1-protease inhibitor
-
additional information
transcription of PR3 is downregulated upon granulocyte and monocyte maturation
-
additional information
-
transcription of PR3 is downregulated upon granulocyte and monocyte maturation
-
additional information
design of ketomethylene-based enzyme inhibitors that show low micromolar IC50 values. Molecular dynamics simulations show that the interactions between enzyme and ketomethylene-containing inhibitors are similar to those with the corresponding substrates. N- and C-terminal FRET groups are important for securing high inhibitory potency toward the enzyme
-
additional information
-
design of ketomethylene-based enzyme inhibitors that show low micromolar IC50 values. Molecular dynamics simulations show that the interactions between enzyme and ketomethylene-containing inhibitors are similar to those with the corresponding substrates. N- and C-terminal FRET groups are important for securing high inhibitory potency toward the enzyme
-
additional information
synthesis and pharmacological characterization of 2-aminobenzaldehyde oxime analogues as dual inhibitors of neutrophil elastase and proteinase 3, structureactivity relationship analysis, overview
-
additional information
-
synthesis and pharmacological characterization of 2-aminobenzaldehyde oxime analogues as dual inhibitors of neutrophil elastase and proteinase 3, structureactivity relationship analysis, overview
-
additional information
potencies of peptidyl di(chlorophenyl)-phosphonate ester inhibitors, kinetics and molecular docking and modeling, overview
-
additional information
-
potencies of peptidyl di(chlorophenyl)-phosphonate ester inhibitors, kinetics and molecular docking and modeling, overview
-
additional information
PR3 inhibitors belong either to the group of peptide analogues (whose structure is directed by the sequence of the substrates) or to non-peptidyl inhibitors, including oxazolidine-2,4-diones, 3,1-benzoxazin-4-ones, isocoumarins, N-hydroxysuccinimides, thiatriazolidines, oximes, Kojic acid derivatives. Analysis of aminophosphonates as potent and selective PR3 inhibitors, overview. Synthesis of alpha-aminoalkylphosphonate diaryl esters. No inhibition by Pro-Tyr-Asp-AlaP(O-C6H4-4-Cl)2
-
additional information
synthesis of a series 2-aminobenzaldehyde oxime and 2-aminobenzoate analogues, their inhibitory effects on neutrophilic serine proteases (NsPs), i.e. cathepsin G, proteinase 3 (Pr3), and human neutrophil elastase (HNE), are determined. A hydroxyl oxime moiety plays an important role in ligand-enzyme affinity through hydrogen bonding, structure-activity relationships, overview. Most of the compounds have a potent and dual inhibitory effect on human neutrophil elastase and Pr3
-
additional information
-
synthesis of a series 2-aminobenzaldehyde oxime and 2-aminobenzoate analogues, their inhibitory effects on neutrophilic serine proteases (NsPs), i.e. cathepsin G, proteinase 3 (Pr3), and human neutrophil elastase (HNE), are determined. A hydroxyl oxime moiety plays an important role in ligand-enzyme affinity through hydrogen bonding, structure-activity relationships, overview. Most of the compounds have a potent and dual inhibitory effect on human neutrophil elastase and Pr3
-
additional information
-
substituted isocoumarins, peptide-phosphonates and chloromethyl ketones inhibit proteinase 3 less potently than human neutrophil elastase, by 1-2 orders of magnitude
-
additional information
-
membrane-bound enzyme is resistant to inhibition by physiologic proteinase inhibitors
-
additional information
-
hydrolysis of N-methoxysuccinyl-Ala-Ala-Pro-Val-pNA by neutrophil PR3 is reduced by 40% as a result of deglycosylation
-
additional information
-
peptide-specific T-cell responses, exemplary for PRTN358 and PRTN3235, can be inhibited by anti-HLA-DR antibodies, but not by an anti-HLAABC antibody
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
cytochalasin B
-
PR3 and CD177 are increased in parallel. Stimulating cells with cytochalasin B in combination with fML, PmPR3- and CD177-negative cells become positive
fMLP
-
PR3 and CD177 are increased in parallel. Causes a moderate increase. stimulating cells with cytochalasin B in combination with fML, PmPR3- and CD177-negative cells become positive
PMA
-
PR3 and CD177 are increased in parallel. Increases 4.9fold. mPR3- and CD177-negative cells become positive
TNF-alpha
-
leads to caspase-3-dependent apoptosis within 3 h accompanied by increased surface expression of PR3 and MPO
-
TNF-alpha
-
PR3 and CD177 are increased in parallel. Causes a moderate increase
-
additional information
-
glycosylation at Asn-147, but not at Asn-102, is critical for optimal hydrolytic activity of PR3. Efficient amino-terminal proteolytic processing of recombinant PR3 is dependent on glycosylation at Asn-102
-
additional information
-
PR3 externalization depends on PLSCR1, but is independently of its serine-proteinase activity. Higher membrane PR3 expression on neutrophils after apoptosis without degranulation. Phospholipid scramblase 1 is involved in membrane PR3 expression during apoptosis-induced phospholipid redistribution between the two plasma membrane leaflets
-
additional information
-
PRTN3235-specific T-cells can be stimulated from the blood of healthy individuals with multiple HLA-DR-genotypes
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.0174
2-aminobenzoyl-Tyr-Tyr-aminobutyl-(5-amino-2-nitrobenzoyl)-Gln-NH2
pH and temperature not specified in the publication
0.0314
2-aminobenzoyl-Tyr-Tyr-aminobutyl-(5-amino-2-nitrobenzoyl)-NH2
pH and temperature not specified in the publication
0.0032
2-aminobenzoyl-Tyr-Tyr-aminobutyl-Asn-Glu-Pro-Tyr(3-NO2)-NH2
pH and temperature not specified in the publication
0.0123
2-aminobenzoyl-Val-Ala-Asp-Cys-Ala-Gln-N-(2,4-dinitrophenyl)-ethylenediamine
pH and temperature not specified in the publication
0.0033
2-aminobenzoyl-Val-Ala-Asp-Cys-Arg-Asp-Arg-Gln-N-(2,4-dinitrophenyl)-ethylenediamine
pH and temperature not specified in the publication
0.0011
2-aminobenzoyl-Val-Ala-Asp-Nva-Ala-Asp-Tyr-Gln-N-(2,4-dinitrophenyl)-ethylenediamine
pH and temperature not specified in the publication
1.2
MeOSuc-AAPV-4-nitroanilide
52 mM NaCl, 0.5% Triton X-100 (w/v), 10% dimethylformamide (v/v), pH 8.0
0.61
MeOSuc-AIPM-4-nitroanilide
52 mM NaCl, 0.5% Triton X-100 (w/v), 10% dimethylformamide (v/v), pH 8.0
0.05
O-methyl-succinyl-Ala-Ala-Pro-Ala-S-benzyl ester
pH and temperature not specified in the publication
0.27
O-methyl-succinyl-Ala-Ala-Pro-Val-4-nitroanilide
pH and temperature not specified in the publication
3.7
Suc-AAPV-4-nitroanilide
52 mM NaCl, 0.5% Triton X-100 (w/v), 10% dimethylformamide (v/v), pH 8.0
0.192
succinyl-Ala-Ala-Nva-S-benzyl ester
pH and temperature not specified in the publication
0.063
tert-butyloxycarbonyl-Ala-Ala-Nva-S-benzyl ester
pH and temperature not specified in the publication
0.028
tert-butyloxycarbonyl-Ala-Ala-Val-S-benzyl ester
pH and temperature not specified in the publication
0.66
tert-butyloxycarbonyl-Ala-O-4-nitrophenyl ester
pH and temperature not specified in the publication
0.0314
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzamide)
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25°C
0.1731
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Ala-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25°C
0.0642
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Arg-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25°C
0.0251
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Asn-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25°C
0.0281
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Asp-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25°C
0.0174
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Gln-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25°C
0.0253
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Glu-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25°C
0.1242
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Gly-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25°C
0.0357
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-His-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25°C
0.2763
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Ile-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25°C
0.2436
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Leu-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25°C
0.0729
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Lys-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25°C
1.126
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Phe-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25°C
0.1823
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Pro-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25°C
0.0278
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Ser-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25°C
0.0321
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Thr-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25°C
1.274
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Trp-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25°C
0.9823
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Tyr-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25°C
0.3124
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Val-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25°C
additional information
additional information
-
Km values of peptidyl thiobenzyl esters
-
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.59
MeOSuc-AAPV-4-nitroanilide
52 mM NaCl, 0.5% Triton X-100 (w/v), 10% dimethylformamide (v/v), pH 8.0
0.26
MeOSuc-AIPM-4-nitroanilide
52 mM NaCl, 0.5% Triton X-100 (w/v), 10% dimethylformamide (v/v), pH 8.0
0.37
Suc-AAPV-4-nitroanilide
52 mM NaCl, 0.5% Triton X-100 (w/v), 10% dimethylformamide (v/v), pH 8.0
5.9
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzamide)
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25°C
2.1
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Ala-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25°C
2.6
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Arg-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25°C
5.3
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Asn-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25°C
4.8
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Asp-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25°C
6.4
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Gln-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25°C
3.3
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Glu-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25°C
3.2
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Gly-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25°C
3.1
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-His-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25°C
1.8
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Ile-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25°C
2
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Leu-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25°C
2.5
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Lys-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25°C
1.3
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Phe-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25°C
1.1
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Pro-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25°C
5.1
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Ser-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25°C
2.8
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Thr-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25°C
1.3
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Trp-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25°C
1.6
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Tyr-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25°C
4.7
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Val-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25°C
additional information
additional information
-
turnover numbers of peptidyl thiobenzyl esters
-
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
1.6
2-aminobenzoyl-Gln-Asp-Met-Ala-Val-Val-Gln-Ser-Val-Pro-Gln-N-(2,4-dinitrophenyl)-ethylenediamine
pH and temperature not specified in the publication
95.7
2-aminobenzoyl-Gln-Pro-Met-Ala-Val-Val-Gln-Ser-Val-Pro-Gln-N-(2,4-dinitrophenyl)-ethylenediamine
pH and temperature not specified in the publication
274.9
2-aminobenzoyl-Tyr-Tyr-aminobutyl-(5-amino-2-nitrobenzoyl)-Gln-NH2
pH and temperature not specified in the publication
188.9
2-aminobenzoyl-Tyr-Tyr-aminobutyl-(5-amino-2-nitrobenzoyl)-NH2
pH and temperature not specified in the publication
1596
2-aminobenzoyl-Tyr-Tyr-aminobutyl-Asn-Glu-Pro-Tyr(3-NO2)-NH2
pH and temperature not specified in the publication
292
2-aminobenzoyl-Val-Ala-Asp-Cys-Ala-Gln-N-(2,4-dinitrophenyl)-ethylenediamine
pH and temperature not specified in the publication
6500
2-aminobenzoyl-Val-Ala-Asp-Cys-Arg-Asp-Arg-Gln-N-(2,4-dinitrophenyl)-ethylenediamine
pH and temperature not specified in the publication
7200
2-aminobenzoyl-Val-Ala-Asp-Nva-Ala-Asp-Tyr-Gln-N-(2,4-dinitrophenyl)-ethylenediamine
pH and temperature not specified in the publication
360
acetyl-Glu(O-benzyl)-Lys(Ac)-Pro(4-O-benzyl)-Nva-7-amido-4-carbamoylmethylcoumarin
pH and temperature not specified in the publication
80.51
biotinyl-Val-Tyr-Asp-Nva-4-nitroanilide
pH and temperature not specified in the publication
220
O-methyl-succinyl-Ala-Ala-Pro-Ala-S-benzyl ester
pH and temperature not specified in the publication
3.05
O-methyl-succinyl-Ala-Ala-Pro-Val-4-nitroanilide
pH and temperature not specified in the publication
470
succinyl-Ala-Ala-Nva-S-benzyl ester
pH and temperature not specified in the publication
1000
tert-butyloxycarbonyl-Ala-Ala-Nva-S-benzyl ester
pH and temperature not specified in the publication
380
tert-butyloxycarbonyl-Ala-Ala-Val-S-benzyl ester
pH and temperature not specified in the publication
15.15
tert-butyloxycarbonyl-Ala-O-4-nitrophenyl ester
pH and temperature not specified in the publication
188.9
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzamide)
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25°C
12.2
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Ala-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25°C
41.1
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Arg-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25°C
201.2
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Asn-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25°C
170.8
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Asp-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25°C
274.9
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Gln-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25°C
138.2
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Glu-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25°C
25.8
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Gly-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25°C
86.7
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-His-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25°C
6.5
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Ile-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25°C
7.2
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Leu-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25°C
34.3
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Lys-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25°C
1.1
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Phe-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25°C
0.5
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Pro-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25°C
183.8
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Ser-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25°C
87.3
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Thr-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25°C
0.9
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Trp-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25°C
1.6
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Tyr-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25°C
15.1
Abz-Tyr-Tyr-Abu-(5-amino-2-nitrobenzoyl)-Val-NH2
-
in 0.1 M Tris-HCl buffer, pH 7.5, with 500 mM NaCl at 25°C
1500
N-Boc-3-[2-[2-(1'-methyl)pyrrolo]benzoxazol-5-yl]-Ala-Tyr-Tyr-Abu-(5-amino-2-nitrobenzamide)
-
-
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.000025
elafin, oxidized with myeloperoxidase
methoxysuccinyl-lysyl-(2-picolinoyl)-Ala-Pro-Val-thiobenzylester as substrate, pH 7.4, 150 mM NaCl, 3 mM 4,4-dithiodipyridine
-
0.000029
elafin, oxidized with N-chlorosuccinimide
methoxysuccinyl-lysyl-(2-picolinoyl)-Ala-Pro-Val-thiobenzylester as substrate, pH 7.4, 150 mM NaCl, 3 mM 4,4-dithiodipyridine
-
0.00000018
trappin
methoxysuccinyl-lysyl-(2-picolinoyl)-Ala-Pro-Val-thiobenzylester as substrate, pH 7.4, 150 mM NaCl, 3 mM 4,4-dithiodipyridine
-
0.000035
trappin, oxidized with myeloperoxidase
methoxysuccinyl-lysyl-(2-picolinoyl)-Ala-Pro-Val-thiobenzylester as substrate, pH 7.4, 150 mM NaCl, 3 mM 4,4-dithiodipyridine
-
0.00005
trappin, oxidized with N-chlorosuccinimide
methoxysuccinyl-lysyl-(2-picolinoyl)-Ala-Pro-Val-thiobenzylester as substrate, pH 7.4, 150 mM NaCl, 3 mM 4,4-dithiodipyridine
-
0.00000018
trappin-2
25°C, recombinant trappin-2 expressed in Pichia pastoris
-
0.00000012
elafin
25°C, recombinant elafin expressed in Pichia pastoris
-
0.00000012
elafin
methoxysuccinyl-lysyl-(2-picolinoyl)-Ala-Pro-Val-thiobenzylester as substrate, pH 7.4, 150 mM NaCl, 3 mM 4,4-dithiodipyridine
-
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
980
alpha1-antitrypsin
Homo sapiens
MeOSuc-AAPV-4-nitroanilide as substrate, 1% Triton X-100 (w/v), 20% dimethylformamide (v/v), pH 8.0, IC50 = 0.98 M
-
117000
Eglin c
Homo sapiens
MeOSuc-AAPV-4-nitroanilide as substrate, 1% Triton X-100 (w/v), 20% dimethylformamide (v/v), pH 8.0, IC50 = 117 M
1900
elafin
Homo sapiens
MeOSuc-AAPV-4-nitroanilide as substrate, 1% Triton X-100 (w/v), 20% dimethylformamide (v/v), pH 8.0, IC50 = 1.9 M
-
0.00173
(E)-4-(N-(2-(1-(hydroxyimino)butyl)phenyl)sulfamoyl)phenyl pivalate
Homo sapiens
pH 7.4, 30°C
0.00173
(E)-4-(N-(2-(1-(hydroxyimino)butyl)phenyl)sulfamoyl)phenyl pivalate
Homo sapiens
pH 7.5, 30°C
0.00022
(E)-4-(N-(2-(1-(hydroxyimino)ethyl)phenyl)sulfamoyl)phenyl pivalate
Homo sapiens
pH 7.4, 30°C
0.00022
(E)-4-(N-(2-(1-(hydroxyimino)ethyl)phenyl)sulfamoyl)phenyl pivalate
Homo sapiens
pH 7.5, 30°C
0.00053
(E)-4-(N-(2-(1-(hydroxyimino)methyl)phenyl)sulfamoyl)phenyl pivalate
Homo sapiens
pH 7.4, 30°C
0.00053
(E)-4-(N-(2-(1-(hydroxyimino)methyl)phenyl)sulfamoyl)phenyl pivalate
Homo sapiens
pH 7.5, 30°C
0.0025
(E)-4-(N-(2-(1-(hydroxyimino)propyl)phenyl)sulfamoyl)phenyl pivalate
Homo sapiens
pH 7.4, 30°C
0.0025
(E)-4-(N-(2-(1-(hydroxyimino)propyl)phenyl)sulfamoyl)phenyl pivalate
Homo sapiens
pH 7.5, 30°C
0.00061
(E)-4-(N-(2-(1-(methoxyimino)ethyl)phenyl)sulfamoyl)phenyl pivalate
Homo sapiens
pH 7.4, 30°C
0.00061
(E)-4-(N-(2-(1-(methoxyimino)ethyl)phenyl)sulfamoyl)phenyl pivalate
Homo sapiens
pH 7.5, 30°C
0.00237
(Z)-4-(N-(2-(1-(methoxyimino)ethyl)phenyl)sulfamoyl)phenyl pivalate
Homo sapiens
pH 7.4, 30°C
0.00237
(Z)-4-(N-(2-(1-(methoxyimino)ethyl)phenyl)sulfamoyl)phenyl pivalate
Homo sapiens
pH 7.5, 30°C
0.00061
2-hydroxyethyl 2-(4-(pivaloyloxy)phenylsulfonamido)benzoate
Homo sapiens
pH 7.4, 30°C
0.00061
2-hydroxyethyl 2-(4-(pivaloyloxy)phenylsulfonamido)benzoate
Homo sapiens
pH 7.5, 30°C
0.00031
4-(N-(2-(2-hydroxyethylcarbamoyl)phenyl)sulfamoyl)phenyl pivalate
Homo sapiens
pH 7.4, 30°C
0.00031
4-(N-(2-(2-hydroxyethylcarbamoyl)phenyl)sulfamoyl)phenyl pivalate
Homo sapiens
pH 7.5, 30°C
0.01
4-(N-(2-acetylphenyl)sulfamoyl)phenyl 2-methylpropane-2-sulfinate
Homo sapiens
pH 7.4, 30°C
0.01
4-(N-(2-acetylphenyl)sulfamoyl)phenyl 2-methylpropane-2-sulfinate
Homo sapiens
above, pH 7.5, 30°C
0.01
4-(N-(2-formylphenyl)sulfamoyl)phenyl 2-methylpropane-2-sulfinate
Homo sapiens
pH 7.4, 30°C
0.01
4-(N-(2-formylphenyl)sulfamoyl)phenyl 2-methylpropane-2-sulfinate
Homo sapiens
above, pH 7.5, 30°C
0.01
ethyl 2-(4-(3,3,3-trifluoro-2,2-dimethylpropanoyloxy)benzamido)benzoate
Homo sapiens
pH 7.4, 30°C
0.01
ethyl 2-(4-(3,3,3-trifluoro-2,2-dimethylpropanoyloxy)benzamido)benzoate
Homo sapiens
above, pH 7.5, 30°C
0.01
methyl 2-(4-(3,3,3-trifluoro-2,2-dimethylpropanoyloxy)benzamido)benzoate
Homo sapiens
pH 7.4, 30°C
0.01
methyl 2-(4-(3,3,3-trifluoro-2,2-dimethylpropanoyloxy)benzamido)benzoate
Homo sapiens
above, pH 7.5, 30°C
0.00494
methyl 2-(4-(3,3,3-trifluoro-2,2-dimethylpropanoyloxy)phenylsulfonamide)benzoate
Homo sapiens
pH 7.4, 30°C
0.00494
methyl 2-(4-(3,3,3-trifluoro-2,2-dimethylpropanoyloxy)phenylsulfonamide)benzoate
Homo sapiens
pH 7.5, 30°C
0.01
methyl 2-(4-pivalamidophenylsulfonamido)benzoate
Homo sapiens
above, pH 7.5, 30°C
0.01
propyl 2-(4-(3,3,3-trifluoro-2,2-dimethylpropanoyloxy)benzamido)benzoate
Homo sapiens
pH 7.4, 30°C
0.01
propyl 2-(4-(3,3,3-trifluoro-2,2-dimethylpropanoyloxy)benzamido)benzoate
Homo sapiens
above, pH 7.5, 30°C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
7.4
pH RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
the mature PR3 has an inactive conformation in the acidic environment of the azurophilic granules, and becomes active upon translocation to a neutral pH environment
additional information
-
the mature PR3 has an inactive conformation in the acidic environment of the azurophilic granules, and becomes active upon translocation to a neutral pH environment
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30
pI VALUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
PR3 plasma concentrations are increased in patients with liver steatosis
-
increased PR-3 on the alveolar macrophage surface in usual interstitial pneumonia relative to healthy controls and sarcoidosis subjects
-
cell associated PR3 levels are lower than in neutrophils, thus sensitivity of the indirect immunofluorescence test is lower
additional information
blood neutrophils from patients with active Wegeners granulomatosis bear greater amounts of PR3 on their cell membranes than do neutrophils from healthy individuals
neutrophil membrane expression of PR3 increases during both activation and apoptosis
-
cell associated PR3 levels are lower than in neutrophils, thus sensitivity of the indirect immunofluorescence test is lower
-
-
-
endogenous annexin 1 and PR3 localization in resting and stimulated blood neutrophils
-
high molecular weight complexes of unstimulated neutrophils comprise PR3, FcgammaRIIIb, the beta2 integrin CD11b/CD18, the membrane and cytosolic subunits of the NADPH oxidase, p22phox and p47phox/p67phox
-
targeting to granules is not dependent on glycosylation, but unglycosylated recombinant PR3 gets secreted preferentially into media supernatants
-
neutrophil extracts from vasculitis patients and healthy controls contain comparable amounts of PR3
-
presence of anti-complementary PR3 and anti-PR3 antibodies in human Wegeners granulomatosis sera
additional information
neutrophil-dereived PR3 is more potent than urinary PR3
additional information
-
neutrophil-dereived PR3 is more potent than urinary PR3
additional information
mRNA for PR3 is transcribed in the promyelocyte and promonocyte stages of myeloid differentiation. Present in mastocytes and no-hematopoietic cell
additional information
-
mRNA for PR3 is transcribed in the promyelocyte and promonocyte stages of myeloid differentiation. Present in mastocytes and no-hematopoietic cell
additional information
proteinase 3 is expressed by myeloid cells and localized within azurophil granules, it is also expressed on the cellular membrane of polymorphonuclear neutrophils (PMN)
additional information
the neutrophil membrane mPR3 is highly induced in patients with sepsis
additional information
-
the neutrophil membrane mPR3 is highly induced in patients with sepsis
additional information
-
PR3 antigen is usually present in granulomas and antigen-presenting cells are found in these lesions as well
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
the extragranular pool of PR3, which is externalized during apoptosis, may be functionally very important in the pathophysiology of vasculitis
-
additional information
a major neutrophilic serine protease expressed in neutrophil azurophil granules
neutrophil membrane expression of PR3 increases during both activation and apoptosis. Membrane expression of PR3 is increased in patients with granulomatosis with polyangiitis. Membrane anchorage of PR3 is dependent on the hydrophobic patch containing four hydrophobic amino acids, Phe180, Phe181, Leu228, and Phe229, molecular simulations. Phospholipid scramblase 1 (PLSCR1) knockdown using siRNA prevents PR3 membrane expression
-
from human polymorphonuclear leukocytes (PMNL)
-
major pool of intracellular PR3 is within the azurophilic granules
-
low levels, CD177 is a receptor for PR3 on the neutrophil membrane, but in CD177 negative neutrophils PR3 is also present and is susceptible to PR3-anti-neutrophil cytoplasmic autoantibodies (ANCA) induced neutrophil activation
-
hydrophobic patch F180-F181-L228-F229 is essential for PR3 membrane anchorage. PR3 membrane insertion appears to be pivotal for its proinflammatory activities, such as extracellular proteolysis and impairment of apoptotic cell clearance, but also for myeloid cell proliferation
-
PR3 and CD177 exhibit a dynamic plasma membrane expression with rapid internalization and re-expression
additional information
during neutrophil activation and apoptosis, membrane expression of PR3 increases, and soluble PR3 is also released into the extracellular environment during degranulation
-
additional information
-
during neutrophil activation and apoptosis, membrane expression of PR3 increases, and soluble PR3 is also released into the extracellular environment during degranulation
-
additional information
proteinase 3, also referred to as myeloblastin, is stored not only in azurophilic granules, but also in secretory vesicles and is translocated onto the cell membrane upon stimuli
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
malfunction
metabolism
physiological function
metabolism
-
pro-PR3 interacts with CD63 upon heterologous co-expression in COS cells but endogenous interaction is not detected although cell surface proPR3 and CD63 are co-endocytosed in myelomonocytic cells. Cell surface pro-PR3 turns over more rapidly than cell surface CD63 consistent with processing/degradation of the pro-protease but recycling of CD63. Colocalization of proPR3 and CD63 with clathrin and Rab 7 suggests trafficking through coated vesicles and late endosomes. Blocking the C-terminus of pro-PR3 by creating a fusion with FK506 binding protein does not inhibit endosomal re-uptake of proPR3
physiological function
additional information
evolution
neutrophil serine proteases, proteinase 3 and human neutrophil elastase, share high sequence similarity, but have different substrate specificities and functions
evolution
presence of an elastase in Xenopus closely related to hPR-3 indicates a relatively early appearance of these enzymes during vertebrate evolution, sequence comparisons and phylogenetic analysis of the hematopoietic serine proteases, overview
malfunction
overexpression of proteinase 3 in chronic myeloid leukemia induces apoptosis of high-affinity PR1-specific T cells, leading to deletional tolerance and leukemia outgrowth
malfunction
phospholipid scramblase 1 (PLSCR1) knockdown using siRNA not only prevents PR3 membrane expression but also increases the rate of apoptotic cell clearance by macrophages
malfunction
ratios between neutrophil serine proteases and their natural inhibitor are altered in non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes when compared to healthy controls
metabolism
histone demethylase JMJD3 (EC 1.14.11.68) regulates the expression of neutrophil membrane proteinase 3 (mPR3) in lipopolysaccharide-stimulated neutrophils during the early inflammatory response in sepsis. JMJD3 regulates the expression of mPR3 by changing the level of trimethylated histone H3 on Lys27 (H3K27me3) in LPS-stimulated neutrophils
metabolism
increased proteinase 3 and neutrophil elastase (EC 3.4.21.37) plasma concentrations are associated with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes, potential role for the neutrophil serine proteases (NSPs), proteinase-3 (PR3) and neutrophil elastase (NE), in NAFLD as well as an imbalance between NSPs and their natural inhibitor alpha-1 antitrypsin (AAT). Circulating levels of NSPs associate with obesity-related metabolic disorders
metabolism
PR3 concentration in azurophilic granules is approximately 3 times higher than that of human neutrophil elastase and cathepsin G, and the enzyme is less susceptible to inhibition by endogenous serine protease inhibitors correlates with PR3 implication in various pathological processes
physiological function
proteinase 3 is a major autoimmune target in systemic vasculitis. Proteinase 3 is an abundant serine protease of neutrophil granules and a major target of PR3 antineutrophil cytoplasmic autoantibodies in granulomatosis with polyangiitis. Some of the enzyme synthesized by promyelocytes in the bone marrow escape the targeting to granules and occur on the plasma membrane of naive and primed neutrophils. This membrane-associated PR3 antigen may represent pro-PR3, mature PR3, or both forms
physiological function
the enzyme is involved in granulomatosis with polyangiitis, anti-neutrophil cytoplasmic antibodies with proteinase 3 specificity are not implicated in the pathogenesis
physiological function
effect of membrane proteinase 3-expressing polymorphonuclear neutrophils (PMN) and acute myeloid leukemia (AML) blasts on the proliferation of CD4 and CD8 T cells in vitro, overview. mP3-expressing PMN significantly inhibits autologous healthy donor T-cell proliferation but does not affect cytokine production in activated T-cells. This effect requires cell proximity and is abrogated by proteinase 3 blockade. This inhibition requires proteinase 3 enzyme activity. The suppression is not reversed by either the addition of catalase or the inhibition of arginase I. PMN inhibit T cell proliferation in a cell contact-dependent manner. In addition to proteinase 3 blockade, anti-low density lipoprotein receptor-related protein 1 (LRP1) Ab also restores T cells' capacity to proliferate. Dose-dependent inhibition of T-cell proliferation by mP3-expressing acute myeloid leukemia blasts
physiological function
membrane proteinase 3 (mPR3) expression on neutrophils plays a critical role in pro-inflammatory cytokine production. Plasma cytokine (interleukin-1beta and TNF-alpha) levels are increased in patients with sepsis exhibiting high mPR3 expression
physiological function
proteinase 3 (PR3), the autoantigen in granulomatosis with polyangiitis, is expressed at the plasma membrane of resting neutrophils, and this membrane expression increases during both activation and apoptosis. Proteinase 3 also is a phosphatidylserine-binding protein that affects the production and function of microvesicles. The interaction is dependent on the hydrophobic patch responsible for membrane anchorage. PR3 interacts with phosphatidylserine via a small number of amino acids, which engage in long lasting interactions with the lipid heads. The binding of PR3 to phosphatidylserine, a major component of microvesicles, leads to reduced production of microvesicles in PR3-expressing cells. PR3-expressing cells produce significantly fewer microvesicles during both activation and apoptosis, and this reduction is dependent on the ability of PR3 to associate with the membrane as mutating the hydrophobic patch restored microvesicle production. Activation-evoked microvesicles from PR3-expressing cells induce a significantly larger respiratory burst in human neutrophils compared with control microvesicles, while microvesicles generated during apoptosis inhibit the basal respiratory burst in human neutrophils, and those generated from PR3-expressing cells hamper this inhibition. Microvesicles generated from neutrophils expressing membrane PR3 may potentiate oxidative damage of endothelial cells and promote the systemic inflammation observed in this disease. PR3 hampers the ability of apoptosis-induced microvesicles to inhibit a respiratory burst in neutrophils. During apoptosis, membrane-bound PR3 serves as a 'don't eat me' signal. It is co-externalized with phosphatidylserine (PS) via its association with phospholipid scramblase 1 (PLSCR1), a protein facilitating membrane flip-flop
physiological function
the neutrophil serine protease proteinase-3 (PR3) is able to process interleukin-1beta to its bioactive form independently of caspase-1-NLRP3 inflammasome complex
physiological function
the neutrophilic serine protease proteinase 3 (PR3) is involved in inflammation and immune response and is a therapeutic target for a variety of infectious and inflammatory diseases
physiological function
the physiological role of PR3 is seen either inside the phagocytic vacuoles or externally where PR3 is engaged in processing of proinflammatory cytokines, receptors, heat shock proteins and other host proteins which after PR3-mediated hydrolysis lead to the generation of antibacterial peptides (e.g. cathelicidin hCAP-18). PR3 is capable of hydrolyzing several extracellular matrix proteins including collagen, elastin, fibronectin and laminin causing the inflammation and tissue injury. PR3 is also known as the antigen in granulomatosis with polyangiitis (GPA), a chronic inflammatory condition that triggers autoimmune response resulting in the production of antineutrophil cytoplasmic antibodies (ANCA). As the binding of ANCA activates neutrophils and therefore increases the level of cell surface PR3, the protein is directly involved in the pathogenesis of the disease
physiological function
-
69-year-old Caucasian female presenting initially with an isolated parotid abscess and only subsequently developing nasal, paranasal sinus and respiratory symptoms, shows anti-neutrophil cytoplasmic antibodies against proteinase 3 titres
physiological function
-
activation of IL-1beta in a manner independent of caspase 1 is especially apparent in the acute phase of inflammation, characterized by a predominantly neutrophilic infiltrate that serves as a source for PR3
physiological function
-
all c-ANCA-positive samples (diagnosed Wegener granulomatosis) show a significant increase of PR3 activity
physiological function
-
anti-neutrophil cytoplasmic antibodies (cANCAs) from Wegeners granulomatosis patients at least in part recognize similar surface structures as do mouse antibodies and compete with the binding of alpha1-protease inhibitor to PR3
physiological function
-
involvement in the regulation of intracellular functions such as proliferation or apoptosis. Its membrane expression is a risk factor in chronic inflammatory diseases. PR3 is the preferred target antigen in Wegener's granulomatosis. Colocalization of PR3 with the integrin CD11b/CD18 (b2 integrin), the Fcgamma receptor FcgRIIIb and the p22phox subunit of cytochrome b558 in the membrane. Both PR3 and phospholipid scramblase 1 are associated within the same protein complex
physiological function
-
is a major anti-neutrophil cytoplasmic autoantibodies (ANCA)-antigen in Wegener's granulomatosis. Abnormally expressed membrane-bound PR3 is involved in the development and severity of Wegener's granulomatosis. Strong correlation of the percentages of membrane-bound PR3 high neutrophils between monozygotic twins but not in dizygotic twins. PR3 is externalized during neutrophil apoptosis independent of degranulation, which is mediated by phospholipid scramblase 1. CD177-deficient neutrophils also can be activated by PR3-anti-neutrophil cytoplasmic autoantibodies in vitro, thus CD177 is not necessary for this signaling
physiological function
-
neutrophil activation by PR3 antineutrophil cytoplasmic autoantibodies (ANCAs). CD177 may be a determinant of membrane expression of PR3 and, as such, influences the potential of neutrophils to be activated by PR3 ANCAs
physiological function
-
neutrophil-derived PR3 can induce kallikrein-independent activation of the kinin pathway
physiological function
-
occurrence of anti-neutrophil-cytoplasmic antibodies (ANCA) directed against proteinase-3 is a hallmark of Wegeners granulomatosis. Association of anti-PR3 titers and disease activity, which remains controversial. PR3 antigen elicits strong Th1-responses via dendritic cell maturation and subsequent antigen presentation to T-cells. Initial immune response in autoimmunity is directed against complementary PR3, resulting in the formation of antibodies against complementary PR3 (idiotypic response). Later on, an anti-idiotypic response against anti-complementary PR3 antibodies evolves. The antibodies formed during this anti-idiotypic response react to the sense autoantigen PR3. ANCA produced by granuloma-resident B cells bind to primed neutrophils that express PR3 on their surface. Genetic sequences complementary to human PR3 gene are detected in pathogens like Staphylococcus aureus, Ross River virus and Entamoeba histolytica. complementary PR3 transcripts are absent from healthy controls, PR3-ANCA-negative or lupus patients. Complementary PR3 mRNA is present in leukocytes of PR3-ANCA patients
physiological function
-
PRTN3-specific CD4+ T-cells precursors are part of normal human T-cell repertoires. T-cell precursors specific for various PRTN3 epitopes can be activated when properly stimulated. T-cell clones proliferate in response to peptides PRTN358 (GTLIHPSFVLTAAHALRDI), PRTN3216 (IDSFVIWGAATRLFPDFF), PRTN3235 (RVALYVDWIRSTLRR), and PRTN3241 (DWIRSTLRRVEAKGRP). T-cell clones specific for these four PRTN3 peptides strongly respond to autologous peripheral blood mononuclear cells in the presence of corresponding peptides. Only PRTN3235 is recognized by CD4+ T-cells as a naturally processed HLAclass-II-epitope. PRTN3235-specific CD4+ T-cells do not proliferate vigorously to stimulation with PRTN3-positive leukemia cell. PRTN3235 is able to induce T-cell responses in individuals with diverse DR genotypes
physiological function
-
significant Pr3 activity at the surface of activated neutrophils but not at the surface of quiescent neutrophils whatever the constitutive expression. Permanent presence of inactive Pr3 at the surface of quiescent neutrophils, which may explain why Pr3 is a major target of anti-neutrophil cytoplasmic antibodies, whose binding activates neutrophils and triggers inflammation, as in Wegener granulomatosis
physiological function
-
PR3 membrane insertion appears to be pivotal for its proinflammatory activities, such as extracellular proteolysis and impairment of apoptotic cell clearance, but also for myeloid cell proliferation
additional information
proteinase 3 is an abundant serine protease with high similarity to neutrophil elastase
additional information
enzyme-microvesicle interaction analysis by surface plasmon resonance spectroscopy. Molecular modeling
additional information
-
enzyme-microvesicle interaction analysis by surface plasmon resonance spectroscopy. Molecular modeling
additional information
similarly to azurocidin or CatG, PR3 can also act via the non-catalytic mechanism
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). PRTN3_HUMAN
256
0
27807
Swiss-Prot
Secretory Pathway (Reliability: 1)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
29000
additional information
-
processing of proteinase 3 in U937 human myelomonocytic cell line: a 35000 MW precursor is converted into a 29000 MW mature form
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
proteolytic modification
the pro-enzyme zymogen has to be proteolytically activated
proteolytic modification
-
pro-PR3 is found to constitute 10% of circulating PR3 but none of the membrane-PR3
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
crystal structure of recombinant PR3. Overall fold consists of two beta-barrel domains. PR3 structure includes a disaccharide unit covalently attached to Asn159. PR3 substrate binding sites at S4 to S3'
molecular dynamics simulations of PR3 anchored at three different phospholipid bilayers: dimyristoylphosphatidylcholine DMPC and dimyristoylphosphatidylglycerol DMPG, and an equimolar mixture of DMPC/DMPG. Basic residues R177, R186A, R186B, K187 and R222 interact via hydrogen bonds with the lipid headgroups to stabilize PR3 at the interfacial membrane region. Hydrophobic amino acids V163, F165, F166, I217, L223, and F224 insert into the hydrophobic core below the carbonyl groups of the bilayers and aromatic amino acids F165, F192, F215, W218, F224, and F227 contribute electrostatic interaction via cation-pi interactions with the choline groups of DMPC. PR3 presents all the characteristics of a peripheral membrane protein with an ability to bind negative phospholipids. The catalytic triad remains unperturbed by the presence of the membrane, the ligand binding sites are located in close proximity to the membrane and amino acids K99 and I217 interact significantly with the lipids
adopts a fold consisting of two beta-barrels made each of six anti-parallel beta-sheets. Crystallizes as a tetramer, which can be regarded as a dimer of dimers: two monomers in a dimer are oriented so that their active sites face each other, preventing the binding of large substrates. The hole in the middle of the tetramer is lined with hydrophobic residues. Contains four disulfide bridges between cysteine pairs 42-58, 136-201, 168-182 and 191-220. No X-ray structure of PR3 with a substrate in its active site available
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
S195A
site-directed mutagenesis, cDNA construction of a catalytically inactive active site enzyme mutant lacking the codons for the N-terminal activation dipeptide, DELTAPR3ctp-S195A
F180A/F181A
-
mutant is still able to display membrane PR3 after degranulation, with similar fluorescence intensity as wild-type
F180A/F181A/L228A/F229A
-
contrary to wild-type, membrane anchorage is abrogated in mutant. Mutant is still able to cleave the synthetic substrate Boc-Ala-Pro-Val in cell lysates, but fails to cleave extracellular fibronectin, is not externalized after apoptosis and does not impair macrophage phagocytosis of apoptotic cells, does not promote myeloid cell proliferation and fails to cleave p21/waf1
F180A/L228A/F229A
-
mutant is still able to display membrane PR3 after degranulation, with similar fluorescence intensity as wild-type
L228A
-
mutant is still able to display membrane PR3 after degranulation, with similar fluorescence intensity as wild-type
L228A/F229A
-
mutant is still able to display membrane PR3 after degranulation, with similar fluorescence intensity as wild-type
N102Q
-
glycosylation deficient recombinant PR3 mutant, hydrolytic activity like recombinant PR3-wild-type. N-terminal processing is delayed
N102Q/N147Q
-
glycosylation deficient recombinant PR3 mutant, reduction in hydrolytic activity in relation to recombinant PR3-wild-type. Reduction in hydrolytic activity is more pronounced than the reduction induced by deglycosylation of purified neutrophil PR3. N-terminal processing is delayed
N147Q
-
glycosylation deficient recombinant PR3 mutant, is processed like recombinant PR3-wild-type
R193A/R194A/K195A/R227A
-
contrary to wild-type, membrane anchorage is abrogated in mutant
S203A
additional information
-
catalytically inactive Ser195-substituted PR3 variant, eliminates quality check of the antigen preperation. Recombinant PR3 variants which only carry a single antigenic region on its surface may be used to neutralize or eliminate circulating anti-neutrophil cytoplasmic antibodies (ANCA) in patients without triggering immune complex-mediated type III reactions
S203A
-
enzymatically inactive. PR3 externalization depends on PLSCR1, but is independently of its serine-proteinase activity
TEMPERATURE STABILITY
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
glycosylation at Asn-147, but not at Asn-102, is critical for thermal stability
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
-
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression of His-tagged wild-type enzyme, expression of C-terminally c-myc-tagged wild-type pro-enzyme and mature enzyme, and of the C-terminally c-myc-His tagged truncated active site mutant enzyme in HEK-293 cells
stable recombinant expression fo wild-type and mutant enzymes in rat basophilic leukemia (RBL) cells
expressed in Sf-9 insect cells, HEK-293, HMC-1, RBL-1 and CHO cells. Expression of PR3 as a completely denatured and aggregated protein in Escherichia coli. Expression in Pichia pastoris or Saccharomyces cerevisiae
-
full-length cDNA amplified, enterokinase cleavage site (DDDDK) introduced at the N terminus of PR3. PCR product digested with PmlI/AgeI and cloned into the reading frame of the S-tag, resulting in construct pcDNA5/FRT/hPR3-H6. Human/gibbon chimeras performed by digestion of pcDNA5/FRT/PR3-H6 with BlpI and AgeI and exchange of the respective cDNA segments. Expression in Flp-in HEK293 cells
-
RBL-2H3 rat mast-cell line stably transfected with PR3 or its inactive mutant S203A
-
recombinant PR3 wild-type and recombinant PR3 glycosylation variants expressed in HMC-1 cells
-
recombinant PRTN3 protein with an amino-terminal histidine tag produced in SF-9 insect cells by use of a baculovirus expression system
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
histone demethylase JMJD3 (EC 1.14.11.68) regulates the expression of neutrophil membrane proteinase 3 (mPR3) in lipopolysaccharide-stimulated neutrophils during the early inflammatory response in sepsis
neutrophil membrane expression of PR3 increases during both activation and apoptosis. Membrane expression of PR3 is increased in patients with granulomatosis with polyangiitis
PR3 plasma concentrations are increased in patients with liver steatosis. PR3 concentration is upregulated in patients with type 2 diabetes when compared to lean and obese controls
activation with the calcium ionophore A23187 to optimize membrane-bound Pr3 exposure at the cell surface, whereby Pr3 activity increases by 5-20fold. Resting neutrophils have a genetically determined distribution of the protease that results in a bimodal membrane-bound Pr3 expression
-
in patients with anti-neutrophil cytoplasmic antibodies-associated systemic vasculitis, increased mRNA levels of both PR3 and CD177 are found, which do not correlate with the proportion of double-positive cells
-
increased percentages of mPR3-expressing neutrophils in patients with ANCA-associated systemic vasculitis (median 67%, range 16-100%) and patients with systemic lupus erythematosus (median 80%, range 25-100%), but not in patients with rheumatoid arthritis (median 61%, range 0-100%). Correlation of CD177 expression with PR3 expression on primed neutrophils. After priming with tumor necrosis factor alpha, neutrophils remain negative for CD177 while PR3 expression is induced. Expression of PR3 on the neutrophil surface can be independent of CD177 expression. Among the patients with PR3 ANCA-associated vasculitis, patients treated with cyclophosphamide or prednisolone have higher percentages of CD177-expressing neutrophils than do patients who have not received these treatments
-
size of the membrane-bound PR3 high expressing neutrophils ranges from 0% to 100% of the total number of neutrophils in a healthy population and remains strikingly constant within one individual over time. Percentage of membrane-bound PR3 expressing neutrophils is genetically determined. Elevated expression levels of membrane-bound PR3 in Wegener's granulomatosis, PR3-anti-neutrophil cytoplasmic autoantibodies associated vasculitis and other chronic inflammatory diseases. TNF-alpha may translocate PR3 to the plasma membrane and raise the expression level up to 2- to 3folds of that on resting neutrophils. IL-8, TGF-beta and GM-CSF upregulate membrane PR3 expression on neutrophils. CD177 is the receptor of membrane-bound PR3 and mediates PR3 expression on the neutrophil membrane
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
diagnostics
anti-neutrophil cytoplasmic antibodies with proteinase 3 specificity are a useful laboratory biomarker for the diagnosis of granulomatosis with polyangiitis, i.e.Wegener's granulomatosis
drug development
medicine
analysis
-
knowledge of the protonation states of the ionizable residues in an enzyme like PR3 is a prerequisite to an accurate description of its structure and mechanism
drug development
medicine
additional information
-
design of potent and highly specific substrates of proteinase 3 and other proteinases optimized in the prime site region
drug development
enzyme inhibitors may prove to be targets for the generation of agents in the treatment of neutrophilic inflammatory disease
drug development
proteinase 3-inhibiting antibodies may play a role in autoimmune vasculitis and can be exploited as highly selective inhibitors
drug development
enzyme Pr3 is a target for the generation of agents in the treatment of neutrophilic inflammatory disease
medicine
specific inhibition of PR3 activity to process IL-32 or neutralization of IL-32 by inactive PR3 or its fragments may reduce the consequences of IL-32 in immune regulated diseases
medicine
responsible for eliminating intracellular pathogens and breaking down tissues at inflammatory sites. Possible molecular target for anti-inflammatory agents. Involved in degradation of ECM components and cleavage of inflammatory mediators, platlet activation, induction of endothelial cells and apoptosis, negative feedback regulation of granulopoiesis. Shows bactericidal properties. Is a target of auto-antibodies in Wegeners granulomatosis
medicine
novel anti-proteinase-3-human native-human recombinant enzyme-linked immunosorbent assay (ELISA) with a very high sensitivity for the detection of proteinase-3-antineutrophil cytoplasmic antibodies (ANCA) in patients with ANCA-associated vasculitis with C-ANCA
drug development
-
design of inhibitors aimed at neutralizing the cleavage activity of PR3 toward endogenous annexin 1 and hence suitable for development as novel anti-inflammatory therapeutics
drug development
-
optimized sequences, which allow close interaction with the extended active site of Pr3 for the development of peptide or pseudopeptide inhibitors that do not interfere with Pr3-related proteases
drug development
-
recombinant PR3 variants have a great potential to study individual anti-PR3 responses and will advance the development of new epitope-based therapeutics
drug development
-
either blocking the membrane presentation of PR3 or neutralizing the functions of its binding partners may generate novel therapeutic strategies for anti-neutrophil cytoplasmic autoantibodies-associated vasculitis
drug development
-
further exploration of the S' subsites of Pr 3 may lead to the identification of highly selective, reversible competitive inhibitors of Pr 3 using a functionalized surrogate scaffold embellished with appropriate recognition elements
medicine
-
major target autoantigen in patients with Wegener's granulomatosis, a systemic vasculitis
medicine
-
down-regulation of anticoagulation during inflammation by rapid endothelial cell protein C receptor proteolysis by PR3
medicine
-
in patients with Wegeners granulomatosis, epitope recognition by anti-neutrophil cytoplasmic antibodies (ANCA) is affected by the glycosylation status of PR3
medicine
-
involved in autoimmune small vessel vasculitides, e. g. Wegener´s granulomatosis. PR3 is the main target autoatigen of antineutrophilic cytoplasmic antibodies (ANCA). Structure(charge)-based binding interactions between PR3-ANCA and conformational epitopes of PR3. Binding of PR3 to physiological molecules as well as to autoantibodies may induce and promote proinflammatory responses
medicine
-
PR3 induces DC maturation via protease-activated receptor-2. Wegeners autoantigen PR3 interacts with a gateway receptor (protease-activated receptor-2) on iDCs in vitro, triggering their maturation and licenses them for a Th1-type response potentially favoring granuloma formation in Wegeners granulomatosis. PR3-anti-neutrophil cytoplasmic antibodies are strongly associated with Wegeners granulomatosis. PR3-anti-neutrophil cytoplasmic antibodies opsonization of apoptotic neutrophils results in effective phagocytosis by human monocyte-derived macrophages and leads to up-regulation of proinflammatory mediator production. An animal model for PR3-anti-neutrophil cytoplasmic antibodies-associated vasculitis that shows characteristics similar to human Wegeners granulomatosis is not yet available
medicine
-
PR3- and CD177-expressing neutrophils constitute a subpopulation of neutrophils with an unknown role in the innate immune system, which may play an important role in diseases such as Wegeners granulomatosis and polycythemia vera
medicine
-
proinflammatory role of membrane PR3 expression may involve interference with macrophage clearance of apoptotic neutrophils
medicine
-
extra-intestinal pulmonary complications of ulcerative colitis with elevated proteinase-3 anti-neutrophil cytoplasmic antibody resembling Wegeners granulomatosis and spontaneous improvement
medicine
-
classic symptoms and clinical findings, together with serology titres positive for anti-neutrophil cytolplasmic antibody against proteinase 3 confirm the diagnosis of Wegener's Granulomatosis, which can occasionally involve other organs as the respiratory and renal tracts and in such cases a differential diagnosis of Wegener's Granulomatosis must be considered, as early recognition and treatment of this potentially fatal disease is paramount
medicine
-
neutrophil-activating potential of cANCAs can vary in patients, depending on the association rates, target specificities, and titers of antibodies, as well as on local concentrations of human PR3 inhibitors
medicine
-
only therapies based on the dual inhibition of caspase 1 and serine proteases will be successful in the management of complex inflammatory diseases in humans
medicine
-
the substrate N-Boc-3-[2-[2-(1'-methyl)pyrrolo]benzoxazol-5-yl]-Ala-Tyr-Tyr-Abu-(5-amino-2-nitrobenzamide) may be used for the construction of a very reliable, inexpensive, and easy to use diagnostic test for PR3 determination
medicine
-
affinity chromatography of neutrophil lysates using epoxy beads coated with Streptococcus sanguinis reveals involvement of PR3 in phagocytosis of Streptococcus sanguinis. Enzymatic cleavage of the glycosylphosphatidylinositol linker of NB1, a co-receptor for membrane-bound PR3, significantly reduces the phagocytosis. The neutralization of membrane-bound PR3 with antibody reduces both binding and phagocytosis of Streptococcus sanguinis. Protease activity is required for phagocytosis, and protease-activated receptor PAR2 is involved in signal transmission from PR3 during this process
medicine
-
in all individuals tested, neutrophils are either double-positive or double-negative for mPR3 and CD177. The proportion of double-positive neutrophils is increased significantly in anti-neutrophil cytoplasmic antibodies-associated systemic vasculitis and systemic lupus erythematosus patients. The proportion of mPR3+/CD177+ cells is not correlated to general inflammation, renal function, age, sex, drug treatment and levels of circulating PR3. The increased membrane expression of PR3 found in anti-neutrophil cytoplasmic antibodies-associated systemic vasculitis is not linked directly to circulating PR3 or PR3 gene transcription, but is dependent upon CD177 expression and correlated with the transcription of the CD177 gene
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Kam, C.M.; Kerrigan, J.E.; Dolman, K.M.; Goldschmeding, R.; von dem Borne, A.E.G.K.; Powers, J.C.
Substrate and inhibitor studies on proteinase 3
FEBS Lett.
297
119-123
1992
Homo sapiens
Labbaye, C.; Musette, P.; Cayre, Y.E.
Wegener autoantigen and myeloblastin are encoded by a single mRNA
Proc. Natl. Acad. Sci. USA
88
9253-9256
1991
Homo sapiens
Rao, N.V.; Wehner, N.G.; Marshall, B.C.; Gray, W.R.; Gray, B.H.; Hoidal, J.R.
Characterization of proteinase-3 (PR-3), a neutrophil serine proteinase. Structural and functional properties
J. Biol. Chem.
266
9540-9548
1991
Homo sapiens
Brubaker, M.J.; Groutas, W.C.; Hoidal, J.R.; Rao, N.V.
Human neutrophil proteinase 3: mapping of the substrate binding site using peptidyl thiobenzyl esters
Biochem. Biophys. Res. Commun.
188
1318-1324
1992
Homo sapiens
Hoidal, J.R.; Rao, N.V.; Gray, B.
Myeloblastin: leukocyte proteinase 3
Methods Enzymol.
244
61-67
1994
Homo sapiens
Dolman, K.M.; van de Wiel, B.A.; Kam, C.M.; Abbink, J.J.; Hack, C.E.; Sonnenberg, A.; Powers, J.C.; van dem Borne, A.E.G.K.; Goldscheding, R.
Determination of proteinase 3-alpha 1-antitrypsin complexes in inflammatory fluids
FEBS Lett.
314
117-121
1992
Homo sapiens
Renesto, P.; Halbwachs-Mecarelli, L.; Nusbaum, P.; Lesavre, P.; Chignard, M.
Proteinase 3. A neutrophil proteinase with activity on platelets
J. Immunol.
152
4612-4617
1994
Homo sapiens
Rao, N.V.; Rao, G.V.; Marshall, B.C.; Hoidal, J.R.
Biosynthesis and processing of proteinase 3 in U937 cells. Processing pathways are distinct from those of cathepsin G
J. Biol. Chem.
271
2972-2978
1996
Homo sapiens
Dolman, K.M.; van de Wiel, B.A.; Kam, C.M.; Kerrigan, J.E.; Hack, C.E.; van dem Borne, A.E.G.K.; Powers, J.C.; Goldschmeding, R.
Proteinase 3: substrate specificity and possible pathogenetic effect of Wegeners granulomatosis autoantibodies (c-ANCA) by dysregulation of the enzyme
Adv. Exp. Med. Biol.
336
55-60
1993
Homo sapiens
Wiedow, O.; Luedemann, J.; Utecht, B.; Christophers, E.
Inhibition of proteinase 3 activity by peptides derived from human epidermis
Adv. Exp. Med. Biol.
336
61-66
1993
Homo sapiens
Korkmaz, B.; Attucci, S.; Hazouard, E.; Ferrandiere, M.; Jourdan, M.L.; Brillard-Bourdet, M.; Juliano, L.; Gauthier, F.
Discriminating between the activities of human neutrophil elastase and proteinase 3 using serpin-derived fluorogenic substrates
J. Biol. Chem.
277
39074-39081
2002
Homo sapiens
Groutas, W.C.; Ruan, S.; Kuang, R.; Hook, J.B.; Sands, H.
Inhibition of human leukocyte proteinase 3 by a novel recombinant serine proteinase inhibitor (LEX032)
Biochem. Biophys. Res. Commun.
233
697-699
1997
Homo sapiens
Groutas, W.C.; Kuang, R.; Ruan, S.; Epp, J.B.; Venkataraman, R.; Truong, T.M.
Potent and specific inhibition of human leukocyte elastase, cathepsin G and proteinase 3 by sulfone derivatives employing the 1,2,5-thiadiazolidin-3-one 1,1 dioxide scaffold
Bioorg. Med. Chem.
6
661-671
1998
Homo sapiens
He, S.; Kuang, R.; Venkataraman, R.; Tu, J.; Truong, T.M.; Chan, H.K.; Groutas, W.C.
Potent inhibition of serine proteases by heterocyclic sulfide derivatives of 1,2,5-thiadiazolidin-3-one 1,1 dioxide
Bioorg. Med. Chem.
8
1713-1717
2000
Homo sapiens
Goldmann, W.H.; Niles, J.L.; Arnaout, M.A.
Interaction of purified human proteinase 3 (PR3) with reconstituted lipid bilayers
Eur. J. Biochem.
261
155-162
1999
Homo sapiens
Witko-Sarsat, V.; Canteloup, S.; Durant, S.; Desdouets, C.; Chabernaud, R.; Lemarchand, P.; Descamps-Latscha, B.
Cleavage of p21waf1 by proteinase-3, a myeloid-specific serine protease, potentiates cell proliferation
J. Biol. Chem.
277
47338-47347
2002
Homo sapiens, Rattus norvegicus
Koehl, C.; Knight, C.G.; Bieth, J.G.
Compared action of neutrophil proteinase 3 and elastase on model substrates. Favorable effect of S'-P' interactions on proteinase 3 catalysts
J. Biol. Chem.
278
12609-12612
2003
Homo sapiens
Campbell, E.J.; Campbell, M.A.; Owen, C.A.
Bioactive proteinase 3 on the cell surface of human neutrophils: quantification, catalytic activity, and susceptibility to inhibition
J. Immunol.
165
3366-3374
2000
Homo sapiens
Stummann, L.; Wiik, A.
A simple high yield procedure for purification of human proteinase 3, the main molecular target of cANCA
J. Immunol. Methods
206
35-42
1997
Homo sapiens
Korkmaz, B.; Attucci, S.; Moreau, T.; Godat, E.; Juliano, L.; Gauthier, F.
Design and use of highly specific substrates of neutrophil elastase and proteinase 3
Am. J. Respir. Cell Mol. Biol.
30
801-807
2004
Homo sapiens (P24158), Homo sapiens
Lombard, C.; Bouchu, D.; Wallach, J.; Saulnier, J.
Proteinase 3 hydrolysis of peptides derived from human elastin exon 24
Amino Acids
28
403-408
2005
Homo sapiens (P24158), Homo sapiens
Csernok, E.; Ai, M.; Gross, W.L.; Wicklein, D.; Petersen, A.; Lindner, B.; Lamprecht, P.; Holle, J.U.; Hellmich, B.
Wegener autoantigen induces maturation of dendritic cells and licenses them for Th1 priming via the protease-activated receptor-2 pathway
Blood
107
4440-4448
2006
Homo sapiens (P24158), Homo sapiens
Zani, M.L.; Nobar, S.M.; Lacour, S.A.; Lemoine, S.; Boudier, C.; Bieth, J.G.; Moreau, T.
Kinetics of the inhibition of neutrophil proteinases by recombinant elafin and pre-elafin (trappin-2) expressed in Pichia pastoris
Eur. J. Biochem.
271
2370-2378
2004
Homo sapiens (P24158), Homo sapiens
Nobar, S.M.; Zani, M.L.; Boudier, C.; Moreau, T.; Bieth, J.G.
Oxidized elafin and trappin poorly inhibit the elastolytic activity of neutrophil elastase and proteinase 3
FEBS J.
272
5883-5893
2005
Homo sapiens (P24158)
Wiesner, O.; Litwiller, R.D.; Hummel, A.M.; Viss, M.A.; McDonald, C.J.; Jenne, D.E.; Fass, D.N.; Specks, U.
Differences between human proteinase 3 and neutrophil elastase and their murine homologues are relevant for murine model experiments
FEBS Lett.
579
5305-5312
2005
Homo sapiens (P24158), Homo sapiens, Mus musculus (Q61096), Mus musculus
Hirche, T.O.; Crouch, E.C.; Espinola, M.; Brokelman, T.J.; Mecham, R.P.; DeSilva, N.; Cooley, J.; Remold-O'Donnell, E.; Belaaouaj, A.
Neutrophil serine proteinases inactivate surfactant protein D by cleaving within a conserved subregion of the carbohydrate recognition domain
J. Biol. Chem.
279
27688-27698
2004
Homo sapiens (P24158), Homo sapiens, Mus musculus (Q61096), Mus musculus
Dublet, B.; Ruello, A.; Pederzoli, M.; Hajjar, E.; Courbebaisse, M.; Canteloup, S.; Reuter, N.; Witko-Sarsat, V.
Cleavage of p21/WAF1/CIP1 by proteinase 3 modulates differentiation of a monocytic cell line. Molecular analysis of the cleavage site
J. Biol. Chem.
280
30242-30253
2005
Homo sapiens (P24158)
Pederzoli, M.; Kantari, C.; Gausson, V.; Moriceau, S.; Witko-Sarsat, V.
Proteinase-3 induces procaspase-3 activation in the absence of apoptosis: potential role of this compartmentalized activation of membrane-associated procaspase-3 in neutrophils
J. Immunol.
174
6381-6390
2005
Homo sapiens (P24158), Homo sapiens, Rattus norvegicus (Q8K597)
Hajjar, E.; Korkmaz, B.; Gauthier, F.; Brandsdal, B.O.; Witko-Sarsat, V.; Reuter, N.
Inspection of the binding sites of proteinase3 for the design of a highly specific substrate
J. Med. Chem.
49
1248-1260
2006
Homo sapiens (P24158), Homo sapiens
Schreiber, A.; Luft, F.C.; Kettritz, R.
Membrane proteinase 3 expression and ANCA-induced neutrophil activation
Kidney Int.
65
2172-2183
2004
Homo sapiens (P24158)
Pendergraft, W.F.3rd.; Rudolph, E.H.; Falk, R.J.; Jahn, J.E.; Grimmler, M.; Hengst, L.; Jennette, J.C.; Preston, G.A.
Proteinase 3 sidesteps caspases and cleaves p21 Waf1/Cip1/Sdi1 to induce endothelial cell apoptosis
Kidney Int.
65
75-84
2004
Homo sapiens (P24158), Homo sapiens
Novick, D.; Rubinstein, M.; Azam, T.; Rabinkov, A.; Dinarello, C.A.; Kim, S.H.
Proteinase 3 is an IL-32 binding protein
Proc. Natl. Acad. Sci. USA
103
3316-3321
2006
Homo sapiens (P24158), Homo sapiens
Korkmaz, B.; Moreau, T.; Gauthier, F.
Neutrophil elastase, proteinase 3 and cathepsin G: physicochemical properties, activity and physiopathological functions
Biochimie
90
227-242
2008
Homo sapiens (P24158), Homo sapiens
Mueller, A.; Voswinkel, J.; Gottschlich, S.; Csernok, E.
Human proteinase 3 (PR3) and its binding molecules: implications for inflammatory and PR3-related autoimmune responses
Ann. N. Y. Acad. Sci.
1109
84-92
2007
Homo sapiens
Kantari, C.; Pederzoli-Ribeil, M.; Amir-Moazami, O.; Gausson-Dorey, V.; Moura, I.C.; Lecomte, M.C.; Benhamou, M.; Witko-Sarsat, V.
Proteinase 3, the Wegener autoantigen, is externalized during neutrophil apoptosis: evidence for a functional association with phospholipid scramblase 1 and interference with macrophage phagocytosis
Blood
110
4086-4095
2007
Homo sapiens
Jenne, D.E.; Kuhl, A.
Production and applications of recombinant proteinase 3, Wegeners autoantigen: problems and perspectives
Clin. Nephrol.
66
153-159
2006
Homo sapiens, Mus musculus
Csernok, E.; Moosig, F.; Gross, W.L.
Pathways to ANCA production: From differentiation of dendritic cells by proteinase 3 to B lymphocyte maturation in Wegeners granuloma
Clin. Rev. Allergy Immunol.
34
300-306
2008
Homo sapiens, Mus musculus
Hajjar, E.; Korkmaz, B.; Reuter, N.
Differences in the substrate binding sites of murine and human proteinase 3 and neutrophil elastase
FEBS Lett.
581
5685-5690
2007
Homo sapiens, Mus musculus, Rattus norvegicus
Specks, U.; Fass, D.N.; Finkielman, J.D.; Hummel, A.M.; Viss, M.A.; Litwiller, R.D.; McDonald, C.J.
Functional significance of Asn-linked glycosylation of proteinase 3 for enzymatic activity, processing, targeting, and recognition by anti-neutrophil cytoplasmic antibodies
J. Biochem.
141
101-112
2007
Homo sapiens
Korkmaz, B.; Hajjar, E.; Kalupov, T.; Reuter, N.; Brillard-Bourdet, M.; Moreau, T.; Juliano, L.; Gauthier, F.
Influence of charge distribution at the active site surface on the substrate specificity of human neutrophil protease 3 and elastase. A kinetic and molecular modeling analysis
J. Biol. Chem.
282
1989-1997
2007
Homo sapiens
Vong, L.; DAcquisto, F.; Pederzoli-Ribeil, M.; Lavagno, L.; Flower, R.J.; Witko-Sarsat, V.; Perretti, M.
Annexin 1 cleavage in activated neutrophils: a pivotal role for proteinase 3
J. Biol. Chem.
282
29998-30004
2007
Homo sapiens
Fridlich, R.; David, A.; Aviram, I.
Membrane proteinase 3 and its interactions within microdomains of neutrophil membranes
J. Cell. Biochem.
99
117-125
2006
Homo sapiens
Bauer, S.; Abdgawad, M.; Gunnarsson, L.; Segelmark, M.; Tapper, H.; Hellmark, T.
Proteinase 3 and CD177 are expressed on the plasma membrane of the same subset of neutrophils
J. Leukoc. Biol.
81
458-464
2007
Homo sapiens
Villegas-Mendez, A.; Montes, R.; Ambrose, L.R.; Warrens, A.N.; Laffan, M.; Lane, D.A.
Proteolysis of the endothelial cell protein C receptor by neutrophil proteinase 3
J. Thromb. Haemost.
5
980-988
2007
Homo sapiens
Damoiseaux, J.; Daehnrich, C.; Rosemann, A.; Probst, C.; Komorowski, L.; Stegeman, C.A.; Egerer, K.; Hiepe, F.; van Paassen, P.; Stoecker, W.; Schlumberger, W.; Tervaert, J.W.
A novel enzyme-linked immunosorbent assay using a mixture of human native and recombinant proteinase-3 significantly improves the diagnostic potential for antineutrophil cytoplasmic antibody-associated vasculitis
Ann. Rheum. Dis.
68
228-233
2009
Homo sapiens (P24158), Homo sapiens
Armstrong, L.; Godinho, S.I.; Uppington, K.M.; Whittington, H.A.; Millar, A.B.
Tumour necrosis factor-alpha processing in interstitial lung disease: a potential role for exogenous proteinase-3
Clin. Exp. Immunol.
156
336-343
2009
Homo sapiens
Kasuga, A.; Mandai, Y.; Katsuno, T.; Sato, T.; Yamaguchi, T.; Yokosuka, O.
Pulmonary complications resembling Wegeners granulomatosis in ulcerative colitis with elevated proteinase-3 anti-neutrophil cytoplasmic antibody
Intern. Med.
47
1211-1214
2008
Homo sapiens
Wysocka, M.; Lesner, A.; Majkowska, G.; Legowska, A.; Guzow, K.; Rolka, K.; Wiczk, W.
The new fluorogenic substrates of neutrophil proteinase 3 optimized in prime site region
Anal. Biochem.
399
196-201
2010
Homo sapiens
Wysocka, M.; Lesner, A.; Guzow, K.; Kulczycka, J.; Legowska, A.; Wiczk, W.; Rolka, K.
Highly specific substrates of proteinase 3 containing 3-(2-benzoxazol-5-yl)-l-alanine and their application for detection of this enzyme in human serum
Anal. Chem.
82
3883-3889
2010
Homo sapiens
Hu, N.; Westra, J.; Huitema, M.G.; Bijl, M.; Brouwer, E.; Stegeman, C.A.; Heeringa, P.; Limburg, P.C.; Kallenberg, C.G.
Coexpression of CD177 and membrane proteinase 3 on neutrophils in antineutrophil cytoplasmic autoantibody-associated systemic vasculitis: anti-proteinase 3-mediated neutrophil activation is independent of the role of CD177-expressing neutrophils
Arthritis Rheum.
60
1548-1557
2009
Homo sapiens
Joosten, L.A.; Netea, M.G.; Fantuzzi, G.; Koenders, M.I.; Helsen, M.M.; Sparrer, H.; Pham, C.T.; van der Meer, J.W.; Dinarello, C.A.; van den Berg, W.B.
Inflammatory arthritis in caspase 1 gene-deficient mice: contribution of proteinase 3 to caspase 1-independent production of bioactive interleukin-1beta
Arthritis Rheum.
60
3651-3662
2009
Homo sapiens, Mus musculus
Hu, N.; Westra, J.; Kallenberg, C.G.
Membrane-bound proteinase 3 and its receptors: relevance for the pathogenesis of Wegeners Granulomatosis
Autoimmun. Rev.
8
510-514
2009
Homo sapiens
Dou, D.; He, G.; Li, Y.; Lai, Z.; Wei, L.; Alliston, K.R.; Lushington, G.H.; Eichhorn, D.M.; Groutas, W.C.
Utilization of the 1,2,3,5-thiatriazolidin-3-one 1,1-dioxide scaffold in the design of potential inhibitors of human neutrophil proteinase 3
Bioorg. Med. Chem.
18
1093-1102
2010
Homo sapiens
Hajjar, E.; Broemstrup, T.; Kantari, C.; Witko-Sarsat, V.; Reuter, N.
Structures of human proteinase 3 and neutrophil elastase - so similar yet so different
FEBS J.
277
2238-2254
2010
Homo sapiens, Mus musculus
Korkmaz, B.; Jaillet, J.; Jourdan, M.L.; Gauthier, A.; Gauthier, F.; Attucci, S.
Catalytic activity and inhibition of Wegener antigen proteinase 3 on the cell surface of human polymorphonuclear neutrophils
J. Biol. Chem.
284
19896-19902
2009
Homo sapiens
Kahn, R.; Hellmark, T.; Leeb-Lundberg, L.M.; Akbari, N.; Todiras, M.; Olofsson, T.; Wieslander, J.; Christensson, A.; Westman, K.; Bader, M.; Mueller-Esterl, W.; Karpman, D.
Neutrophil-derived proteinase 3 induces kallikrein-independent release of a novel vasoactive kinin
J. Immunol.
182
7906-7915
2009
Homo sapiens
Kuhl, A.; Korkmaz, B.; Utecht, B.; Kniepert, A.; Schoenermarck, U.; Specks, U.; Jenne, D.E.
Mapping of conformational epitopes on human proteinase 3, the autoantigen of Wegener's granulomatosis
J. Immunol.
185
387-399
2010
Homo sapiens, Macaca mulatta, Hylobates pileatus, Pan troglodytes verus
Geyer, M.; Kulamarva, G.; Davis, A.
Wegeners Granulomatosis presenting with an abscess in the parotid gland: a case report
J. Med. Case Rep.
3
19
2009
Homo sapiens
Hajjar, E.; Dejaegere, A.; Reuter, N.
Challenges in pKa predictions for proteins: the case of Asp213 in human proteinase 3
J. Phys. Chem. A
113
11783-11792
2009
Homo sapiens
Hua, F.; Wilde, B.; Dolff, S.; Witzke, O.
T-lymphocytes and disease mechanisms in Wegeners granulomatosis
Kidney Blood Press. Res.
32
389-398
2009
Homo sapiens
Piesche, M.; Hildebrandt, Y.; Chapuy, B.; Wulf, G.G.; Truemper, L.; Schroers, R.
Characterization of HLA-DR-restricted T-cell epitopes derived from human proteinase 3
Vaccine
27
4718-4723
2009
Homo sapiens
Abdgawad, M.; Gunnarsson, L.; Bengtsson, A.A.; Geborek, P.; Nilsson, L.; Segelmark, M.; Hellmark, T.
Elevated neutrophil membrane expression of proteinase 3 is dependent upon CD177 expression
Clin. Exp. Immunol.
161
89-97
2010
Homo sapiens
Kaellquist, L.; Rosen, H.; Nordenfelt, P.; Calafat, J.; Janssen, H.; Persson, A.M.; Hansson, M.; Olsson, I.
Neutrophil elastase and proteinase 3 trafficking routes in myelomonocytic cells
Exp. Cell Res.
316
3182-3196
2010
Homo sapiens
Kantari, C.; Millet, A.; Gabillet, J.; Hajjar, E.; Broemstrup, T.; Pluta, P.; Reuter, N.; Witko-Sarsat, V.
Molecular analysis of the membrane insertion domain of proteinase 3, the Wegeners autoantigen, in RBL cells: implication for its pathogenic activity
J. Leukoc. Biol.
90
941-950
2011
Homo sapiens
Kim, Y.C.; Shin, J.E.; Lee, S.H.; Chung, W.J.; Lee, Y.S.; Choi, B.K.; Choi, Y.
Membrane-bound proteinase 3 and PAR2 mediate phagocytosis of non-opsonized bacteria in human neutrophils
Mol. Immunol.
48
1966-1974
2011
Homo sapiens
Broemstrup, T.; Reuter, N.
How does proteinase 3 interact with lipid bilayers?
Phys. Chem. Chem. Phys.
12
7487-7496
2010
Homo sapiens (P24158)
Hwang, T.L.; Wang, W.H.; Wang, T.Y.; Yu, H.P.; Hsieh, P.W.
Synthesis and pharmacological characterization of 2-aminobenzaldehyde oxime analogs as dual inhibitors of neutrophil elastase and proteinase 3
Bioorg. Med. Chem.
23
1123-1134
2015
Homo sapiens (P24158), Homo sapiens
Hinkofer, L.C.; Hummel, A.M.; Stone, J.H.; Hoffman, G.S.; Merkel, P.A.; Spiera, E.R.; St Clair, W.; McCune, J.W.; Davis, J.C.; Specks, U.; Jenne, D.E.
Allosteric modulation of proteinase 3 activity by anti-neutrophil cytoplasmic antibodies in granulomatosis with polyangiitis
J. Autoimmun.
59
43-52
2015
Homo sapiens (P24158), Homo sapiens
Hinkofer, L.C.; Seidel, S.A.; Korkmaz, B.; Silva, F.; Hummel, A.M.; Braun, D.; Jenne, D.E.; Specks, U.
A monoclonal antibody (MCPR3-7) interfering with the activity of proteinase 3 by an allosteric mechanism
J. Biol. Chem.
288
26635-26648
2013
Homo sapiens (P24158)
Budnjo, A.; Narawane, S.; Grauffel, C.; Schillinger, A.S.; Fossen, T.; Reuter, N.; Haug, B.E.
Reversible ketomethylene-based inhibitors of human neutrophil proteinase 3
J. Med. Chem.
57
9396-9408
2014
Homo sapiens (P24158), Homo sapiens
Grzywa, R.; Lesner, A.; Korkmaz, B.; Sienczyk, M.
Proteinase 3 phosphonic inhibitors
Biochimie
166
142-149
2019
Homo sapiens (P24158)
Popow-Stellmaszyk, J.; Bajorowicz, B.; Malankowska, A.; Wysocka, M.; Klimczuk, T.; Zaleska-Medynska, A.; Lesner, A.
Design, synthesis, and enzymatic evaluation of novel ZnO quantum Dot-based assay for detection of proteinase 3 activity
Bioconjug. Chem.
29
1576-1583
2018
Homo sapiens (P24158)
Hwang, T.; Wang, W.; Wang, T.; Yu, H.; Hsieh, P.
Synthesis and pharmacological characterization of 2-aminobenzaldehyde oxime analogs as dual inhibitors of neutrophil elastase and proteinase 3
Bioorg. Med. Chem.
23
1123-1134
2015
Homo sapiens (P24158), Homo sapiens
Fu, Z.; Thorpe, M.; Akula, S.; Chahal, G.; Hellman, L.T.
Extended cleavage specificity of human neutrophil elastase, human proteinase 3, and their distant ortholog clawed frog PR3 - three elastases with similar primary but different extended specificities and stability
Front. Immunol.
9
2387
2018
Xenopus laevis, Homo sapiens (P24158), Homo sapiens
Chen, Y.; Liu, Z.; Pan, T.; Chen, E.; Mao, E.; Chen, Y.; Tan, R.; Wang, X.; Tian, R.; Liu, J.; Qu, H.
JMJD3 is involved in neutrophil membrane proteinase 3 overexpression during the hyperinflammatory response in early sepsis
Int. Immunopharmacol.
59
40-46
2018
Homo sapiens (P24158), Homo sapiens
Martin, K.R.; Kantari-Mimoun, C.; Yin, M.; Pederzoli-Ribeil, M.; Angelot-Delettre, F.; Ceroi, A.; Grauffel, C.; Benhamou, M.; Reuter, N.; Saas, P.; Frachet, P.; Boulanger, C.M.; Witko-Sarsat, V.
Proteinase 3 is a phosphatidylserine-binding protein that affects the production and function of microvesicles
J. Biol. Chem.
291
10476-10489
2016
Homo sapiens (P24158), Homo sapiens
Yang, T.H.; St John, L.S.; Garber, H.R.; Kerros, C.; Ruisaard, K.E.; Clise-Dwyer, K.; Alatrash, G.; Ma, Q.; Molldrem, J.J.
Membrane-associated proteinase 3 on granulocytes and acute myeloid leukemia inhibits T cell proliferation
J. Immunol.
201
1389-1399
2018
Homo sapiens (P24158)
Guarino, C.; Gruba, N.; Grzywa, R.; Dyguda-Kazimierowicz, E.; Hamon, Y.; Legowska, M.; Skorenski, M.; Dallet-Choisy, S.; Marchand-Adam, S.; Kellenberger, C.; Jenne, D.E.; Sienczyk, M.; Lesner, A.; Gauthier, F.; Korkmaz, B.
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
1858-1870
2018
Homo sapiens (P24158), Homo sapiens
Mirea, A.M.; Toonen, E.J.M.; van den Munckhof, I.; Munsterman, I.D.; Tjwa, E.T.T.L.; Jaeger, M.; Oosting, M.; Schraa, K.; Rutten, J.H.W.; van der Graaf, M.; Riksen, N.P.; de Graaf, J.; Netea, M.G.; Tack, C.J.; Chavakis, T.; Joosten, L.A.B.
Increased proteinase 3 and neutrophil elastase plasma concentrations are associated with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes
Mol. Med.
25
16
2019
Homo sapiens (P24158), Homo sapiens
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